[Prevention of operational thromboembolic risk in plastic and aesthetic surgery. Analysis of cases, inquiries of practice and recommendations of professional practices].
Thromboembolic accidents are a frightening complication of plastic and aesthetic surgery. The absence of recommendations for professional practices for the prevention of such accidents justified this work. The therapeutic practices of the surgeons were analysed and the results were then compared with those of the international literature. The analysis by a group of experts made it possible to establish recommendations for professional practices. This work consisted in collecting, retrospectively, the therapeutic practices and the complications of 440 surgeons, concerning four types of interventions (abdominoplasty, mammoplasty, abdominal lift and liposuction), from 2006 to 2008, i.e., approximately 110.000 interventions. The intervention with the greatest risk is abdominoplasty with 0.9% of thromboembolic accidents; the intervention with the least risk is mammoplasty with 0.1% of accidents. The risk with the abdominal lift and liposuction of more than three zones is similar and intermediate with 06% of accidents. A protocol of prevention of thromboembolic accidents in plastic surgery is proposed.


Ultradian mitotic rhythms in culture of human sarcomatous bone cells originating from the patient before and after chemotherapy.
Bone sarcomatous cells derived from human malignant tumors were cultured. The mitotic index was recorded for 39 hr. When the cultured cells originated from patients with cancer disease before any chemotherapy, ultradian mitotic rhythms of a 6-9-hr period were detected, but in many cases only after a sensitive statistical analysis was performed. When the cultured cells originated from cancer patients undergoing chemotherapy, the mitotic index was decreased, and the amplitudes of the 6-9-hr component oscillations of the mitotic index were highly significantly increased. Damping and fading out of an ultradian mitotic rhythmicity was a bad prognostic portent in bone cancer. With reference to chemotherapy, the restored and amplified ultradian rhythmicity disclosed an appreciable antitumor effect and better survival prospects for the patient.


cAMP-response element-binding protein mediates prostaglandin F2alpha-induced hypertrophy of vascular smooth muscle cells.
Prostaglandin F(2alpha) (PGF(2alpha)) is a vasoactive factor that causes constriction and hypertrophy of vascular smooth muscle cells (VSMCs). However, the mechanism of PGF(2alpha)-induced hypertrophy is largely unknown. Cyclic AMP-response element (CRE)-binding protein (CREB), the best characterized stimulus-induced transcription factor, activates transcription of target genes with CRE and promotes cell growth. We examined the role of CREB in PGF(2alpha)-induced hypertrophy of VSMCs. PGF(2alpha) induced phosphorylation of CREB at serine 133, which is a critical marker of activation, after 5-10min of stimulation in a dose-dependent manner. Pharmacological inhibition of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase (p38-MAPK) suppressed PGF(2alpha)-induced CREB phosphorylation. Inhibition of epidermal growth factor receptor (EGFR) and mitogen- and stress-activated protein kinase-1 also suppressed PGF(2alpha)-induced CREB phosphorylation. Overexpression of dominant-negative form of CREB (AdCREB M1), of which serine 133 was replaced with alanine, inhibited PGF(2alpha)-induced c-fos mRNA expression as well as hypertrophy of VSMCs [hypertrophy index (microg/10(4)cell); control 8.13, PGF(2alpha) 9.85, AdCREB M1 7.91, and AdCREB M1+PGF(2alpha) 8.43]. These results suggest that PGF(2alpha) activated CRE-dependent gene transcription through EGFR transactivation, and the CREB pathway plays a critical role in PGF(2alpha)-induced hypertrophy of VSMCs.


Characterization of microsatellite markers for the Restinga Antwren, Formicivora littoralis (Thamnophilidae), an endangered bird endemic to Brazil.
Molecular markers are important tools in determining parentage, gene flow, and the genetic structure of species. In the case of rare, endemic, and/or threatened species, these markers can be used to understand key ecological questions and support conservation actions. We developed seven microsatellite markers for the only bird endemic to the Restinga ecosystem. Microsatellite loci were isolated from a library that was based on 10 individuals (six males and four females). Primers were tested in 107 individuals of the same population. The number of alleles per locus ranged from 4 to 19, and the observed and expected heterozygosity varied from 0.15 to 0.84 and from 0.60 to 0.89, respectively. We expect that the polymorphic microsatellite loci we describe will be useful for other studies, particularly in the Tropics.


Antigenic similarity between cells transformed by ultraviolet radiation in vitro and in vivo.
Cells of the 10T 1/2 mouse fibroblast line transformed in vitro by ultraviolet radiation are antigenically similar to those from skin cancers produced in mice by repeated exposure to ultraviolet radiation. Both types of tumor cells grew preferentially in ultraviolet-irradiated syngeneic mice relative to untreated animals, and both were recognized by ultraviolet radiation-induced tumor-specific suppressor lymphocytes. These properties were not shared by 10T 1/2 cells transformed in vitro by x-rays or 3-methylcholanthrene.


Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata.
The substantia nigra pars reticulata belongs to the brain regions with the highest density of CB(1) cannabinoid receptors. Since the level of CB(1) receptor messenger RNA is very low in the pars reticulata, most of the receptors are probably localized on terminals of afferent axons. The hypothesis was tested that terminals of glutamatergic afferents of substantia nigra pars reticulata neurons possess CB(1) cannnabinoid receptors, the activation of which presynaptically modulates neurotransmission. Rat midbrain slices were superfused and the electrophysiological properties of substantia nigra pars reticulata neurons were studied with the patch-clamp technique. Focal electrical stimulation in the presence of bicuculline evoked excitatory postsynaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate glutamate receptors. The excitatory postsynaptic currents were reduced by the metabotropic glutamate receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 10(-4)M). The mixed CB(1)/CB(2) cannabinoid receptor agonists R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2, 3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone (WIN55212-2; 10(-8)-10(-5)M) and (-)-cis-3-[2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55940; 10(-6)M) also produced inhibition. The maximal inhibition by WIN55212-2 was 54+/-6%. The CB(1) cannabinoid antagonist N-piperidino-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A; 10(-6)M) prevented the effect of WIN55212-2, but had no effect when superfused alone. WIN55212-2 (10(-6)M) increased the amplitude ratio of two excitatory postsynaptic currents evoked with an interstimulus interval of 100ms. Currents evoked by short ejection of glutamate on to the surface of the slices were not changed by WIN55212-2. The results show that activation of CB(1) cannabinoid receptors inhibits glutamatergic synaptic transmission between afferent axons and neurons in the substantia nigra pars reticulata. The lack of effect of the cannabinoids on glutamate-evoked currents and the increase of the paired-pulse ratio indicate that the mechanism of action is presynaptic inhibition of transmitter release.


An unsymmetrical non-fullerene acceptor: synthesis via direct heteroarylation, self-assembly, and utility as a low energy absorber in organic photovoltaic cells.
This study reports on the design and synthesis of an unsymmetrical π-conjugated organic molecule composed of perylene diimide, thienyl diketopyrrolopyrrole, and indoloquinoxaline pieced together using direct heteroarylation. This material demonstrates unprecedented response in the thin-film upon post-deposition solvent vapor annealing, resulting in dramatic red-shifts in optical absorption. Such changes were utilized to enhance photocurrent generation in P3HT based organic solar cells.


Oxidative stress in ventral prostate, ovary, and breast by 2,4-dichlorophenoxyacetic acid in pre- and postnatal exposed rats.
The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been widely used in agriculture and forestry since the 1940s. 2,4-D has been shown to produce a wide range of adverse effects-from embryotoxicity and teratogenicity to neurotoxicity-on animal and human health. The purpose of this study was to determine the possible effects of pre- and postnatal exposure to 2,4-D on oxidative stress in ventral prostate, ovary and breast. Pregnant rats were daily exposed to oral doses of 70 mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the pups were sacrificed by decapitation at postnatal day (PND) 45, 60, or 90. Antioxidant enzyme activities and some parameters of the oxidative stress were assessed in ventral prostate, breast, and ovary. Results show that 2,4-D produced three different effects. First, it increased the concentration of some radical oxygen species and the rates of lipid peroxidation and protein oxidation in ventral prostate, thereby causing oxidative stress at all ages studied. Although an increase in the activity of some antioxidant enzymes was detected, this seemed to have been not enough to counteract the oxidative stress. Second, 2,4-D promoted the oxidative stress in the breasts, mainly during puberty and adulthood, probably because the developing gland is more sensitive to xenobiotics than the adult organ. Third, 2,4-D altered the activity of some antioxidant enzymes and increased lipid peroxide concentration in the ovary. This effect could reflect the variety of ovarian cell types and their different responses to endocrine changes during development.


The effect of clinically relevant thermocycling on the flexural properties of endodontic post materials.
It is suggested that fibre-reinforced composite (FRC) posts have lower elastic moduli than metal posts and this will reduce the incidence of root fracture. However, the mechanical properties may be altered in the oral environment. The aims of this study were to determine the effect on the flexural properties of FRC and metal post materials produced by: (1) a thermocycling regime which was clinically relevant and representative of that which would occur during 1 year in the mouth and (2) storage for 1 year at body temperature. Nine FRC and two metal post material samples were sealed in polythene sleeves and thermocycled between 10 degrees C and 50 degrees C for 10,000 cycles. Additional samples were stored dry at 37 degrees C for 1 year. The flexural strength and moduli were determined by three-point bending and compared with untreated control samples. Thermocycling and storage at 37 degrees C for 1 year decreased the mean flexural modulus of all materials. This was statistically significant for 8 of 11 materials after thermocycling, and 4 of 11 materials after storage at 37 degrees C (p<0.05). Thermocycling and storage at 37 degrees C produced a non-significant increase in yield strength for both metal post materials. Thermocycling significantly increased the flexural strength of Postec while it decreased for the other FRC materials. Storage at 37 degrees C increased the flexural strength of three FRC materials (significantly for Postec) while it was decreased among the other materials. Although some of the changes noticed in flexural properties were statistically significant, it is doubtful that they are of sufficient magnitude to affect clinical performance.


[Comparative study of moderate and virulent phages of mesophilous lactic acid streptococci].
A method has been developed to identify phage containing mesophilous lactic acid streptococci. The method is based on the chloroform treatment of young cultures. The isolated moderate phages P4St and P6St are morphologically identical and serologically related to one another and to virulent phages P1Sv, P2Sv, P3Sv, P12Sv, P13Sv that can be isolated in industrial phagolysis.


Fall about laughing: a case of laughter syncope.
Laughter syncope is an unusual but recognized form of situational syncope likely to have a similar pathophysiological origin to tussive syncope. There are few case reports of this syndrome in the literature. Patients, as in this case, might present initially to the ED, and laughter should be considered among the numerous differentials for syncope.


Inflammatory demyelinating polyradiculoneuropathy associated with interstitial lung disease.
A 58-year-old woman presented with inflammatory demyelinating polyradiculoneuropathy accompanied by sensory and motor disturbance and interstitial lung disease. Corticosteroid therapy led to a marked amelioration of both the neuropathy and the lung disease. We suggest that a demyelinating neuropathy is associated with an interstitial lung disease.


Single molecule atomic force microscopy of aerolysin pore complexes reveals unexpected star-shaped topography.
Aerolysin is the paradigmatic member of a large family of toxins that convert from a water-soluble monomer/dimer into a membrane-spanning oligomeric pore. While there is x-ray crystallographic data of its water-soluble conformation, the most recent structural model of the membrane-inserted pore is based primarily on data of water-soluble tetradecamers of mutant protein, together with computational modeling ultimately performed in vacuum. Here we examine this pore model with atomic force microscopy (AFM) of membrane-associated wild-type complexes and all-atom molecular dynamics (MD) simulations in water. In striking contrast to a disc-shaped cap region predicted by the present model, the AFM images reveal a star-shaped complex, with a central ring surrounded by seven radial projections. Further, the MD simulations suggest that the locations of the receptor-binding (D1) domains in the present model are not correct. However, a modified model in which the D1 domains, rather than localized at fixed positions, adopt a wide range of configurations through fluctuations of an intervening linker is compatible with existing data. Thus our work not only demonstrates the importance of directly resolving such complexes in their native environment but also points to a dynamic receptor binding region, which may be critical for toxin assembly on the cell surface.


Respiratory disorders in stainless steel workers.
The study involved 106 workers exposed to stainless steel dust (47 stainless steel welders, 59 stainless steel handling workers) and 80 controls. Respiratory impairment was evaluated by means of a standardised questionnaire, clinical examination and lung function tests (spirometry, forced expiratory flow). Dyspnoea was encountered more frequently among exposed workers but there was no greater prevalence of chronic bronchitis compared to the control group. Lung function tests (FEV1, PEF, FEF75, FEF50, FEF25) were significantly lower in the exposed group. Smoking did not contribute essentially to these changes. The results confirm that stainless steel dust is an important cause of the development of respiratory obstructive disorders in the industrial working population.


Percutaneous suprapubic cystolithotripsy for pediatric bladder stones in a developing country.
To evaluate our experience with percutaneous suprapubic cystolithotripsy (PCCL) in Yemeni children with endemic urinary bladder stones. Between January 1993 and December 1998, 117 children underwent percutaneous suprapubic lithotripsy in Arabia Felix Modern Hospital, Sana'a Republic of Yemen. The patients' ages ranged from 8 months to 14 years (average 3.7 years). Ninety patients (77%) were under 5 years old; 20 patients (16%) were between 6 and 10 years old, and 7 patients (6%) were between 11 and 14 years old. There were 116 boys and 1 girl. The stone size ranged from 0.7 to 4 (average 2.3) cm. Five patients had coexisting urinary bilharziasis and another 5 patients had coexisting renal stone. In 10 patients, the stone was in the urethra. The procedure was done under general anesthesia. Dilation of the tract was made under fluoroscopy. The instrument was an adult 26-french nephroscope, the same as that used for percutaneous nephrolithotripsy. Ultrasound disintegration was needed for stones of > 1 cm. A suprapubic catheter was left for 24 h, and a urethral catheter was kept for 48 h. All patients became stone free. The average operating time was 15 (5-50) min. The average hospital stay was 2.7 (2-5) days. No severe intra- or postoperative complication was observed. The nucleus and/or the main component of the stones were ammonium acid urate in 109 patients (93%). Based on our experience we can conclude that percutaneous suprapubic lithotripsy is a safe and effective method for the treatment of bladder stones in children. It reduces morbidity and hospital stay and thus the cost of treatment. Our series proves the nutritional etiology of endemic pediatric bladder stones. To our knowledge, this is the largest series reported on percutaneous suprapubic management of endemic bladder stones in children.


Thoracoscopic lobectomy for type I pleuropulmonary blastoma in an infant.
Pleuropulmonary blastoma (PPB) is a rare, aggressive, intrathoracic mesenchymal neoplasm associated with cystic lung lesions. The authors describe an 8-month-old male who underwent thoracoscopic left upper lobectomy for a cystic lung lesion initially diagnosed as congenital pulmonary airway malformation. Pathology revealed type I PPB.


Muscarinic modulation of TREK currents in mouse sympathetic superior cervical ganglion neurons.
Muscarinic receptors play a key role in the control of neurotransmission in the autonomic ganglia, which has mainly been ascribed to the regulation of potassium M-currents and voltage-dependent calcium currents. Muscarinic agonists provoke depolarization of the membrane potential and a reduction in spike frequency adaptation in postganglionic neurons, effects that may be explained by M-current inhibition. Here, we report the presence of a riluzole-activated current (IRIL ) that flows through the TREK-2 channels, and that is also inhibited by muscarinic agonists in neurons of the mouse superior cervical ganglion (mSCG). The muscarinic agonist oxotremorine-M (Oxo-M) inhibited the IRIL by 50%, an effect that was abolished by pretreatment with atropine or pirenzepine, but was unaffected in the presence of himbacine. Moreover, these antagonists had similar effects on single-channel TREK-2 currents. IRIL inhibition was unaffected by pretreatment with pertussis toxin. The protein kinase C blocker bisindolylmaleimide did not have an effect, and neither did the inositol triphosphate antagonist 2-aminoethoxydiphenylborane. Nevertheless, the IRIL was markedly attenuated by the phospholipase C (PLC) inhibitor ET-18-OCH3. Finally, the phosphatidylinositol-3-kinase/phosphatidylinositol-4-kinase inhibitor wortmannin strongly attenuated the IRIL , whereas blocking phosphatidylinositol 4,5-bisphosphate (PIP2 ) depletion consistently prevented IRIL inhibition by Oxo-M. These results demonstrate that TREK-2 currents in mSCG neurons are inhibited by muscarinic agonists that activate M1 muscarinic receptors, reducing PIP2 levels via a PLC-dependent pathway. The similarities between the signaling pathways regulating the IRIL and the M-current in the same neurons reflect an important role of this new pathway in the control of autonomic ganglia excitability.


The development of health care-seeking behaviors in traditional-age undergraduate college students.
Traditional-age undergraduate college students are embarking into the world of autonomous decision making. These decisions encompass not only academics but also lifestyle and life-skills. One of the life-skill areas in which students have difficulty is seeking health care independently. The aim of this pilot study is to gather qualitative data to help illuminate the process of the development of health care-seeking behaviors in traditional-age undergraduate college students (18-23 years). A purposive focus group sample of eight traditional-age undergraduate college students was recruited from a private university in the northeastern United States. Five major themes emerged: needing help or care, expectations, decision making, healthcare accessibility, and future needs. Health care for these student participants is expected upon demand by them in this "age of convenience." The findings indicate these traditional-age undergraduate college students view themselves as independent but still rely on parental supervision of health care. Implications for providing primary health care for this generation may include marketing strategies to meet this perspective of "24-7" care based upon this limited focus group, but further expanded studies are needed for generalizations.


US demonstration of a thrombosed persistent median artery in carpal tunnel syndrome.
Median artery of the forearm and wrist is not very frequently observed because it normally involutes before birth. Only a few cases of persistent median artery thrombosis associated with compression of the median nerve in the carpal tunnel have been reported. In these cases symptoms arise suddenly and surgery consists of the excision of the thrombosed arterial branch. In cases of large persistent unthrombosed median artery associated with carpal tunnel syndrome (CTS), excision of the unthrombosed median artery is not indicated because it may sometimes substantially contribute to the circulation of the hand. We report the case of a 39-year-old man with CTS associated with a thrombosis of a persistent median artery detected by high-resolution US and Doppler ultrasound. US can be also useful to exclude other causes of CTS such as tenosynovitis of the flexor tendons, ganglion cyst, musculotendinous variants, and various soft tissue tumors.


Prevention of eating disorders and obesity via the internet.
Internet technology has been expanding rapidly and has had a dramatic impact on how people communicate, learn and share information. This article presents applications of internet technology to the psychological domain, particularly in the prevention and treatment of eating disorders and obesity. Information regarding advantages and disadvantages of computerized interventions are discussed and several examples of randomized controlled trials with this technology are presented. The studies presented are not meant to be comprehensive of psychological interventions in general, but are examples of computerized applications from the eating disorder and obesity literatures. Ethical considerations and areas for future direction are also discussed.


The value of neuroendocrine markers in non-small cell lung cancer: a comparative immunohistopathologic study.
In order to estimate the value of immunohistochemical identification of neuroendocrine (NE) differentiation markers in non-small cell lung carcinomas (NSCLCs), we investigated the expression of five neuroendocrine and neural differentiation-related antigens in 51 NSCLCs. Additionally, 20 epithelial lung tumors with NE differentiation [15 carcinoids and five small cell lung carcinomas (SCLCs)] and 61 epithelial tumors of various other origin (breast, prostate, colon and head-neck carcinomas) were studied. An indirect two-stage immunoperoxidase method was performed in formalin-fixed and paraffin-embedded tissue specimens, by using commercially available monoclonal antibodies. These antibodies are directed against neuron-specific enolase (NSE), chromogranin-A and Leu-7 which are general markers of NE differentiation, bombesin, which is a specific NE secretory product and neurofilament triplet protein (NFTP), an intermediate filament protein of neuronal differentiation. All five markers demonstrated a positive immunoreactivity in NSCLCs, equally distributed to all three histologic subtypes, ranging from 16 to 47% of the cases (NSE 47%, bombesin 21.5%, Leu-7 21.5%, chromogranin-A 18% and NFTP 16%). Most of the carcinoids and SCLCs expressed multiple or all NE markers. The other four epithelial tumors showed a positive immunoreactivity for bombesin, Leu-7 and NFTP, ranging from 11 to 40% of the cases. Chromogranin-A was not expressed in any of these tumors, whereas NSE was demonstrated only in 17% of breast carcinomas. The following remarks can be drawn from this study: (1) some NSCLCs showed immunophenotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (specificity, 100%); and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable neuroendocrine differentiation in lung epithelial tumors.


Simultaneous determination of 6,7-dimethylesculetin and geniposide in rat plasma and its application to pharmacokinetic studies of Yin Chen Hao Tang preparation.
A method for the rapid and simultaneous determination of 6,7-dimethylesculetin (CAS 120-08-1) and geniposide (CAS 24512-63-8) in rat plasma has been developed, using validated high performance liquid chromatography (HPLC) with solid phase extraction (SPE). The HPLC analysis was performed on a commercially available column (200 mm x 4.6 mm, 5 microm) with acetonitrile-methanol-0.1% aqueous formic acid as mobile phase and the UV detection at 343 nm and 238 nm for 6,7-dimethylesculetin and geniposide, respectively. The calibration curves for 6,7-dimethylesculetin and geniposide were linear over the range 0.4-25.6 microg/mL and 1.12-71.68 microg/mL, respectively. The lower limits of quantitation were 0.40 microg/ mL and 1.12 microg/mL, and the lower limits of detection were 0.06 microg/mL and 0.09 microg/ mL, respectively. The intra-day and inter-day precision for 6,7-dimethylesculetin and geniposide were < 5%, whereas the absolute recovery percentages were > 74%. A successful application of the developed HPLC analysis was demonstrated for the pharmacokinetic study of a Traditional Chinese Medicine formula of Yin Chen Hao Tang preparation.


Dissipative Remote-State Preparation in an Interacting Medium.
Standard quantum state preparation methods work by preparing a required state locally and then distributing it to a distant location by a free-space propagation. We instead study procedures of preparing a target state at a remote location in the presence of an interacting background medium on which no control is required, manipulating only local dissipation. In mathematical terms, we characterize a set of reduced steady states stabilizable by local dissipation. An explicit local method is proposed by which one can construct a wanted one-site reduced steady state at an arbitrary remote site in a lattice of any size and geometry. In the chain geometry we also prove uniqueness of such a steady state. We demonstrate that the convergence time to fixed precision is smaller than the inverse gap, and we study robustness of the scheme in different medium interactions.


Ultrahigh Aspect Ratio Copper-Nanowire-Based Hybrid Transparent Conductive Electrodes with PEDOT:PSS and Reduced Graphene Oxide Exhibiting Reduced Surface Roughness and Improved Stability.
Copper nanowires (CuNWs) with ultrahigh aspect ratio are synthesized with a solution process and spray-coated onto select substrates to fabricate transparent conductive electrodes (TCEs). Different annealing methods are investigated and compared for effectiveness and convenience. The CuNWs are subsequently combined with the conductive polymer poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) ( PSS) or with reduced graphene oxide (rGO) platelets in order to reduce the surface roughness and improve the durability of the fabricated TCEs. Our best-performing PSS/CuNW films have optical transmittance T550 = 84.2% (at λ = 550 nm) and sheet resistance Rs = 25 Ω/sq, while our best CuNW/rGO films have T550 = 84% and Rs = 21.7 Ω/sq.


Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22.
Bacteriophages P22, T4+, and T4os (osmotic shock-resistant mutant with altered capsids) were diluted in 0.85% NaCl and exposed to gamma irradiation (2.79 Gy/min) at room temperature (24 degrees C). T4+ was more sensitive to inactivation than was P22, and the T4os mutant was even more sensitive than T4+. Catalase exhibited a strong protective effect and superoxide dismutase a weaker protection, indicating that H2O2 or some product derived therefrom was predominant in causing inactivation of plaque formation. Low but significant (0.1-0.3 mM) reduced glutathione (GSH) enhanced phage inactivation, but a higher (1 mM) GSH concentration protected. A similar effect was found for the polyamine, spermidine. In contrast, 0.1 mM L-ergothioneine (2-thiol-L-histidine betaine) exhibited strong protection and 1 mM afforded essentially complete protection. L-Ergothioneine is present in millimolar concentrations in some fungi and is conserved up to millimolar concentrations in critical tissues when consumed by man. L-Histidine and two histidine-containing dipeptides, carnosine and anserine, protected at a concentration of 1 mM, a level at which they are present in striated muscles of various animals.


Synthesis of indolo[1,2-f]phenanthridines by Pd-catalyzed domino C-N coupling/hydroamination/C-H arylation reactions.
A new and convenient method for the synthesis of indolo[1,2-f]phenanthridines via palladium-catalyzed domino C-N coupling/hydroamination/C-H arylation reactions was developed. The reactions allow for the synthesis of various phenanthridines in good yields from easily accessible starting materials using a single palladium catalyst.


Water load test in children.
The purpose of this study was to estimate values for the water load test in healthy elementary school children. We measured the volume of water consumed by 176 children (71 boys and 105 girls) using the water load test at school. Children completed a questionnaire, which included self-efficacy and abdominal pain history. Then subjects drank water for 3 minutes or until full. Children drank 630 +/- 260 ml. Water consumption correlated with age, weight, and height. Children who believed they could drink a lot, drank more than those who thought they could not, < 0.01. The water load test is a simple and inexpensive method to estimate onset of satiety and may be useful in future studies now that there are values for healthy children.


A note on the prebiotic synthesis of organic acids in carbonaceous meteorites.
Strong similarities between monocarboxylic and hydroxycarboxylic acids in the Murchison meteorite suggest corresponding similarities in their origins. However, various lines of evidence apparently implicate quite different precursor compounds in the synthesis of the different acids. These seeming inconsistencies can be resolved by postulating that the apparent precursors also share a related origin. Pervasive D enrichment indicates that this origin was in a presolar molecular cloud. The organic acids themselves were probably synthesized [correction of synthesised] in an aqueous environment on an asteroidal parent body, the hydroxy (and amino) acids by means of the Strecker cyanohydrin reaction.


Integration of local and regional species-area relationships from space-time species accumulation.
A long-standing observation in community ecology is that the scaling of species richness, as exemplified by species-area curves, differs on local and regional scales. This decoupling of scales may be largely due to sampling processes (the increasing constraint imposed by sampling fewer individuals at fine scales), as distinct from ecological processes, such as environmental heterogeneity, that operate across scales. Removal of the sampling constraint from fine-scale richness estimates should yield species-area curves that behave like those of the regions in which they are embedded, but an effective method for this removal has not been available. We suggest an approach that incorporates the manner in which small areas accumulate species over time as a way to remove the signature of sampling processes from fine-scale species-area curves. We report for three species-rich grasslands from two continents how local plant species richness is distributed through time at multiple, nested spatial scales, and we ask whether sampling-corrected curves reflect the spatial scaling of richness of each larger floristic province. Our analysis suggests that fine-scale values of richness are highly constrained by sampling processes, but once these constraints are removed, the spatial scaling of species richness is consistent from the scale of individuals to that of an entire province.


Vulvodynia and fungal association: a preliminary report.
Vulvodynia (vulvar pain syndrome) is a chronic multifactorial disease affecting almost 13 million women in the USA and can lead to morbidity and a reduced quality of life. We hypothesize that an initial microbiological insult in the vagina causes modifications in the biological vaginal milieu and/or an alteration on the lactobacilli flora. The vaginal milieu responds to the insult by developing an inflammatory reaction with abnormal cytokine production. These hypotheses were tested quantifying vaginal lactobacillus and cytokines, in patients with vulvodynia compared to matched healthy controls. Our preliminary data suggest a vaginal flora alteration and an immunological response involving Candida in patients with vulvodynia. Ongoing studies will assist us to clarify these findings.


The medical management of abnormal uterine bleeding in reproductive-aged women.
In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention.


Natural sesquiterpenoids.
This review covers the isolation, structural determination, synthesis and chemical and microbiological transformations of natural sesquiterpenoids. The literature is reviewed, and 435 references are cited.


[Cysteinyl leukotriene receptor 1 is involved in rotenone-induced injury of PC12 cells].
To investigate whether cysteinyl leukotriene receptor 1 (CysLT₁ receptor) is involved in rotenone-induced injury of PC12 cells. After 24 h treatment with rotenone or with rotenone and the CysLT₁ receptor antagonist montelukast, PC12 cell viability was determined by the colorimetric MTT reduction assay. After PC12 cells were treated with various concentrations of rotenone for 24 h or with 3 μmol/L rotenone for various durations, the expression of CysLT(1) receptor was determined by Western blotting, and its intracellular distribution was detected by immunocytochemistry. Rotenone (0.3-30 μmol/L) induced PC12 cell injury; this injury was significantly attenuated by montelukast at 1 and 5 μmol/L.The expression of CysLT(1) receptor increased after rotenone treatment at 1-10 μmol/L, or at 3 μmol/L for 3 and 24 h. Rotenone caused concentration-and time-dependent translocation of CysLT₁ receptor from the nucleus to the cytosol. Cysteinyl leukotriene receptor 1 is involved in rotenone-induced injury of PC12 cells.


Effect of a cocoa polyphenol extract in spontaneously hypertensive rats.
In this study, we evaluated the short-term effect of a cocoa polyphenol extract (CPE), in spontaneously hypertensive rats (SHR). Male 17-22-week-old SHR were administered by intragastric gavage water, 50 mg kg(-1) Captopril or CPE at different doses (13, 26, 80 and 160 mg kg(-1)). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by the tail cuff method before the administration and also 2, 4, 6, 8, 24, 48 and 72 h post-administration. Highly significant decreases in the SBP and in the DBP were observed when captopril or CPE was administered to SHR. The cocoa extract produced a dose dependent effect in the SBP of the SHR up to the dose of 80 mg kg(-1). Nevertheless this dose of CPE did not decrease the arterial blood pressure in the normotensive Wistar Kyoto rats. The decrease in the SBP caused by 80 mg kg(-1) of CPE in the SHR (-39.1 ± 3.7 mm Hg) was maximum 6 h post-administration, and the initial values of SBP were recovered 72 h post-administration of this extract. Paradoxically, 160 mg kg(-1) of the cocoa extract caused a decreased antihypertensive effect than lower doses of CPE. In addition, the decrease in DBP was always more accentuated when the dose of CPE administered was lower. Our results suggest that CPE may be used as a functional food ingredient with beneficial effects for controlling arterial blood pressure.


Is gastrin partially responsible for body weight reduction after gastric bypass?
The rationale for bariatric surgery is to reduce food intake by gastric restriction and/or malabsorption by intestinal bypass. Unlike ghrelin, gastrin is released in response to food intake. Here we studied the possible role of gastrin in the reduction of body weight after gastric bypass surgery. Rats were divided into four experimental groups and were subjected to different treatments: sham operation, gastric bypass, sham operation + gastrin infusion, and gastric bypass + gastrin infusion. The gastric bypass was done by anastomosing the esophagus to the duodenal bulb without bypassing the intestine. Gastrin-17 was infused continuously for 2 months via subcutaneously implanted osmotic minipumps. Body weights were recorded; serum gastrin and ghrelin levels were measured, and the stomachs were analyzed morphologically. Gastric bypass resulted in reducing the body weight, stomach weight, thickness of the oxyntic mucosa, serum gastrin concentration, and activity of the ECL cells. Gastrin infusion prevented mucosal atrophy and ECL cell inactivation, and attenuated the body weight reduction that occurred following gastric bypass. Circulating ghrelin and ghrelin-producing A-like cells in stomachs that had undergone gastric bypass were unchanged with or without gastrin infusion and are thus unlikely to be responsible for the reduced body weight. We suggest that hypogastrinemia and impaired ECL cell function in the oxyntic mucosa of the stomach might be partially responsible for the reduction in body weight that occurs after gastric bypass.


DFT study of Fe-Ni core-shell nanoparticles: stability, catalytic activity, and interaction with carbon atom for single-walled carbon nanotube growth.
Metal catalysts play an important role in the nucleation and growth of single-walled carbon nanotubes (SWCNTs). It is essential for probing the nucleation and growth mechanism of SWCNTs to fundamentally understand the properties of the metal catalysts and their interaction with carbon species. In this study, we systematically studied the stability of 13- and 55-atom Fe and Fe-Ni core-shell particles as well as these particles interaction with the carbon atoms using the density functional theory calculations. Icosahedral 13- and 55-atom Fe-Ni core-shell bimetallic particles have higher stability than the corresponding monometallic Fe and Ni particles. Opposite charge transfer (or distribution) in these particles leads to the Fe surface-shell displays a positive charge, while the Ni surface-shell exhibits a negative charge. The opposite charge transfer would induce different chemical activities. Compared with the monometallic Fe and Ni particles, the core-shell bimetallic particles have weaker interaction with C atoms. More importantly, C atoms only prefer staying on the surface of the bimetallic particles. In contrast, C atoms prefer locating into the subsurface of the monometallic particles, which is more likely to form stable metal carbides. The difference of the mono- and bimetallic particles on this issue may result in different nucleation and growth mechanism of SWCNTs. Our findings provide useful insights for the design of bimetallic catalysts and a better understanding nucleation and growth mechanism of SWCNTs.


A GRAS-type transcription factor with a specific function in mycorrhizal signaling.
Legumes establish mutualistic associations with mycorrhizal fungi and with nitrogen-fixing rhizobial bacteria. These interactions occur following plant recognition of Nod factor from rhizobial bacteria and Myc factor from mycorrhizal fungi. A common symbiosis signaling pathway is involved in the recognition of both Nod factor and Myc factor and is required for the establishment of these two symbioses. The outcomes of these associations differ, and therefore, despite the commonality in signaling, there must be mechanisms that allow specificity. In Nod factor signaling, a complex of GRAS-domain transcription factors controls gene expression downstream of the symbiosis signaling pathway. Here, we show that a GRAS-domain transcription factor, RAM1, functions in mycorrhizal-specific signaling. Plants mutated in RAM1 are unable to be colonized by mycorrhizal fungi, with a defect in hyphopodia formation on the surface of the root. RAM1 is specifically required for Myc factor signaling and appears to have no role in Nod factor signaling. RAM1 regulates the expression of RAM2, a glycerol-3-phosphate acyl transferase that promotes cutin biosynthesis to enhance hyphopodia formation. We conclude that mycorrhizal signaling downstream of the symbiosis-signaling pathway has parallels with nodulation-specific signaling and functions to promote mycorrhizal colonization by regulating cutin biosynthesis.


Biological asymmetries and the fidelity of eukaryotic DNA replication.
A diploid human genome contains approximately six billion nucleotides. This enormous amount of genetic information can be replicated with great accuracy in only a few hours. However, because DNA strands are oriented antiparallel while DNA polymerization only occurs in the 5'----3' direction, semi-conservative replication of double-stranded DNA is an asymmetric process, i.e., there is a leading and a lagging strand. This provides a considerable opportunity for non-random error rates, because the architecture of the two strands as well as the DNA polymerases that replicate them may be different. In addition, the proteins that start or finish chains may well be different from those that perform the bulk of chain elongation. Furthermore, while replication fidelity depends on the absolute and relative concentrations of the four deoxyribonucleotide precursors, these are not equal in vivo, not constant throughout the cell cycle, and not necessarily equivalent in all cell types. Finally, the fidelity of DNA synthesis is sequence-dependent and the eukaryotic nuclear genome is a heterogeneous substrate. It contains repetitive and non-repetitive sequences and can actually be considered as two subgenomes that differ in nucleotide composition and gene content and that replicate at different times. The effects that each of these asymmetries may have on error rates during replication of the eukaryotic genome are discussed.


Maximized song learning of juvenile male zebra finches following BDNF expression in the HVC.
During song learning, vocal patterns are matched to an auditory memory acquired from a tutor, a process involving sensorimotor feedback. Song sensorimotor learning and song production of birds is controlled by a set of interconnected brain nuclei, the song control system. In male zebra finches, the beginning of the sensorimotor phase of song learning parallels an increase of the brain-derived neurotrophic factor (BDNF) in just one part of the song control system, the forebrain nucleus HVC. We report here that transient BDNF-mRNA upregulation in the HVC results in a maximized copying of song syllables. Each treated bird shows motor learning to an extent similar to that of the selected best learners among untreated zebra finches. Because this result was not found following BDNF overexpression in the target areas of HVC within the song system, HVC-anchored mechanisms are limiting sensorimotor vocal learning.


Epilepsy and driving in Belgium: proposals and justification.
Proposals about the regulations and medical criteria concerning epilepsy and driving, originally drawn up by the Commission on Epilepsy and Risk from the Belgian League against Epilepsy were discussed and amended by a panel of representatives of several scientific societies and of all Belgian universities in order to establish a broad consensus among Belgian epileptologists. The history of driving licencing in Belgium is discussed and some background information given to put the regulations in perspective. A proposal is made for an acceptable level of risk. Subsequently, a quantification of risk for different situations concerning seizures is attempted. The proposals will be discussed and some further practical advice given. Individual assessment of the ability to drive remains indispensable.


Assessing communication between oncology professionals and their patients.
Effective communication with cancer patients continues to be an elusive goal for health care professionals (HCPs) and cancer educators. We posted a survey on the ConversationsInCare.com Web site to collect information from oncology HCPs regarding attitudes, effectiveness, and specific patient communication skills. The 291 respondents agreed that good communication enhances patient satisfaction (76%) and treatment compliance (88%). Only 34% of respondents felt comfortable discussing complementary or alternative therapies, and approximately half of all respondents felt they lack the skills to help patients maintain hope. Oncology HCPs believe that good communication is important and wish to improve their skills. Implications for cancer educators are discussed.


Activation of mPTP-dependent mitochondrial apoptosis pathway by a novel pan HDAC inhibitor resminostat in hepatocellular carcinoma cells.
Over-expression and aberrant activation of histone deacetylases (HDACs) are often associated with poor prognosis of hepatocellular carcinoma (HCC). Here, we evaluated the potential anti-hepatocellular carcinoma (HCC) cell activity by resminostat, a novel pan HDAC inhibitor (HDACi). We demonstrated that resminostat induced potent cytotoxic and anti-proliferative activity against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, resminostat treatment in HCC cells activated mitochondrial permeability transition pore (mPTP)-dependent apoptosis pathway, which was evidenced by physical association of cyclophilin-D and adenine nucleotide translocator 1 (ANT-1), mitochondrial depolarization, cytochrome C release and caspase-9 activation. Intriguingly, the mPTP blockers (sanglifehrin A and cyclosporine A), shRNA knockdown of cyclophilin-D or the caspase-9 inhibitor dramatically attenuated resminostat-induced HCC cell apoptosis and cytotoxicity. Reversely, HCC cells with exogenous cyclophilin-D over-expression were hyper-sensitive to resminostat. Intriguingly, a low concentration of resminostat remarkably potentiated sorafenib-induced mitochondrial apoptosis pathway activation, leading to a profound cytotoxicity in HCC cells. The results of this preclinical study indicate that resminostat (or plus sorafenib) could be further investigated as a valuable anti-HCC strategy.


Characterization of a novel serine/threonine kinase associated with nuclear bodies.
A novel protein kinase, Mx-interacting protein kinase (PKM), has been identified in a yeast two-hybrid screen for interaction partners of human MxA, an interferon-induced GTPase with antiviral activity against several RNA viruses. A highly conserved protein kinase domain is present in the N-terminal moiety of PKM, whereas an Mx interaction domain overlaps with C-terminal PEST sequences. PKM has a molecular weight of about 127,000 and exhibits high sequence homology to members of a recently described family of homeodomain-interacting protein kinases. Recombinant PKM has serine/threonine kinase activity that is abolished by a single amino acid substitution in the ATP binding domain (K221W). PKM catalyzes autophosphorylation and phosphorylation of various cellular and viral proteins. PKM is expressed constitutively and colocalizes with the interferon-inducible Sp100 protein and murine Mx1 in discrete nuclear structures known as nuclear bodies.


Spondyloepiphyseal dysplasia Omani type: a new recessive type of SED with progressive spinal involvement.
We report a large inbred kindred from Oman with a distinct type of spondyloepiphyseal dysplasia (SED). We evaluated eight individuals from two consanguineous sibships, one male and seven females between the ages of 2 and 22. The pedigrees strongly suggest autosomal recessive inheritance and both families are likely to be related through distant consanguineous loops. The clinical features include near to normal length at birth, short stature with final height of 110-130 cm, shortening of the upper segment due to severe progressive kyphoscoliosis, severe arthritic changes with joint dislocations, rhizomelic limbs, genu valgum, cubitus valgus, mild brachydactyly, camptodactyly, microdontia, and normal intelligence. Minor radiographic metaphyseal changes were found, but major manifestations were in the spine and the epiphyses. During the first year of life the vertebral bodies are of normal height but the endplates are irregular and intervertebral space is narrow. With age, the vertebral endplates become increasingly irregular, the intervertebral space diminishes further and individual vertebrae start to fuse resulting in a severe short trunk dwarfism with kyphoscoliosis. The epiphysis are small and precocious osteoarthropathy was observed involving small and large joints. The elbow, wrist, and hip joints were affected starting in infancy and showed restricted movement. Osteoarthropathy and spinal involvement resulted in physical handicap in early adulthood. Comparison of these patients with other skeletal dysplasias suggests that they represent a previously undescribed variant of SED.


Smoking, ignorance, and peripheral vascular disease.
The effect of the surgeon's advice to give up smoking was studied in a group of 43 patients with peripheral vascular disease (PVD), using blood carboxyhemoglobin levels to detect deception. Only seven of 40 patients (17.5%) actually stopped smoking, but the remainder appeared fairly honest in reporting their continued habits. Few patients were aware of the possible harmful effect of smoking on the peripheral arteries. The 43 patients with PVD who smoked had significantly higher carboxyhemoglobin levels than a group of 25 smokers without PVD although their cigarette consumption was the same. This suggests that carboxyhemoglobin levels may provide a better indication of the risk of smoking than overall cigarette consumption alone in the development of PVD.


EGR1 expression: a calcium and ERK1/2 mediated PPARγ-independent event involved in the antiproliferative effect of 15-deoxy-Δ12,14-prostaglandin J2 and thiazolidinediones in breast cancer cells.
Our aim was to get new information about the Peroxisome Proliferator Activated Receptor gamma (PPARγ)-independent pathway involved in the antiproliferative action of PPARγ ligands in breast cancer cells. We investigated the effects of Troglitazone (TGZ), Ciglitazone (CGZ), Rosiglitazone (RGZ) and, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ(2)) on the hormone-dependent breast cancer cell line MCF7. The early transcription factor EGR1 (Early Growth Response gene 1) mRNA and protein levels peaked after 3h of incubation with 25μM TGZ, CGZ or 15d-PGJ(2) and then gradually decreased. RGZ, the most potent activator of PPARγ, did not show this effect. The PPARγ antagonist GW 9662 did not block EGR1 mRNA induction which also still occurred in case of PPARγ silencing as well as in case of treatment with the PPARγ-inactive compound Δ2-TGZ. EGR1 mRNA induction required ERK1/2 phosphorylation which was not blocked by EGF Receptor (EGFR) inhibition. The ERK1/2 pathway was also involved in Δ2-TGZ-induced EGR1 mRNA expression in the hormone-independent breast cancer cell line MDA-MB-231. Using the fluorescent dye Fura2, we showed in MCF7 that TGZ or Δ2-TGZ induced an immediate increase in cytosolic calcium which was required for ERK1/2 phosphorylation and EGR1 mRNA induction as demonstrated by calcium chelation experiments. Furthermore, in MCF7 transfected with siRNA targeting EGR1, Δ2-TGZ inhibited less efficiently cell proliferation.


Phosphate-solubilizing bacteria will not significantly remobilize soil cadmium remediated by weathered coal.
Cadmium (Cd) re-mobilize by phosphate-solubilizing bacteria (PSB) from immobilization contaminated soil has drawn great attention due to its serious threat to human health through food chain. However, Cd binding with weathered coal (WC), an effective Cd immobilization material, will be re-mobilized by PSB or not is still unclear. In this study, the soil and sand pots with Cd were respectively mixed with the weight fractions of 0‰, 2‰, and 3‰ WC, inoculated with or without PSB, and planted with Amaranthus mangostanus L. The experimental results indicated that: (i) Cd in soil was transformed into organic fraction with WC, which has been led to the Cd accumulation concentrations in roots and shoots reduced by 38.8% and 20.5%, respectively; (ii) PSB could promote the concentration of exchangeable-Cd fraction and soil Cd uptake by amaranth in all treatments; and (iii) WC application in sand pot respectively reduced the Cd accumulation by 47.5% in roots and 24.1% in shoots, but PSB inoculation showed no significant effect on Cd accumulation in plants under WC application. SEM, zeta potential, and FT-IR results showed that PSB inoculation after Cd immobilized by WC had no influence on the microstructure, amount of negative charge, type, and content of functional groups in WC, indicating that organic fraction Cd in WC was not re-mobilized by PSB. Therefore, the application of WC in contaminated soil was conducive to transforming Cd in organic-bound forms and intensifying Cd immobilization effects.


[Utility of random amplified polymorphic DNA in the discrimination between Candida albicans and Candida dubliniensis].
Candida dubliniensisis a recently described species closely related to Candida albicans. Since the discrimination between both species by conventional mycological methods is not easy, many researchers have been trying DNA-related techniques in order to identify C. dubliniensis correctly. In this study, we propose the use of the random amplification of polymorphic DNA (RAPD) with a commercialized short primer which discriminates between both species. This oligonucleotide, AB1-12, allowed also separating C. albicans isolates into four different genotypes. These genotypes were different from the unique genotype observed in C. dubliniensis.


Drawing the line: the boundaries of volunteering in the community care of older people.
Volunteers can play important roles in the provision of support and care to frail or confused older people living in their own homes. There are conflicting expectations as to what these roles should be since there are unclear boundaries with those of paid care and with informal care. The present article explores some of these boundaries, drawing on material from a study of 14 volunteer schemes in England. The aim of the research was to explore the roles played by volunteers in the overall care division of labour. The main method used was that of semistructured interviews with organizers and volunteer coordinators of the schemes involved. The findings presented here relate to the limitations on the type of cases taken on, and to the boundaries with professional care, paid manual work and informal care. It concludes that the ways in which these boundaries are established and maintained depends not only on legal and policy constraints at the level of the state, but also on negotiation between organizations and individuals at a local level. The issues raised are of importance not only to research in the area, but to anyone planning similar schemes in the future.


Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients.
This investigation was designed to determine whether the five genes, CLC, DSG3, EMP3, S100A2 and SLPI, are differentially expressed in keratoconus, as indicated from another study. Gene expression was monitored using quantitative real-time PCR on 14 keratoconus samples and 16 controls, and normalized to GAPDH and B2M. The DSG3, S100A2, and SLPI proteins were quantified by Western blotting, and the cellular localization was determined by immunohistochemistry. One of the genes, CLC, was reduced in gene expression and its four exons were sequenced. The five genes were all differentially expressed in keratoconus (P < 0.04) and so were at least three of the encoded proteins (P = 0.009). DSG3 was expressed in association with the cell membrane of the basal and suprabasal epithelial cells, and S100A2 was expressed in the nucleus and cytoplasm, often as intracellular granules. Two SNPs (rs374185 and rs384138) were observed in the CLC gene, each with an allele frequency of 68%. No other mutations were detected. The five genes, and three of the encoded proteins, were shown differentially expressed between a group of keratoconus patients and a reference group using different techniques. These alterations, in combination with earlier findings, strongly demonstrate the genes to be involved in the corneal disease. We suggest the unambiguously expressed DSG3 protein to be used as a marker for keratoconus.


On the local representation of the electronic momentum operator in atomic systems.
The local quantum theory is applied to the study of the momentum operator in atomic systems. Consequently, a quantum-based local momentum expression in terms of the single-electron density is determined. The limiting values of this function correctly obey two fundamental theorems: Kato's cusp condition and the Hoffmann-Ostenhof and Hoffmann-Ostenhof exponential decay. The local momentum also depicts the electron shell structure in atoms as given by its local maxima and inflection points. The integration of the electron density in a shell gives electron populations that are in agreement with the ones expected from the Periodic Table of the elements. The shell structure obtained is in agreement with the higher level of theory computations, which include the Kohn-Sham kinetic energy density. The average of the local kinetic energy associated with the local momentum is the Weizsacker kinetic energy. In conclusion, the local representation of the momentum operator provides relevant information about the electronic properties of the atom at any distance from the nucleus.


Diseases of the intracranial meninges: MR imaging features.
Although the meninges are often thought of simplistically as a connective tissue sac that contains the CSF and the contents of the CNS, they are far more complex. Anatomically, they comprise several layers. Pathologically, numerous disease processes may affect the meninges; different processes may even involve different areas of the meninges. These factors all influence the MR imaging characteristics of meningeal lesions. This review briefly discusses the anatomy of the meninges, the MR imaging technique when meningeal disease is suspected, and the appearance of the normal meninges. It then focuses on tumors, infections, cysts, and other lesions that primarily involve the meninges, excluding lesions that secondarily involve the meninges.


Weight training in youth-growth, maturation, and safety: an evidence-based review.
To review the effects of resistance training programs on pre- and early-pubertal youth in the context of response, potential influence on growth and maturation, and occurrence of injury. Evidence-based review. Twenty-two reports dealing with experimental resistance training protocols, excluding isometric programs, in pre- and early-pubertal youth, were reviewed in the context of subject characteristics, training protocol, responses, and occurrence of injury. Experimental programs most often used isotonic machines and free weights, 2- and 3-day protocols, and 8- and 12-week durations, with significant improvements in muscular strength during childhood and early adolescence. Strength gains were lost during detraining. Experimental resistance training programs did not influence growth in height and weight of pre- and early-adolescent youth, and changes in estimates of body composition were variable and quite small. Only 10 studies systematically monitored injuries, and only three injuries were reported. Estimated injury rates were 0.176, 0.053, and 0.055 per 100 participant-hours in the respective programs. Experimental training protocols with weights and resistance machines and with supervision and low instructor/participant ratios are relatively safe and do not negatively impact growth and maturation of pre- and early-pubertal youth.


Effects of age and calcium ion on testis carbonyl reductase in rats.
To examine the role of carbonyl reductase (CR) in the development and function of testis, age-related changes in CR and the effect of exogenous calcium on CR in rat testis were studied. Testicular CR activity was the highest at 3 weeks of age when the enzyme activity was measured at 2, 3, 4, 8 and 20 weeks of age. The intensity of positive protein bands in testicular cytosol was similar among these age groups in Western blot analysis with anti-rat ovarian CR antibody. In 3-week-old rats, intravenous administration of 4 mg/kg calcium markedly suppressed the activity to about 50% of the control level 1 min after the treatment. Pretreatment with nicardipine prevented the inhibitory effect of exogenous calcium on the testicular CR activity in 3-week-old rats, indicating that the suppressing action of calcium on the enzyme activity was mediated by the entry of extracellular calcium via calcium channels. There were no significant changes in the CR activity following the treatment with calcium and nicardipine in the other 3 age groups examined. These findings suggest that testicular CR plays an important role in the functional development of the testis during the infantile period in rats.


Daily stress and the trajectory of mood: spillover, response assimilation, contrast, and chronic negative affectivity.
Experience sampling methodology was used to examine the effects of current and prior problems on negative mood within and across days. Forty male community residents wore signal watches and kept dairy records of problem occurrence and mood 8 times a day for 8 consecutive days. Trait negative affectivity (NA), prior mood, and concurrent stress were related to mood during the day. Mood in response to a current problem was worse if the prior time had been problem free than if the prior time had been stressful. High NA Ss were more reactive to concurrent stressors than were low NAs, but the effect was small. NA and current-day stress were the major influences of mood across days. High NAs were more distressed by current-day problems and recovered more slowly from problems of the preceding day. The benefits of conceptualizing the effects of daily stressors on mood in terms of spillover, response assimilation, habituation, and contrast are discussed.


Proteome analysis of the rat cornea during angiogenesis.
Angiogenesis is the formation of new blood vessels from the pre-existing vasculature. However, the study of this complex process is often hampered by the lack of a suitable cell-based model and the tools to study the biochemical events that lead to new blood vessel growth. The most widely accepted model for angiogenesis is the in vivo rat corneal model. In this model, the cornea, which is normally an avascular tissue, is stimulated to undergo angiogenesis in response to silver nitrate cauterization or to the implantation of an exogenous angiogenic agent. The physical changes associated with the new vessel growth can be readily monitored visually, but the regulated biochemical events that result in the growth and remodeling of the new vessels are much more challenging to decipher. In this report, a proteomics approach is evaluated for its utility in deciphering the biochemical events during a time course of angiogenic stimulation. At various time points post-silver nitrate cautery, corneas were harvested, solubilized, and analyzed by two-dimensional gel electrophoresis. Protein expression profiles at the various stages of angiogenesis were compared to those of control corneas. One hundred and eleven differentially-expressed proteins were identified by either matrix-assisted laser desorption/ionization-time of flight mass spectrometry or liquid chromatography-coupled electrospray ionization tandem mass spectrometry. Many of the proteins up-regulated during the angiogenesis process were identified as blood-related proteins, thus validating the development of functional blood vessels in the normally avascular tissue of the cornea. Furthermore, detection of differentially-regulated proteins in cauterized versus control tissue clearly validated the utility of a proteomics approach to study this model of angiogenesis. However, in order to get at the key regulatory proteins in the angiogenesis process, it is clear that additional scale-up and enrichment approaches will be required.


Laparoscopic Antireflux Surgery: Importance of Patient's Selection and Preoperative Workup.
Laparoscopic antireflux surgery (LARS) is an excellent option for patients with symptoms refractory to medical treatment, for patients who have complications secondary to the use of proton pump inhibitors, and for those who do not want to take medications for a long period of time. We hypothesized that (1) LARS has excellent outcomes if a complete preoperative workup and proper patient selection are performed and (2) recurrent symptoms often are not due to failure of the fundoplication to control the pathologic reflux. Every patient referred for antireflux surgery underwent a detailed symptomatic evaluation, barium swallow, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM), and pH monitoring. A fundoplication was performed in all of them. Data were analyzed to determine outcomes across 8 years. From 2008 to 2016, 176 patients with gastroesophageal reflux disease (GERD) underwent LARS. One hundred and thirty-four patients (76.1%) had a total fundoplication, 31 (17.6%) had an anterior partial fundoplication, and 11 (6.3%) had a posterior partial fundoplication. Thirty-nine patients (22.2%) referred persistent or recurrent symptoms after the procedure and underwent EGD, HRM, and pH monitoring. Abnormal reflux was documented in 5 patients (2.8%). Among these failures, 3 patients had a body mass index (BMI) ≥30 and 2 had ≥35. The results of this study showed that (1) laparoscopic fundoplication is an effective procedure for GERD; (2) patient's BMI can affect the outcome of a fundoplication; and (3) pH monitoring is important to establish if recurrent symptoms are secondary to failure of the operation.


Effect of immune manipulation on natural immune responses to murine mammary tumor antigens.
The virus-host relationship in BALB/cfC3H virgin female mice neonatally infected with an oncogenic virus (mammary tumor virus) (MuMTV) was significantly altered by a brief immunosuppressive treatment during young adult life. Natural immune responses were augmented and changed. The ability of lymphoid cells to attack target cells expressing MuMTV-associated antigens was significantly increased, and a new component, a non-T-cell reactivity, was added to the T-cell reactivity found in normal females. Serum blocking factors were both quantitatively and qualitatively altered.


Effects of acute hyperammonemia on cerebral amino acid metabolism and pHi in vivo, measured by 1H and 31P nuclear magnetic resonance.
The effects of an acute intravenous infusion of ammonium acetate on rat cerebral glutamate and glutamine concentrations, energy metabolism, and intracellular pH were measured in vivo with 1H and 31P nuclear magnetic resonance (NMR). The level of blood ammonia maintained by the infusion protocol used in this study (approximately 500 microM, arterial blood) did not cause significant changes in arterial PCO2, PO2, or pH. Cerebral glutamate levels fell to at least 80% of the preinfusion value, whereas glutamine concentrations increased 170% relative to the preinfusion controls. The fall in brain glutamate concentrations followed a time course similar to that of the rise of brain glutamine. There were no detectable changes in the content of phosphocreatine (PCr) or nucleoside triphosphates (NTP), within the brain regions contributing to the sensitive volume of the surface coil, during the ammonia infusion. Intracellular pH, estimated from the chemical shift of the inorganic phosphate resonance relative to the resonance of PCr in the 31P spectrum, was also unchanged during the period of hyperammonemia. 1H spectra, specifically edited to allow quantitation of the brain lactate content, indicated that lactate rose steadily during the ammonia infusion. Detectable increases in brain lactate levels were observed approximately 10 min after the start of the ammonia infusion and by 50 min of infusion had more than doubled. Spectra acquired from rats that received a control infusion of sodium acetate were not different from the spectra acquired prior to the infusion of either ammonium or sodium acetate.(ABSTRACT TRUNCATED AT 250 WORDS)


Single EDL Myofiber Isolation for Analyses of Quiescent and Activated Muscle Stem Cells.
Adult satellite cells are quiescent, but are poised for activation in response to exercise, injury, or disease allowing adult muscle growth or repair. Once activated, satellite cells proliferate extensively to produce enough myogenic progenitors in order to regenerate the muscles. In order to self-renew, a subset of activated satellite cells can resist the myogenic differentiation and return to quiescence to replenish the satellite cell pool. These cellular processes that normally occur during skeletal muscle regeneration can be recapitulated ex vivo using isolated and cultured myofibers. Here, we describe a protocol to isolate single myofibers from the extensor digitorum longus muscle. Moreover, we detail experimental conditions for analyzing satellite cells in quiescence and progression through the myogenic lineage.


Invasive Streptococcus pneumoniae infections in children in Kamikawa and Soya subprefecture, Hokkaido, Japan, 2000-2010, before the introduction of the 7-valent pneumococcal conjugate vaccine.
We evaluated 103 cases of invasive pneumococcal disease (IPD) encountered in 99 children (two developed the disease twice and one, three times) treated in the northern district of Hokkaido (Kamikawa and Soya subprefecture) from April 2000 until March 2010, before the introduction of the 7-valent pneumococcal conjugate vaccine. The main diseases were as follows: pneumonia, 54 cases (52.9%); occult bacteremia, 34 cases (33.3%); meningitis, five cases (4.9%). There were 42 cases during the first half of the study period (from April 2000 to March 2005) and 61 during the second half (from April 2005 to March 2010). The IPD morbidity rate for the 10-year period was 41.3 per 100,000 population in children <5 years and 79.2 per 100,000 population in children <2 years. Serotype analysis of the 77 strains was performed. The most frequent serotype isolated was 6B (31.2%), followed by 23F (14.3%), 19F (13.0%), 9V (7.8%), 6A (7.8%), and 14 (3.9%). The number of strains that could potentially be covered by heptavalent pneumococcal conjugate vaccine was 55 (71.4%), and the number of strains that could potentially be covered by 13-valent pneumococcal conjugate vaccine was 64 (83.1%). Analysis of penicillin-binding protein (PBP) genes was performed of the 82 strains. The percentages of resistant bacteria caused by PBP gene mutations were 42.7% (35 strains) for gPRSP, 48.8% for gPISP (40 strains), and 8.5% for gPSSP (7 strains).


Slow oxidation of acetoxime and methylethyl ketoxime to the corresponding nitronates and hydroxy nitronates by liver microsomes from rats, mice, and humans.
Acetoxime and methylethyl ketoxime (MEKO) are tumorigenic in rodents, inducing liver tumors in male animals. The mechanisms of tumorigenicity for these compounds are not well defined. Oxidation of the oximes to nitronates of secondary-nitroalkanes, which are mutagenic and tumorigenic in rodents, has been postulated to play a role in the bioactivation of ketoximes. In these experiments, we have compared the oxidation of acetoxime and methylethyl ketoxime to corresponding nitronates in liver microsomes from different species. The oximes were incubated with liver microsomes from mice, rats, and several human liver samples. After tautomeric equilibration and extraction with n-hexane, 2-nitropropane and 2-nitrobutane were quantitated by GC/MS-NCI (limit of detection of 250 fmol/injection volume). In liver microsomes, nitronate formation from MEKO and acetoxime was dependent on time, enzymatically active proteins, and the presence of NADPH. Nitronate formation was increased in liver microsomes of rats pretreated with inducers of cytochrome P450 and reduced in the presence of inhibitors (n-octylamine and diethyldithiocarbamate). Rates of oxidation of MEKO (Vmax) were 1.1 nmol/min/mg (mice), 0.5 nmol/min/mg (humans), and 0.1 nmol/min/mg (rats). In addition to nitronates, several minor metabolites were also enzymatically formed (two diastereoisomers of 3-nitro-2-butanol, 2-hydroxy-3-butanone oxime and 2-nitro-1-butanol). Acetoxime was also metabolized to the corresponding nitronate at rates approximately 50% of those observed with MEKO oxidation in the three species examined. 2-Nitro-1-propanol was identified as a minor product formed from acetoxime. No sex differences in the capacity to oxidize acetoxime and MEKO were observed in the species examined. The observed results show that formation of sec-nitronates from ketoximes occurs slowly, but is not the only pathway involved in the oxidative biotransformation of these compounds. Due to the lack of sex-specific oxidative metabolism, other metabolic pathways or mechanisms of tumorigenicity not involving bioactivation may be involved in the sex-specific tumorigenicity of ketoximes in rodents.


A gene encoding a new ONECUT class homeodomain protein in the ascidian Halocynthia roretzi functions in the differentiation and specification of neural cells in ascidian embryogenesis.
Genes encoding a novel group of homeodomain transcription factors, ONECUT class homeodomain proteins, have previously been isolated from vertebrate and insect. Among them, vertebrate HNF-6 is expressed in hepatocytes and the central nervous system during embryogenesis. Although the functions of HNF-6 in hepatocytes have been well studied, the functions of HNF-6 in the central nervous system remain unknown. In this study, we isolated HrHNF-6, which encodes a new ONECUT class homeodomain protein, from an ascidian, Halocynthia roretzi. HrHNF-6 mRNA was expressed exclusively in neural cells, just posterior to the expression of Hroth during embryogenesis. One of the functions of HrHNF-6 in neural cells is the activation of the expression of HrTBB2, the ascidian beta-tubulin gene. Another is the restriction of the expression of HrPax-258 (which is expressed in the neural tube), suggesting that HrHNF-6 functions in the specification of the neural tube. These results indicate that HrHNF-6 functions in the differentiation and regional specification of neural cells during ascidian embryogenesis.


Embelin-loaded oral niosomes ameliorate streptozotocin-induced diabetes in Wistar rats.
Embelin is a natural compound possessing a plethora of pharmacological activities, including antidiabetic activity. When formulated as niosomes, embelin offers additional advantages of nanoformulations and can be further exploited for clinical use. An oral niosome formulation of embelin was developed using a thin-film hydration technique, and its antidiabetic activity was studied. The formulation was characterized in terms of entrapment efficiency, vesicle size and morphology, in vitro release profile, and stability. Antidiabetic evaluation was performed in streptozotocin (STZ)-induced diabetic Wistar rats. An antioxidant assay was carried out by evaluating superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), and glutathione (GSH). The optimized formulation showed a significant hypoglycemic effect, which was comparable with that of repaglinide. Moreover, significant increases in SOD, CAT, and GSH, along with a decrease in the lipid peroxidation level, were observed, which confirmed the antioxidant efficacy of the formulation. Thus, it is evident that the embelin-loaded niosome formulation was efficacious in diabetes management in Wistar rats.


Information technologies. Physician-hospital networks.
Patient care efficiencies and quality of care improvements require progressive efforts to integrate the patient information systems and allow for on-demand accessibility to authorized information users. The dilemma facing the designers and managers of these systems is that each step toward improving accessibility seems to introduce another potential information leakage point. We are reminded once again that information is a very difficult resource to control because it is possible to steal it without removing it physically from its storage place. The essence of information security in physician links is captured by establishing mechanisms for identifying system users, limiting user authority, assuring the privacy of transmitted data, and monitoring system use and users.


Diffusion constant of a nonspecifically bound protein undergoing curvilinear motion along DNA.
The mechanism of a protein's diffusion along a DNA segment is a subject of much current interest because of the involvement of this diffusion in numerous biological processes, including the recognition of DNA sequences and chemical modifications of DNA. In this work we present a theoretical derivation of the diffusion coefficient of a nonspecifically bound protein, assuming that the protein follows a helical track along the DNA. It is shown that, for protein-sized molecules, the principal contribution to the total translational friction comes from the curvilinear motion along the helix, and this contribution is given by 6pietaRR(oc)(2) + 8pietaR(3), where R is the protein radius, ROC is the distance of separation between the center of mass of the protein and the helical axis of DNA, and eta is the viscosity of the medium. The translational diffusion of the protein along the helical track of DNA is thus predicted to have a nearly R(-3) size dependence, not the R(-1) dependence characterizing simple translational diffusion. It is shown that this expression gives rather good estimates of the translational diffusion coefficient measured in single molecule experiments.


Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease.
Hydrogen sulfide (H2S)-a potent gaseous signaling molecule-has emerged as a critical regulator of cardiovascular homeostasis. H2S is produced enzymatically by 3 constitutively active endogenous enzymes in all mammalian species. Within the past 2 decades, studies administering H2S-donating agents and the genetic manipulation of H2S-producing enzymes have revealed multiple beneficial effects of H2S, including vasodilation, activation of antiapoptotic and antioxidant pathways, and anti-inflammatory effects. More recently, the heightened enthusiasm in this field has shifted to the development of novel H2S-donating agents that exert favorable pharmacological profiles. This has led to the discovery of novel H2S-mediated signaling pathways. This review will discuss recently developed H2S therapeutics, introduce signaling pathways that are influenced by H2S-dependent sulfhydration, and explore the dual-protective effect of H2S in cardiorenal syndrome.


A robust fluorescent probe for detection of telomerase activity in vitro and imaging in living cells via telomerase-triggering primer extension to desorb DNA from graphene oxide.
We have developed a robust nanoprobe, named graphene oxide (GO) loaded fluorophore labeled DNA oligonucleotide probe (GO nanoprobe), for the detection of telomerase activity and demonstrated its application for imaging of telomerase in living cells. Two DNA oligonucleotides were used in the sensing system including a FAM-DNA template probe and a short TS primer. Upon the addition of telomerase and dNTPs, the TS primer produced a telomeric repeated sequence at the 3' end, which was just complementary to the single strand tail of FAM-DNA absorbed on the GO surface; the resulting DNA duplex chain could easily detach from the GO, due to the weak binding force between long dsDNA and GO, which led to the separation of the FAM from the GO surface and brought about an amplified fluorescence emission. The fluorescence signal intensity depended on the amount of telomerase, leading to a novel strategy for detecting and in situ imaging of the cytoplasmic telomerase activity. The GO nanoprobe provided a one-step incubation technique for monitoring the telomerase activity in living cells. The proposed approach also distinguished normal cells from cancer cells and monitored the change in telomerase activity in response to a telomerase inhibitor, demonstrating its potential in clinical diagnostic and therapeutic monitoring.


Adalimumab keeps bowel disease in remission aft er up to four years of treatment.
Long-term treatment with adalimumab can help patients with Crohn's disease maintain remission for up to four years, with no increased risk of adverse effects, according to an analysis of data from two clinical trials.


[Blood-brain barrier breakdown following gliotoxic drug injection in the brainstem of Wistar rats].
Ethidium bromide (EB) causes local astrocytic disappearance, with glia limitans disruption and supposed blood-brain barrier (BBB) breakdown The aim of this study was to investigate the BBB integrity after the injection of 0.1% EB (group E) or 0.9% saline solution (group C) into cisterna pontis of Wistar rats. Brainstem fragments were collected from 24 hours to 31 days post-injection for ultrastructural study and GFAP immuno-histochemical staining. Some animals received colloidal carbon ink by intravenous route at the same periods. In rats from group C, there was no sign of astrocyte loss and no leakage of ink from blood vessels in the injection site. In group E, astrocyte disappearance began at 48 hours and some areas were still devoid of astrocytic processes 31 days after. Leakage of carbon particles was seen from 48 hours to 7 days in the EB-induced lesions. Tight junctions did not show any detectable ultrastructural change due to the lack of perivascular astrocytes.


Specific binding of lactoferrin to brush-border membrane: ontogeny and effect of glycan chain.
Bioavailability of iron from human milk is exceptionally high. It has been suggested that lactoferrin, the major iron-binding protein in human milk, may participate in this high iron bioavailability from milk. We examined the interaction of lactoferrin with the intestinal brush-border membrane using the rhesus monkey as a model. Brush-border membrane vesicles were prepared from monkeys of various ages. Binding studies with 59Fe-labeled human and monkey lactoferrin were performed to examine interaction of lactoferrin with the brush-border membrane. Specific saturable binding of lactoferrin was found at all ages studied (fetal, suckling infant, weaned infant, juvenile, and adult). The dissociation constant for lactoferrin-receptor binding was 9 X 10(-6) M. In contrast, no binding of serum transferrin or bovine lactoferrin occurred. Removal of fucose from the lactoferrin glycans resulted in a significant decrease in binding. It was concluded that lactoferrin in milk may function in the process of iron absorption through interaction with a small intestinal receptor and that fucosylated glycans on the carbohydrate chain of lactoferrin are necessary for receptor recognition.


Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity.
Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi-agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment-related toxicity. Fourteen patients with Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two categories: low-risk (normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate, regimen A). High-risk patients received four alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The modified treatment regimen was associated with no grade 3/4 neuropathy and only one episode of grade 3/4 mucositis. All patients completed protocol therapy and there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients (64%) are alive and disease free at a median follow-up of 29 months. This modified Magrath regimen is effective and well-tolerated in a representative group of older adult patients.


Towards a Holistic Biomedical Information Platform for Primary and Secondary Use Settings.
Clinical information is often used for biomedical research. Data warehouses can help providing researchers with data and the opportunity to find eligible participants for clinical trials. To define an information platform for healthcare and biomedical research based on requirements by clinicians and researchers. Interviews with clinicians, researchers, data privacy officers, IT and hospital administration combined with a questionnaire sent to 60 medical departments at our hospital were conducted. Resulting requirements were grouped and a platform architecture was designed based on the requirements. Requirements lead to a single platform supporting both, patient care and biomedical research.


Recovery of protein from green leaves: Overview of crucial steps for utilisation.
Plant leaves are a major potential source of novel food proteins. Till now, leaf protein extraction methods mainly focus on the extraction of soluble proteins, like rubisco protein, leaving more than half of all protein unextracted. Here, we report on the total protein extraction from sugar beet leaves (Beta vulgaris L.) by a traditional thermal extraction method consisting of mechanical pressing, heating to 50 °C and centrifugation. The resulting streams (i.e. supernatant, green-protein pellet and fibrous pulp) were characterised in terms of composition, physical structure and processing options. The protein distributed almost equally over the supernatant, pellet and pulp. This shows that thermal precipitation is an unselective process with respect to fractionation between soluble (rubisco) and insoluble (other) proteins. About 6% of the total protein could be extracted as pure rubisco (90% purity) from the supernatant. Surfactants commonly used for protein solubilisation could hardly re-dissolve the precipitated proteins in the pellet phase, which suggested that irreversible association was induced between the co-precipitated proteins and cell debris. Thus, the extraction of this protein will require prevention of their co-precipitation, and should take place in the original juice solution.


Study of amphotericin B magnetic liposomes for brain targeting.
This study aims to prepare amphotericin B magnetic liposomes (AmB-MLPs), which may improve drug concentration in brain, enhance magnetic targeting for brain and reduce drug toxicity in the presence of magnetic field. AmB-MLPs were prepared by means of film dispersion-ultrasonication, and their physical properties were characterized. In vivo, the magnetic targeting for brain by carotid artery administration was investigated. The particle size of AmB-MLPs was 240±11 nm, the encapsulation efficiency was 79.32±2.03%, and the saturation magnetization was 32.54 memu g⁻¹ at room temperature, which had good magnetic responsiveness. The group of AmB injection was delivered by carotid artery, nevertheless they all died after 20 min. AmB-MLPs were injected by carotid artery, and the drug concentration in brain tissue was obviously increased in presence of magnetic field than that of in absence of magnetic field (P<0.05). The Prussian blue staining in brain of SD rats showed that the density of blue staining-positive particles in brain tissue of applying magnetic field group was higher than that of non magnetic field group. These results suggested that AmB-MLPs could reinforce brain targeting and reduce drug toxicity when they were injected by carotid artery under the effect of magnetic field.


Effects of cortical activations on enhancement of handgrip force during teeth clenching: an fMRI study.
We assessed the effect of teeth clenching on handgrip force behaviorally, and investigated cortical activity during the occurrence of facilitatory effects using functional magnetic resonance imaging (fMRI). Twenty-three participants were assessed as to whether they had habitual teeth clenching during maximal voluntary contraction (MVC) exertion, and 21 of them were identified to have such a habit. For those participants, behavioral testing showed that MVC with clenching was greater compared with without clenching (approximately 108% greater on average). Next, cortical activity was measured under gripping with clenching (GwC), gripping without clenching (GwoC), and teeth clenching (C) conditions. We found that the activity of the hand region in primary motor cortex (M1), cingulate motor area/supplementary motor area (CMA/SMA) and anterior cerebellum (AC) was greater in contrast of GwC vs. (GwoC+C). Furthermore, significant correlation was observed between the increasing ratio of the handgrip force and the % signal change in the hand region of M1 and AC, but not in CMA/SMA. These results suggest that the activation in the hand region of M1 and AC may facilitate the spinal motoneurons, and the activation in the hand region in M1 by clenching may be due to a signal from CMA/SMA.


Sensory testing in non-human primates.
Sensory testing in non-human primates can be used to detect subtle sensory toxicity of chemicals. Examples are given covering the determination of spatial contrast sensitivity in monkeys exposed to methyl mercury as an example of visual psychophysics, and the assessment of vibration sensitivity in monkeys exposed to acrylamide, as an example of somatosensory psychophysics.


[Asthma in elderly--diagnostic and therapeutic difficulties].
Bronchial asthma is a frequent cause of respiratory symptoms in elderly. In majority of cases asthmatic patients develop their disease before the age of 45 years, but sometimes the first episode of asthma occurs after the age of 60 years. Except for pharmacological methods, non-pharmacological therapies are recommended which include education of patients and his family and vaccination for influenza and pneumococcal infections. Two cases of bronchial asthma in patients over 60 years were analyzed. The first case illustrates coexistence of chronic heart-depending circulatory failure, complicated with episode of thromboembolic disease which occurred in the past, obesity and bronchial asthma, in 69 years old man. The second case illustrates 61 years old woman with chronic severe asthma from childhood, rheumatoid arthritis and tuberculous infection of the knee. It is known that evaluation of asthma severity in elderly is more difficult than in young people because of high frequency of comorbidities. An appropriate anti-asthmatic medication and education of patient and his family may enrich quality of live in elderly asthmatics.


Virulence associations in oat crown rust.
ABSTRACT Isolates of Puccinia coronata obtained from natural populations of Avena sterilis in Israel, winter oat (A. sativa) cultivars in Texas, and spring oat cultivars in the Northern Plains states of Minnesota, North Dakota, and South Dakota were analyzed for significance of pairwise virulence associations. Isolates from all three regions were tested on 25 oat lines with single P. coronata (Pc) genes for crown rust resistance from A. sterilis and one line with a Pc gene from A. sativa. Isolates from Israel were tested also on 11 Iowa backcross lines with undesignated crown rust resistance genes from A. sterilis. Four associated virulence groups were identified from significant positive virulence associations that were consistent across all three regions. Group 38 included virulence to Pc-38, Pc-39, Pc-55, Pc-63, and Pc-71; group 45 included virulence to Pc-45, Pc-46, Pc-48, Pc-52, Pc-54, and Pc-57; group 58 included virulence to Pc-35, Pc-40, Pc-58, and Pc-59; and group 61 included virulence to Pc- 36, Pc-51, Pc-56, Pc-60, and Pc-61. Virulence to Pc-70 showed the strongest association to virulences in group 38 but also showed significant association with virulence to Pc-45, Pc-35, and Pc-58. Virulences in group 61 were consistently negatively associated with virulences in group 38 in each region. In Israel, virulences to five of the Iowa lines showed positive associations to virulences in group 61 and negative associations to virulences in groups 38 and 45. Close similarity of reactions of nearly all isolates to Pc-39, Pc-55, and Pc-71 suggest that these genes may be identical or nearly identical alleles.


Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p53 and hDM2 and characterization of the confirmed hits.
In recent years, advances in structure-based drug design and the development of an impressive variety of high-throughput screening (HTS) assay formats have yielded an expanding list of protein-protein interaction inhibitors. Despite these advances, protein-protein interaction targets are still widely considered difficult to disrupt with small molecules. The authors present here the results from screening 220,017 compounds from the National Institute of Health's small-molecule library in a novel p53-hDM2 protein-protein interaction biosensor (PPIB) assay. The p53-hDM2 positional biosensor performed robustly and reproducibly throughout the high-content screening (HCS) campaign, and analysis of the multiparameter data from images of the 3 fluorescent channels enabled the authors to identify and eliminate compounds that were cytotoxic or fluorescent artifacts. The HCS campaign yielded 3 structurally related methylbenzo-naphthyridin-5-amine (MBNA) hits with IC(50)s between 30 and 50 microM in the p53-hDM2 PPIB. In HCT116 cells with wild-type (WT) p53, the MBNAs enhanced p53 protein levels, increased the expression of p53 target genes, caused a cell cycle arrest in G1, induced apoptosis, and inhibited cell proliferation with an IC(50) ~4 microM. The prototype disruptor of p53-hDM2 interactions Nutlin-3 was more potent than the MBNAs in the p53-hDM2 PPIB assay but produced equivalent biological results in HCT116 cells WT for p53. Unlike Nutlin-3, however, MBNAs also increased the percentage of apoptosis in p53 null cells and exhibited similar potencies for growth inhibition in isogenic cell lines null for p53 or p21. Neither the MBNAs nor Nutin-3 caused cell cycle arrest in p53 null HCT116 cells. Despite the relatively modest size of the screening library, the combination of a novel p53-hDM2 PPIB assay together with an automated imaging HCS platform and image analysis methods enabled the discovery of a novel chemotype series that disrupts p53-hDM2 interactions in cells.


NMR studies on the surface accessibility of the archaeal protein Sso7d by using TEMPOL and Gd(III)(DTPA-BMA) as paramagnetic probes.
Understanding how proteins are approached by surrounding molecules is fundamental to increase our knowledge of life at atomic resolution. Here, the surface accessibility of a multifunctional small protein, the archaeal protein Sso7d from Sulfolobus solfataricus, has been investigated by using TEMPOL and Gd(III)(DTPA-BMA) as paramagnetic probes. The DNA binding domain of Sso7d appears very accessible both to TEMPOL and Gd(III)(DTPA-BMA). Differences in paramagnetic attenuation profiles of (1)H-(15)N HSQC protein backbone amide correlations, observed in the presence of the latter paramagnetic probes, are consistent with the hydrogen bond acceptor capability of the N-oxyl moiety of TEMPOL to surface exposed Sso7d amide groups. By using the gadolinium complex as a paramagnetic probe a better agreement between Sso7d structural features and attenuation profile is achieved. It is interesting to note that the protein P-loop region, in spite of the high surface exposure predicted by the available protein structures, is not approached by TEMPOL and only partially by Gd(III)(DTPA-BMA).