Four promoters subject to regulation by ExoR and PhoB direct transcription of the Sinorhizobium melilotiexoYFQ operon involved in the biosynthesis of succinoglycan.
Succinoglycan (EPS I), the main acidic exopolysaccharide of Sinorhizobium meliloti, is required for the initiation and elongation of infection threads during nodulation of the host plant alfalfa. The gene products of the exoYFQ operon are involved in the first step of succinoglycan biosynthesis as well as in the polymerisation of subunits to the high-molecular-mass form of this exopolysaccharide. One promoter region that directs transcription of exoX and two promoter regions that drive transcription of exoY were mapped in the exoX-exoY intergenic region. The distal exoY promoter region containing three putative -10 promoter elements was active under standard growth conditions and was subject to ExoR-dependent regulation. Although this promoter region was stimulated in a phoB mutant, no PHO box-like sequences were found, suggesting an indirect regulatory effect of PhoB. The proximal promoter contains a PHO box-like sequence in the putative -35 region and was affected by low and high phosphate concentrations dependent on PhoB. In the case of deleted upstream regions, this promoter was also controlled by ExoR. An additional promoter displaying activity in exoR, mucR and phoB mutants under standard conditions was identified upstream of exoF. The putative -35 promoter element of this promoter is covered by a second PHO box-like sequence.


Dental fluorosis in primary teeth: a study in rural schoolchildren in Shaanxi Province, China.
The aim of this study was to assess the prevalence and severity of fluorosis in the primary dentition of 7-8-year-old Chinese schoolchildren in areas with fluoride concentrations in the drinking water ranging from 0.35 to 7.6 mg L-). Four hundred and seventy-two children from 13 different schools were divided into four groups according to the fluoride concentration of the drinking water: (A) <or=1.0 mg L-1; (B) 1.1-2.0 mg L-1; (C) 2.1-3.8 mg L-1; and (D) 7.6 mg L-1. Clinical examinations were made under field conditions, and dental fluorosis on the buccal surfaces of all teeth was recorded using the Thylstrup-Fejerskov Index (TFI). The prevalence of dental fluorosis in primary teeth varied from 6.2% to 96.6% according to the fluoride concentration of the drinking water. The differences of median of TFI scores between all groups were statistically significant (P<0.001) except for groups B and C. No statistically significant difference in the severity of dental fluorosis was observed between genders. The second primary molars were most severely affected by dental fluorosis. Disregarding group A, TFI scores between 3 and 4 were most frequently recorded. Dental fluorosis was symmetrically distributed in both jaws. Dental fluorosis is prevalent in the primary teeth of children living in areas supplied with drinking water with fluoride concentrations higher than 1.0 mg L-1. The primary teeth may act as biomarkers of fluoride exposure. The examination of primary teeth may give an early warning of this condition, and thus, provide a basis for intervention to prevent dental fluorosis in the permanent teeth.


Evidence for the glycoprotein nature of retina glycogen.
Incubation of a bovine retina membrane preparation with micromolar amounts of UDP-[14C]glucose resulted in the incorporation of [14C]glucose into endogenous (1----4)-alpha-glucan, insoluble in trichloroacetic acid, and acid-soluble ethanol-insoluble glycogen. The trichloroacetic-acid-insoluble glucan fraction of retina migrated in 2.6-3% acrylamide gels when subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and was rendered acid-soluble by digestion with pronase. The solubility of the acid-insoluble glucan in acidified organic solvent was different from that of amylose or glycogen and similar to membrane proteins and glycoproteins. The glycogen fraction of retina contained 1.5-2.0 micrograms protein/100 micrograms glucose. When this fraction was analyzed by SDS-PAGE only one band, which moved near the top of 3% acrylamide gels, was stained with periodic acid Schiff reagent and Coomassie blue. The protein nature of the Coomassie-blue-stainable material was demonstrated by iodination of the glycogen fraction with [131I]iodide and identification of labeled monoiodotyrosine and diiodotyrosine. The bulk of the label comigrated with carbohydrate near the top of gels in SDS-PAGE and treatment with alpha- amylse decreased the molecular size of both labeled and stainable material. Physical dissociative conditions (7.5 M urea/0.83% SDS/0.83% mercaptoethanol) and the following chemical treatments failed to dissociate the iodinated protein from glycogen: (a) 0.1 M NaOH/0.1 M NaBH4 at room temperature for 24 h; (b) 1 M HCl in methanol at 50 degrees C for 10 min; (c) trifluoroacetic acid at 50 degrees C for 6 min. 131I-labeled glycogenpeptide was isolated after 131I-labeled protein-bound glycogen had been subjected to digestion with papain/pronase and passed through a Sepharose column. The results suggest that at least part of glycogen in bovine retina is firmly combined to protein as a single proteoglycogen molecule. Furthermore some of the proteoglycogen might be present as a trichloroacetic-acid-precipitable proteoglucan owing to its lower glucose content.


[Clinical and pathological study on effects of Qianggan Capsule combined lamivudine on hepatic fibrosis in patients with chronic hepatitis B].
To study the therapeutic effects of Qianggan Capsule (QC) combined Lamivudine on hepatic fibrosis in patients with chronic hepatitis B. Eighty-five patients were randomly divided into two groups, group A (40 cases) were treated with QC and Lamivudine and group B (45 cases) were treated with QC alone both for 6 months. Hepatic fibrosis related indexes and pathologic examination of liver biopsy were performed within 3 months before treatment and in 1 month after treatment. Serum levels of hyaluronic acid, collagen N and laminin decreased markedly after treatment in both groups (P < 0.05). Hepatic histopathological examination showed that the total effective rate of impovement in activity of inflammation-necrosis and fibrosis was 80.0% and 70.0% in group A, 57.8% and 75.6% in group B, respectively, the combined treatment showed a better effect in improving the activity of inflammation-necrosis than QC alone (P < 0.05), but with no significant difference to the latter in improving fibrosis. QC combined Lamivudine could markedly reduce the activity of hepatic inflammation-necrosis, QC alone could also improve hepatic fibrosis.


Investigating the Association Between Periodontal Disease and Risk of Pancreatic Cancer.
Periodontal disease (PD) is increasingly recognized as an emerging risk factor for various systemic diseases, including diabetes, cardiovascular diseases, and cancer. The current study examined the association between PD (periodontitis, gingivitis, and others) and pancreatic cancer. A total of 139,805 subjects with PD and 75,085 subjects without PD were identified from the National Health Insurance Research Database of Taiwan. Cox proportional hazards regression was performed to compare the incidence of pancreatic cancer between the 2 groups. Periodontal disease was positively associated with pancreatic cancer risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.02-2.33). This positive association occurred predominantly among those aged 65 years or older (HR, 2.17; 95% CI, 1.03-4.57) and was not observed among those aged younger than 65 years (HR, 0.83; 95% CI, 0.52-1.34). Further analysis showed that PD is a risk factor for pancreatic cancer independent of diabetes, hyperlipidemia, allergies, viral hepatitis, peptic ulcer, pancreatitis, chronic obstructive pulmonary disease (as a proxy for cigarette smoking), and alcoholic-related conditions (as a proxy for alcohol drinking). Our results indicated a significantly positive association between PD and risk of pancreatic cancer. The underlying biological mechanisms for the positive association between PD and pancreatic cancer require further investigation.


Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia.
The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC. Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41-50 years, BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively). The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.


Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8.
Functional interleuin-8 (IL-8) receptors (IL-8RA and IL-8RB: CXCR1 and CXCR2, respectively) have been described in human, monkey, dog, rabbit, and guinea pig. Although three IL-8R homologues have been found in rat, only one of these, rat CXCR2, appears to be functional based on responsiveness to ligands. Similarly, CXC chemokines induce biological responses through the murine homolog of CXCR2, but the identification of functional rodent CXCR1 homologues has remained elusive. We have identified and characterized the mouse CXCR1 homologue (mCXCR1). Murine CXCR1 shares 68 and 88% amino acid identity with its human and rat counterparts, respectively. Similar to the tissue distribution pattern of rat CXCR1, we found murine CXCR1 mRNA expression predominantly in lung, stomach, bone marrow, and leukocyte-rich tissues. In contrast to previous reports, we determined that mCXCR1 is a functional receptor. We show predominant engagement of this receptor by mouse GCP-2/CXCL6, human GCP-2, and IL-8/CXCL8 by binding, stimulation of GTPgammaS exchange, and chemotaxis of mCXCR1-transfected cells. Furthermore, murine CXCR1 is not responsive to the human CXCR2 ligands ENA-78/CXCL5, NAP-2/CXCL7, GRO-alpha, -beta, -gamma/CXCL1-3, or rat CINC-1-3. In addition, we show concomitant elevation of mCXCR1 and its proposed major ligand, GCP-2, positively correlated with paw swelling in murine collagen-induced arthritis. This report represents the first description of a functional CXCR1-like receptor in rodents.


Relationship between milkability and adrenoceptor concentrations in teat tissue in primiparous cows.
Milking characteristics were measured on 19 primiparous cows of the Red Pied breed at morning milkings. Measurements included maximum and average rate of flow, yield of milk through the 1st, 2nd, and 3rd min, amount of milk through the first 2 and first 3 min of milking, and milking time. Subsequently cows were slaughtered and teats immediately removed. Adrenoceptors on membranes isolated from teat tissue were identified by radiolabeled antagonists: [3H]dihydroalprenolol for beta 2-adrenoceptors, [3H]rauwolscine for alpha 2-adrenoceptors, and [3H]prazosin for alpha 1-adrenoceptors. Measurements of milking characteristics were highly repeatable within cow. Cows showed five distinct and significantly different milk flow patterns, which were characteristic for fast (type I, II), relatively fast (type III), and slow (type IV, V) milking cows. Covariance analysis for the five different types revealed an average regression between alpha 2-adrenoceptor density and milking rate 1st min as well as between beta 2:alpha 2-adrenoceptor ratios and milking rate 2nd min and milking time. A hypothesis is presented to explain these observations. During milking, tone of efferent sympathetic nerves in the teat is low. This phenomenon is more pronounced in fast milking cows. The typical presynaptic adrenoceptor pattern in the teat of fast milkers (low beta 2:alpha 2-adrenoceptor ratio) results in a decline of norepinephrine release by feedback mechanisms.


Preparation and Application of Amino Phosphine Ligands Bearing Spiro[indane-1,2'-pyrrolidine] Backbone.
P,Nsp3-bidentate chiral ligands bearing spiro[indane-1,2'-pyrrolidine] backbone were prepared in gram scale for the first time. Pd complexes of these air-stable amino phosphine ligands could catalyze asymmetric allylic substitutions of malonate-, alcohol-, and amine-type nucleophiles in up to 97% ee and 99% yield. A crystal structure of [Pd(II)(η3-1,3-diphenylallyl)(ligand)]PF6 indicated possible transition states of the catalytic reactions. These ligands are characteristic of a very rigid backbone, which is simple but highly effective. They rival C2-symmetric bisphosphine, P,Nsp2-bidentate, and P,Nsp3-bidentate ligands in tested allylic substitutions.


Glycosylation and cold platelet storage.
Platelets, unlike red blood cells and plasma, are stored at room temperature because platelets transfused after refrigeration at 4 degrees C are rapidly cleared from the circulation. Storage at room temperature promotes bacterial proliferation, however, and transfusion-transmitted bacteremia has become an increasing problem. Traditionally, the cold storage lesion has been attributed to a change in platelet shape from disc to sphere, but Hoffmeister et al. revisited this issue and have shown that the shape change induced by cold storage does not result in poor platelet survival. Instead, they showed that poor survival results from a virtually irreversible clustering of alpha subunits of glycoprotein Ib (GPIbalpha)) on the platelet surface. In a series of elegant papers, these researchers change the way we view platelet clearance. That is, they show that exposed, terminal, beta-linked N-acetylglucosamine (beta-GlcNAc) residues on clustered GPIbalpha are recognized by the lectin domain of type 3 complement receptors on liver macrophages, leading to rapid clearance by phagocytosis. They also demonstrate that phagocytosis of chilled platelets can be inhibited--and in vivo survival prolonged--by enzymatically galactosylating the terminal beta-GlcNAc residues on GPIbalpha. Disguising the exposed beta-GlcNAc residues on the N-glycans of the clustered GPIbalpha molecules by galactosylation is a promising approach to storing platelets at 4 degrees C without affecting platelet function. Cold storage would limit bacterial proliferation and extend the duration of platelet storage, reducing the incidence of transfusion-transmitted bacteremia and improving the availability of this scarce resource.


BIOLAB, EPU and EMCS for cell culture experiments on the ISS.
Two ESA facilities are under development for biological research on the International Space Station: BIOLAB as part of the European "Columbus" Laboratory and the European Modular Cultivation System (EMCS), foreseen for accommodation in the US Lab "Destiny". Both facilities have an incubator (18-40 degrees C) and use standard Experiment Containers, mounted on two centrifuge rotors providing either microgravity or variable g-levels from 0.001 x g to 2.0 x g. Standard interface plates supply each container with power and data lines, with gas (controlled CO2, O2 and water vapour concentration; trace gas removal), and--for EMCS only--with water. The degree of automation is higher in BIOLAB: it contains a robotic Handling Mechanism for automatic sampling and handling of liquids, which can be stored at cool or cold temperatures or injected for automatic on-board analysis into a microscope or a spectrophotometer. For analyses on the running centrifuge, small automatic microscopes can be installed in the Experiment Containers. Several designs for supporting cell culture experiments have been studied for BIOLAB and EMCS. BIOLAB has in addition a Bio-Glovebox, which can be sterilised and where new cell cultures may be prepared under 1 x g conditions from deep-frozen samples in the Experiment Preparation Unit (EPU): the cryo-protectant will be removed by automatic washing cycles. Both facilities, EMCS and BIOLAB (with EPU), have also provisions for telescience operations through video, data and command lines, either operated by the crew or by the experimenter on ground.


Outcomes of Head and Neck Free Tissue Transfer in Renal Failure Patients.
To assess if there is increased risk of free flap failure in renal failure patients undergoing head and neck reconstruction. We seek to primarily assess free flap outcomes based on stages of chronic kidney disease (CKD) and secondarily determine increased risk for postoperative complications. Retrospective chart review was performed at five tertiary care centers. Patients were identified that had undergone microvascular free flap reconstruction of the head and neck with diagnosis of renal failure, classified as Stage 3 CKD or higher. Demographic data was collected. Outcomes in the postoperative period were examined. Seventy-three patients met inclusion criteria. The average patient age was 69 years with a male predominance (n = 48). The majority of patients had CKD Stage 3 (n = 52). Overall flap failure rate was 12.33% (n = 9, CKD stage 3 = 7.69%, CKD stage 4 = 30%, CKD stage 5 = 18%). There was an increased risk of flap failure on multivariate analysis for CKD stage 4/5 patients when compared to CKD 3 patients (p = 0.0095). When compared to matched controls, there was an increased risk of flap failure in CKD patients (p = 0.01) as well as an increased risk of overall complications (p < 0.0001). Patients with CKD undergoing head and neck reconstruction are at a higher risk of flap failure and overall complications. When comparing CKD stages there may be increased risk of flap failure in later stages of CKD compared to CKD 3. Appropriate patient counseling is recommended pre-operatively in this patient population with consideration for regional flaps in the appropriate patient. III Laryngoscope, 2023.


The risk of intussusception following monovalent rotavirus vaccination in England: A self-controlled case-series evaluation.
To investigate the risk of intussusception after monovalent rotavirus vaccine (RV1) given to infants aged 2 and 3 months in England. Hospital Episode Statistics (HES) were used to identify infants aged 48-183 days admitted between 11/03/2013 and 31/10/2014 with intussusception. Diagnosis was confirmed from medical records and HES procedure codes. Vaccination status was obtained from general practitioners. The risk of admission within 1-7 and 8-21 days of vaccination was analysed using the self-controlled case-series (SCCS) method with age effect adjustment by including historical data before RVI introduction in July 2013. A total of 119 cases were identified during the study period and intussusception confirmed in 95 of whom 39 were vaccinated 1-21 days before onset. An increased relative incidence (RI) in this period was found, 4.53 (95% confidence interval 2.34-8.58) and 2.60 (1.43-4.81) respectively after the 1st and 2nd doses with an attributable risk of 1.91 and 1.49 per 100,000 doses respectively. The peak risk was 1-7 days after the first dose, RI 13.81 (6.44-28.32), with an estimated 93% of the 15 cases being vaccine-attributable. Mean interval between onset and admission, and clinical features were similar between vaccine-associated and background cases. Despite intussusception being a contraindication to rotavirus vaccination, 10 infants received a further dose; none had a recurrence. The RIs in a meta-analysis combing our results with Australia, Mexico, Brazil and Singapore using RV1, a 2, 4 month schedule and SCCS gave pooled RI estimates of 2.35 (1.45-3.8) and 1.77 (1.29-2.43) in the 21 day period after the 1st and 2nd doses, respectively. The earlier age at the 2nd dose in England did not affect the risk. We estimate that the RVI programme causes around 21 intussusception admissions annually in England but, since it prevents around 25,000 gastro-intestinal infection admissions, its benefit/risk profile remains strongly positive.


Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial.
We examined how the use of bone turnover markers and educational information affects persistence of bisphosphonate use in osteoporotic patients. We found that reporting bone turnover results and/or educational information did not affect persistence. Long-term adherence and persistence to osteoporosis medication are poor. We examined whether reporting of bone turnover marker results, education about osteoporosis, or a combination of both would increase persistence to oral bisphosphonates. Two hundred and forty women who were 5 years postmenopausal with BMD at least 2.0 standard deviations below normal were recruited for the study. All women were given a new prescription for alendronate and randomly assigned to one of four groups: (1) bone marker results at baseline, 3 and 12 months; (2) educational materials every month and a membership in the National Osteoporosis Foundation; (3) bone marker and educational information; and (4) control, no information other than usual care. Persistence among randomization groups was tested using survival analysis adjusting for the delay between intervention methods. Of those filling their initial prescription, 95.5% refilled their prescription at the end of the first month, 87% at 3 months, 82% at 6 months, and 78% at 10 months. Overall persistence through 12 months was 54%. There was no difference found among the four groups for persistence time using (p > 0.58). Providing bone turnover marker results is not an effective way to enhance early compliance and persistence with drug therapy. While the women in our study felt that bone marker results and educational information were helpful to them, there was no difference in persistence between those who received either bone marker information and/or educational information and those who did not. Because of the unexpected rate of primary nonadherence, this study may be underpowered.


Acrolein depletes the neuropeptides CGRP and substance P in sensory nerves in rat respiratory tract.
The mammalian respiratory tract is densely innervated by autonomic and sensory nerves around airways and blood vessels. Subsets of these nerves contain a number of putative neurotransmitter peptides, such as substance P and calcitonin gene-related peptide (CGRP) in sensory nerves and vasoactive intestinal polypeptide (VIP), possibly serving autonomic functions. CGRP is also found in endocrine cells in rat airway epithelium. These peptides are all pharmacologically potent effectors of bronchial and vascular smooth muscle and bronchial secretion. Their functions in vivo are less well established. We have therefore examined the effects of inhaled acrolein, a sensory irritant, on three pulmonary neuropeptides: CGRP, substance P, and VIP. Groups of rats (n = 3 each) were exposed for 10 min to acrolein in air (Ct = 510, 1858, and 5693 mg.min/m3) or to air alone. Fifteen minutes later they were killed (pentabarbitone IP) and their respiratory tracts were dissected and fixed in 0.4% p-benzoquinone solution. Cryostat sections were stained by indirect immunofluorescence for a general nerve marker (PGP 9.5) and neuropeptides. The acrolein-treated animals had a dose-related decrease in tracheal substance P- and CGRP-immunoreactive nerve fibers compared with controls. No change was seen in total nerve fiber distribution and number (PGP 9.5) or VIP immunoreactivity, nor in CGRP-immunoreactive epithelial endocrine cells. It is concluded that the rat tracheal peptidergic nerves are a sensitive indicator of inhaled irritant substances. Their reduced immunoreactivity may be because of a release of sensory neuropeptides that could play a role in the physiological response to irritant or toxic compounds.


Surprising good antioxidant status in patients with Balkan Endemic Nephropathy on hemodialysis undergoing vitamin C therapy. A pilot study.
End Stage Renal Disease (ESRD) represents a microinflammatory state accompanied by oxidative stress and an imbalance between pro- and antioxidants. Vitamin C is a highly effective antioxidant, acting to lessen oxidative stress. The aim of our study was to assess the Antioxidant Capacity of Water soluble substances (ACW) and the Antioxidant Capacity of Liposoluble substances (ACL) in patients with Balkan Endemic Nephropathy (BEN) on hemodialysis undergoing Vitamin C therapy as compared to healthy controls. Twenty-one patients with BEN on hemodialysis (HD), mean age: 63.33 +/- 5.42 years, 6 M and 15 F, were enrolled into the study. All patients received 10 vials of Vitamin C 750 mg/5 ml every 2 months. Eleven apparently healthy subjects, mean age: 63.73 +/- 5.21 years, 6 M and 5 F, served as controls. The photochemiluminescence assay was used to measure the antioxidant activity of plasma samples. The results are presented in equivalent concentration units of Vitamin C for water soluble antioxidants and in equivalent concentration units of Trolox (synthetic Vitamin E) for lipid soluble antioxidants. Both concentrations are expressed in micromols/L. Statistical analysis (non-parametric Wilcoxon test) was performed using NCSS. Mean duration since BEN diagnosis was: 8.24 +/- 3.5 years. Mean duration since HD initiation was: 4.92 +/- 3.4 years. Smoking status was negative in all patients. Hypertension was present in 15 patients (71.42%), cardiovascular disease in 10 (47.61%), HCV infection in 13 (61.9%), 1 patient had HBV + HCV infection, 1 had renal tuberculosis, 1 had upper urinary tract cancer, 1 genital cancer, and I autoimmune thyroid disease. The Antioxidant Capacity of Water soluble substances (ACW) in patients with BEN was 477.6 +/- 177.63 micromols/L, significantly higher as compared to controls: 198.05 +/- 196.63 micromols/L; p = 0.01, whereas the Antioxidant Capacity of Liposoluble substances (ACL) in patients with BEN was 33.9 +/- 22.99 micromols/L, non-significantly different as compared to controls: 27.38 +/- 4.21 micromols/L; p = 0.22. We conclude that Vitamin C therapy in patients with BEN on HD significantly increases the Antioxidant Capacity of Water soluble substances (ACW) as compared to controls and could be used to counter oxidative stress in patients with ESRD.


Cost-effective sib-pair designs in the mapping of quantitative-trait loci.
The extreme discordant-sib-pair design has been found to be the most powerful, across most genetic models. In this paper, we address two of the most frequently asked questions related to this design. First, under the extreme discordant-sib-pair design, a large number of people have to be screened for the phenotype of interest, before the desired number of discordant sibs can be collected for genotyping and linkage analysis. When the phenotyping cost is not negligible compared with the genotyping cost, such methods might not be cost effective. The second question is how sensitive the cost is to the genetic model and allele frequency. In this paper, we compare the cost under different sampling strategies, different genetic models, and different phenotyping:genotyping cost ratios. Because our knowledge of the underlying genetic model for a trait is limited, the discordant-sib-pair design proves to be the most robust. When the cost for screening probands is not included, the design that genotypes sibs with one sib in the top 10% and the other sib in the bottom 30% of the population with respect to the trait of interest is, across most models studied, the optimum among the designs considered in this paper. The cost under this design, across different genetic models, appears to be relatively robust to allele frequency and model type, whether additive or dominant. If probands initially must be screened as well, then 25% appears to be the optimal portions of the upper and lower distributions to be studied.


GABA signaling stimulates α-cell-mediated β-like cell neogenesis.
Diabetes is a chronic and progressing disease, the number of patients increasing exponentially, especially in industrialized countries. Regenerating lost insulin-producing cells would represent a promising therapeutic alternative for most diabetic patients. To this end, using the mouse as a model, we reported that GABA, a food supplement, could induce insulin-producing beta-like cell neogenesis offering an attractive and innovative approach for diabetes therapeutics.


Role of natriuretic peptide signaling in modulating asthma and inflammation.
Atrial natriuretic peptide (ANP), the C-terminal peptide comprising residues 99-126 of the pro-ANP hormone, has been studied for 3 decades for its cardiovascular effects. Recent reports suggest that it plays a significant role in modulation of the immune system. Immune cells, including macrophages, dendritic cells, and T lymphocytes, express receptors for ANP. ANP plays a significant role in shaping the early immune response to environmental antigens and may play a critical role in the interaction between cells of the innate and adaptive immune systems; it also appears to be involved in polarizing the immune response to allergens. Thus, ability to alter the magnitude of natriuretic peptide receptor A (NPRA) signaling could be exploited to develop therapeutics for several allergic diseases, including asthma. This report will review and critically evaluate the role of the ANP pathway in asthma and inflammation.


A study of the Ca antigen in epithelial tumours of the ovary.
The expression of Ca antigen in ovarian epithelial tumours has been studied by an immunohistochemical technique using the Ca 1 monoclonal antibody. The antigen was found to be present in some examples of each of the histological subtypes of ovarian epithelial neoplasms and was detected in benign, borderline and malignant tumours. It is concluded that the presence of Ca antigen is of no discriminatory value in the assessment of malignancy in ovarian epithelial neoplasms.


Mild and severe salt stress responses are age-dependently regulated by abscisic acid in tomato.
Salt stress hampers plant growth and development through both osmotic and ionic imbalances. One of the key players in modulating physiological responses towards salinity is the plant hormone abscisic acid (ABA). How plants cope with salinity largely depends on the magnitude of the soil salt content (stress severity), but also on age-related developmental processes (ontogeny). Here we studied how ABA directs salt stress responses in tomato plants for both mild and severe salt stress in leaves of different ages. We used the ABA-deficient mutant notabilis, which contains a null-mutation in the gene of a rate-limiting ABA biosynthesis enzyme 9-cis-epoxycarotenoid dioxygenase (NCED1), leading to impaired stomatal closure. We showed that both old and young leaves of notabilis plants keep a steady-state transpiration and photosynthesis rate during salt stress, probably due to their dysfunctional stomatal closure. At the whole plant level, transpiration declined similar to the wild-type, impacting final growth. Notabilis leaves were able to produce osmolytes and accumulate ions in a similar way as wild-type plants, but accumulated more proline, indicating that osmotic responses were not impaired by the NCED1 mutation. Besides NCED1, also NCED2 and NCED6 are strongly upregulated under salt stress, which could explain why the notabilis mutant did not show a lower ABA content upon salt stress, except in young leaves. This might be indicative of a salt-mediated feedback mechanism on NCED2/6 in notabilis and might explain why notabilis plants seem to perform better under salt stress compared to wild-type plants with respect to biomass and water content accumulation.


Male courtship behavior and weapon trait as indicators of indirect benefit in the bean bug, Riptortus pedestris.
Females prefer male traits that are associated with direct and/or indirect benefits to themselves. Male-male competition also drives evolution of male traits that represent competitive ability. Because female choice and male-male competition rarely act independently, exploring how these two mechanisms interact is necessary for integrative understanding of the evolution of sexually selected traits. Here, we focused on direct and indirect benefits to females from male attractiveness, courtship, and weapon characters in the armed bug Riptortus pedestris. The males use their hind legs to fight other males over territory and perform courtship displays for successful copulation. Females of R. pedestris receive no direct benefit from mating with attractive males. On the other hand, we found that male attractiveness, courtship rate, and weapon size were significantly heritable and that male attractiveness had positive genetic covariances with both courtship rate and weapon traits. Thus, females obtain indirect benefits from mating with attractive males by producing sons with high courtship success rates and high competitive ability. Moreover, it is evident that courtship rate and hind leg length act as evaluative cues of female choice. Therefore, female mate choice and male-male competition may facilitate each other in R. pedestris. This is consistent with current basic concepts of sexual selection.


In Vitro Stimulation of Multidrug Resistance-Associated Protein 2 Function Is Not Reproduced In Vivo in Rats.
Previously we reported that coproporphyrin-I (CP-I) is an optimal probe substrate for multidrug resistance-associated protein 2 (MRP2), and stimulation of MRP2-mediated transport is probe substrate-dependent. In the present investigation, we assessed if the in vitro stimulation is physiologically relevant. Similar to human MRP2 transport, CP-I was transported by rat Mrp2 in a typical Michaelis-Menten kinetics with apparent Km and Vmax values of 15 ± 6 µM and 161 ± 20 pmol/min/mg protein, respectively. In vivo Mrp2 functions were monitored by biliary and renal secretion of CP-I and its isomer CP-III, in bile-duct cannulated rats before and after treatment with mitoxantrone, progesterone, and verapamil. These compounds stimulated Mrp2-mediated CP-I transport in vitro. No significant increase in biliary or renal clearances, as well as in the cumulative amount of CP-I or CP-III eliminated in bile, were detected following treatment with the in vitro stimulators, indicating an in vitro to in vivo disconnect. In presence of 10 µM bilirubin, the in vitro stimulation was suppressed. We concluded that the in vitro stimulation of CP-I transport mediated by Mrp2 is not translatable in vivo, and proposed that the presence of endogenous compounds such as bilirubin in the liver may contribute to the in vitro to in vivo disconnect.


Early Antithrombotic Therapy after Bioprosthetic Aortic Valve Replacement in Elderly Patients: A Single-Center Experience.
Early antithrombotic therapy after bioprosthetic aortic valve replacement (AVR) is controversial. This study aimed to retrospectively compare between warfarin and aspirin treatment in the 3 months after bioprosthetic AVR for elderly patients more than 60 years old, and to determine the optimal antithrombotic therapy. This retrospective study included 479 patients in single center from January 1994 to June 2014. Patients were divided into two groups (Wa group, warfarin; As group, aspirin). We searched our computerized clinical database for thromboembolic or bleeding events. Propensity score analysis was conducted to adjust for selection bias. All patients, except one patient, were followed-up in the out-patient department for 3 months after the operation. In all, 86 propensity-matched patient-pairs were derived. Early operative outcomes were similar in both the groups. There are one patient of thromboembolic event and three patients of bleeding events, but the prevalence was not significantly different (p >0.999). The incidence of thromboembolic and bleeding events during early 3 months after bioprosthetic AVR were similar in Wa and As groups. If the patient does not have indications of warfarin, early antithrombotic therapy with aspirin only may be easier and more feasible for elderly patients.


Ammonia diffusion through Nalophan double bags: effect of concentration gradient reduction.
The ammonia loss through Nalophan bags has been studied. The losses observed for storage conditions and times as allowed by the reference standard for dynamic olfactometry (EN 13725:2003) indicate that odour concentration values due to the presence of small molecules may be significantly underestimated if samples are not analysed immediately after sampling. A diffusion model was used in order to study diffusion through the bag. The study discusses the effect of concentration gradient (ΔC) across the polymeric membrane of the analyte. The ΔC was controlled by using a setup bag called "double bags." Experimental data show a reduction of ammonia percentage losses due to the effect of the external multibarrier. The expedient of the double bag loaded with the same gas mixture allows a reduced diffusion of ammonia into the inner bag. Comparing the inner bag losses with those of the single bag stored in the same conditions (T, P, u) and with equal geometrical characteristics (S/V, z), it was observed that the inner bag of the double bag displays a 16% loss while the single bag displays a 37% loss. Acting on the ΔC it is possible to achieve a gross reduction of 57% in the ammonia leakage due to diffusion.


Blood Sampling and Preparation Procedures for Proteomic Biomarker Studies of Psychiatric Disorders.
A major challenge in proteomic biomarker discovery and validation for psychiatric diseases is the inherent biological complexity underlying these conditions. There are also many technical issues which hinder this process such as the lack of standardization in sampling, processing and storage of bio-samples in preclinical and clinical settings. This chapter describes a reproducible procedure for sampling blood serum and plasma that is specifically designed for maximizing data quality output in two-dimensional gel electrophoresis, multiplex immunoassay and mass spectrometry profiling studies.


Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. The Swedish CDAD Study Group.
92 patients with antibiotic-associated diarrhea were randomized to receive oral teicoplanin 100 mg twice daily for 7 days (BID group); or 50 mg 4 times daily for 3 days, followed by 100 mg twice daily for 4 days (QID group) in a randomized, double-blind, multicentre study. Clostridium difficile was demonstrated by culture and/or cytotoxin test in 49 (53%) patients, of whom 47 (23 male, 24 females, mean age 65 years; 23 in the BID group, 24 in the QID group) were evaluable for clinical efficacy. Prior treatment with cephalosporins was registered in 49%, isoxazolyl-penicillins in 33% and clindamycin in 20% of the C. difficile positive patients. On the last day of treatment, 96% (23 of 24 patients) in the QID group were found cured, compared with 70% (16 of 23 patients) in the BID group (p = 0.02). On days 2 and 3 of treatment, QID group patients had significantly fewer loose stools per day (p < 0.05) than those of the BID group. Clinical recurrence, within 4 weeks post-treatment, occurred in 35% and 33% of the patients in the BID and QID groups, respectively. The bacteriological elimination rate 4 weeks post-treatment was 55% in the BID group and 59% in the QID group. The study was terminated prematurely due to the unexpectedly high clinical failure and recurrence rate in C. difficile positive patients treated with the BID dosage regimen.


Rifaximin and Helicobacter pylori eradication.
In this study, we tested the effectiveness of Rifaximin, a surface antibiotic which is not absorbed when given orally, in the eradication of Helicobacter pylori (HP). The drug was combined in triple therapy either with Amoxicillin and Omeprazole or with Erythromycin-ethylsuccinate and Omeprazole. Twenty-three patients complaining of dyspeptic symptoms and gastric infection due to HP were evaluated. The patients were randomly given one of the following therapeutic protocols: Rifaximin susp. 600 mg/day x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Amoxicillin tab. 1 g x 2/day (at least two hours after meals: 10:00 am, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol A) and Rifaximin susp. 600 mg/day x 3/day and Erythromycin-ethylsuccinate tab. 600 mg x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol B). Both therapeutic protocols were prescribed for two weeks. At least one month after the end of the treatment the patients were controlled to ascertain eradication of the infection. The follow-up carried out after treatment showed that HP infection was eradicated in 6 of 10 patients in the first group (protocol A) and in 1 of 10 in the second group (protocol B). These patients were HP-negative in all the tests performed: histological, CP-TEST, culture test. The data collected showed a reasonable level of effectiveness of the protocol using the combination Rifaximin-Amoxicillin and Omeprazole. However, they do not differ from the reported data in the literature which show a similar effectiveness of the combination Omeprazole-Amoxicillin at the same doses. Different formulations that makes it possible for the drug to reach these "protected areas" would probably be more effective.


Dynamic imaging of the lungs using x-ray phase contrast.
High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.


Stability of ferrous-iron-rich bridgmanite under reducing midmantle conditions.
Our current understanding of the electronic state of iron in lower-mantle minerals leads to a considerable disagreement in bulk sound speed with seismic measurements if the lower mantle has the same composition as the upper mantle (pyrolite). In the modeling studies, the content and oxidation state of Fe in the minerals have been assumed to be constant throughout the lower mantle. Here, we report high-pressure experimental results in which Fe becomes dominantly Fe2+ in bridgmanite synthesized at 40-70 GPa and 2,000 K, while it is in mixed oxidation state (Fe3+/∑Fe = 60%) in the samples synthesized below and above the pressure range. Little Fe3+ in bridgmanite combined with the strong partitioning of Fe2+ into ferropericlase will alter the Fe content for these minerals at 1,100- to 1,700-km depths. Our calculations show that the change in iron content harmonizes the bulk sound speed of pyrolite with the seismic values in this region. Our experiments support no significant changes in bulk composition for most of the mantle, but possible changes in physical properties and processes (such as viscosity and mantle flow patterns) in the midmantle.


An Accuracy Study of the Intracavitary Electrocardiogram (IC-ECG) Guided Peripherally Inserted Central Catheter Tip Placement among Neonates.
To explore the clinical application of the intracavitary electrocardiogram (IC-ECG) guided Peripherally Inserted Central Catheter (PICC) tip placement among neonates. the ECGs of neonates are difficult to perform and their wave shapes are of doubtful accuracy due to various interfering factors. 115 neonates were admitted to perform PICC guided by IC-ECG. Logistic regression was performed to analyze all possible influencing factors of the accuracy from the tip placement. The puncture site of the PICC, gestational age, height, weight, basal P/R amplitude and positioning P/R amplitude might be related to the accuracy of IC-ECG location. The accuracy in the lower extremity was higher than that in the upper extremity. Multivariate logistic regression analysis showed that the weight (Odds Ratio (OR)=1.93, 95%Confidence Interval(CI):1.06-3.50) and positioning P/R amplitude (OR=32.33, 95%CI: 2.02-517.41) are statistically significant risks to the accuracy PICC tip placement. Possible methods to improve the accuracy might be Catheterizing through lower extremity, keeping the neonates calm, enhancing the electrocardiogram signal and strengthening technical training. Therefore it is practical to perfrom a tip placement by the dynamic change in the P waves from an electrocardiogram (ECG) guided PICC among neonates and as reliable as using X-rays.


[Application of continuous blood purification combined with hemoperfusion in the treatment of hemolytic-uremic syndrome in children].
To observe the therapeutic effect of continuous blood purification (CBP) combined with hemoperfusion (HP) in children with hemolytic-uremic syndrome (HUS) and to investigate its possible mechanism. Eight children with HUS received CBP combined with HP on the basis of internal medicine treatment in the acute stage. Before and after treatment, serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) were measured by chemiluminescence method, and levels of blood urea nitrogen (BUN), serum creatinine (SCr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase MB (CKMB), hemoglobin (Hb), platelet (PLT) and C-reactive protein (CRP) were measured. Eight healthy children undergoing physical examination were used as controls. The 8 children with HUS all survived after CBP combined with HP and showed improved conditions. They had increased Hb and PLT levels and decreased serum levels of IL-6, IL-8, TNF-α, BUN, SCr, ALT, CK and CRP after treatment (P<0.05). CBP combined with HP can quickly remove pathogenic factors, continually eliminate inflammatory mediators and toxins, and reverse multiple organ dysfunction, and is one of effective methods for treating HUS in children.


Patient Satisfaction Following Primary Total Knee Arthroplasty: Contributing Factors.
The reported dissatisfaction rate after primary total knee arthroplasty (TKA) ranges between 15% and 25%. The purpose of this article is to perform a narrative review of the literature with the aim of answering the following question: What are the main factors contributing to patient dissatisfaction after TKA? A review of the literature was performed on patient satisfaction after TKA. The search engines used were MedLine (PubMed) and the Cochrane Library. The keywords used were "TKA" and "satisfaction". The main reported preoperative factors positively contributing to patient satisfaction were the following: fulfilment of preoperative expectations, preoperative complete joint space collapse, increasing patellar and lateral compartment osteophyte size, and TKA communication checklist. The principal preoperative factors negatively contributing to patient satisfaction included female sex, comorbidities, and Hispanic race. The chief perioperative factor positively contributing to patient satisfaction was cosmetic closure, whereas the fundamental perioperative factors negatively contributing to patient satisfaction included joint laxity, anterior tibial component slope, and greater femoral component valgus angle. The principal postoperative factors positively contributing to patient satisfaction were the following: ameliorated walking distance, improved range of motion, and improvements in pain. The most important postoperative factors negatively contributing to patient satisfaction included poor postoperative knee stability and soft-tissue balance, functional limitation, surgical complication and reoperation, staff or quality of care issues, and increased stiffness.


Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.
Constitutive activation of the FLT3 receptor tyrosine kinase, either by internal tandem duplication (ITD) of the juxtamembrane region or by point mutations in the second tyrosine kinase domain (TKD), has been described in patients with acute myelogenous leukemia (AML). We analyzed the prevalence and the potential prognostic impact of FLT3 mutations in 979 AML patients. Results were correlated with cytogenetic data and the clinical response. FLT3-ITD mutations were found in 20.4% and FLT3-TKD mutations in 7.7% of the patients. Each mutation was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype. Significantly more FLT3 aberrations were found in patients with FAB M5, and fewer were found in patients with FAB M2 and M6. Although less frequent in patients with cytogenetic aberrations, FLT3-ITDs were found in 13 of 42 patients with t(15;17) and in 9 of 10 patients with t(6;9). The prevalence of the ITD allele on the DNA level was heterogeneous, ranging from faint mutant bands in some patients to predominant mutant bands in others. Based on quantitative analysis, the mutant-wild-type (wt) ratio ranged from 0.03 to 32.56 (median, 0.78). Patients with a high mutant/wt ratio (ie, greater than 0.78) had significantly shorter overall and disease-free survival, whereas survival in patients with ratios below 0.78 did not differ from those without FLT3 aberrations. Multivariate analysis confirmed a high mutant/wt ratio to be a strong independent prognostic factor. Taken together, these data confirm that FLT mutations represent a common alteration in adult AML. Constitutive activation may be associated with monocytoid differentiation. A high mutant/wt ratio in ITD-positive patients appears to have a major impact on the prognostic relevance.


Lung tumorigenesis promoted by anti-apoptotic effects of cotinine, a nicotine metabolite through activation of PI3K/Akt pathway.
We previously found that genetic polymorphism in cytochrome P450 2A6 (CYP2A6) is one of the potential determinants of tobacco-related lung cancer risk. It has been reported that the plasma concentration of cotinine, a major metabolite of nicotine, in carriers of wild-type alleles of CYP2A6 is considerably higher than that in carriers of null or reduced-function alleles of CYP2A6, raising the possibility that cotinine plays an important role in the development of lung cancer. As a novel mechanism of lung tumorigenesis mediated by CYP2A6, we investigated the effects of cotinine on the suppression of apoptosis and promotion of lung tumor growth. In human lung adenocarcinoma A549 cells, cotinine inhibited doxorubicin-induced cell death by suppressing caspase-mediated apoptosis. Enhanced phosphorylation of Akt, a key factor responsible for cell survival and inhibition of apoptosis, was detected after cotinine treatment. These data suggest that cotinine suppresses caspase-mediated apoptosis induced by doxorubicin through activation of the PI3K/Akt pathway. Furthermore, we clarified that cotinine significantly facilitated tumor growth in the Lewis lung cancer model and accelerated development of lung adenomas induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mice. We herein propose that cotinine induces tumor promotion by inhibiting apoptosis and enhancing cellular proliferation, thus underlining the importance of CYP2A6 in tobacco-related lung tumorigenesis.


The small GTPase ARF6 stimulates β-catenin transcriptional activity during WNT5A-mediated melanoma invasion and metastasis.
β-Catenin has a dual function in cells: fortifying cadherin-based adhesion at the plasma membrane and activating transcription in the nucleus. We found that in melanoma cells, WNT5A stimulated the disruption of N-cadherin and β-catenin complexes by activating the guanosine triphosphatase adenosine diphosphate ribosylation factor 6 (ARF6). Binding of WNT5A to the Frizzled 4-LRP6 (low-density lipoprotein receptor-related protein 6) receptor complex activated ARF6, which liberated β-catenin from N-cadherin, thus increasing the pool of free β-catenin, enhancing β-catenin-mediated transcription, and stimulating invasion. In contrast to WNT5A, the guidance cue SLIT2 and its receptor ROBO1 inhibited ARF6 activation and, accordingly, stabilized the interaction of N-cadherin with β-catenin and reduced transcription and invasion. Thus, ARF6 integrated competing signals in melanoma cells, thereby enabling plasticity in the response to external cues. Moreover, small-molecule inhibition of ARF6 stabilized adherens junctions, blocked β-catenin signaling and invasiveness of melanoma cells in culture, and reduced spontaneous pulmonary metastasis in mice, suggesting that targeting ARF6 may provide a means of inhibiting WNT/β-catenin signaling in cancer.


Cell-mediated autoimmune response to testis induced by bilateral testicular injury can be suppressed by cyclosporin A.
Since the delayed type hypersensitivity (DTH) response to testis antigens plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis, we have investigated the immunosuppressive effect of cyclosporin A (CsA) on the DTH response to autologous testicular cells (TC). A DTH response to autologous TC was induced in C3H/HeN mice by bilateral testicular injury (trauma). CsA was administered intraperitoneally for 10 consecutive days before and after injury. A DTH response was assessed by measuring delayed footpad reaction (DFR) to autologous TC 9 days after injury. When the mice were traumatized alone, 10 mg./kg. or more of CsA suppressed the DTH response to autologous TC significantly. In mice traumatized with 100 mg./kg. of cyclophosphamide (CY)-pretreatment, 30 mg./kg. or more of CsA was needed to suppress the DTH response. In mice traumatized with 200 mg./kg. of CY-pretreatment, 50 mg./kg. of CsA was needed to suppress the autoimmune response. The DTH response to autologous TC was suppressed significantly by administration of CsA in a dose-dependent manner. We have also shown the direct suppressive effect of CsA on effector cells for DTH by means of local passive transfer of DTH. Administration of CsA had no augmenting or suppressive effect on suppressor cells for DTH. CsA might be a significant drug for the immunosuppression of EAO and possibly for immunological male infertility.


Alpha-thalassemia haplotypes in the Algerian population.
DNA mapping was performed in seven unrelated Hb H patients and nine carriers for alpha-thalassemia trait originating from Algeria. This study has allowed us to identify four alpha-thalassemia haplotypes: the (-alpha 3.7) haplotype, which is the most frequent (18 of 23 alpha-thalassemic chromosomes), the (-(alpha)20.5) haplotype, a (--) haplotype, and an (alpha alpha)T haplotype. Our results also show that the (-alpha 3.7) haplotypes encountered in the Algerian population are heterogeneous and differ by the site of the unequal crossover responsible for the 3.7-kb deletion and the size of the interzeta fragment. In addition, during this survey we observed that normal chromosomes bearing a polymorphic BglII site are associated with different interzeta fragments.


Bradykinin B2 receptor gene polymorphism is associated with altered urinary albumin/creatinine values in diabetic patients.
Diabetic nephropathy (DN) is an important microvascular complication of both insulin-dependent and non-insulin-dependent diabetes mellitus. Considerable evidence exists that genetic predisposition is a major determinant in the development of DN. Progress in the understanding of the kinin receptor gene expression indicates their relevance in nephrology and renal pathology. In order to investigate whether clinically relevant polymorphisms of the kinin receptor genes contribute to the genetic predetermination of the renal complication of diabetes, we have initiated a retrospective study with a mixed population of 49 type 1 and 112 type 2 diabetic patients who have been followed for several years by an endocrinologist and (or) nephrologist with periodical functional tests relevant to DN (microalbuminuria, serum and urinary creatinine). The allelic frequencies of four kinin receptor polymorphisms, including three B2R polymorphisms (the C/T-58 promoter polymorphism, the exon 2 and exon 1 polymorphisms, all of them with assumed clinical significance) and the putative nephroprotective (G/C-699) B1R promoter polymorphism, were analyzed in all recruited diabetic patients. Our results indicate a significant association of the B2R exon 1 (+/-) genotype with increased urinary albumin/creatinine values (P = 0.026) and serum creatinine levels (P = 0.028). More importantly, the (+) allele of B2R exon 1 polymorphism was associated very significantly with lower albumin/creatinine values in these patients (P = 0.0087). Thus, the B2R exon 1 polymorphism may represent a susceptibility marker for nephropathy progression in diabetic patients.


Bidynamical all-optical reservoir computing for parallel task processing.
A bidynamical all-optical reservoir computing (RC) system for parallel task processing is proposed based on a unidirectional semiconductor optical amplifier optical fiber loop. The polarization dynamics and intensity dynamics are excited by the input signals injected into the reservoir via phase modulation and intensity modulation, respectively. Simultaneous computation of two independent tasks is implemented based on the dynamical responses in polarization and intensity of the optical fiber loop. To our knowledge, this is the first time that two kinds of dynamical responses of an all-optical RC system are used as independent task processing channels to implement parallel task processing. The proposed RC system can achieve good parallel task processing performance with low system cost.


Validation of baking as a kill-step for controlling Shiga toxin-producing Escherichia coli during traditional crust pizza baking process.
A study was conducted to validate a simulated traditional crust pepperoni pizza baking process to control Shiga toxin-producing Escherichia coli (STEC) and to determine the heat resistance characteristics of STEC in pizza dough. Pizza dough and pepperoni slices were inoculated with 7 strains STEC cocktail and baked at 500°F (260°C) for 12 min using a conventional kitchen oven followed by 15 min of ambient air cooling. The mean internal temperature of the pizza reached 209.32 ± 1.94°F by the end of 12 min of baking and dropped to 137.90 ± 2.88°F after the 15 min ambient air cooling. The aw and pH of the traditional crust pizza did not alter significantly during the baking process. The STEC population decreased by >5 log CFU/g in traditional crust pizza after 12 min of baking. Where pepperoni slices were used as a source of STEC introduction, a reduction of >6.5 log CFU/g was observed. The D-values of STEC cocktail in pizza dough at 55, 58, 61°C were 49.5 ± 4.10, 15.3 ± 0.68, and 2.8 ± 0.31 min, respectively. The z-value of STEC was 4.8 ± 0.16°C. This study validated that a typical traditional crust pizza baking process with ~209°F internal temperature for at least 12 min will result in 5 log reductions in STEC population.


Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity.
K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R). JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251. Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis.


End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System.
We sought to assess accurately the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the United States Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in patients with the Wilms tumor-aniridia syndrome (WAGR). ESRD was ascertained in 5,910 patients enrolled in NWTSG studies during 1969 to 1994 by record linkage to USRDS and by direct followup. Cumulative ESRD incidence was estimated accounting for intercurrent mortality. Of 115 cases of ESRD 10 (9%) were ascertained by the NWTSG alone, 13 (11%) by USRDS alone and 92 (80%) by both. Cumulative incidence of ESRD at 20 years from diagnosis of unilateral Wilms tumor was 74% for 17 patients with the Denys-Drash syndrome, 36% for 37 patients with WAGR, 7% for 125 male patients with hypospadias or cryptorchidism (genitourinary [GU] anomalies) and 0.6% for 5,347 patients with none of these conditions. The incidence of ESRD after diagnosis of bilateral Wilms tumor was 50% for the Denys-Drash syndrome (6 patients), 90% for WAGR (10), 25% for GU anomaly (25) and 12% for other (409). ESRD in patients with WAGR or GU anomalies tended to occur relatively late, often during or after adolescence. The risk of ESRD is remarkably low for the majority of patients with Wilms tumor. However, those with WAGR or associated GU anomalies are at higher risk and should be screened indefinitely to facilitate prospective treatment of impaired renal function.


Neural tube defects: the experience of the registry of congenital malformations of Alsace, France, 1995-2009.
Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.


[Analysis of changes in percentage of phenotype CD4 + CD45RA + and CD4+ CD45RO + in peripheral blood and effect of immunomodulation in aged male patients with chronic cardiac insufficiency].
Autoimmunity participates in chronic heart failure (CCI), it is CD4+ T lymphocytes that mainly induces myocardial infiltration and the progression of the disease. The purpose of this research is to assess changes of CD4+, CD8+ T lymphocyte subset, and phenotype of primary T cell (CD4+ CD45RA+) and memory T cells (CD4+ CD45RO+) in peripheral blood in aged male patients with CCI. And to investigate the immunomodulatory effects on subsets of CD4+, CD8+ and phenotype of CD4+ CD45RA+ and CD4+ CD45RO+ and the possible therapeutic mechanism. The participant were 155 aged men among whom 94 cases were diagnosed as CCI and heart function of the rest 41 cases were normal. All patients underwent echocardiography examination and were collected peripheral blood before and after treatment. Serum N terminal pro-brain natriuretic peptide (NT-proBNP) levels were detected by heterogeneous immunoassay. Serum C reactive protein (CRP) were measured by immunoturbidimetry assay. T lymphocytes in peripheral blood were separated and determined distribution of CD4+, CD8+, CD4+ CD45RA+, CD4+ CD45RO+ using flow cytometry. Participants were divided into 3 groups: the CCI intervention group, who received regular therapy and thymopentin (20 mg intramuscular injection, once every other day for 3 month; n = 60) , the CCI control group, who received regular therapy (n = 54) and 41 healthy individual older than 57 years of age, who served as normal controls. Compared with the control group, left ventricular ejection fraction (LVEF) and CD4+ CD45RO+ levels decreased, left ventricular end diastolic diameter (LVEDD), NT-proBNP, CRP, CD4+, CD4+ CD45RA+, CD4+/CD8+, CD4+ CD45RA+/CD4+ CD45RO+ levels were obviously higher in CCI group. Distribution of CD8+ was not significantly changed. The level of NT-proBNP, CRP, CD4+/CD8+, CD4+ CD45RA+/CD4+ CD45 RO+ was negatively correlated with LVEF. LVEF could be much improved via decreasing distribution of CD4+/CD8+, CD4+ CD45RA+/CD4+ CD45RO in CCI intervention group than in CCI control group. The changes of CD4+/CD8+ and CD4+ CD45RA+/CD4+ CD45RO+ suggest that CD4+ T lymphocyte subset and its phenotype play an important role in the process of CCI. The regulation of CD4+ T lymphocyte and its phenotype may be one of the strategy in the treatment of CCI.


Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine.
Thyroid hormone transporters are responsible for the cellular uptake of thyroid hormones, which is a prerequisite for their subsequent metabolism and action at nuclear thyroid hormone receptors. A recently discovered thyroid hormone derivative, 3-iodothyronamine (T(1)AM), has distinct biological effects that are opposite those of thyroid hormone. Here we investigate the effects of T(1)AM on thyroid hormone transporters using COS-1 cells transfected with the multispecific organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 1C1, as well as the specific thyroid hormone transporters MCT8 and MCT10, and show that T(1)AM displays differential inhibition of T(3) and T(4) cellular uptake by these transporters. T(1)AM inhibits T(3) and T(4) transport by OATP1A2 with IC(50) values of 0.27 and 2.1 microM, respectively. T(4) transport by OATP1C1, which is thought to play a key role in thyroid hormone transport across the blood-brain barrier, is inhibited by T(1)AM with an IC(50) of 4.8 microM. T(1)AM also inhibits both T(3) and T(4) uptake via MCT8, the most specific thyroid hormone transporter identified to date, with IC(50) values of 95 and 31 microM, respectively. By contrast, T(1)AM has no effect on thyroid hormone transport by OATP1B3 and MCT10. Given that OATP1A2, OATP1C1, and MCT8 are all present in the brain, T(1)AM may play an important role in modulating thyroid hormone delivery and activity in specific target regions in the central nervous system.


Flattening filter-free technique in volumetric modulated arc therapy for lung stereotactic body radiotherapy: A clinical comparison with the flattening filter technique.
The present study sought to evaluate the impact of the flattening filter-free (FFF) technique in volumetric modulated arc therapy for lung stereotactic body radiotherapy. Its clinical safety and availability were compared with the flattening filter (FF) method. The cases of 65 patients who underwent lung volumetric modulated arc therapy-stereotactic body radiotherapy (VMAT-SBRT) using FF or FFF techniques were reviewed. A total of 55 Gy/4 fractions (fr) was prescribed for peripheral lesions or 56 Gy/7 fr for central lesions. The total monitor units (MU), treatment time, dose to tumors, dose to organs at risk, tumor control (local control rate, overall survival, progression-free survival) and adverse events between cases treated with FF and cases treated with the FFF technique were compared. A total of 35 patients were treated with conventional FF techniques prior to November 2014 and 30 patients were treated with FFF techniques after this date. It was revealed that the beam-on time was significantly shortened by the FFF technique (P<0.01). Other factors were similar for FFF and FF plans in respect to conformity (P=0.95), homogeneity (P=0.20) and other dosimetric values, including total MU and planning target volume/internal target volume coverage. The median follow-up period was 18 months (range, 2-35). One-year local control rates were 97.1 and 90.0% in the FF group and FFF groups, respectively (P=0.33). Grade 3 pneumonitis was observed in 5.8% of FF patients and 3.4% of FFF patients (P=1.00). No other adverse events ≥grade 3 were observed. The results of the study suggest that VMAT-SBRT using the FFF technique shortens the treatment time for lung SBRT while maintaining a high local control rate with low toxicity.


Encoding of coordinated grasp trajectories in primary motor cortex.
Few studies have investigated how the cortex encodes the preshaping of the hand as an object is grasped, an ethological movement referred to as prehension. We developed an encoding model of hand kinematics to test whether primary motor cortex (MI) neurons encode temporally extensive combinations of joint motions that characterize a prehensile movement. Two female rhesus macaque monkeys were trained to grasp 4 different objects presented by a robot while their arm was held in place by a thermoplastic brace. We used multielectrode arrays to record MI neurons and an infrared camera motion tracking system to record the 3-D positions of 14 markers placed on the monkeys' wrist and digits. A generalized linear model framework was used to predict the firing rate of each neuron in a 4 ms time interval, based on its own spiking history and the spatiotemporal kinematics of the joint angles of the hand. Our results show that the variability of the firing rate of MI neurons is better described by temporally extensive combinations of finger and wrist joint angle kinematics rather than any individual joint motion or any combination of static kinematic parameters at their optimal lag. Moreover, a higher percentage of neurons encoded joint angular velocities than joint angular positions. These results suggest that neurons encode the covarying trajectories of the hand's joints during a prehensile movement.


Nedaplatin-based chemotherapy regimens combined with concurrent radiotherapy as first-line treatment for stage II-III esophageal squamous cell carcinoma.
Concurrent chemoradiotherapy (CCRT) is an effective first-line treatment for esophageal squamous cell carcinoma (ESCC). The present study aimed to compare clinical outcomes between three nedaplatin-based regimens for CCRT of ESCC. Patients with stage II-III thoracic ESCC in China between January 2012 and May 2016 were included. Patients received esophageal ultrasonography prior to treatment. Chemotherapy was as follows: i) 100 mg/m2 nedaplatin intravenously on day 1 and 70 mg/m2 tegafur-gimeracil-oteracil potassium (S-1) orally twice daily for 2 weeks; ii) 50 mg/m2 nedaplatin intravenously on days 1 and 2 and 35 mg/m2 docetaxel intravenously on days 1 and 8; or iii) 60 mg/m2 nedaplatin intravenously on days 1 and 2. Intensity-modulated radiotherapy was used to administer a total dose of 60-66 Gy (1.8-2.0 Gy per fraction) to the primary tumor and 45-50 Gy to the subclinical region. A total of 70 patients were enrolled (median age, 66 years; range, 50-81 years). T4 disease was identified in 45 (64.3%) patients. All patients completed radiotherapy and received ≥2 chemotherapy cycles. Estimated 1-, 2- and 3-year overall survival (OS) rates were 82.9, 53.9 and 31.4%, respectively. OS and progression-free survival were similar between the three treatment groups. Grade 3/4 hematological toxicities were observed in 35 (50%) patients. The incidence of serious treatment-associated toxicities was numerically highest for the nedaplatin/docetaxel combination. Patients with thoracic ESCC had good clinical outcomes following CCRT. With similar survival rates and disease responses yet lower hematological toxicities, nedaplatin/S-1 and single-agent nedaplatin may be preferable to nedaplatin/docetaxel. Poor control of distant metastasis may be a disadvantage of single-agent chemotherapy use in CCRT, and a further study with larger cohorts is required to confirm this.


Effect of Preoperative Antianxiety Medications on Blood Pressure and Blood Loss in Total Knee Arthroplasty: A Case-Control Study.
The increasing number of canceled operations in patients undergoing total knee arthroplasty (TKA) due to high blood pressure readings has put a considerable burden on surgeons. In this study, we aim to assess the effect of giving antianxiety drugs preoperatively on maintaining blood pressure (BP) and blood loss for patients undergoing TKA surgery. This retrospective case-control study included patients who underwent total knee arthroplasty and divided them into two main groups: those who had taken a 3 mg bromazepam oral tablet at the night preoperatively and the control group. The blood pressure of patients was then measured preoperatively (baseline), in the morning of surgery, in the operating room before anesthesia, and during the surgery. The percentage of measured BP was calculated by dividing the measured BP by the baseline, then multiplying by 100. 301 patients were included in our study: 137 received bromazepam and 164 as a control group. The ratio of systolic BP (SBP) in the morning of surgery to the baseline (percentage of morning SBP) decreased significantly in the bromazepam group compared with the controls. The ratio of SBP, in the operating room before anesthesia (percentage of preanesthesia SBP) also decreased significantly in the bromazepam group. However, the percentage of SBP in the middle of surgery did not change significantly. In addition, there was a significant difference change from the baseline in diastolic BP and mean arterial BP between the two groups in the morning of surgery, inside the theatre, and in the middle of the operation. The bromazepam group also showed a significant decrease in blood loss. Preoperative oral antianxiety drugs (bromazepam) helps in controlling hemodynamic changes associated with anxiety, including maintaining BP in well-controlled hypertensive and healthy patients undergoing TKA, and it plays a role in decreasing the total blood loss.


In vitro study of the adherence of Candida albicans to acrylic resins: relationship to surface energy.
This study aimed to determine whether small variations in the composition of the polymethylmethacrylate (PMMA) of widely used dentures produce differences in the degree of Candida albicans adherence and to relate any differences found to the surface energy of the resins, which appears to play a major role in the initial phases of microorganism adhesion. A reference strain of C albicans (18.804 ATCC) and 11 different PMMAs (Vacalon, Inkotherm 85, Veracril, Probase Cold, Inkotherm Press, Inkotherm 85 T, Ruthinium, Vertex, SR Ivocap, Idoacryl, Lucitone) were used. Fifty specimens (15 x 10 x 1 mm) of each type were prepared. C albicans adhesion was determined by microorganism count under fluorescent optical microscope, and the surface energy of the resins was calculated by the contact angle method. P < .05 was regarded as significant. C albicans adhesion on the resins ranged from 7.12 cells/mm2 to 330.8 cells/mm2, with statistically significant (P > .05) differences in some cases. Despite small variations in the composition of the resins, their surface energy values were very similar (38.78 to 41.2 mJ/m2), and no relationship was found between C albicans adhesion and surface energy. The adhesion of C albicans to different resins varied in vitro, possibly as a result of the action of residual postpolymerization products. According to these results, variations in surface energy that result from differences in the composition of the different PMMA resins appear to have no influence on the adhesion of C albicans or, therefore, on the onset of denture stomatitis.


Water-Mediated Reduction of Aqueous N-Nitrosodimethylamine with Pd.
Pd-catalyzed reduction has emerged as a promising treatment strategy to remove the recalcitrant disinfection byproduct N-nitrosodimethylamine (NDMA). However, the reaction pathways remain unexplored, and questions remain about how water solvent influences NDMA reduction mechanisms and selectivity. Here, we compute the energies and barriers of all relevant elementary steps in NDMA reduction by H2 on Pd(111) using density functional theory. We further calculate water-assisted H-shuttling for all hydrogenation reactions explicitly and include water solvation for all elementary reactions implicitly. We parametrize microkinetic models to predict product formation rates and selectivities over a wide range of NDMA concentrations. We show that H2O-mediated H-shuttling lowers the reaction barriers for all hydrogenation reactions involved in NDMA reduction while implicit solvation has negligible impact on the reaction and activation energies. We further conduct batch experiments with SiO2-supported Pd nanoparticles and compare them with the microkinetic models. The predicted rates, selectivity, and apparent activation energy from the model parametrized with both explicit H2O-mediated H-shuttling and implicit solvation correspond well with experimental observations. Models that ignore water as an H-shuttle or solvent fail to recover the experimental rates and apparent activation energy. We identified the rate-determining steps of the reaction and show the reaction flow pathways of the complicated reaction network. Finally, we demonstrate that water-mediated H-shuttling changes the rate-determining steps and reaction flows of elementary reactions.


Microleakage of root restorations.
This study evaluated the microleakage of various restorative materials placed in root surfaces. A minimum of 20 freshly extracted single-rooted teeth were used for each combination of restorative materials. Four preparations were made on the root surface and each restored with a different material. After thermocycling in dye, the root was cut transversely in several sections through the restoration, and microscopically examined to record the microleakage at the interface between restorative materials and tooth. Results indicated that fewer composite resin specimens allowed microleakage into dentin as compared with either amalgam or glass ionomer materials.


Identification of a conserved epitope cluster in the N protein of porcine reproductive and respiratory syndrome virus.
In this study, 4 overlapping fragments and 12 overlapping peptides of the nucleocapsid (N) protein from porcine reproductive and respiratory syndrome virus (PRRSV) were expressed as glutathione S-transferase (GST) fusion proteins and used to probe a panel of 16 anti-N protein monoclonal antibodies (mAbs) by ELISA. The minimal epitope sequence of the following seven mAbs was determined by sequential deletion of terminal amino acid residues from each peptide: N2H7 corresponded to H54FPLA58; N2F7 corresponded to K52PHFPLA58; and N1A2, N1E3, N1G4, and N2E5 were reactive against E51KPHFP56. Furthermore, a polypeptide containing this epitope cluster was recognized by PRRSV-immune pig serum by Western blot, suggesting that residues 51-58 represent an immunodominant region of the N protein. Sequence alignment revealed that these epitopes are well conserved among North American and European genotypes of PRRSV. These findings enhance our knowledge of the antigenic structure of N protein and may facilitate the development of better diagnostic methods for PRRSV.


Improving access to knowledge-based health sciences information: early results from a statewide collaborative effort.
Access to biomedical literature has been shown to reduce the patient's length of stay and thus reduce the cost of the hospital visit. Unfortunately, access to the most current information, at the time and place of need, requires a substantial commitment of resources in the form of staff expertise, computer hardware and software, and user training. The cost of these resources may be prohibitively high for all but the largest institutions. The Arizona Health Information Network (AZHIN) brings together librarians, information systems specialists, and health care professionals from hospitals throughout the state in an effort to share resources and expertise. By reducing the cost of access, AZHIN has increased the availability of health-related information across the state. Progress in AZHIN's first two years is described.


Demonstration of the ascending aorta in infective endocarditis by intravenous digital subtraction angiography.
Four patients with infective endocarditis were examined by digital subtraction angiography immediately before operation. In three a root abscess was suspected and the remaining patient was believed to have a false aneurysm at an infected aortic cannulation site. In all the cases digital subtraction angiography showed the structure in several projections and confirmed the presence of a cavity. Subsequent operation confirmed the site and nature of the lesions.


Evaluation of a culturally adapted German version of the Patient Assessment of Chronic Illness Care (PACIC 5A) questionnaire in a sample of osteoarthritis patients.
The chronic care model and the 5A approach have achieved widespread acceptance and reflect the core elements of patient-centred care in chronic diseases, including arthritis. Appropriate assessment tools are indispensable to assess whether provided care is in alignment with these evidence-based conceptual frameworks of care. The aim of this study was to examine the validity of a translated and culturally adapted version of the Patient Assessment of Chronic Illness Care (PACIC 5A) questionnaire among osteoarthritis (OA) patients. Of 300 administered questionnaires, 236 (78.6%) were returned. Established statistical approaches were used in order to assess psychometric properties. Test-retest reliability was tested in 75 randomly selected patients who received the questionnaire a second time after 2 weeks. The EUROPEP questionnaire was used in order to address external validity. Scale internal consistency was confirmed with values ranging from 0.52 to 0.97 for Pearson's r. Internal consistency reliability was satisfying: Cronbach's alpha was 0.78 or higher for all scales. Test-retest reliability (intraclass correlation coefficient) exceeded 0.77. Correlations with the EUROPEP, which is not organized according to a conceptual approach to care, were only strong in corresponding scales. The PACIC 5A is a reliable and valid instrument to assess the congruency of care to the chronic care model of OA patients. Its use is encouraged in quality improvement projects but also in further research.


Safety of nab-paclitaxel plus sunitinib: analysis of three cases.
Second-line treatment options are limited in controlling advanced thoracic cancer in patients who have progressed following first-line chemotherapy. The safety of combination therapy with nab-paclitaxel, an albumin-bound paclitaxel, and sunitinib, a tyrosine kinase receptor inhibitor, was evaluated retrospectively in three patients with advanced, previously treated metastatic esophageal cancer, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC), respectively. Grade 3 and 4 toxicities were mainly hematological and manageable. A notable improvement in cancer symptoms and reduction in tumor size were seen in all three patients. Based on the easily managed toxicities and apparent efficacy of the regimen of weekly nab-paclitaxel and daily sunitinib, we conclude that further evaluation is warranted to assess the efficacy of this combination therapy in previously chemotherapy-treated patients with advanced thoracic cancer.


Attitudes toward embodied old age among Swedes.
Messages in the consumer culture are often youth oriented, aiming at the prevention of the bodily decay associated with biological aging. In gerontological discourses, this has been hypothesized to generate negative attitudes toward embodied aging and old age. Studies about general attitudes toward old age show that younger respondents have more negative attitudes than do older respondents, and gerontological discourses also hypothesize a gendered ageism, with especially negative attitudes toward elderly women. The empirical study of embodied aging among 1,250 Swedes aged 20-85 years contradicts these hypotheses. The results show rather positive attitudes toward embodied old age, especially among young and middle-aged respondents. Neither do the results unequivocally confirm the hypothesis of gendered ageism, which predicts considerably more negative attitudes toward old women than toward old men. One interpretation of the results is that, counter to many hypotheses, the consumer culture, with its new opportunities and roles for old people, may positively affect these attitudes.


[Ultrasonic echolocation of soft tissues in dogs during decompression].
Ultrasonic location of femoral soft tissues of anesthetized dogs was performed using a modified unit UZKAP-3. The animals were exposed to 0.5 mPa for 2 hours and then to decompression to sea level pressure. The concomitant echographic changes pointed to the formation of extra- and intravascular gas bubbles in the above tissues. The bubbles could be identified visually in the nearest echographic band because the instrumentation used made it possible to eliminate the background image of structural inhomogeneities of the tissue layer.


Muscle lipid metabolism in two rabbit lines divergently selected for intramuscular fat.
A divergent selection experiment for intramuscular fat (IMF) of LM at 9 wk of age was performed in rabbits. The objective of this work was to compare the lipid metabolism in muscles and fat tissues of the high-IMF and low-IMF lines. Lipogenic, catabolic, and lipolytic activities were studied in 2 muscles with different oxidative patterns (LM and semimembranosus proprius) and in the perirenal fat depot at 2 ages, 9 and 13 wk. In addition, adipocytes were characterized in perirenal fat. In the fifth generation, direct response to selection was 0.26 g IMF/100 g muscle. Lines showed differences in their lipogenic activities of muscles and fat tissues at 13 wk but not at 9 wk. The high-IMF line showed greater glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (EM), and fatty acid synthase (FAS) activities in LM than the low-IMF line, with probabilities = 1.00, 0.93, and 0.90, respectively. Differences between lines were particularly great for G6PDH activity, representing 1.13 SD. The high-IMF line also showed greater G6PDH and FAS activities in semimembranosus proprius (P = 0.98 for G6PDH and 0.95 for FAS) and perirenal fat (P = 0.91 for G6PDH and 0.96 for FAS). However, in perirenal fat, EM activity was greater in the low-IMF line (P = 0.90). No differences between lines were found in almost any catabolic or lipolytic activities of muscles. Regarding adipocyte characteristics, the high-IMF line showed larger adipocytes in perirenal fat depot tissue (P = 0.97) compared to the low-IMF line, but no differences between lines were observed in the number of adipocytes. This study sheds light on the metabolic activities involved in the genetic differentiation of lipid deposition in rabbits. This study shows that lipogenic activities in muscles and fat tissues, in particular G6PDH in LM, are involved in the lipid accumulation in muscle and adipose tissues.


Polyvinyl alcohol-based economical triboelectric nanogenerator for self-powered energy harvesting applications.
Triboelectric nanogenerators (TENGs) have emerged as a promising alternative for powering small-scale electronics without relying on traditional power sources, and play an important role in the development of the internet of things (IoTs). Herein, a low-cost, flexible polyvinyl alcohol (PVA)-based TENG (PVA-TENG) is reported to harvest low-frequency mechanical vibrations and convert them into electricity. PVA thin film is prepared by a simple solution casting technique and utilized to serve as the tribopositive material, polypropylene film as tribonegative, and aluminum foil as electrodes of the device. The dielectric-dielectric model is implemented with an arch structure for the effective working of the PVA-TENG. The device showed promising electrical output by generating significant open-circuit voltage, short-circuit current, and power . Also, PVA-TENG is subjected to a stability test by operating the device continuously for 5000 cycles. The result shows that, the device is mechanically durable and electrically stable. Further, the as-fabricated PVA-TENG is demonstrated to show feasible applications, such as charging two commercial capacitors with capacitances 1.1 and 4.7μF and powering green light-emitting diodes. The stored energy in the 4.7μF capacitor is utilized to power a digital watch and humidity and temperature sensor without the aid of an external battery. Thus, the PVA-TENG facilitates ease of fabrication, robustness, and cost-effective strategy in the field of energy harvesting for powering lower-grid electronics by demonstrating their potential as a sustainable energy source.


[N-acetyl-L-cysteine inhibits adenoviral E1A-involved transactivation of nuclear factor-kappaB in rat alveolar epithelial cells.].
the relationship between latent adenovirus infection and airway inflammation had not been well documented. The aim of this study was to illustrate the roles of adenovirus E1A protein on the transactivation of NF-kappaB, AP-1 in response to inflammatory stimuli and the effect of N-Acetylcysteine (NAC) upon the transactivation of NF-kappaB and AP-1 in cells stably expressing E1A protein. rat alveolar epithelial cells stably expressing adenoviral E1A or control plasmid were developed. For isolation of nuclear extracts, 5 x 10(5) cells were plated and grown overnight in 60 mm dishes. Experiments were repeated 3 times. The cell model of stably expressing adenoviral E1A was stimulated by LPS or TNF-alpha and treated with NAC, a precursor for cysteine. The NF-kappaB and AP-1 transcriptional activity were measured by LUC report system. The expression of NF-kappaB and AP-1 were measured by Western blot. Differences between groups were assessed for significance by Student' t test, and multiple comparisons were made by one-way ANOVA. the luciferase activity derived by NF-kappaB element was (9 698 +/- 98) RLU in untreated E1A-positive clones and (101 195 +/- 234), and (170 385 +/- 443) RLU in LPS and TNF-alpha-stimulated cells, which were significantly higher than that of the control group 2 077 +/- 107, 67 846 +/- 332, 95 743 +/- 211 respectively. The luciferase activity derived by AP-1 element was 9 034 +/- 78 RLU in untreated E1A-positive clones and 26 343 +/- 398 and 31 731 +/- 332 RLU in LPS and TNF-alpha-stimulated cells, which were significantly higher than that of the control group 2 845 +/- 93, 10 772 +/- 432, 11 005 +/- 556 respectively. The densitometry of the NF-kappaB expression in E1A-positive clones were 79.3 +/- 4.6 and 80.3 +/- 3.8 respectively without treatment and were 81.8 +/- 3.9 - 89.9 +/- 1.6 and 94.1 +/- 1.9 to 99.8 +/- 1.6 respectively under LPS or TNF-alpha stimulation, which were significantly higher than that of the control group (68.3 +/- 3.8, 69.4 +/- 4.3 respectively) without stimulation and 70.1 +/- 2.8 to 80.8 +/- 3.6, 73.4 +/- 4.9 to 83.2 +/- 6.7 respectively under stimulation. The level of AP-1 expression did not show difference upon treatment with LPS or TNF-alpha in either cell clones. The densitometry of the NF-kappaB expression in E1A-positive clones were 3.2 +/- 0.1 and 3.3 +/- 0.1 respectively under LPS and TNF-alpha-stimulation and 1.98 +/- 0.2 and 1.9 +/- 0.2 respectively upon treatment for LPS and TNF-alpha with NAC pre-incubation. these results indicate that E1A protein upregulated NF-kappaB transcription activity induced by LPS and TNF-alpha in rat alveolar epithelial cells and this effect could be repressed by NAC. The mechanisms underlying transactivation of NF-kappaB involved by E1A may be related to oxidative stress.


The Effect of the PEEK Cage on the Cervical Lordosis in Patients Undergoing Anterior Cervical Discectomy.
Loss of cervical lordosis is a significant factor in the development of degeneration of the spine with aging. This degenerative changings of the cervical spine would cause pressure effect on the cervical root and/or medulla spinalis. Our goal is to understand the effect of the PEEK cage on cervical lordosis in the early postoperative period. Also, to interpret the effects of one- level, two- level, three-level and four- level disc pathologies on cervical lordosis. We retrospectively investigated our archive, and we selected thirty-four patients undergoing anterior cervical discectomy and fusion with PEEK cage filled with demineralized bone matrix (ACDFP). We determined that ACDFP provides improvement in the cervical lordosis angle in both groups. Also, we found statistically significant difference between group 1 and 2 regarding causes of radiculomyelopathy statistically. We achieved better cervical lordotic angles at the postoperative period by implanting one-level, two-level, three-level or four-level PEEK cage filled with demineralized bone matrix. Also, the causes of cervical root and or medulla spinalis impingement were different in group1 and 2. While extruded cervical disc impingement was the first pathology in group 1, osteophyte formation was the first pathology in group 2.


Superconducting 7 T wiggler for LSU CAMD.
A superconducting 7 T wiggler is under fabrication in a collaboration between Budker INP and LSU CAMD. The wiggler magnet has been successfully tested inside a bath cryostat and a maximum field of 7.2 T was achieved after six quenches. The main parameters of the wiggler and the method of the wiggler installation onto the storage ring are discussed.


[Prevention and treatment of congenital toxoplasmosis: organization protocol].
Prevention and treatment of congenital toxoplasmosis are still a matter of debate among obstetricians, pediatricians and epidemiologists. There is no consensus about antenatal screening and diagnostic tests, nor there is about treatment for presumed infection in pregnancy. As an example of this type of organisation for health care delivery, a regional model has been promoted as a multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis. The model had been designed on the national guidelines of the National Health Institute (Istituto Superiore di Sanità, ISS). Suspected maternal infections are referred and seen as outpatients at our centre on a specific day of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity titres) are performed at the Institute of Virology of the University of Bari, and patients are started on spiramycin. All cases of true or presumed seroconversion are counselled for amniotic fluid sampling and the sample is sent to ISS. In cases of late seroconversion and positive amniotic fluid results, patients are prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until the end of pregnancy. A fetal-neonatal follow-up is performed in all cases. During the period 1999-2001, 180 cases of presumed toxoplasmosis infection have been referred (average 60 cases per year). We have been able to reclute, since the adoption of the national network protocol, 1/3 of presumed regional cases with a positive increasing trend. The service for prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from the adoption of this protocol, which combines adherence to a national network and pays respect to regional requirements.