Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives.
An enzymatic route for phosphorous-carbon- bond formation is developed by discovering new promiscuous activity of lipase. This biocatalytic transformation of phosphorous-carbon- bond addition leads to biologically and pharmacologically relevant α-acyloxy phosphonates with methyl group in α-position. A series of target compounds were synthesized with yields ranging from 54% to 83% by enzymatic reaction with Candida cylindracea (CcL) lipase via Markovnikov addition of H-phosphites to vinyl esters. We carefully analyzed the best conditions for the given reaction such as the type of enzyme, temperature, and type of solvent. The developed protocol is applicable to a range of H-phosphites and vinyl esters significantly simplifying the preparation of synthetically challenging α-pivaloyloxy phosphonates. Further, the obtained compounds were validated as new potential antimicrobial drugs with characteristic E. coli bacterial strains and DNA modification recognized by the Fpg protein, N-methyl purine glycosylases as new substrates. The impact of the methyl group located in the α-position of the studied α-acyloxy phosphonates on the antimicrobial activity was demonstrated. The pivotal role of this group on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.


RNA virus diversity in three parasitoid wasps of tephritid flies: insights from novel and known species.
Parasitoid wasp populations have developed persistent beneficial symbiotic relationships with several viruses through repeated evolution. However, there have been limited reports on RNA viruses in parasitoid wasps of tephritid flies, a significant pest group affecting fruits and vegetables. This study explores the diversity of RNA viruses in three parasitoid wasps of tephritid flies and highlights the potential biological significance of specific viruses in Diachasmimorpha longicaudata. These findings have important implications for the development of sustainable pest management strategies and the enhancement of artificial rearing techniques for parasitoid wasps.


Plant immunity induced by COS-OGA elicitor is a cumulative process that involves salicylic acid.
Plant innate immunity offers considerable opportunities for plant protection but beside flagellin and chitin, not many molecules and their receptors have been extensively characterized and very few have successfully reached the field. COS-OGA, an elicitor that combines cationic chitosan oligomers (COS) with anionic pectin oligomers (OGA), efficiently protected tomato (Solanum lycopersicum) grown in greenhouse against powdery mildew (Leveillula taurica). Leaf proteomic analysis of plants sprayed with COS-OGA showed accumulation of Pathogenesis-Related proteins (PR), especially subtilisin-like proteases. qRT-PCR confirmed upregulation of PR-proteins and salicylic acid (SA)-related genes while expression of jasmonic acid/ethylene-associated genes was not modified. SA concentration and class III peroxidase activity were increased in leaves and appeared to be a cumulative process dependent on the number of sprayings with the elicitor. These results suggest a systemic acquired resistance (SAR) mechanism of action of the COS-OGA elicitor and highlight the importance of repeated applications to ensure efficient protection against disease.


Why do we have to review our experience in managing cases with idiopathic fistula-in-ano regularly?
"Why do we have to review our experience in managing idiopathic fistula-in-ano regularly?" In order to answer this apparently simple question, we reviewed our clinical and surgical cases and most important relevant literature to find a rational and scientific answer. It would appear that whatever method you adopt in fistula management, there is a price to pay regarding either rate of recurrence (higher with conservative methods) or impairment of continence (higher with traditional surgery). Since, at the moment, reliable data to identify a treatment as a gold standard in the management of anal fistulas are lacking, the correct approach to this condition must consider all the anatomic and clinicopathological aspects of the disease; this knowledge joined to an eclectic attitude of the surgeon, who should be familiar with different types of treatment, is the only guarantee for a satisfactory treatment. As a conclusion, it is worthwhile to remember that adequate initial treatment significantly reduces recurrence, which, when it occurs, is usually due to failure to recognise the tract and primary opening at the initial operation.


Genetic and epigenetic interactions between folate and aging in carcinogenesis.
Folate is among the most strongly implicated dietary components to convey protection against colon cancer, and diminished folate status is associated with an enhanced risk of colon cancer. Age is also regarded as one of the most important risk factors for colonic carcinogenesis. It is therefore of considerable interest to determine whether the process of aging influences folate metabolism in the colon and whether folate supplementation might prevent the procarcinogenic effects associated with aging. Recent studies in our laboratory demonstrated that the colonic mucosa of elder rats is more susceptible to folate depletion than that of young rats. Depletion of folate results in a shift in the forms of folate in the colon as well as increased uracil incorporation into DNA, a purported mechanism for colonic carcinogenesis. However, modest folate supplementation eliminates evidence of inadequate folate status in the colons of elder rats, suggesting that the relation between age and folate status in the colon might be one mechanism by which aging modulates colorectal cancer risk. Interactions between folate and aging also affect a spectrum of epigenetic and genetic phenomena such as uracil misincorporation, DNA methylation, protein methylation, mitochondrial deletion, and critical gene expression, which could be related to carcinogenesis. Aging and inadequate dietary folate may interact and collectively induce derangements in folate metabolism, thereby provoking subsequent molecular aberrations, which may enhance carcinogenesis. However, folate supplementation appears to reverse these adverse effects of aging, which is potentially of substantial import because the latter is an unmodifiable risk factor.


Crystallographic Effects of GaN Nanostructures in Photoelectrochemical Reaction.
Tuning the surface structure of the photoelectrode provides one of the most effective ways to address the critical challenges in artificial photosynthesis, such as efficiency, stability, and product selectivity, for which gallium nitride (GaN) nanowires have shown great promise. In the GaN wurtzite crystal structure, polar, semipolar, and nonpolar planes coexist and exhibit very different structural, electronic, and chemical properties. Here, through a comprehensive study of the photoelectrochemical performance of GaN photocathodes in the form of films and nanowires with controlled surface polarities we show that significant photoelectrochemical activity can be observed when the nonpolar surfaces are exposed in the electrolyte, whereas little or no activity is measured from the GaN polar c-plane surfaces. The atomic origin of this fundamental difference is further revealed through density functional theory calculations. This study provides guideline on crystal facet engineering of metal-nitride photo(electro)catalysts for a broad range of artificial photosynthesis chemical reactions.


Measuring FMD in the brachial artery: how important is QRS gating?
Recommendations for the measurement of brachial flow-mediated dilation (FMD) typically suggest images be obtained at identical times in the cardiac cycle, usually end diastole (QRS complex onset). This recommendation presumes that inter-individual differences in arterial compliance are minimized. However, published evidence is conflicting. Furthermore, ECG gating is not available on many ultrasound systems; it requires an expensive software upgrade or increased image processing time. We tested whether analysis of images acquired with QRS gating or with the more simplified method of image averaging would yield similar results. We analyzed FMD and nitroglycerin-mediated dilation (NMD) in 29 adults with type 2 diabetes mellitus and in 31 older adults and 12 young adults without diabetes, yielding a range of brachial artery distensibility. FMD and NMD were measured using recommended QRS-gated brachial artery diameter measurements and, alternatively, the average brachial diameters over the entire R-R interval. We found strong agreement between both methods for FMD and NMD (intraclass correlation coefficients = 0.88-0.99). Measuring FMD and NMD using average diameter measurements significantly reduced post-image-processing time (658.9 ± 71.6 vs. 1,024.1 ± 167.6 s for QRS-gated analysis, P < 0.001). FMD and NMD measurements based on average diameter measurements can be performed without reducing accuracy. This finding may allow for simplification of FMD measurement and aid in the development of FMD as a potentially useful clinical tool.


Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon.
The development of novel artemisinin-combination therapies suitable for the treatment of pediatric patients suffering from malaria is a research priority. The aim of this study was to investigate a novel fixed-dose pyronaridine-artesunate combination for the treatment of uncomplicated falciparum malaria in Gabonese patients 2-14 years old. The study was designed as an open-label dose-escalation study recruiting 60 pediatric patients sequentially in 4 treatment cohorts: study drugs were administered once daily for 3 days, as tablet coformulations (pyronaridine:artesunate ratios of 6:2, 9:3, and 12:4 mg/kg) and as a granule coformulation (pyronaridine:artesunate ratio of 9:3 mg/kg). The primary end points were tolerability, safety, and pharmacokinetics of pyronaridine-artesunate treatment. Efficacy was treated as a secondary outcome measure. The drugs had a good tolerability and safety profile, at all dose levels. Pharmacokinetic analysis revealed a dose-dependent increase in the maximum plasma/blood concentration and the area under the curve, as well as comparable relative bioavailability for the granule coformulation. Polymerase chain reaction-corrected cure rates at day 28 were 100% in per-protocol analysis, at all dose levels. Pyronaridine-artesunate is a promising novel artemisinin-combination therapy for pediatric patients with uncomplicated Plasmodium falciparum malaria, and the development of both the tablet and the granule coformulations is warranted.


The neural habituation to hedonic and eudaimonic rewards: Evidence from reward positivity.
Rewards play an important role in people's well-being. However, the mechanisms underlying neural habituation to hedonic rewards (attainment of pleasure) and eudaimonic rewards (attainment of meaning and self-realization) and their implications for longitudinal changes in well-being remain unknown. By operationalizing hedonic rewards as "winning money for oneself" and eudaimonic rewards as "winning money for a charity", 78 participants (41 women, aged from 17 to 24 years) completed a revised monetary gambling task during event-related potential (ERP) recording. Subsequently, the participants' well-being was measured after one year. The results showed that the reward positivity (RewP) effect readily decreased as the hedonic rewards were repeated, whereas the RewP effect in response to eudaimonic rewards was relatively sustained over time. Moreover, the declining RewP effect for repeated eudaimonic rewards was marginally positively associated with longitudinal decreases in well-being. These findings demonstrate at the neural level that sensitivity to repeated hedonic rewards is more prone to decrease than sensitivity to repeated eudaimonic rewards, and sustained eudaimonic reward sensitivity in the short term has greater implications for changes in well-being in the long term.


A review of the diagnosis and treatment of rosacea.
Rosacea is a common chronic inflammatory disease of the skin and is associated with a number of etiological causes and inciting factors. It is characterized by erythematous changes of the facial skin, and commonly presents with papules, pustules, or telangiectasias. The 4 subtypes of rosacea are categorized according to secondary symptoms, such as pain, erythema, dryness, and edema. A number of therapies are available to treat rosacea, some of which can be used in combination. The mainstays of therapy are topical metronidazole, topical azelaic acid, and oral tetracyclines. Other pharmacotherapeutic interventions have been shown to improve the signs and symptoms of rosacea, although many of these have not yet received approval by the US Food and Drug Administration for this indication.


Long-term nitrogen addition in maize monocultures reduces in vitro inhibition of actinomycete standards by soil-borne actinomycetes.
Management of soil microbial communities for enhanced crop disease suppression is an attractive approach to biocontrol, but the effects of agricultural practices on the disease-suppressive potential of the soil microbial community remain unknown. We investigated the effects of long-term nitrogen addition (103 kg ha-1 nitrogen as urea vs. no fertilizer) and crop residue incorporation vs. removal on in vitro antibiotic inhibitory capacities of actinomycetes from 57-year maize (Zea mays L.) monocultures in southeastern Minnesota. We hypothesized that both nitrogen and crop residue addition would increase inhibitor frequencies by increasing microbial population densities and thus increasing the importance of competitive interactions among microbes to their fitness. We found that although soil carbon and nitrogen and microbial densities (actinomycete and total colony-forming units) tended to be greater with nitrogen fertilizer, the frequency of in vitro inhibitory phenotypes among culturable actinomycetes in fertilized plots was approximately half that in non-fertilized plots. Residue incorporation had little to no effect on soil chemistry, microbial density and inhibitor frequency. These results suggest that density-mediated processes alone cannot explain the effects of amendments on inhibitor frequencies. Fitness costs and benefits of inhibitory phenotypes may vary over time and may depend on the type of resource amendment.


Suppression of collagen-induced arthritis by an angiogenesis inhibitor, AGM-1470, in combination with cyclosporin: reduction of vascular endothelial growth factor (VEGF).
Pannus formation characterized by neovascularization is a prominent pathologic finding in both rheumatoid arthritis (RA) and rat collagen-induced arthritis (CIA). CIA is a T-cell-dependent process induced by immunization of inbred LOU rats with native type II collagen in incomplete Freund's adjuvant. AGM-1470 is a highly specific inhibitor of new blood vessel formation by its effects on endothelial cell migration, endothelial cell proliferation, and capillary tube formation. Cyclosporin A (CSA) is an immunomodulating agent that inhibits IL-2 and other cytokine production involved in early antigen activation of T-cells. In this study the effects of single and combination therapy with AGM-1470 (27 mg/kg alternate days) and low-dose CSA (4 mg/kg/day continuous infusion via osmotic pump) on established CIA (total n = 62) were examined. At Day 18 post arthritis onset, clinical arthritis was significantly reduced in rats treated with single-agent AGM-1470 (1.88 +/- 0.33) or combination therapy (1.13 +/- 0.32) (P < 0.00001 and 0.000001, respectively) versus control. Single-agent CSA-treated rats, even if given CSA beginning on the day of immunization, did not attenuate arthritis severity. THe longitudinal mean arthritis score of combination-treated rats was significantly lower than that of rats receiving AGM-1470 (P < 0.0001), reflecting a more moderate early disease course in combination-treated rats. Disease severity in rats treated with single-agent CSA was not significantly different from control rats. Mean WBC counts, differentials, and delayed-type hypersensitivity responses were similar in all groups. CII antibody levels were lower in AGM-1470 protocols compared to CSA or controls. Flow cytometry of peripheral blood, spleen, and lymph nodes demonstrated decreased levels of CD4+ cells in rats given CSA. TNF-alpha levels remained elevated, even in treated rats, while vascular endothelial growth factor levels were reduced in rats receiving AGM-1470 compared to both arthritic controls and naive rats. Both single-agent and combination therapies were well tolerated. This is the first study to examine the effects of AGM-1470 together with CSA. Combination therapy was more effective than single-agent therapy. The results suggest that the use of interventions with distinct mechanisms of action may be efficacious in the treatment of RA.


Expression of adrenocorticotrophic hormone receptor mRNA in human adrenocortical neoplasms: correlation with P450scc expression.
Adrenocorticotrophin (ACTH) is the main hormone-regulating steroid secretion from the adrenal cortex. The ACTH receptor (ACTH-R) has recently been cloned, allowing systematic evaluation of its expression and function in adrenal tumorigenesis. We investigated ACTH-R and P450 side-chain cleavage enzyme (P450scc) mRNA expression in a variety of neoplastic adrenocortical tissues by Northern blot and reverse-transcriptase-PCR (RT-PCR). We studied tissue from eight normal adrenals, six diffuse adrenocortical hyperplasias in patients with ACTH-dependent Cushing's syndrome, 22 adrenal adenomas, six carcinomas and two carcinoma cell lines. Poly A mRNA was electrophoresed, immobilized on a nylon membrane and hybridized using alpha 32P-CTP labelled human ACTH-R and P450scc cDNAs. Mean ACTH-R mRNA expression showed significant differences between groups (P = 0.0001), but appeared to be independent of plasma ACTH concentrations. Compared to normal adrenal (= 100 +/- 12%), expression was low in non-functional adenomas (23 +/- 11%) and carcinomas (19 +/- 12%), intermediate in adrenocortical hyperplasias (88 +/- 6%) and cortisol-producing adenomas (81 +/- 15%) and high in aldosteronomas (175 +/- 29%). In adenomas, ACTH-R mRNA expression correlated closely with the expression of P450scc mRNA(r = 0.8, P = 0.0001) suggesting regulation by similar factors. However, carcinomas and cancer cell lines did not show a positive correlation between these two parameters (r = -0.44, P = 0.3). We have demonstrated that plasma ACTH is not the major factor influencing ACTH-receptor mRNA expression in neoplastic adrenal tissue. In benign tumours of the adrenal cortex there was a close positive correlation between ACTH-receptor mRNA and P450scc mRNA which was missing in adrenocortical carcinomas, probably as a result of tumour dedifferentiation.


Discontinuation of oral antivirals in chronic hepatitis B: A systematic review.
The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for ≥12 months thereafter. Twenty-five studies with 1716 patients were included. The pooled rates of durable VR remission were 51.4%, 39.3%, and 38.2% at 12, 24, and 36 months, respectively, after NA discontinuation, being relatively higher in initially hepatitis B e antigen (HBeAg)-positive patients (62.5%, 53.4%, 51.5%) than HBeAg-negative patients (43.7%, 31.3%, 30.1%) (P = 0.064). The weighted probability of durable biochemical remission was 65.4%, being numerically higher in HBeAg-positive than HBeAg-negative patients (76.2% versus 56.7%, P = 0.130). The weighted probability of hepatitis B surface antigen loss was 2.0%. The rates of durable VR did not significantly differ according to the VR definition (hepatitis B virus DNA <200, < 2000, < 20,000 IU/mL) or duration of on-therapy VR in HBeAg-positive patients, but they were significantly higher in studies with HBeAg-negative patients and on-therapy VR > 24 than ≤ 24 months (VR at 12 months off-NAs: 75.0% versus 35.6%, P = 0.005). The weighted probability of durable HBeAg seroconversion was 91.9% and 88.0% at 12 and 24 months, respectively, after NA discontinuation without being affected by the duration of on-therapy VR or consolidation therapy (>6 months in all studies). Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis B.


Nosocomial meningitis caused by multiresistant enterococcus as a life-threatening complication of pelvic injury: case report.
Bacterial meningitis after pelvic trauma has never been described. We recently treated a patient who developed, during the course of his hospitalization, multiresistant enterococcal meningitis after severe pelvic injury, including a comminutive sacral fracture. Dural tear may have been the main factor leading to secondary infection of the cerebrospinal fluid. Treatment with intravenous continuous infusion of vancomycin plus rifampin, associated with closed subarachnoid drainage, resulted in a complete cure. Therapeutic cerebrospinal fluid levels of vancomycin were obtained only during the first 8 days of treatment. Use of glycopeptides in meningitis and the role of cerebrospinal fluid drainage are discussed. Physicians should be aware of the diagnosis and therapeutic features of this life-threatening complication.


Use of Coroner's reports for surveillance of accidental death.
The objective of this study was to investigate the possibility of using Coroner's reports on accidental deaths as the basis of a surveillance system. The Coroner's reports of childhood accidental deaths in Northern Ireland over a five-year period (224 deaths) were reviewed. Outcome measures included the delay between time of death and registration of death and the usefulness of the report in assessing the preventability of the accident. The timing of Coroner's reports could facilitate monitoring of trends for particular categories of accident and allow information in the reports to be used as a basis for preventive programmes. At present, however, the reports which the Coroner uses to inform the Registrar-General of his or her findings are not of a standard format, and in many cases do not report enough detail to allow an analysis of the circumstances of the accidents which could be used to establish opportunities for prevention.


National Toxicology Program Position Statement on Informed ("Nonblinded") Analysis in Toxicologic Pathology Evaluation.
The National Toxicology Program (NTP) uses histopathological evaluation of animal tissues as a key element in its toxicity and carcinogenicity studies. The initial histopathological evaluations are subjected to a rigorous peer review process involving several steps. The NTP peer review process is conducted by multiple, highly trained, and experienced toxicological pathologists employing standardized terminology. In addition, ancillary data, such as body and organ weights and clinical pathology findings, are used to corroborate the diagnoses. The NTP does employ masked analysis to confirm subtle lesions or severity scores, as needed, and during its Pathology Working Groups. The use of masked analysis can have a negative effect on histopathological evaluation because it is important for the pathologist to compare treated groups to the concurrent controls, which would not be possible in a blinded evaluation. Therefore, the NTP supports an informed approach to histopathological evaluation in its toxicity and carcinogenicity studies.


[Gallbladder torsion].
We report two cases of gallbladder torsion, which were diagnosed intraoperatively. This rare condition should be suspected in elderly women with acute abdominal pain of unknown origin. The treatment is cholecystectomy. Promptly treated, the prognosis is good.


A Scoping Study of Parents With a History of Childhood Sexual Abuse and a Theoretical Framework for Future Research.
Transitioning to a parenting role is a complex psychological process that can be stressful for a parent with a history of childhood sexual abuse (CSA). Over the past decade, important advances have been made in identifying the effects of childhood trauma on parents' relationships with their children. This article presents a new theoretical framework that emerged from a scoping study of parenting experiences among adults who experienced CSA. The methods of Arksey and O'Malley were used to conduct the scoping study, and the guidelines for theory construction and model building developed by Jaccard and Jacoby were adopted. Only peer-reviewed published journal articles in English that studied exclusively CSA and its effects on parenting among individuals aged 18 years or older were included. Three resources for collecting data were used: (1) internet databases including PsycINFO and PubMed, (2) reference lists of review articles, and (3) the citation index functionality of Google Scholar for review articles. Forty-six articles were included in the scoping study. These studies mainly focused on mothers and their relationships with their children. No articles considered the age(s) at which parents experienced CSA and potential effects on parenting outcomes. In addition, there is limited knowledge about fathers with a history of CSA and their relationship with their children. The development of a theoretical framework designed through a methodologically driven identification of gaps in the body of knowledge provides a foundation for future research in this area.


Rapid and Specific Detection of the Poplar Black Spot Disease Caused by Marssonina brunnea Using Loop-Mediated Isothermal Amplification Assay.
Marssonina brunnea is the main pathogen that causes poplar black spot disease, which leads to the decrease of the photosynthetic efficiency and significantly affects the production and quality of timber. Currently, no in-field diagnostic exists for M. brunnea. Here, we described a loop-mediated isothermal amplification (LAMP) assay for the rapid and sensitive detection of M. brunnea. A set of six oligonucleotide primers was designed to recognize eight distinct sequences of the internal transcribed spacer (ITS) region of M. brunnea. The LAMP assay was optimized by the combination of high specificity, sensitivity, and rapidity for the detection of less than 10 pg/μL of target genomic DNA in 60 min per reaction at 65 °C, whereas with PCR, there was no amplification of DNA with concentration less than 1 ng/μL. Among the genomic DNA of 20 fungalisolates, only the samples containing the genomic DNA of M. brunnea changed from violet to sky blue (visible to the naked eye) by using hydroxynaphthol blue (HNB) dye. No DNA was amplified from the eight other fungus species, including two other Marssonina pathogens, three other foliar fungi pathogens of poplar, and three common foliar fungal endophytes of poplar. Moreover, the detection rates of M. brunnea from artificially and naturally infected poplar leaves were 10/16 (62.5%) and 6/16 (37.5%) using PCR, respectively, while the positive-sample ratios were both 16/16 (100%) using the LAMP assay. Overall, the ITS LAMP assay established here can be a better alternative to PCR-based techniques for the specific and sensitive detection of M. brunnea in poplar endemic areas with resource-limited settings.


[Pain relief in induced abortion--considerable differences between hospital departments].
Women undergoing medical abortions require different types of pain relief, severe pain being a problem. This study compared the pain relief required during a medical abortion at the Departments of Gynecology in Kalmar and Karlskrona. The case notes of 100 women at each department were examined. Considerable differences between the two departments were found. In Kalmar women were mainly given paracetamol and dextropropoxyphene at the start of the procedure, while in Karlskrona women were usually given suppository diclofenac. In Kalmar 42 per cent of the women needed some form of opiate during the abortion, while in Karlskrona only 8 per cent required opiates.


The Treviso Dementia (TREDEM) Study: A Biomedical, Neuroradiological, Neuropsychological and Social Investigation of Dementia in North-Eastern Italy.
The incidence of dementia increases exponentially with age but knowledge of real disease-modifying interventions is still limited. To describe the study design and methods of a large prospective cohort study aimed at exploring the complex underlying relationships existing among cognition, frailty, and health-related events in older persons with cognitive impairment. Prospective cohort study of a representative population of outpatients attending the Treviso Cognitive Impairment Center between 2000 and 2010. The TREVISO DEMENTIA (TREDEM) Study conducted in Treviso, Italy. 490 men and 874 women, mean age 79.1 ± 7.8 years (range 40.2-100 years). Physiological data, biochemical parameters, clinical conditions, neuroradiological parameters (e.g., brain atrophy and cerebral vascular lesions identified by computerized tomography scans), neuropsychological assessment, and physical function markers were measured at baseline. Patients were followed-up to 10 years. The final sample included in the study was predominantly composed of women and characterized by an initial physical function impairment and increased vascular risk profile. Cognitive function of the sample population showed moderate cognitive impairment (Mini Mental State Examination 20.2 ± 6.3; Clinical Dementia Rating 1.2 ± 0.7), and a prevalence of vascular dementia of 26.9%. Cortical, subcortical and hippocampus atrophy were all significantly correlated with age and cognitive function. Results obtained from the preliminary analyses conducted in the TREDEM study suggest that the database will support the accomplishment of important goals in understanding the nature of cognitive frailty and neurodegenerative diseases.


Rheum palmatum L. Attenuates High Fat Diet-Induced Hepatosteatosis by Activating AMP-Activated Protein Kinase.
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by the accumulation of excess fat in the liver. Rheum palmatumL. (RP) decoctions have been reported to ameliorate NAFLD. The aim of the present study was to investigate the effects and underlying mechanisms of RP in fatty liver disease induced by a high-fat diet (HFD) in rats. Low and high doses of aqueous RP extraction were orally administered to HFD-fed rats for six weeks. Body weight, tissue weight, glucose tolerance, insulin tolerance, hepatic morphology, and liver triglyceride (TG) content were assessed. The effects of RP on the expressions of lipogenic and lipolysis genes were measured by quantitative real-time PCR. The phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) was determined by Western blotting. Treatment with low-dose RP significantly reduced liver weight, liver TG content, and improved glucose tolerance in HFD-fed rats. Consistently, RP attenuated excess fat accumulation and downregulated the expression of lipogenic genes in the liver. Further, an increased phosphorylation of AMPK and ACC was observed. These findings suggest that low-dose RP alleviates hepatosteatosis, at least in part, by stimulating AMPK activity.


Changes in adenine nucleotides and energy charge in isolated winter wheat cells during low temperature stress.
Adenylate energy charge (AEC) and adenine nucleotide levels of isolated winter wheat (Triticum aestivum L. cv Kharkov 22 MC) cells exposed to various low temperature stresses were determined. During ice encasement at -1 degrees C, nucleotide levels decreased gradually in approximate relation to a decline in cell viability. AEC values remained high even after 5 weeks of icing when cell viability was severely reduced. When isolated cell suspensions were exposed to various cooling and freezing regimes ranging from -10 to -30 degrees C, cell damage was dependent on the minimum temperature imposed and the duration of exposure to the freezing stress. The levels of all three adenine nucleotides declined with increasing severity of the imposed stress, but AEC values remained high even at -30 degrees C when nearly all of the cells were killed. The addition of 10 millimolar Ca(2+) to cell suspensions enhanced survival during low temperature stresses, but did not influence nucleotide levels other than through its effect on cell viability. These results indicate that impairment of the ion transport system during the early stages of ice encasement prior to a detectable decline in cell viability cannot be attributed to changes in the adenylate energy charge system of the cell.


Size threshold perimetry performs as well as conventional automated perimetry with stimulus sizes III, V, and VI for glaucomatous loss.
It is thought that large perimetric stimuli are insensitive for demonstrating visual field defects. To test the hypothesis that there is no difference in the total number of abnormal test locations with total deviation empiric probability plots in glaucoma patients, we compared results of glaucoma patients tested with sizes III (0.43° diameter), V (1.72°), and VI (3.44°), and size threshold perimetry (STP), a method that finds threshold by changing stimulus size. We derived normative limits for total deviation probability plots using the second test from 60 age-matched normals. We analyzed the probability plots of 120 glaucoma patients (mean deviation was -9.3 ± 6.1 dB with a range of -0.2 to -31.6) at the 42 nonblind spot locations common to the tests. We compared the number of abnormal test locations at the 5% level among the tests using one-way repeated measures ANOVA on ranks. We stratified the results by mean deviation. There was a statistically significant difference in the number of abnormal test locations among the tests: III, 28.5; V, 29.7; VI, 27.0; and STP, 28.8, P = 0.001; Tukey pairwise comparisons were statistically significant for the assessments between sizes V and VI and between STP and size VI. When stratifying by mean deviation, with mild visual loss, size V was most sensitive, followed by STP; size VI appeared slightly less sensitive. Size V and STP provide favorable stimulus methodology for detection of mild to moderate glaucoma. Size VI appears slightly less sensitive for glaucoma with mild loss.


Evolution in health and medicine Sackler colloquium: a public choice framework for controlling transmissible and evolving diseases.
Control measures used to limit the spread of infectious disease often generate externalities. Vaccination for transmissible diseases can reduce the incidence of disease even among the unvaccinated, whereas antimicrobial chemotherapy can lead to the evolution of antimicrobial resistance and thereby limit its own effectiveness over time. We integrate the economic theory of public choice with mathematical models of infectious disease to provide a quantitative framework for making allocation decisions in the presence of these externalities. To illustrate, we present a series of examples: vaccination for tetanus, vaccination for measles, antibiotic treatment of otitis media, and antiviral treatment of pandemic influenza.


Withdrawal of antiepileptic medication in children--effects on cognitive function: The Multicenter Holmfrid Study.
We present 100 children diagnosed with epilepsy who were seizure-free for more than 1 year and still on monotherapy of antiepileptic drugs (AEDs). We matched each child with a healthy classmate and performed neuropsychological testing and EEG before and after complete withdrawal of the AEDs. The withdrawal phase lasted 3 months, but the dose decrease was individualized for each patient. Three to 4 months after complete withdrawal of the drug all patients were reassessed. Patients with seizure relapse are excluded from the study. Seventeen patients are regarded as dropout, 11 because of seizure relapse and six because of protocol violation. The remaining 83 patients were treated with carbamazepine (n = 56), valproic acid (n = 17), or phenytoin (n = 10). Serum concentrations of the AEDs were measured using peak plasma levels that were taken immediately before or after psychological testing. We used neuropsychological tests to assess psychomotor function and "central" cognitive processing such as information processing or memory function. We found significant improvement attributable to drug withdrawal on only one of the cognitive tests, namely, psychomotor speed, suggesting that the impact of AED treatment on higher-order cognitive function is rather limited. In addition, we found group differences between the epilepsy group and the control group at baseline that persisted after drug withdrawal. Subsequent analysis showed some factors that may have contributed to these group differences. First, patients with a former diagnosis of absence seizures show lower scores both at baseline and after drug withdrawal. We may assume that the seizure propensity has not disappeared completely in these patients. Some evidence is found that phenytoin may have a different cognitive profile than carbamazepine, with more impairment on tests that measure motor and mental speed. Again, this impairment persists after drug withdrawal.


Laboratory diagnosis of Haemophilus ducreyi: sensitivity of culture media.
Laboratory confirmation of the clinical diagnosis of chancroid requires the isolation of Haemophilus ducreyi. Enriched gonococcal (GcHbS) and Mueller-Hinton agar (MHHb) both support the growth of most strains of H. ducreyi. In this study we compared the isolation rate of H. ducreyi on GcHbs and MHHb media in 111 men with genital ulcer disease. A second culture was obtained in 84 men at 48 hr in order to determine the reproducibility of H. ducreyi culture. The sensitivity of a single and a sequential pair of cultures on GcHbS was 67% and 74%, respectively, on men with presumed chancroid. The sensitivity of the MHHb as a single culture was 53%. Using both media for the initial culture of genital ulcers, and repeating the culture on GcHbs at 48 hr, increased the sensitivity of the isolation of H. ducreyi to 92% in men who had no prior antimicrobial use and who had no laboratory evidence of primary syphilis.


Contrasting pharmacological ETB receptor blockade with genetic ETB deficiency in renal responses to big ET-1.
Renal clearance studies were conducted to determine the role of ET(B) receptors in the renal response to big endothelin-1 (big ET-1). Two series of experiments were conducted on Inactin-anesthetized rats to contrast acute pharmacological blockade of ET(B) receptors vs. genetic ET(B) receptor deficiency. In the first series, Sprague-Dawley rats were given either ET(B)-selective antagonist, A-192621, or vehicle (0.9% NaCl) prior to infusion of big ET-1 (10 pmol.kg(-1).min(-1)) for 60 min. A-192621 significantly increased baseline mean arterial pressure (MAP; 102 +/- 4 vs. 141 +/- 6 mmHg, P < 0.05) and urine flow rate (0.5 +/- 0.1 vs. 1.3 +/- 0.2 microl/min, P < 0.05) without any effect on glomerular filtration rate (GFR) or effective renal plasma flow (ERPF). Big ET-1 significantly increased MAP in both groups but to a higher level in rats given antagonist (120 +/- 6 vs. 169 +/- 6 mmHg, P < 0.05). Big ET-1 increased urine flow in control rats but decreased in rats given antagonist. GFR and ERPF were decreased in rats given big ET-1, an effect that was exaggerated by ET(B) blockade. Another series of experiments examined the response to big ET-1 in rats lacking functional renal ET(B) receptors, known as spotting lethal (sl) rats. Surprisingly, rats heterozygous (sl/+) for ET(B) receptor deficiency had a significantly higher baseline MAP compared with homozygous (sl/sl) rats (134 +/- 6 vs. 112 +/- 7 mmHg, P < 0.05), although other variables were similar. Big ET-1 produced no significant change in MAP in either group. Urine flow, GFR, and ERPF were significantly decreased in both groups, although these changes were much larger in sl/sl rats. These experiments indicate that the ET(B) receptor plays an important role in limiting the renal hemodynamic response to big ET-1. Furthermore, the diuretic actions of big ET-1 require a functional ET(B) receptor.


Palladium-catalyzed carbohalogenation: bromide to iodide exchange and domino processes.
Aryl bromides have been used to prepare a variety of nitrogen- and oxygen-containing heterocycles featuring new carbon-carbon and carbon-iodine bonds. This palladium-catalyzed carbohalogenation requires potassium iodide for the reaction to proceed in high yields. Additionally, the first examples of domino carbohalogenation reactions have been demonstrated using both aryl iodide and aryl bromide starting materials. Complex products with multiple rings and stereogenic centers are generated in excellent yields with moderate to excellent diastereoselectivities.


[Heme oxgenase-1 gene induction and the mechanism in the rat vasospasm model].
Using fluorescent differential display and quantitative reverse-PCR, we found in the rat vasospasm model that heme oxygenase-1 messenger RNA was induced in basilar artery. Intracistemal injection of antisense OH-1 oligodeoxynucleotide significantly reduced HO-1 mRNA and HO-1 protein levels and enhanced angiographic vasospasm. Thus, we demonstrate that HO-1 induction may play a important role in the resolution of delayed vasospasm after subarachnoid hemorrhage.


Listeriosis: a resurgent foodborne infection.
Listeria monocytogenes is the causative agent of human listeriosis, a potentially fatal foodborne infection. Clinical manifestations range from febrile gastroenteritis to more severe invasive forms, including sepsis, meningitis, rhombencephalitis, perinatal infections, and abortions. In recent years, an increasing rate of listeriosis has been reported in several European countries. These increases primarily reflect a higher rate of bacteraemic listeriosis in those > or =65 years of age, and are not otherwise correlated with geography, gender, ethnicity, socioeconomic factors or infectious serotypes. In the late 1980s, an upsurge in listeriosis rates was due to the contamination of a small number of food products. However, a restricted range of strains was responsible for most of the additional cases at that time, and no evidence exists for such a pattern since 2001. From a clinical perspective, the importance of isolating the pathogen as a prerequisite for an accurate epidemiological investigation and ultimately stopping transmission cannot be overemphasized.


Symposium on roles of and cooperation between academic- and practice-based pharmacy clinicians.
The findings of an academic symposium as they relate to the history and role of the academic pharmacy clinician, the strengths and limitations of the academic pharmacy clinician model, and the framework for future synergistic work relations among clinical pharmacy practitioners are summarized. On April 23, 2008, a symposium was convened to bring key thought leaders together to discuss the relationship of the academic-based pharmacy clinician and the practice-based pharmacy clinician. Participants included clinical faculty and administrators from two colleges of pharmacy, practice-based clinical pharmacists and pharmacy managers from seven health care institutions, and representatives from the American Association of Colleges of Pharmacy, the American College of Clinical Pharmacy, and the American Society of Health-System Pharmacists. Symposium participants discussed the roles and expectations of clinical pharmacists based on primary affiliation within the contemporary practice model for academic- and practice-based pharmacy clinicians and identified sources of conflict for academic- and practice-based pharmacy clinicians. Symposium participants agreed that in order to succeed, the academic-based and the practice-based pharmacy clinicians must function in a true partnership as each individual has strengths, resources, and benefits to bring to the relationship. Furthermore, knowledge, consideration, and an understanding of the potentially different goals and objectives of each institution are critical. A symposium attended by clinical faculty members and administrators from two colleges of pharmacy, practice-based clinical pharmacists and pharmacy managers from seven health care institutions, and representatives from three national pharmacy organizations was conducted to discuss the roles of and cooperation between academic- and practice-based pharmacy clinicians.


Endogenous anticancer mechanisms (EACMs).
Cells capable of starting the track towards cancer are probably abundant in an organism, but the likelihood of any of these cells to evolve to a deadly disease is very low. This occurs in part due to several safekeeping mechanisms shaped by evolution to detect and eliminate potential cancer-forming cells, which will be defined here as endogenous anticancer mechanisms (EACMs). Virtually any cellular process has safekeeping mechanisms that detect and correct mishaps that could evolve into potentially harmful cellular behavior, but some aspects of these mechanisms seem to have been selected by evolution to protect organisms against cancer. The mechanisms that will be discussed here and in the reviews of this series are: cell senescence, DNA repair, cell cycle control, apoptosis, autophagy, block of the invasion and metastasis cascade, block of cell reprogramming and immune surveillance. Here I will present the basic features and the importance of each EACM and review the involvement of these processes in preventing cancer growth together with their importance in cancer prevention and therapeutics.


Sphenoid Sinusitis Complicated by Pneumococcal Meningitis and an Infectious Aneurysm in the Intracavernous Carotid Artery.
A 61-year-old Japanese woman presented with a headache and appetite loss lasting for nine days and was admitted to our hospital, where she was diagnosed with pneumococcal meningitis associated with acute sphenoid sinusitis. While the administration of meropenem and dexamethasone ameliorated the meningitis, right third and sixth nerve palsy suddenly developed 10 days after admission. CT angiography subsequently demonstrated an aneurysm in the cavernous portion of the right internal carotid artery. This is the first reported case of sphenoid sinusitis simultaneously complicated by both pneumococcal meningitis and an infectious aneurysm in the intracavernous carotid artery.


Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas.
Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division. We evaluated the expression of the chemokine stromal cell-derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation. The expression of SDF1 and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitaries was determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1 was evaluated in eight fibroblast-free human pituitary adenoma cell cultures. CXCR4 mRNA was expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1 showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1 were expressed only in a subset of anterior pituitary cells, with a lower expression of SDF1 compared with its cognate receptor. CXCR4 and SDF1 were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone-secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1 induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin. CXCR4 and SDF1 are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development in humans.


[Metastasizing pleomorphic adenomas. Clinical and cytometric analysis].
Metastasizing pleomorphic adenoma is a rare lesion, histologically benign but with a malignant clinical behaviour. Two cases are reported with a flow cytometric study. Recurrent adenoma and its metastasis were aneuploid in one case.


[Antero-superior impingement of the shoulder. Indications for and options in surgical treatment].
Many therapeutic questions and controversies surround the impingement syndrome of the shoulder, however it appears that the major procedure is rotator cuff decompression. This is achieved by antero-inferior acromioplasty and section of the coracoacromial ligament, during open or arthroscopic surgery. Which patients will be helped by this procedure? When does the surgical decision have to be taken? Is the suture of the rotator cuff tear and the removal of intratendinous calcifications needed in addition to the acromioplasty? Many major questions remain unanswered.


Impact of smoking history on the association between Eicosapentaenoic acid to arachidonic acid ratio and acute coronary syndrome: A multicenter cross-sectional study.
The association among smoking history, eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio and acute coronary syndrome (ACS) is yet to be investigated. The present study aimed to clarify the association between the EPA/AA ratio and ACS prevalence in patients admitted to the cardiology department based on their smoking history. We enrolled 1733 patients from five cardiology divisions located in Tokyo, Japan, and measured their levels of polyunsaturated fatty acids, including EPA and AA, from January 2004 to May 2011. We assessed the association between the EPA/AA ratio and ACS in the subgroups stratified according to smoking history (never, former, current smokers) using multivariate logistic models. A high EPA/AA ratio was significantly associated with decreased odds of ACS among patients without a smoking history (adjusted odds ratio AOR=0.20, 95% CI: 0.04-0.86) but not in patients with a smoking history (former smoker, AOR=1.50, 95% CI: 0.44-5.03; current smoker, AOR=3.73, 95% CI: 0.34-40.6). The EPA/AA ratio and ACS occurrence were found to be significantly associated in patients without a smoking history; however, no such association existed in patients with a smoking history. AA: arachidonic acid, ACS: acute coronary syndrome, CVD: cardiovascular disease, DGLA: dihomo-gamma-linolenic acid, DHA: docosahexaenoic acid, EPA: eicosapentaenoic acid, JELIS: Japan EPA Lipid Intervention Study, PUFA: polyunsaturated fatty acid, RAS: renin angiotensin system, TG: triglyceride.


Effect of flow reduction on coronary blood flow heterogeneity.
The purpose of this study was to test the hypothesis that under reduced flow conditions, spatial heterogeneity (segment-to-segment variability) of myocardial blood flow would be inversely proportional to the rate of perfusion and that vasoconstriction would alter this relationship in anesthetized open-chest dogs. A carotid-left circumflex coronary artery shunt was created. Coronary blood flow determinations employed the radioactive microsphere technique. Fifty tissue samples were obtained from the affected left ventricle, including subepicardial and subendocardial samples. The coefficient of variation (CV = 100 x SD/mean), an index of spatial heterogeneity, was computed. Flows were obtained under three separate conditions: control, a 50% flow reduction in the circumflex artery, and vasopressin infusion, in which the administered dose reduced circumflex artery flow by 50%. The within-animal CV increased from a control of 18 +/- 9 to 45 +/- 25 with partial occlusion and 46 +/- 18 with vasopressin. No significant differences in CV were found between the two reduced flow conditions. A significant linear relationship between CV and mean coronary flow was found (r = 0.51, P < 0.001) over the entire range of flows studied (CV = -0.34*flow + 50.91) for control, 50% occlusion, and vasopressin treatment. The correlation was significantly improved (r = 0.69) using the equation CV = (1319.06/flow) + 4.44. Thus, the relative heterogeneity of coronary blood flow increased with reductions in coronary blood flow, regardless of the means of flow reduction.


A comparison of the energetics of annexin I and annexin V.
The annexins comprise a family of soluble Ca2+- and phospholipid-binding proteins. Although highly similar in three-dimensional structure, different annexins are likely to exhibit different biochemical and functional properties and to play different roles in various membrane related events. Since it must be expected that these functional differences arise from differences in the characteristic thermodynamic parameters of these proteins, we performed high-sensitivity differential scanning microcalorimetry (DSC) and isothermal guanidinium hydrochloride (GdnHCl)-induced unfolding studies on annexin I and compared its thermodynamic parameters with those of annexin V published previously. The DSC data were analyzed using a model that permits quantitative treatment of the irreversible reaction. It turned out, however, that provided a heating rate of 2 K min-1 is used, unfolding of annexin I can be described satisfactorily in terms of a simple two-state reaction. At pH 6.0 annexin I is characterized by the following thermodynamic parameters: t1/2=61.8 degrees C, DeltaHcal=824 kJ mol-1 and DeltaCp=19 kJ mol-1 K-1. These parameters result in a stability value of DeltaG0D (20 degrees C)=51 kJ mol-1. The GdnHCl induced isothermal unfolding of annexin I in Mes buffer (pH 6.0), yielded DeltaG0D (buffer) values of 48, 60 and 36 kJ mol-1 at 20, 12 and 5 degrees C, respectively. These DeltaG0D values are in reasonable agreement with the values obtained from the DSC studies. The comparison of annexin I and annexin V under identical conditions (pH 8.0 or pH 6.0) shows that despite the pronounced structural homology of these two members of the annexin familiy, the stability parameters are remarkably different. This difference in stability is consistent with and provides a thermodynamic basis for the potential different in vivo functions proposed for these two annexins.


Breast Reconstruction with Enhanced Stromal Vascular Fraction Fat Grafting: What Is the Best Method?
Actually, there are 2 main methods to obtain stromal vascular fraction (SVF): enzymatic digestion and mechanical filtration; however, the available systems report heterogeneous and sometimes not univocal results. The aim of this study is to evaluate different procedures for SVF isolation and compare their clinical efficacy in the treatment of soft-tissue defects in plastic and reconstructive surgery. The authors evaluated Celution and Medikhan, enzymatic systems, and Fatstem and Mystem system, mechanical separation systems. Fifty patients affected by breast soft-tissue defects were treated in the Plastic and Reconstructive Surgery Department of Tor Vergata University of Rome. Four groups of 10 patients were managed with enhanced SVF fat grafts using cells obtained by Celution (Cytori Therapeutics, Inc., San Diego, Calif.), Medikhan (Medi-Khan Inc., West Hollywood, Calif.), Fatstem (Fatstem CORIOS Soc. Coop, San Giuliano Milanese, Italy), and Mystem (Mystem evo Bi-Medica, Treviolo, Italy) systems. A control group of 10 patients was treated with only centrifuged fat according to Coleman's technique. In enhanced SVF-treated patients treated with cells obtained by Celution system, we observed a 63% ± 6.2% maintenance of contour restoring after 1 year, compared with 39% ± 4.4% of control group. In patients treated with SVF obtained by Medikhan system, we observed a 39% ± 3.5% maintenance, whereas enhanced SVF with Fatstem and Mystem systems gave a 52% ± 4.6% and 43% ± 3.8% maintenance of contour restoring, respectively. SVF cell counting indicated that Celution and Fatstem were the most efficient systems to obtain SVF cells. Celution and Fatstem were the 2 best automatic systems to obtain SVF and to improve maintenance of fat volume and prevent the reabsorption.


Remedial hydration reduces the incidence of contrast-induced nephropathy and short-term adverse events in patients with ST-segment elevation myocardial infarction: a single-center, randomized trial.
The aim of this study was to investigate whether remedial hydration (RH) reduces the incidence of contrast-induced nephropathy (CIN) and short-term adverse events in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). A total of 216 consecutive STEMI patients were prospectively and randomly assigned into two groups: 108 patients in the RH group and 108 patients in the no RH (control) group. The serum creatinine (SCr) and creatinine clearance (CCr) levels were measured on admission and at 24, 48 and 72 hours after primary PCI. The rates of CIN and short-term adverse events were analyzed for each group. After surgery, the patients were categorized into four groups according to the Mehran risk score: low (≤5, n =98), moderate (6-10, n=56), high (11-15, n=40) or very high (≥16, n=22). The incidence of CIN in the RH group was lower than that observed in the control group (22/108; 20.4% vs. 38/108; 35.2%, p<0.05). The subgroup analysis showed that the rate of CIN was lower in the moderate (6/29; 20.7% vs. 13/30; 43.3%, p<0.10) and significantly lower in both the high (5/21; 23.8% vs. 10/18; 55.6%, p<0.05) and very high score groups (3/12; 25.0% vs. 8/12; 66.7%, p<0.05) among the RH patients compared to the controls. At 24, 48 and 72 hours after PCI, the patients in the RH group exhibited lower SCr levels and higher CCr levels than the patients in the control group (both p<0.05). A lower incidence of in-hospital clinical events was also observed in the RH group. Remedial hydration decreases the occurrence of CIN and improves the short-term prognosis of STEMI patients undergoing primary PCI.


Familial cutaneous malignant melanoma and tumors of the nervous system. A hereditary cancer syndrome.
Excessive risk of cutaneous melanoma as a second cancer has been associated with benign or malignant tumors of the nervous system. Cutaneous melanoma and nervous system tumors may independently aggregate in families. There are, however, no previous reports of increased likelihood of tumors of the nervous system in families of patients with cutaneous melanoma or--of cutaneous melanoma in families with tumors of the nervous system. The occurrence of nervous system tumors as second cancers was examined in a series of 904 patients with cutaneous melanoma and/or their family members. Fifteen families with 17 members with cutaneous melanoma from this series had one or more additional relatives with tumors of the nervous system, including astrocytoma, medulloblastoma, glioblastoma multiforme, ependymoma, glioma, meningioma, and acoustic neurilemmoma. Another subgroup of 10 patients with cutaneous melanoma had either a meningioma (n = 9) or acoustic neurilemmoma (n = 1) as a second tumor. The pattern of atypical melanocytic nevi occurring in the majority (20/25) of cutaneous melanoma patients in our series and in additional first degree relatives of 9 of 11 of the affected families, has been previously associated with the Familial Atypical Multiple Mole-Melanoma syndrome. This unusual familial and personal occurrence of tumors, showing differentiation toward tissues of the neural crest, neuroepithelium, and/or mesenchymal derivation, supports a putative association with a hereditary cancer susceptibility trait.


NSAID use and the risk of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease with limited pharmacologic therapies. Recent animal studies and one large retrospective study have found NSAIDs to be protective against the development of PD. We decided to test this hypothesis by conducting a nested case-control study using the Saskatchewan drug plan database. Entry to the cohort was defined as the first prescription of an antihypertensive agent between 1980 and 1987 and followed until 1999. Cases were defined as those having received three prescriptions for a dopamine agonist within a year. For each case, ten controls were selected matched to the case by age, calendar time and index date. Conditional logistic regression was used to estimate rate ratios adjusting for gender, previous use of arthritis medication and previous antipsychotic use. Current users of NSAIDs had a slightly higher risk of developing PD (RR=1.49 [95% CI, 1.11-2.01]). This effect was not seen with past users (RR=1.18 [95% CI, 0.89-1.59]). Based on the results of our study current users of NSAIDs may be at a slightly higher risk of developing PD. More studies are needed to confirm this finding.


Lifelong self-directed learning using a computer database of clinical questions.
Physicians often have self-perceived knowledge gaps when they are seeing patients. Traditional continuing medical education is designed to meet the knowledge gaps of groups rather than individual physicians with specific patient problems. Physicians with clinical information needs are advised to critically evaluate high-quality original research in order to practice "evidence-based medicine." But this advice may be unrealistic for busy clinicians. We propose a system for documenting self-perceived information needs using a computer database. Concise answers to these needs are included in the database along with reference citations supporting the answers. The system tracks continuing education efforts, directs patient care decisions, and focuses lifelong learning on relevant topics. We emphasize the importance of being sensitive to personal information needs and the benefits of maintaining a record of these needs.


IL-23 promotes tumour incidence and growth.
Chronic inflammation has long been associated with increased incidence of malignancy and similarities in the regulatory mechanisms have been suggested for more than a century. Infiltration of innate immune cells, elevated activities of matrix metalloproteases and increased angiogenesis and vasculature density are a few examples of the similarities between chronic and tumour-associated inflammation. Conversely, the elimination of early malignant lesions by immune surveillance, which relies on the cytotoxic activity of tumour-infiltrating T cells or intra-epithelial lymphocytes, is thought to be rate-limiting for the risk to develop cancer. Here we show a molecular connection between the rise in tumour-associated inflammation and a lack of tumour immune surveillance. Expression of the heterodimeric cytokine interleukin (IL)-23, but not of its close relative IL-12, is increased in human tumours. Expression of these cytokines antagonistically regulates local inflammatory responses in the tumour microenvironment and infiltration of intra-epithelial lymphocytes. Whereas IL-12 promotes infiltration of cytotoxic T cells, IL-23 promotes inflammatory responses such as upregulation of the matrix metalloprotease MMP9, and increases angiogenesis but reduces CD8 T-cell infiltration. Genetic deletion or antibody-mediated elimination of IL-23 leads to increased infiltration of cytotoxic T cells into the transformed tissue, rendering a protective effect against chemically induced carcinogenesis. Finally, transplanted tumours are growth-restricted in hosts depleted for IL-23 or in IL-23-receptor-deficient mice. Although many strategies for immune therapy of cancer attempt to stimulate an immune response against solid tumours, infiltration of effector cells into the tumour tissue often appears to be a critical hurdle. We show that IL-23 is an important molecular link between tumour-promoting pro-inflammatory processes and the failure of the adaptive immune surveillance to infiltrate tumours.


Total Synthesis and Structure Confirmation of (-)-Asimitrin, a C37 Annonaceous Acetogenin with a Hydroxylated Adjacent Bis-Tetrahydrofuran Core.
The total synthesis and structure confirmation of the potent cytotoxic agent (-)-asimitrin (1), a C37 annonaceous acetogenin having a hydroxylated adjacent bis-tetrahydrofuran (THF) core, are described. The present synthesis features a highly stereoselective, chelate-controlled intramolecular amide enolate alkylation (IAEA) for the synthesis of key intermediate 17-hydroxy-16,17-erythro-16,19-trans-THF 6, our direct ketone synthesis/l-Selectride reduction protocol for stereoselective introduction of the C(21)-C(34) unit, Sharpless asymmetric dihydroxylation (SAD), and internal Williamson etherification for construction of the 20,23-trans-THF ring.


A new species of the Agriotes nuceus species group from Turkey.
A new Elateridae species, Agriotes longipronotum n. sp. (Coleoptera: Elateridae: Elaterinae: Agriotini), is described from Siirt province, Turkey. Photographs of the imago and the aedeagus, and drawings of the aedeagus of the new species, A. sameki , A. bulgaricus , and A. rahmei are given. A rearranged diagnostic key of all Turkish species of nuceus -group is given. The new species is discussed in relation with closely related species. The species of the Agriotes nuceus -group from Turkey are listed, and their distributions are given.


Thumb infection caused by Streptococcus pseudoporcinus.
Streptococcus pseudoporcinus, a recently described organism found in the genitourinary tract of women, was isolated from a thumb wound in a male patient subsequent to trauma. This case describes a rarely reported non-genitourinary tract clinical isolate of S. pseudoporcinus.


Assessment of elemental concentrations in the urban air (case study: Tehran city).
Tehran is one of the megacities of the world with a population of over eight million. Its air is highly polluted mainly due to the suspended particulate matters, which encompasses a wide spectrum of chemical elements. These elements based on their type, size, and impact on the life cycle have various environmental and heath risks. In this research, the neutron activation method is used to determine the concentration levels of Al, Ba, Fe, Mg, and V in the urban air. Thus, two districts of Tehran with different characteristics are selected. District 21 includes much of the industries located in Tehran metropolitan and is considered as an industrial area. In contrast, district 22 lacks any significant industrial activity. It is a newly established and expanding district adjacent to district 21 with a great deal of constructional activities. For the measurement of the suspended particulate matters in the air, the various sections of the aforesaid districts with industrial, residential, heavily congested traffic, residential/commercial, residential/heavily congested traffic, and residential/industrial classifications were identified. Subsequently, 24 sampling stations were selected. The sampling of the suspended particulate matters was conducted with the aid of a high volume pump containing 125 mm cellulose filters in two different time intervals. After completion of the sampling process, the samples were prepared and sent to the research reactor of the Iran Nuclear Energy Organization for Neutron Activation. During the next steps, the radiations emitted from the samples were registered, the radiation curves were plotted, and the amounts of the trace elements were determined. As a result, the average concentration levels of Al, Ba, Fe, Mg, and V were identified to be 3.301140, 2.273658 x 10, 4.0681696 x 10(-1), 3.5525475 x 10(-1), and 3.04075 x 10(-2) microg/m(3), respectively. Moreover, the emission sources of the aforesaid elements into the air were identified. The concentration levels of these elements in the industrial and heavily congested traffic sections were higher. Finally, it was concluded that the statistical analysis of these elements presents a meaningful correlation among them.


PTHR1 May Be Involved in Progression of Osteosarcoma by Regulating miR-124-3p-AR-Tgfb1i1, miR-27a-3p-PPARG-Abca1, and miR-103/590-3p-AXIN2 Axes.
Our previous study has indicated that the parathyroid hormone type 1 receptor (PTHR1) may play important roles in development and progression of osteosarcoma (OS) by regulating Wnt, angiogenesis, and inflammation pathway genes. The goal of this study was to further illuminate the roles of PTHR1 in OS by investigating upstream regulation mechanisms (including microRNA [miRNA] and transcription factors [TFs]) of crucial genes. The microarray dataset GSE46861 was downloaded from the Gene Expression Omnibus database, in which six tumors with short hairpin RNA (shRNA) PTHR1 knockdown (PTHR1.358) and six tumors with shRNA control knockdown (Ren.1309) were collected from mice. Differentially expressed genes (DEGs) between PTHR1.358 and Ren.1309 were identified using the linear models for microarray data (LIMMA) method, and then the miRNA-TF-mRNA regulatory network was constructed using data from corresponding databases, followed by module analysis, to screen crucial regulatory relationships. OS-related human miRNAs were extracted from the curated Osteosarcoma Database. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. As a result, the miRNA-TF-mRNA regulatory network, including 1049 nodes (516 miRNA, 25 TFs, and 508 DEGs) and 15942 edges (interaction relationships, such as Pparg-Abca1 and miR-590-3p-AXIN2), was constructed, from which three significant modules were extracted and modules 2 and 3 contained interactions between miRNAs/TFs and DEGs such as miR-103-3p-AXIN2, miR-124-3p-AR-Tgfb1i1, and miR-27a-3p-PPARG-Abca1. miR-27a-3p was a known miRNA associated with OS. Abca1, AR, and miR-124-3p were hub genes in the miRNA-TF-mRNA network. Tgfb1i1 was involved in cell proliferation, Abca1 participated in the cholesterol metabolic process, and AXIN2 was associated with the canonical Wnt signaling pathway. Furthermore, we also confirmed upregulation of miR-590-3p and downregulation of AXIN2 in the mouse OS cell line K7M2-WT transfected with PTHR1 shRNA. In conclusion, PTHR1 may play important roles in progression of OS by activating miR-124-3p-AR-Tgfb1i1, miR-27a-3p-PPARG-Abca1, and miR-103/590-3p-AXIN2 axes.


Random-covariances and mixed-effects models for imputing multivariate multilevel continuous data.
Principled techniques for incomplete-data problems are increasingly part of mainstream statistical practice. Among many proposed techniques so far, inference by multiple imputation (MI) has emerged as one of the most popular. While many strategies leading to inference by MI are available in cross-sectional settings, the same richness does not exist in multilevel applications. The limited methods available for multilevel applications rely on the multivariate adaptations of mixed-effects models. This approach preserves the mean structure across clusters and incorporates distinct variance components into the imputation process. In this paper, I add to these methods by considering a random covariance structure and develop computational algorithms. The attraction of this new imputation modeling strategy is to correctly reflect the mean and variance structure of the joint distribution of the data, and allow the covariances differ across the clusters. Using Markov Chain Monte Carlo techniques, a predictive distribution of missing data given observed data is simulated leading to creation of multiple imputations. To circumvent the large sample size requirement to support independent covariance estimates for the level-1 error term, I consider distributional impositions mimicking random-effects distributions assigned a priori. These techniques are illustrated in an example exploring relationships between victimization and individual and contextual level factors that raise the risk of violent crime.


Hepatitis B sero-prevalence and risk factors among school-age children in a low socioeconomic community, Bangkok.
A cross-sectional study of 165 school-age children who had no history of HBV vaccination was carried out in a low socioeconomic community of Din-Daeng, Bangkok. Blood specimens were collected for determination of HBV seromarkers (HBsAg, Anti-HBs and Anti-HBc) by EIA commercial kits. The results showed that the prevalence of HBV seromarkers was 24.85%, the HBsAg carrier rate was 3.64%, the anti-HBs positive rate was 15.15%, and the prevalence of only anti-HBc was 6.06%. To investigate factors associated with the positivity of HBV seromarkers, children were divided into two groups--the first group consisted of 41 children with HBV seromarkers and the second consisted of 124 children without HBV seromarkers. The study variables between the two groups were compared and analysed. The results revealed that factors associated with HBV positivity were (a) child factors: child's age, child's sex, ear piercing in female, sharing blade during haircutting, contact wound from other persons, using wares with other persons, searching things in garbage, and (b) family factors: older parent, low education in parent, low family income per month, low parent's knowledge and attitude about HBV infection and vaccination, (P < 0.05). After using stepwise regression analysis, the factor of ear piercing in female was only one significant variable.


[Relationship between exposure to environmental toxins and motor neuron disease: a case report].
A case is reported of amyotrophic lateral sclerosis with occupational exposure to solvents and metals. The environmental toxin theory of motorneuron disease, including aspects of epidemiological, clinical, experimental and individual susceptibility is discussed. An overall evaluation of animal and human data was made using a methodological approach developed by the International Agency for Research on Cancer and a Scandinavian group of experts. It is concluded that there is a probable linkage between metals/solvents exposure and motorneuron disease.


Critical role of tryptophanyl residues in the conformational stability of goose delta-crystallin.
Delta-crystallin is the major structural protein in avian and reptilian eye lenses but its sequence is highly homologous with the urea cycle enzyme, argininosuccinate lyase (ASL). In previous studies the multi-step unfolding process of this protein in the presence of GdmCl was sensitively probed using tryptophan fluorescence. In this study the contribution of single tryptophan residues to the stability of the local environment was monitored by mutation of two highly conservative tryptophan residues in goose delta-crystallin, Trp 74 and Trp 169. These residues behaved differently in terms of fluorescence intensity and maxima emission wavelength, consistent with their structural location in buried or solvent accessible regions. No gross changes in the secondary structure after mutation were observed, as judged by far-UV CD. The side chains of tryptophan residues in the structure of wild-type goose delta-crystallin possess both hydrophobic and hydrogen bonding interactions. Replacement of the side chain with phenylalanine or alanine led to expose of a hydrophobic area and a reduction in thermal stability; W169A particularly has a T(m) value that was 10 degrees C lower than the wild type enzyme. In the presence of GdmCl, a sharp red shift in fluorescence wavelength due to subunit dissociation can be sensitively detected using a single tryptophan, with the region surrounding W74 undergoing the first transition with a [GdmCl](1/2) of 0.45 M. Further measurement of unfolding curves by CD revealed that the W169A mutant was most unstable with a [GdmCl](1/2) of 0.22 M. From sedimentation velocity analysis, the unstable conformation of the W169A mutant affected the assembly of the quaternary structure. Our studies demonstrate the critical role for the tryptophan residues in stabilizing protein conformations and subunit assembly in delta-crystallin.


Differential gene profiles in developing embryo and fetus after in utero exposure to ethanol.
Alcohol consumption during pregnancy results in morphological abnormalities in the fetuses of humans and experimental animals, and is referred to as fetal alcohol syndrome (FAS). However, the molecular mechanism underlying FAS has not been completely elucidated. The aim of the present study was to investigate the potential molecular mechanisms of ethanol-induced FAS in the developing embryo and fetus. cDNA microarray analysis was used to screen for altered gene profiles. Ethanol at a teratogenic dosage (3.8 g/kg, twice a day) was administered intraperitoneally to pregnant C57Bl/6J mice from gestation day (GD) 6 to 8. Morphologic observations showed excessive malformations of the craniofacial regions (reduction of the face, the absence of eyes, nose, jaw, and mandible, underdevelopment of vibrissae areas, cleft lip, and palate) in ethanol-exposed embryos (GD 10) and fetusus (GD 15). cDNA microarray analysis showed alterations in several gene profiles, including the "palate, lung, and nasal epithelium clone (plunc), "neurofilament, " and "pale ear. " Of these genes, the expressions of plunc were confirmed by reverse-transcription polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization. The plunc was highly expressed in the craniofacial region, specifically in upper airways and nasopharyngeal epithelium. RT-PCR analysis revealed that normal plunc mRNA expression levels were present in GD 15 fetuses, but not in GD 10 embryos. Interestingly, ethanol significantly downregulated the plunc expression in GD 15 fetuses. Our results suggest that ethanol-induced FAS is due in part to the downregulation of plunc expression in the fetus, and this gene may be a candidate biological marker for FAS.


Measurement of human serum immunoreactive gamma-glutamyl transpeptidase in patients with malignant tumors using enzyme-linked immunosorbent assay.
An enzyme-linked immunosorbent assay for human immunoreactive gamma-glutamyl transpeptidase (gamma-GTP) was developed. This assay was found to be simple, reproducible, and sensitive to 10 ng of the enzyme. Serum immunoreactive gamma-GTP content was significantly elevated in patients with various malignant tumors including liver cell cancer, lung cancer, gastric cancer, esophageal cancer, and colorectal cancer. On the other hand, in sera of patients with nonneoplastic diseases, the immunoreactive gamma-GTP content was not significantly elevated. No correlation was found between the serum levels of gamma-GTP determined by enzymatic assay and enzyme-linked immunosorbent assay, which indicates that, due to the presence of endogenous inhibitors and/or activators in sera, the enzyme activity may not reflect the true amount of enzyme protein. The measurement of immunoreactive gamma-GTP protein in sera appears to be useful for the detection and monitoring of certain malignant tumors.


Improvements following multimodal pelvic floor physical therapy in gynecological cancer survivors suffering from pain during sexual intercourse: Results from a one-year follow-up mixed-method study.
A large proportion of gynecological cancer survivors suffer from pain during sexual intercourse, also known as dyspareunia. Following a multimodal pelvic floor physical therapy (PFPT) treatment, a reduction in pain and improvement in psychosexual outcomes were found in the short term, but no study thus far has examined whether these changes are sustained over time. To examine the improvements in pain, sexual functioning, sexual distress, body image concerns, pain anxiety, pain catastrophizing, painful intercourse self-efficacy, depressive symptoms and pelvic floor disorder symptoms in gynecological cancer survivors with dyspareunia after PFPT, and to explore women's perceptions of treatment effects at one-year follow-up. This mixed-method study included 31 gynecological cancer survivors affected by dyspareunia. The women completed a 12-week PFPT treatment comprising education, manual therapy and pelvic floor muscle exercises. Quantitative data were collected using validated questionnaires at baseline, post-treatment and one-year follow-up. As for qualitative data, semi-structured interviews were conducted at one-year follow-up to better understand women's perception and experience of treatment effects. Significant improvements were found from baseline to one-year follow-up on all quantitative outcomes (P ≤ 0.028). Moreover, no changes were found from post-treatment to one-year follow-up, supporting that the improvements were sustained at follow-up. Qualitative data highlighted that reduction in pain, improvement in sexual functioning and reduction in urinary symptoms were the most meaningful effects perceived by participants. Women expressed that these effects resulted from positive biological, psychological and social changes attributable to multimodal PFPT. Adherence was also perceived to influence treatment outcomes. Findings suggest that the short-term improvements following multimodal PFPT are sustained and meaningful for gynecological cancer survivors with dyspareunia one year after treatment.


Polysaccharide from Angelica sinensis attenuates SNP-induced apoptosis in osteoarthritis chondrocytes by inducing autophagy via the ERK1/2 pathway.
Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.


VATS right upper lobe bronchial sleeve resection.
The aim of this study is to discuss video-assisted thoracic surgery (VATS) sleeve bronchial lobectomy when handling the locally advanced central lung cancer (involving the trachea and/or main bronchus). A 2.5 cm × 1.0 cm mass was found in the right upper lobe. Bronchoscopy demonstrated the tumor obstructing the right upper lobe bronchus and involved the right main bronchus and bronchus intermedius. Interrupted sutures were chosen for bronchial anastomosis. Bronchial membrane was sutured first, and then circumference end-to-end anastomoses were carried out using 3-0 absorbable sutures. There were no complications and the patient was discharged 8 days postoperatively. The third intercostal space of the anterior axillary line was suggested for right upper lobe bronchial sleeve resection. This incision can reduce the distance and angle between the anastomosis to the incision, and facilitate anastomosis. This approach can also prevent operator from fatigue for keeping one posture for a long time. Clearance of the mediastinal lymph nodes before cutting the bronchus was helpful for exposing the right main bronchus, the upper lobe bronchus and bronchus intermedius satisfied. And this option would avoid pulling bronchial anastomosis during mediastinal lymph nodes clearance. Interrupted suture was safe and effective for VATS bronchial anastomosis.


People don't exercise because they can't think of reasons to exercise: an examination of causal reasoning within the Transtheoretical Model.
This study compared the accessibility of the pros (advantages) and cons (disadvantages) of exercise in a group of non-exercisers and regular exercisers, using the Transtheoretical Model of behaviour change as a theoretical framework. Pre-contemplators (n = 18), and maintainers (n = 25), were asked to generate a list of 'advantages to taking part in exercise' (pro reasons), and a list of 'disadvantages to taking part in exercise' (con reasons). The time to generate their first item was recorded as well as the total number of items generated within 60 s. The results showed that pre-contemplators provided more con reasons relative to pro reasons; and maintainers provided more pro reasons relative to con reasons for exercise. Pre-contemplators were also quicker to provide their first con reason, relative to their first pro reason, but there was no difference in pro and con latencies in the maintainers. It was concluded that one reason pre-contemplation individuals do not participate in regular exercise may be because they cannot think of reasons to exercise.


Fabrication of doxorubicin functionalized gold nanorod probes for combined cancer imaging and drug delivery.
A novel strategy was utilized to develop a stable probe based on thiolated poly(ethylene glycol) (SH-PEG) and polyacrylic acid (PAA) functionalized gold nanorods (GNRs), following the attachment of an anti-cancer drug, doxorubicin (DOX), to obtain PAA-PEG-GNRs@DOX assemblies. Importantly, the obtained probe as a novel drug-delivery and fluorescent imaging agent for simultaneous imaging of and drug delivery to prostate cancer cells has also been demonstrated. In addition to designing PAA-PEG-GNRs that passively target tumor cells for cancer-fighting drug therapy, GNRs are also regarded as hyperthermia agents for photokilling cancer cells, so that the tumor would be attacked on two fronts simultaneously.


Optical response of small closed-shell sodium clusters.
Absorption spectra of closed-shell Na(2), Na(3) (+), Na(4), Na(5) (+), Na(6), Na(7) (+), and Na(8) clusters are calculated using a complex Bethe-Salpeter equation derived using a conserving linear response method. In the framework of a quasiparticle approach, we determine electron-hole correlations in the presence of an external field. The calculated results are in excellent agreement with experimental spectra, and some possible cluster geometries that occur in experiments are analyzed. The position and the broadening of the resonances in the spectra arise from a consistent treatment of the scattering and dephasing contributions in the linear response calculation. Comparison between the experimental and the theoretical results yields information about the cluster geometry, which is not accessible experimentally.


Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine-Binding Site.
CCL21 chemokine binds the G protein-coupled receptor CCR7, aiding not only in immune response but also in cancer metastasis. Compared with other chemokines, CCL21 has a unique extended unstructured C-terminus that is truncated in some naturally occurring variants. We have determined the X-ray crystallographic structure of a truncated CCL21 (residues 1-79) lacking the extended C-terminus and identified, via two-dimensional nuclear magnetic resonance (NMR), a putative sulfotyrosine-binding site that may recognize such post-translationally modified tyrosine residues on the receptor. Compared to the previously determined NMR structure of full-length CCL21, the crystal structure presents new druggable binding hot spots resulting from an alternative N-loop conformation. In addition, whereas the previous NMR structure did not provide any structural information after residue 70, the C-terminus of the truncated CCL21, ordered up to Ala77 in our crystal structure, is placed near the N-loop and sulfotyrosine-binding site, indicating that the extended C-terminus of full-length CCL21 can interact with this important region for receptor binding. These observations suggest a potential origin for the autoinhibition of CCL21 activity that was recently described. The new crystal structure and binding hot spot analysis have important implications for the function of the CCL21 C-terminus and drug discovery.


Effect of chronic treatment with morphine on the binding of 3H-N-n-propylnorapomorphine to striatal membranes of rats: influence of prolyl-leucyl-glycinamide.
The effect of chronic administration of morphine to Sprague-Dawley rats on the binding of dopamine receptor agonist, 3H-N-n-propylnorapomorphine (3H-NPA) to striatal membranes was determined. For chronic administration of morphine, rats were implanted subcutaneously with four morphine pellets (each containing 75 mg of morphine free base) during a 3-day period. Placebo pellet-implanted rats served as controls. Two experimental protocols were followed. In one, the rats were sacrificed 70 h after the implantation of first pellet and in the other, the pellets were removed and the animals were sacrificed 24 h later, and the binding of 3H-NPA was determined. Rats receiving morphine showed no difference in the total number of binding sites (Bmax value) but there was a decrease in the apparent dissociation constant (Kd value) compared with placebo controls. Moreover, such a decrease in Kd in morphine-treated rats persisted even 24 h after removal of morphine pellets. The effect of prolyl-leucyl-glycinamide (MIF; 2 mg/kg), which has been shown to inhibit the development of tolerance to and dependence on morphine, on the changes in the binding of 3H-NPA induced by the implantation of morphine pellets was also determined. MIF antagonized the decreases in Kd values induced by the administration of morphine. However, when administered chronically by itself, MIF had no effect on either the Bmax or Kd values of 3H-NPA. It is concluded that the chronic administration of morphine is associated with enhanced activity of dopamine receptors in the central nervous system as revealed by lowering of the Kd value of the agonist, NPA.(ABSTRACT TRUNCATED AT 250 WORDS)


Absolute pressure measurements and analysis of diamonds subjected to maximum static pressures of 1.3-1.7 Mbar.
Force per unit area measurements made in the megabar pressure cell, independently of other pressure calibration systems, are consistent with the ruby R1 scale of Mao, Bell, Shaner, and Steinberg and its extrapolation to 1.4 Mbar. Physical analysis of diamond anvils removed after experiments to maximum pressures of 1.3-1.7 Mbar suggests that the nitrogen platelet concentration may be related to the strength of the diamonds. The pressure face of one of the diamonds from the 1.7-Mbar experiment was deformed plastically by a macroscopic amount.


Amputation trauma of the face: surgical techniques and microsurgical replantations.
The reconstruction of facial parts after traumatic amputation is of special interest because of the psychological and functional implications such accidents have on the patient. Most amputations result from dog bites or knife wounds and are often sustained by children and young adults. The amputated part may be an anatomic structure of functional importance (e.g. , the lips) or a static structure of primarily aesthetic importance (e.g. , the ear or nose). Here, the Authors present results in 6 cases of facial amputation reconstructed using microsurgical replantation for upper lip amputation, with use of the facial artery musculomucosal flap to fill labial defects, and the Mladick method for ear replantation.


An enhanced two-dimensional hole gas (2DHG) C-H diamond with positive surface charge model for advanced normally-off MOSFET devices.
Though the complementary power field effect transistors (FETs), e.g., metal-oxide-semiconductor-FETs (MOSFETs) based on wide bandgap materials, enable low switching losses and on-resistance, p-channel FETs are not feasible in any wide bandgap material other than diamond. In this paper, we propose the first work to investigate the impact of fixed positive surface charge density on achieving normally-off and controlling threshold voltage operation obtained on p-channel two-dimensional hole gas (2DHG) hydrogen-terminated (C-H) diamond FET using nitrogen doping in the diamond substrate. In general, a p-channel diamond MOSFET demonstrates the normally-on operation, but the normally-off operation is also a critical requirement of the feasible electronic power devices in terms of safety operation. The characteristics of the C-H diamond MOSFET have been analyzed with the two demonstrated charge sheet models using the two-dimensional Silvaco Atlas TCAD. It shows that the fixed-Fermi level in the bulk diamond is 1.7 eV (donor level) from the conduction band minimum. However, the upward band bending has been obtained at Al2O3/SiO2/C-H diamond interface indicating the presence of inversion layer without gate voltage. The fixed negative charge model exhibits a strong inversion layer for normally-on FET operation, while the fixed positive charge model shows a weak inversion for normally-off operation. The maximum current density of a fixed positive interface charge model of the Al2O3/C-H diamond device is - 290 mA/mm, which corresponds to that of expermental result of Al2O3/SiO2/C-H diamond - 305 mA/mm at a gate-source voltage of - 40 V. Also, the threshold voltage Vth is relatively high at Vth = - 3.5 V, i.e., the positive charge model can reproduce the normally-off operation. Moreover, we also demonstrate that the Vth and transconductance gm correspond to those of the experimental work.


To assess the effectiveness of a chlorhexidine chip in the treatment of chronic periodontitis: A clinical and radiographic study.
Controlled local delivery of disinfecting agents has been demonstrated to be efficient in improving the outcome of periodontal therapy. The aim of the present study was to evaluate the efficacy of a controlled-release biodegradable chlorhexidine chip (Periocol CG) when used as an adjunct to scaling and root planing in the treatment of periodontitis. The study was carried out as randomized controlled two-group parallel clinical trial. Forty patients in the age group of 30-65 years suffering from mild to moderate chronic periodontitis, having pocket depth ranging between 5 and 8 mm, were selected for the study. At the screening visit, complete history taking, periodontal examination and full-mouth supragingival scaling was carried out for each patient. At the baseline visit (on the 7(th) day), all clinical parameters and radiographic parameters were recorded at selected sites and patients were randomly assigned to either the control group (group A) or the treatment group (group B). All patients in both the groups received complete subgingival scaling and root planing. Then, in group B, chlorhexidine chip (Periocol CG) was inserted at the selected site. Patients were recalled at 1 month, 2 months and 3 months from the baseline for recording clinical observations, and radiographic parameters were recorded at the end of the study. Mean, standard deviation, Chi-square test, "t" test for equality of means and paired samples correlations were used. There was a statistically significant clinical attachment gain, reduction in bleeding index scores, probing pocket depth reduction and bone gain in both the groups, but group B showed better results than group A, and these differences were statistically significant. The results of this study show that chlorhexidine chip (PerioCol-CG) is an effective adjunctive therapy to scaling and root planing in the treatment of chronic periodontitis.


Chemoselective oxidation of primary alcohols catalysed by Ce(III)-complex intercalated LDH using molecular oxygen at room temperature.
Herein we describe the preparation of an efficient heterogeneous catalyst consisting of an anionic Ce(III)-complex immobilized Zn/Al-layered double hydroxide (LDH) and its use in the catalytic liquid phase oxidation of primary alcohols using molecular O(2) at room temperature. Various primary alcohols could be transformed to their corresponding aldehydes in good to excellent yields using the set of optimal conditions. The heterogeneous catalytic system can also be recovered and reused for several cycles without a significant loss of catalytic activity.


Initial structure design of coaxial six-ten mirror central-obscured extreme ultraviolet lithographic objective.
The high numerical aperture projection objective for industrial extreme ultraviolet lithography (EUVL) usually includes several mirrors with central obscuration in the light path. We apply the grouping design method on the spherical initial structure of central-obscured six-ten mirrors EUVL objective. A new condition called obscuration condition is introduced for the parameter calculation of the central-obscured mirror groups. The non-obscured mirror groups in the projection objective were calculated by the non-obstruction condition and conjugation condition, which is based on the object-image relationship and the pupil-stop relationship. By analyzing the expression of obscuration condition and the non-obstruction condition, the combined available ranges of parameters can be obtained. The available mirror group is picked up from that available range and connected to form a whole initial spherical structure. The design process of a six-mirror objective with central obscuration and initial structures with eight-ten mirrors designed by the same process is shown in this article.