Virus encoded circulatory miRNAs for early detection of prostate cancer.
Prostate cancer (PCa) is the most commonly diagnosed cancer and kills about 28,000 American men annually. Although progress has been made in understanding the molecular features of different forms of the disease, PCa is considered incurable when it becomes resistant to standard therapies. Prostate specific antigen (PSA) test has been a gold standard of diagnosis for PCa, however, it can result in lead to the unnecessary biopsies and treatment of indolent cancers due to the low specificity. Thus, the limitations of PSA screening for PCa have prompted much focus on strategies how to enhance the accuracy of PSA for distinction between aggressive and indolent cancers. Studies of miRNAs in PCa patients have suggested differentially expressed miRNAs between healthy controls and those with PCa, providing potential biomarker candidates using body fluids including urine and blood. Virus infection has been considered to associate with PCa incidence. Virus infected PCa cells may shed extracellular vesicles and communicate with neighboring cells, which were not infected yet, however, no mechanistic approaches were performed to understand the biology. The miRNAs composition in the shedding extracellular vesicles, and its role in PCa are completely undefined. In the near future, new insights to connect between the viral derived miRNAs and PCa progression might provide an opportunity to diagnose, risk prediction and therapeutic strategies. The goal of this debate article is to provide a short review on miRNAs, virus infection and viral encoded miRNAs in PCa, with a primary focus on circulating miRNAs as potential non-invasive biomarkers for PCa patients.


The effect of polymerization of horseradish peroxidase on the peroxidase activity in the presence of excess H2O2: a background for a homogeneous enzyme immunoassay.
The phenol oxidation catalyzed by horseradish peroxidase (HRP) is slowed down by the presence of excess H2O2. This inhibition is due to accumulation of Compound III, which is a catalytically sluggish form of HRP. When HRP is polymerized through covalent bonds, Compound III becomes unstable and the peroxidase activity is less sensitive to excess H2O2. Under suitable experimental conditions, the phenol oxidation is increased by about 20-fold upon polymerization of the enzyme. This fact represents the principle of a homogeneous enzyme immunoassay reported by Hoshino et al. (J. Biochem. 97, 113-118 (1985)). The ratio of the peroxidase activities of monomeric and polymerized HRPs is 1 : 4 when phenol is replaced by resorcinol, and the difference is no larger when guaiacol and catechol are used as electron donors.


Leg strength in peripheral arterial disease: associations with disease severity and lower-extremity performance.
The purpose of this study was to determine relationships between lower-extremity arterial obstruction, leg strength, and lower-extremity functioning. The study design was cross-sectional. A total of 514 outpatients (269 with ankle-brachial index [ABI] <0.90), aged 55 and older, were identified from three Chicago-area hospitals. Individuals with history of lower-extremity revascularization were excluded. Main outcome measures Strength in each leg, 6-minute walk, 4-meter walking velocity, accelerometer-measured physical activity, and a summary performance score were measured. The summary performance score is a composite measure of lower-extremity functioning, ranging from 0 to 12 (12 = best). The leg with the lower ABI was defined as the "index" leg, and the leg with higher ABI was defined as the "contralateral" leg. Index leg ABI levels were associated linearly and significantly with strength for hip extension (P <.001), hip flexion (P <.001), knee extension (P =.066), and knee flexion (P =.003), adjusting for known and potential confounders. In adjusted analyses, the index ABI was also associated linearly and significantly with strength in the contralateral leg. Adjusting for confounders, including ABI, knee extension strength, was associated independently with functional measures. Among patients without prior leg revascularization, strength in each leg is highly correlated with the lower-leg ABI. Leg strength is associated independently with functional performance. Further study is needed to determine whether lower-extremity resistance training improves functioning in patients with peripheral arterial disease.


Antioxidant activity and lipid peroxidation in preeclampsia.
Epidemiologic studies demonstrate a relation between preeclampsia and an increased risk of future maternal coronary heart disease. The pathophysiology of the underlying mechanism is unknown. Disorders of lipoprotein metabolism may contribute to endothelial dysfunction. Oxidative stress and decreased antioxidant defense enhances free radical-mediated membrane lipid peroxidation and possibly vascular endothelial damage. The aim of this study was to elucidate the possible relation between lipidemic status, lipid peroxidation and albumin with total antioxidant activity (AOA) that may contribute to atherogenicity in preeclamptic women. Twenty-five women with preeclampsia and 25 normal pregnant women who were matched for maternal and gestational age were selected for the study. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), atherogenic index (AI), malondialdehyde (MDA), a marker of lipid peroxidation, AOA and albumin levels were measured. MDA, TC and AI were significantly elevated (p < 0.001), and HDL-C, AOA and albumin levels were significantly decreased (p < 0.001) in preeclamptic patients compared to the control group. We conclude that hypercholesterolemia leads to excessive lipid peroxidation. Coexistent diminution in antioxidant activity leads to an imbalance between prooxidants and antioxidants, resulting in oxidative stress. Oxidative stress and elevated AI may contribute to atherogenicity in preeclampsia.


Role of Plasmid in Pesticide Degradation and Metal Tolerance in Two Plant Growth-Promoting Rhizobacteria Bacillus cereus (NCIM 5557) and Bacillus safensis (NCIM 5558).
Disha A (Bacillus cereus) and Disha B (Bacillus safensis) were isolated from pesticide-infested agricultural field and showed tolerance against pesticides, heavy metals, and antibiotics. The isolates exhibited PGPR activities in vitro as well as in field conditions in lentil (Lens culinaris) and cow pea (Vigna unguiculata). Both the Bacillus species could not be grown in mineral salt medium but efficiently grown in the media supplemented with pesticide (imidacloprid/carbendazim) demonstrating the utilization of pesticide as carbon/nitrogen source. The HPLC studies exhibited the pesticide (imidacloprid/carbendazim) degradation by both the bacteria. B. safensis showed better degradation of carbendazim (88.93%) and imidacloprid (82.48%) than that of B. cereus 78.07% and 49.12%, respectively. The bacterial isolates showed high concentration of heavy metal tolerance viz. lead, molybdenum, cadmium, copper, cobalt, and zinc, except mercury. Both the bacteria possessed single plasmid. The plasmid-cured isolates of B. cereus did not tolerate any pesticide, whereas that of B. safensis tolerated all the pesticides, like wild strains. The plasmid curing experiments did not affect the heavy metal tolerance ability of both the bacteria indicating the genomic nature of heavy metal tolerance genes, whereas pesticide resistance genes are plasmid-dependent in B. cereus but genomic in B. safensis.


Cell Viability Multiplexing: Quantification of Cellular Viability by Barcode Flow Cytometry and Computational Analysis.
Fluorescent cell barcoding (FCB) is a useful flow cytometric technique for high-throughput multiplexed analyses and can minimize technical variations after preliminary optimization and validation of protocols. To date, FCB is widely used for measurement of phosphorylation status of certain proteins, while it can be also employed for cellular viability assessment. In this chapter, we describe the protocol to perform FCB combined with viability assessment on lymphocytes and monocytes using manual and computational analysis. We also provide recommendations for FCB protocol optimization and validation for clinical sample analysis.


Determination of Heavy Metals in a Variety of Cannabis and Cannabis-Derived Products, First Action 2021.03.
The legalization of medicinal or recreational marijuana across many states in the United States and other countries has driven demand for cannabis, hemp, and related products. In the absence of federal regulations to ensure the product quality and safety of these products, each state issues its own guidance and sets its own regulations. Like food and pharmaceuticals, cannabis testing should include the analysis of heavy metals, which may be toxic if ingested or inhaled. Based on established methods for the preparation and multi-elemental analysis of plant materials, a range of cannabis and cannabis-related products were prepared for analysis using microwave-assisted acid digestion followed by testing with inductively coupled plasma-mass spectrometry (ICP-MS). The sample preparation procedure was validated by measuring arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in four plant-based certified reference materials (CRMs). The mean ICP-MS results for As, Cd, Hg, and Pb were in good agreement (85-110%) with the certified concentrations. The accuracy and precision of the ICP-MS method for the determination of As, Cd, Hg, and Pb, as well as other elements, were tested by spiking the various cannabis samples at different concentration levels and determining the spike recoveries. The spike recoveries for As, Cd, Hg, and Pb in all spiked samples met the AOAC Standard Method Performance Requirements (SMPR®) for Determination of Heavy Metals in a Variety of Cannabis and Cannabis-Derived Products (SMPR 2020.001) of 60-115% for low-level spike and 80-115% for mid- and high-level spikes. Microwave-assisted acid digestion and ICP-MS are suitable for trace metal preparation and analysis of cannabis, as well as related products, as shown by the results of this method. The repeatability and recovery results for As, Cd, Hg, and Pb met the method requirement criteria in the AOAC SMPR 2020.001. This method can be used for all stages of production to ensure safety with respect to toxic metals. A wide range of cannabis and hemp samples, from raw materials to finished products, are within scope for analysis using the microwave-assisted acid digestion/ICP-MS method.


Interactions of lamotrigine with topiramate and first-generation antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis.
The study investigated the types of interactions between lamotrigine (LTG) and first-generation antiepileptic drugs (AEDs) or topiramate (TPM) with isobolographic analysis. Anticonvulsant and adverse-effect profiles of combinations of LTG with other AEDs, at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the maximal electroshock (MES)-induced seizures and the chimney test (motor performance) in mice, which allowed the determination of benefit indices (BIs) for individual combinations. Combinations of LTG with TPM or valproate (VPA), at fixed ratios of 1:1, were significantly supraadditive (synergistic) in the MES test and, simultaneously, subadditive (antagonistic) in the chimney test, showing the best profile for AED combinations. In contrast, combinations between LTG and carbamazepine (CBZ), in terms of antiseizure protection against MES, were subadditive (antagonistic) and additive in the chimney test, resulting in unfavorable AED combinations. Moreover, the combination of LTG with phenobarbital (PB), at a fixed ratio of 1:1, despite synergy in the MES test, also was synergistic in the chimney test, resulting in a modest BI for AED combination. LTG combined with phenytoin was additive in both the MES and chimney tests in mice. The remaining combinations, at fixed ratios not mentioned earlier, also showed an average BI for AED combinations. Furthermore, LTG combined with all studied AEDs did not affect long-term memory in mice. None of the AEDs influenced the free plasma level of LTG, whereas LTG slightly reduced the free plasma concentration of PB. Interactions between LTG and TPM or LTG and VPA at a fixed ratio of 1:1 might be profitable from a preclinical point of view, displaying the most optimal BI.


Illness and demographic correlates of chronic pain among a community-based sample of people with multiple sclerosis.
To investigate the prevalence, nature, and correlates of pain among a community-based sample with multiple sclerosis (MS). A cross-sectional survey and structured pain interview. Community. People with MS (N=219) recruited through systematic sampling from a randomly ordered MS society membership database. Not applicable. Pain presence or absence, pain intensity (numeric rating scales), pain quality (McGill Pain Questionnaire), pain location(s) and extent (pain drawing), pain duration and frequency, provoking and relieving pain factors, and pain management techniques. Pain was common with some 67.1% of the sample reporting pain during the 2 weeks preceding the study. Comprehensive pain assessment revealed that a substantial subset of these subjects experience chronic pain conditions characterized by moderate-to-severe pain intensity. Among those with pain, 75% reported pain in 3 or more locations, with participants reporting an average of 4.0+/-1.8 distinct pain sites. Women and people with more severe MS-related disability were significantly more likely to report both the presence of pain and greater pain intensity. In contrast, being in a married or in a de facto relationship and longer time since MS diagnosis were significantly associated with lower pain intensity. Given the high prevalence and nature of pain experienced by people with MS, health care providers need to approach pain with a priority similar to that given to other MS-related problems such as mobility and functional independence. Women and people with more severe MS-related disability appear to be at particular risk for significant pain problems and therefore these groups warrant particular attention, such that routine clinical assessment should trigger routine pain assessment.


Inspiratory muscle training on quality of life and functional capacity after hospital discharge in patients submitted to coronary artery bypass grafting: A controlled clinical trial.
There is a gap in knowledge about functional capacity and quality of life in patients undergoing coronary artery bypass grafting (CABG) after hospital discharge and the contribution of inspiratory muscle training (IMT). To evaluate the influence of IMT on functional capacity and quality of life after hospital discharge of patients undergoing CABG. Clinical trial. In the preoperative period, patients assessed maximum inspiratory pressure (MIP), quality of life using the SF-36 and functional capacity using the Six-Minute Walk Test (6MWT). On the first postoperative day, they were randomized into: control group (CG) receiving routine assistance from the hospital; intervention group(IG) in addition to conventional physical therapy and submitted to an IMT protocol based on the glycemic threshold. Being reevaluated on the day of hospital discharge and post-discharge month. 41 patients were included. In the preoperative period of the MIP assessment of the CG, it was 104 ± 14 cmH2O already in GI it was 103 ± 19cmH2O (p = 0.78) CG at discharge 80 ± 13 cmH2O already in GI it was 92 ± 15cmH2O(p < 0.01), revaluation CG 91 ± 11 cmH2O versus 98 ± 12 cmH2O (p < 0.01) of the IG. In the 6MWT the preoperative of the GC group was 420 ± 70 m already in GI it was 429 ± 71 m (p = 0,89), CG at discharge 326 ± 79 m versus 373 ± 55 m and revaluation of the CG 377 ± 75 m and IG 410 ± 57 m (p < 0.01). Functional capacity, general health status, emotional aspects and limitations due to physical aspects were significant when the three moments were compared. IMT increases functional capacity, inspiratory muscle strength and quality of life after discharge from patients undergoing CABG.


[Checking current uteroplacental circulation by placental flow measurement in normal pregnancies].
The uteroplacental circulation has a decisive influence on the growth and development of the fetus. On the basis of personal investigations in 57 women whose course of pregnancy was normal, the method of measuring placental blood flow with 113m-indium chloride is described, the results obtained are presented. The possibility of a connection between uteroplacental circulation and increasing age of the mother, as well as with gestational age, is examined.


Use of N-methyliminodiacetic acid boronate esters in suzuki-miyaura cross-coupling polymerizations of triarylamine and fluorene monomers.
Polytriarylamine copolymers can be prepared by Suzuki-Miyaura cross-coupling reactions of bis N-methyliminodiacetic acid (MIDA) boronate ester substituted arylamines with dibromo arenes. The roles of solvent composition, temperature, reaction time, and co-monomer structure were examined and (co)polymers prepared containing 9, 9-dioctylfluorene (F8), 4-sec-butyl or 4-octylphenyl diphenyl amine (TFB), and N, N'-bis(4-octylphenyl)-N, N'-diphenyl phenylenediamine (PTB) units, using a Pd(OAc)2/2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) catalyst system. The performance of a di-functionalized MIDA boronate ester monomer was compared with that of an equivalent pinacol boronate ester. Higher molar mass polymers were produced from reactions starting with a difunctionalized pinacol boronate ester monomer than the equivalent difunctionalized MIDA boronate ester monomer in biphase solvent mixtures (toluene/dioxane/water). Matrix-assisted laser desorption/ionization mass spectroscopic analysis revealed that polymeric structures rich in residues associated with the starting MIDA monomer were present, suggesting that homo-coupling of the boronate ester must be occurring to the detriment of cross-coupling in the step-growth polymerization. However, when comparable reactions of the two boronate monomers with a dibromo fluorene monomer were completed in a single phase solvent mixture (dioxane + water), high molar mass polymers with relatively narrow distribution ranges were obtained after only 4 h of reaction. © 2017 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2798-2806.


Health-related quality of life in community-dwelling men with pneumoconiosis.
There have been few data on the health-related quality of life (HRQOL) in patients with pneumoconiosis. HRQOL is an important aspect of daily living in patients with industrial diseases. To investigate the HRQOL and factors that contribute to the impairment of HRQOL in patients with pneumoconiosis. 297 patients with pneumoconiosis were recruited from a community-based case registry. The HRQOL was measured with the St. George's Respiratory Questionnaire (SGRQ). Pulmonary function, comorbidity and psychosocial variables were also assessed. Patients' mood state was evaluated with the Geriatric Depression Scale (GDS). The mean SGRQ symptom, activity, impact and total scores were 38.0 +/- 19.3, 44.5 +/- 21.9, 34.2 +/- 17.9 and 39.4 +/- 17.4, respectively. These figures were lower than those reported in patients with chronic obstructive pulmonary disease who attended chest clinics. The GDS score (r = 0.38), forced expiratory volume in 1 s predicted (FEV(1)% predicted;r = -0.33) and comorbidity (r = 0.21) were the most important predictors of the HRQOL. Besides lung functions, chest clinicians should consider the impact of mood symptoms and comorbidity on the HRQOL in the management of patients with pneumoconiosis.


Inter- versus intra-molecular cyclization of tripeptides containing tetrahydrofuran amino acids: a density functional theory study on kinetic control.
Density functional B3LYP method was used to investigate the preference of intra- and inter-molecular cyclizations of linear tripeptides containing tetrahydrofuran amino acids. Two distinct model pathways were conceived for the cyclization reaction, and all possible transition states and intermediates were located. Analysis of the energetics indicate intermolecular cyclization being favored by both thermodynamic and kinetic control. Geometric and NBO analyses were performed to explain the trends obtained along both the reaction pathways. Conceptual density functional theory-based reactive indices also show that reaction pathways leading to intermolecular cyclization of the tripeptides are relatively more facile compared to intramolecular cyclization.


Serotonin 5-HT7 receptor agonist, LP-211, exacerbates Na(+), K(+)-ATPase/Mg(2+)-ATPase imbalances in spinal cord-injured male rats.
The observed controversy that N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211), a selective serotonin (5-HT7) receptor agonist, may either modify or exacerbate imbalances in serum electrolyte concentrations and renal tissue of spinal cord trauma cases has not been reported yet. The aim of this study was to better understand the effects of a new 5-HT7 receptor agonist, LP-211, on serum electrolyte changes in spinal cord injured- (SCI) rats. Sixty male rats were assigned to the following groups: A) Intact (saline as vehicle, 1 ml/kg, i.p.), B) Intact [LP-211, (0.003-0.3 mg/kg, i.p.)], C) Sham-operated [laminectomy + vehicle (1 ml/kg, i.p.)], D) Sham-operated [laminectomy + LP-211 (0.003-0.3 mg/kg, i.p.)], E) Treatment [laminectomy + spinal trauma (SCI) + vehicle (1 ml/kg, i.p.)], F) Treatment [laminectomy + spinal trauma + LP-211 (0.003-0.3 mg/kg, i.p.)]. SCI was performed by placing an aneurysm clip, extradurally at the level of T10. After two weeks, LP-211 was administered cumulatively and each dose was injected (i.p.) with 20 min interval. At the end of the experiment, blood samples were collected for biochemical evaluations of the electrolytes employing standard commercial kits. The present results indicate elevated serum levels of Na(+), K(+), and Mg(2+) in SCI rats and significant differences demonstrated between the groups [P < 0.001, F(5, 35) = 23.92], [P < 0.001, F(5, 35) = 67.63], [P < 0.001, F(5, 35) = 71.144], respectively. So that, in groups B, D and F, there was a significant increase in K(+) and Mg(2+) serum levels compared to the groups A, C, and E (P < 0.001). Furthermore, Na(+) serum levels in SCI (LP-211), laminectomy (LP-211), and intact (LP-211) groups tended to be statistically lower than SCI (saline), laminectomy (saline) and intact (saline) groups. Infact, hyponatremia, hyperkalemia and hypermagnesemia was obtained in group F. Nevertheless, in the remaining measured serum electrolytes such as calcium (Ca(2+)), iron (Fe(2+)) and phosphorus (P(3-)), chlorine (Cl(-)), copper (Cu(+)), and zinc (Zu(+)), no significant changes were observed. It was shown that acute additive LP-211 treatments in the SCI group led to hyponatremia, hyperkalemia and hypermagnesemia, it may be stated that LP-211 treatment as a promising candidate for treating SCI complications in some systems especially urinary tract might take into consideration and further studies would be needed to clarify its benefits or drawbacks. The observed discrepancies, nevertheless; will also pose new questions. Altogether, this will ultimately contribute to further understanding the pathophysiological role regarding 5-HT7 receptor activation.


A role for Epstein-Barr viral BALF1 in facilitating tumor formation and metastasis potential.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that triggers transformation and tumorigenesis of latently infected B cells in vitro. BALF1, a Bcl-2-like EBV gene expressed in both latent and lytic stages, was recently characterized in EBV-infected cells; however, the role and function of BALF1 has remained elusive. Here, we demonstrate that BALF1 expression alters cellular morphology. Importantly, BALF1 promotes cellular transformation, with tumorigenicity assays showing larger and substantially greater numbers of tumors in BALF1 transfectant-injected mice compared to mice injected with pcDNA control transfectants. In addition, BALF1 expression increases cell survival under low-serum conditions, an effect that is attributable to suppression of apoptosis, not to promotion of cell-cycle progression. Furthermore, BALF1 transfectants exhibit markedly increased tumor metastasis in vitro and in vivo. Taken together, these findings suggest that BALF1 may be a new tumor marker for EBV diagnosis and provide a new direction for research on treatments of EBV-associated tumors.


Reactivity of Desulfovibrio gigas hydrogenase toward artificial and natural electron donors or acceptors.
A purified preparation of hydrogenase from D. gigas was inactive toward ferredoxin, flavodoxin or rubredoxin in the absence of cytochrome c3 (M.W. 13,000), in an atmosphere of hydrogen, although direct reduction of benzyl viologen or FMN was possible. The hydrogen evolution reaction from dithionite was possible with methyl viologen. The same reaction also occured with cytochrome c3 (M.W. 13,000) or cytochrome c3 (M.W. 26,000). Addition of either ferredoxin or flavodoxin did not accelerate the reaction.


Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure.
Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA.


Bacterial cellulose to reinforce urethrovesical anastomosis. A translational study.
To evaluate the efficacy of the cellulosic exopolysaccharide membrane (CEM) as a urethral reinforcement for urethrovesical anastomosis. Twenty eight rabbits were submitted to urethrovesical anastomosis with or without CEM reinforcement. The animals were divided into 4 groups: C7, CEM7, C14 and CEM14: (C= only anastomosis or CEM = anastomosis + CEM), evaluated after 7 weeks, and 14 weeks. The biointegration and biocompatibility of CEM were evaluated according to stenosis, fistula, urethral wall thickness, urethral epithelium, rate of inflammation and vascularization. Between the two experimental groups, the difference in the number of stenosis or urinary fistula was not statistically significant. The morphometric analysis revealed preservation of urethral lumen, well adhered CEM without extrusion, a controlled inflammatory process and implant vascularization. The urothelium height remained constant over time after CEM reinforcement and the membrane wall was thicker, statistically, after 14 weeks. The absence of extrusion, stenosis or urinary fistula after 14 weeks of urethrovesical anastomosis demonstrates cellulosic exopolysaccharide membrane biocompatibility and biointegration with tendency to a thicker wall.


[Validation of a knowledge-questionnaire about asthma applied to teachers of elementary school of Monterrey, Mexico].
asthma is one of the most common chronic childhood diseases; is increasing in prevalence and an important cause of school absenteeism. Previous studies have failed to evaluate knowledge about asthma among elementary school teachers worldwide because of the lack of validated questionnaires. to validate a questionnaire about asthma knowledge for elementary school teachers in Monterrey, Nuevo Leon. an observational, cross sectional, descriptive study, from February to December 2004, by applying a questionnaire to a group of elementary school teachers in Monterrey, Nuevo Leon. The questionnaire is a translation and adaptation to the questionnaire of 13 questions used to assess the knowledge about asthma among parents, according to the National Asthma Education Program of US. a total of 179 questionnaires were applied, in which 6 of the 13 questions were answered correctly by more than 90% of the teachers. The internal consistency reliability was adequate with a Cronbach a coefficient of 0.75. in order to obtain reliable data using questionnaires, these must undergo a validation process. Our questionnaire got validation because of the reliability shown according to the internal consistency analysis.


René Küss (1913-2006)-a transplant pioneer in Paris.
René Küss (1913-2006), an outstanding urologic surgeon, was one of the leading pioneers in kidney transplantation. He suggested and perfected the retroperitoneal placement of the donor kidney into the iliac fossa and its anastomosis to the iliac vessels in the early 1950s. He was one of the first to introduce an immunosuppressive regimen in kidney transplantation a decade later. Küss established the first multiple department of urology at the Paris hospitals, served as General Secretary and later as President for the Société Internationale d'Urologie from 1952 until 1985, and founded "La Société Francaise de Transplantation" as the first scientific society dedicated to transplantation medicine in Europe in 1971. Moreover, Küss was an art connoisseur and collector, an automobiliste, and a medical historian.


Depth Map for Face and Neck Deep Chemical Peel Resurfacing.
Chemical peels are applied to the face and neck to improve rhytides and the photoaged appearance of the skin. Peels can be applied to different skin depths depending on the types of chemicals, the volume of solution, and the amount of pressure or friction applied. If a peel is applied too superficially, rhytides will not be removed. If a peel is applied too deeply, scarring or hypopigmentation could occur. To create face and neck depth maps for chemical peeling, which can guide safety when removing rhytides and improving the skin's appearance. A multicenter retrospective review of records was conducted of patients who underwent phenol-croton oil peeling, from January 1, 2018, to December 31, 2018. Information was collected on facial and neck cosmetic units peeled, peel formula and strength used, outcomes, and complications. A total of 410 patients received deep peels. Two depth maps were created that corresponded to the most common patterns of deep chemical peel applications. Different areas of the face and neck are treated with different chemical peel application depths to safely improve rhytides and appearance. Depth maps are created to balance safety and efficacy.


Accurate Control of Initial Coulombic Efficiency for Lithium-rich Manganese-based Layered Oxides by Surface Multicomponent Integration.
Low initial Coulombic efficiency (ICE) is an obstacle for practical application of Li-rich Mn-based layered oxides (LLOs), which is closely related with the irreversible oxygen evolution owing to the overoxidized reaction of surface labile oxygen. Here we report a NH4 F-assisted surface multicomponent integration technology to accurately control the ICE, by which oxygen vacancies, spinel-layered coherent structure, and F-doping are skillfully integrated on the surface of treated LLOs microspheres. Though the regulation on the removed amount of labile oxygen by surface integrated structure, the ICE of LLOs cathodes can adjust from starting value to 100 %. X-ray absorption spectroscopy, refined X-ray diffraction, and scanning transmission electron microscopy show that the removed labile oxygen mainly comes from Li2 MnO3 -like structure. Even operating at a high cut-off voltage of 5 V, the capacity retention of integrated sample at 200 mA g-1 is still larger than 98 % after 100 cycles.


Isolation and identification of age-related DNA methylation markers for forensic age-prediction.
Age-prediction is an important part of forensic science. There is no available method of individual age-prediction for general forensic biological samples at crime scenes. Accumulating evidence indicates that aging resembles a developmentally regulated process tightly controlled by specific age-associated methylation exists in human genome. This study isolated and identified eight gene fragments in which the degree of cytosine methylation is significantly correlated with age in blood of 40 donors. Furthermore, we validated two CpG sites of each gene fragment and replicated our results in a general population sample of 40 males and 25 females with a wide age-range (11-72 years). The methylation of these fragments is linear with age over a range of six decades (Fragment P1 (r=-0.64), P2 (r=-0.58), P3 (r=-0.79), R1 (r=0.82), R2 (r=0.63), R3 (r=0.59), R4 (r=0.63) and R5 (r=0.62)). Using average methylation of two CpG sites from each fragment, we built a regression model that explained 95% of the variance in age and is able to predict the age of an individual with great accuracy (R(2)=0.918). The predicted values are highly correlated with the observed age in the sample (r=0.91). This study implicates that DNA methylation will be an available biological marker of age-prediction. Furthermore, measurement of relevant sites in the genome could be a tool in routine forensic screening to predict age of biological samples.


Mechanism of resistance of mice to syngeneic methylcholanthrene induced fibrosarcomas.
Mice become resistant to challenge with certain fibrosarcomas when bearing a tumor graft (concomitant immunity) or after injection of a low, non-tumorigenic dose of cells (sinecomitant immunity). Resistance to footpad challenge was depressed or abolished by treatment with carrageenan, niridazole or reserpine, or by sublethal irradiation, all of which also depressed delayed-type hypersensitivity (DTH) reactions. Immune lymphocytes initiating tumor-suppressive reactions in the feet of non-immune mice were Thy-1+, Ly-1+, Ly-2- and Ly-3-. Injection of tumor cells into the peritoneal cavities of immune mice specifically elicited an influx of macrophages. There was evidence of macrophage stimulation in tumor-immune mice. In vitro, anti-tumor effector cells lacking individual tumor specificity could be detected among the resident peritoneal cells of tumor-immune mice and among peritoneal exudate cells of non-immune mice. The expression of acquired resistance to some tumors may involve reactions akin to DTH in which a specific reaction triggers an accumulation of nonspecific effectors.


Testosterone stimulates growth of tibial epiphyseal growth plate and insulin-like growth factor-1 receptor abundance in hypophysectomized and castrated rats.
Puberty is associated with an increase in the plasma concentration of sex steroids, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Gonadal steroid hormones are important for the normal pubertal growth spurt and skeletal growth. The mechanism by which gonadal steroids induces skeletal growth is still not fully understood. To study the GH-independent effect of testosterone on growth, we investigated the effect of testosterone injections on the tibial epiphyseal growth plate (EGP) in an in vivo model of hypophysectomized and castrated male rats. Four groups (six animals each) of 28-d-old male rats were studied. Groups A, B, and C were hypophysectomized and castrated and received 500 microg/(kg x d) of hydrocortisone and 15 microg/(kg x d) of levothyroxine sodium. Groups A and B were also treated with daily sc injections of 10 microg of testosterone/100 g of body wt and 100 microg of testosterone/100 g of body wt, respectively, for 7 d. Group C was injected with vehicle alone. Group D were intact animals injected with saline (controls). Animals were sacrificed on 8 d. As expected, serum GH levels were found to be very low (1.13+/-0.1 ng/mL) in the hypophysectomized animals (group C, hypopit), and testosterone treatment did not change them significantly. Serum IGF-1 decreased from 502.9+/-13 ng/mL in group D to 167+/-41.4 ng/mL in group C (p < 0.001). Testosterone therapy had no stimulatory effect on serum IGF-1 levels in the hypopit + low-dose group (A) (220+/-94.8 ng/mL) and had an inhibitory effect in the hypopit + high-dose group (B) (39.3+/-17.5). Histomorphometric determinations demonstrated an EGP width of 472.3+/-39 microm in the intact animals but only 336.9+/-1.6 microm in the hypopit group (C) (p < 0.01). High-dose testosterone treatment (group B) significantly increased the EGP width (to 438.8+/-27.8), (p < 0.001), whereas low-dose testosterone (group A) did not. Immunohistochemistry studies revealed that the levels of IGF-1 in the EGP of the control animals were almost negligible and that testosterone did not change them. However, testosterone increased in a dose-dependent manner the abundance of IGF-1 receptor EGP. We conclude that testosterone has a direct, local, GH-independent effect on the EGP growth and IGF-1 receptor abundance.


The effects of the myosin-II inhibitor N-benzyl-p-toluene sulphonamide on fatigue in mouse single intact toe muscle fibres.
This study determined whether fatigue in skeletal muscle is primarily due to the repeated elevations of myoplasmic free calcium concentration ([Ca(2+)](i)) or to metabolite accumulation. We examined the effects of N-benzyl-p-toluene sulphonamide (BTS) which is a potent and specific inhibitor of fast muscle myosin-II on the development of fatigue in mouse flexor digitorum brevis (FDB) muscle fibres. Single intact FDB fibres were micro-injected with indo-1 to monitor changes in [Ca(2+)](i) and stimulated repeatedly for a maximum of 150 tetani or until force declined to 40%. BTS markedly reduced tetanic force but had no effect on the tetanic [Ca(2+)](i) transients. When fatigue was induced in the presence of BTS, the reduction in [Ca(2+)](i) and force transients occurred much more slowly than in the absence of BTS. The extent of force depression was similar after induction of fatigue in fibres exposed to Tyrode only or to BTS and force recovered to the same extent. The results suggest that the decrease in tetanic [Ca(2+)](i) and force caused during fatigue are due mainly to accumulated metabolic changes.


C12-Ag wire as solid-phase microextraction fiber for determination of benzophenone ultraviolet filters in river water.
In the present study, a novel approach for fabrication of solid-phase microextraction (SPME) fiber based on silver wire was proposed. 3-(Mercaptopropyl) trimethoxysilane (MPTS) was self-assembled on the silver wire by the special interaction between Ag and S, producing MPTS-Ag wire. The MPTS-Ag wire was then functionalized with dodecyltrimethoxysilane via sol-gel approach, giving C12-Ag wire. The preparation conditions were systematically optimized. The prepared fiber was then used as the SPME fiber to extract three benzophenone UV filters from the river water. The developed method showed good linearity between 0.005 and 0.200 μg mL(-1) with regression determination coefficients in the range of 0.9929-0.9988 and detection limits ranging from 0.58 to 1.86 ng mL(-1). The C12-Ag fiber exhibited good stability and long lifetime, and could be an alternative to the traditional fused silica fiber.


5-Aminomethylquinoxaline-2,3-diones. Part II: N-aryl derivatives as novel NMDA/glycine and AMPA antagonists.
Potent antagonists at the glycine-binding site of NMDA receptors, as well as dual antagonists acting also at AMPA receptors have been identified in a series of 5-arylaminomethylquinoxaline-2,3-diones. A study of the structure-activity relationship of these compounds is reported here.


A novel cell line derived from de novo acute myeloblastic leukaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta-1 protein.
A novel human leukaemia cell line, designated TMD7, was established from blast cells of a patient with de novo acute myeloblastic leukaemia with trilineage myelodysplasia (AML/TLD). As seen in the original blast cells, TMD7 cells expressed CD7, CD13, CD33 and CD34 and showed an abnormal karyotype containing -5, -7, -8, der(16)t(10;16)(q22;q13). The cells proliferated without added growth factors. Growth was stimulated with the addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and interleukin 3. Differentiation was not observed with the addition of various cytokines. As a cell line derived from AML/TLD has not been reported, TMD7 will be a useful tool as a model of AML/TLD cells. Recently, it was reported that the Notch system has crucial roles to regulate the self-renewal and differentiation of haematopoietic stem cells. We found that TMD7 cells expressed Notch-1 and Notch-2 mRNA. The exposure to recombinant Delta-1 protein, which was one of the Notch ligands, significantly stimulated the growth of TMD7 cells. This is the first human cell line which was shown to proliferate in response to Delta-1, without artificially expressed Notch protein. Therefore, TMD7 will also be a useful tool to study the mechanism of the Notch-Notch ligand interaction.


Human primordial germ cells and embryonic germ cells, and their use in cell therapy.
Human embryonic germ (hEG) cells derive from the transformation of primordial germ cells (PGCs) under appropriate culture conditions with embryonic fibroblast feeder cells. Although the pluripotent and proliferative capacity of hEG cells is thought to be equivalent to that of human embryonic stem (hES) cells, the difficulties of isolating and maintaining hEG cell lines in vitro have restricted their availability for experimental use. Despite this, some of the factors involved in PGC development, their transformation into embryonic germ cells and the differentiation of embryonic germ cells to specific cell phenotypes have been explored. The potential use of hEG cells in cell therapy applications will, however, depend on a more thorough understanding of how to derive and maintain these cells in vitro.


Surgical management of chronic calcific deposit resembling tendon sheath infection in the index finger: A rare case report and literature review.
Calcific tendonitis rarely occurs in the fingers, and it is easily misdiagnosed. Herein we describe the case of a patient with multiple calcific lesions within the flexor digitorum superficialis and the extensor digitorum tendons of the distal interphalangeal joints of the right index finger, and the surgical treatment of those lesions. The patient was a 66-year-old man who reported pain and swelling in his right index finger for one year. He was diagnosed with chronic calcific tendonitis based on his symptoms and radiology images. He was successfully treated surgically, and histopathological examination confirmed the diagnosis. After one month, the patient had healed well, and there was no recurrence. This is the first report of a patient suffering from chronic calcific tendonitis in a finger who failed conservative treatment and was successfully treated with surgery. The outcome demonstrates that surgical debridement can yield a good outcome in patients with chronic calcific tendonitis.


A novel procedure for reconstruction utilizing superficial femoral vein grafts following en bloc resection of carotid artery and head and neck malignant tumours.
The objective of our study was to investigate the effectiveness of reconstructing the carotid artery using a superficial femoral vein (SFV). Ten patients with malignant tumours involving the carotid artery underwent carotid artery resection and reconstruction with the SFV. We use the SFV between the deep femoral vein and perforator branches to the great saphenous vein or deep femoral vein at the popliteal region reconstructive vessel. The mean length and diameter of the grafted SFVs were 13.9 and 11.2 mm, respectively. The mean time for SFV acquirement was 18 min. The mean cerebral ischaemic period was 23.1 min. Nine patients did not experience any neurological complications. One patient experienced slight temporary hemiparesis. There was no postoperative vascular graft thrombosis. Donor site complications did not occur. Reconstructing the carotid artery using an SFV is very effective due to the ease in harvesting the vessel and its optimal size and length for carotid artery replacement.


Competition between mobile species using patchy resources: an example from a freshwater, symbiotic assemblage.
Three species of freshwater mites that are symbiotic with mussels in St Mark's River, north Florida, have consistently high rates of colonization to and occupy high proportions of mussels. The mites Unionicola poundsi and U. serrata are territorial and have limited numbers/host, whereas the non-territorial U. abnormipes has highly variable numbers/host. U. abnormipes and U. serrata are most common in Villosa villosa and Uniomerus declivis respectively, patterns that can not be explained by host species preferences, whereas U. poundsi is equally abundant in both host species. Field experiments showed that both U. poundsi and U. serrata were limited most by intraspecific competition between adult mites, presumably for access to food and oviposition sites. Additionally, U. serrata did not remain within small hosts, most of which were V. villosa. In contrast, numbers of U. abnormipes were limited by both other mite species although the nature of the interactions differed. U. serrata may prey on U. abnormipes when they co-occur, whereas U. poundsi probably only excludes U. abnormipes from certain areas within hosts. Hence, U. abnormipes occurs mostly in V. villosa because most of these mussels do not contain U. serrata, but even so its numbers are still depressed by U. poundsi. The results were consistent with the general expectation of Holmes and Price (1986) that parasite assemblages where species have high colonization levels should be organized primarily by biotic interactions. However, specific outcomes of competition between mites were consistent with the more general model of Levins (1979) for competition between species using variable resources. Failure of other models to apply to Unionicola pinpointed at least five key biological characters that may form a better basis of comparison than taxonomic or habitat-based contrasts.


Social correlates of total cancer in adults and the very old: UK Understanding Society Cohort, 2009-2010.
Understanding of the social determinants of cancer in adults and the very old is still limited. The aim of this study was to provide recent evidence on the social correlates of adult total cancer in a national and population-based setting. A cross-sectional study in the recent years between 2009 and 2010. Data was retrieved and analysed from the UK Longitudinal Household Survey. Information on demographics, living and work conditions, self-reported cancer and age of onset was obtained by household interview. Analyses included Chi-squared test, t-test, and multilevel logistic regression modelling. Of 50,994 people included in the cohort, 1623 (3.5%) had ever cancer. Of these, 1592 (98.0%) occurred in adulthood (16y+) and only 109 people had their first cancer (incident cancer) at the age when they were interviewed. In the middle-aged and young adults, being female (OR 1.57, 95%CI 1.20-2.06, P = 0.001 and OR 2.04, 95%CI 1.07-3.87, P = 0.03, respectively), not born in the UK (OR 0.54, 95%CI 0.34-0.88, P = 0.01 and OR 0.31, 95%CI 0.09-1.02, P = 0.05, respectively), and being obese/overweight (OR 1.49, 95%CI 1.07-2.07, P = 0.02 and OR 2.34, 95%CI 1.17-4.66, P = 0.02, respectively) were associated with total cancer. However, no associated social factors of cancer in the very old were found. Moreover, prevalence was higher in East Midlands (OR 1.73, 95%CI 1.00-3.00, P = 0.05) but not other regions, compared to London region. Social environment seems to continue playing a role in the aetiology of cancer in adults, although novel and/or pooled investigation for the very old would be warranted.


Dietary patterns and the risk of Alzheimer's disease in an elderly Iranian population: a case-control study.
An increasing number of studies in Western countries have shown that healthy eating patterns have a protective effect against cognitive decline and dementia, however, information about this relationship among non-western populations with different cultural environments is scarce. The present study investigated the association between dietary patterns (DPs) and cognitive function in the Iranian elderly. In this case-control study, the data of 290 elderly people in two groups of case and control (Mean age in case: 74.2 ± 8.6, in control: 67.3 ± 7.3 year) were analyzed. Two DPs of healthy and unhealthy were extracted from a 142-item dish-based food frequency questionnaire, and patterns driven by principal components analysis (PCA) of 25 food groups. Multivariate binary logistic regression calculated the odds ratio (OR) of cognitive impairment with adjustment for potential confounding factors. A healthy DP, characterized by high consumption of fruits and vegetables, legumes, and nuts, was related to a decrease in the odds of Alzheimer's disease in Iranian elderly people. Also, moderate adherence to an unhealthy food pattern was associated with an increase in the probability of the disease; however, the association was not statistically significant. In this elderly population, a healthy eating pattern was associated with reducing the risk of Alzheimer's disease. Further prospective studies are recommended.


Factors influencing sensorineural hearing loss in chronic otitis media.
Sensorineural hearing loss was studied in 874 chronically infected ears and was found to occur more frequently in cases of cholesteatoma and in the presence of discharge. Sensorineural hearing loss is not dependent on the type of causative microorganism. Older patients exhibited sensorineural hearing loss more often than did younger patients, this disorder being more common in affected ears than in control ears (the contralateral ear in unilateral cases).


MicroRNA let-7i Inhibits Histone Lysine Demethylase KDM5B to Halt Esophageal Cancer Progression.
Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.


Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1.
Lymphocyte enhancer factor 1 (LEF1), a member of the LEF/T-cell-specific factor (TCF) family of the high mobility group domain transcription factors, acts downstream in canonical Wnt signaling. Aberrant transactivation of LEF1 contributes to the tumorigenesis of colonic neoplasms, sebaceous skin tumors, and lymphoblastic leukemia. LEF1-associated proteins are crucial for regulating its transcriptional activity. In this study, glutathione-S-transferase pull-down assay and mass spectrometry enabled identification of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel interaction partner for LEF1. The interaction between LEF1 and DNA-PKcs was confirmed using in vivo co-immunoprecipitation. Furthermore, double immunofluorescence observations showed that LEF1 and DNA-PKcs colocalized in the nuclei of colon adenocarcinoma cell lines. Identification of the interaction between LEF1 and DNA-PKcs may provide clues for a novel therapy for cancer treatment as well as for understanding LEF1-mediated transcriptional regulation.


Safety, Mortality, and Hemodynamic Impact of Patients with MitraClip Undergoing Left Ventricular Assist Device Implantation.
The interactions and hemodynamic impact of transcatheter percutaneous mitral valve repair (TMR) have not yet been investigated in patients undergoing left ventricular assist device (LVAD) implantation, but hemodynamic adverse effects are feared in the combination of TMR and LVAD for altered mitral valve flow. This study investigated the hemodynamic interplay in combination of TMR and LVAD in 119 patients, and propensity score match analysis revealed no difference in both perioperative mortality and 2-year follow-up survival (p = 0.84). Nonetheless, postoperatively mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac index improved, and multivariable cox regression analysis at 2 years identified preoperative total bilirubin and temporary right ventricular mechanical circulatory support as independent risk factors for all-cause mortality but not TMR. Prior TMR has no impact on mortality or cardiovascular complications in patients with LVAD.


The SSV Evaluation System: A Tool to Prioritize Short Structural Variants for Studies of Possible Regulatory and Causal Variants.
Short structural variants (SSVs) are short genomic variants (<50 bp) other than SNPs. It has been suggested that SSVs contribute to many human complex traits. However, high-throughput analysis of SSVs presents numerous technical challenges. In order to facilitate the discovery and assessment of SSVs, we have developed a prototype bioinformatics tool, "SSV evaluation system," which is a searchable, annotated database of SSVs in the human genome, with associated customizable scoring software that is used to evaluate and prioritize SSVs that are most likely to have significant biological effects and impact on disease risk. This new bioinformatics tool is a component in a larger strategy that we have been using to discover potentially important SSVs within candidate genomic regions that have been identified in genome-wide association studies, with the goal to prioritize potential functional/causal SSVs and focus the follow-up experiments on a relatively small list of strong candidate SSVs. We describe our strategy and discuss how we have used the SSV evaluation system to discover candidate causal variants related to complex neurodegenerative diseases. We present the SSV evaluation system as a powerful tool to guide genetic investigations aiming to uncover SSVs that underlie human complex diseases including neurodegenerative diseases in aging.


Working memory still needs verbal rehearsal.
The causal role of verbal rehearsal in working memory has recently been called into question. For example, the SOB-CS (Serial Order in a Box-Complex Span) model assumes that there is no maintenance process for the strengthening of items in working memory, but instead a process of removal of distractors that are involuntarily encoded and create interference with memory items. In the present study, we tested the idea that verbal working memory performance can be accounted for without assuming a causal role of the verbal rehearsal process. We demonstrate in two experiments using a complex span task and a Brown-Peterson paradigm that increasing the number of repetitions of the same distractor (the syllable ba that was read aloud at each of its occurrences on screen) has a detrimental effect on the concurrent maintenance of consonants whereas the maintenance of spatial locations remains unaffected. A detailed analysis of the tasks demonstrates that accounting for this effect within the SOB-CS model requires a series of unwarranted assumptions leading to undesirable further predictions contradicted by available experimental evidence. We argue that the hypothesis of a maintenance mechanism based on verbal rehearsal that is impeded by concurrent articulation still provides the simplest and most compelling account of our results.


Diagnosis of anxiety and depression.
The differential diagnosis of anxiety and depression is often difficult as symptoms of generalized anxiety, panic disorder, and depression frequently coexist.


Tibial anterior compartment compressibility in healthy subject, measured using compression sonography.
Compression sonography has been introduced for non-invasive measurement of compartment compressibility and possible diagnostic tool for acute or chronic compartment syndrome in studies using human cadavers and animal models. To date, standard values in healthy subjects are not yet defined. The aim was to define standard compartment compressibility values in healthy human subjects and to assess the reliability of this measurement method. In 60 healthy volunteers, using ultrasound, the diameter of the tibial anterior compartment was measured while applying no pressure, 10mbar and 80mbar of external pressure. A pressure manometer on the ultrasound head was used to monitor the externally applied pressure. Compartment compressibility ratio (R0-80, respectively R10-80) was calculated as following: The delta of the compartment diameter with high and low external pressure, divided through the diameter with low external pressure. In 10 volunteers, two examinators conducted each two measurements to assess the reliability. Mean compartment compressibility ratio R10-80 was 15.9% ±3.6 (range: 7.2 - 22.2). Mean compartment compressibility ratio R0-80 was 18.2% ±5.0 (3.0 - 32.1). There was no significant correlation with lower leg circumference, height, weight, BMI, gender, hours of sport per week and type of sport (e.g. weightlifting/ cardio). For R10-80, intraobserver ICC 2.1 was 0.89 for an experienced observer and 0.79 for a non-experienced observer. Interobserver ICC 2.1 was 0.78. For R0-80, intraobserver ICC 2.1 was 0.71 for the experienced and 0.56 for the unexperienced observer. Interobserver ICC 2.1 was 0.59. In healthy volunteers between 18 and 50 years of age, mean compartment compressibility ratio R10-80 was 15.9% ±3.6, independent of demographic factors and sport activity. Application of 10mbar instead of 0mbar increased image quality. Subsequently, R10-80 showed lower standard deviation and both higher intraobserver and interobserver reliability than R0-80. Using R10-80, this measurement method is reliable with very high intra- and interobserver correlation.


Electromechanical gait training with functional electrical stimulation: case studies in spinal cord injury.
Single case studies. To describe the technique of intensive locomotor training on an electromechanical gait trainer (GT) combined with functional electrical stimulation (FES). Neurological Rehabilitation Clinic, Berlin, Germany. Four spinal cord-injured (SCI) patients, one tetraparetic, two paraparetic, and one patient with an incomplete cauda syndrome, more than 3 months postinjury, who were unable to walk at all, or with two therapists. They received 25 min of locomotor training on the GT plus FES daily for 5 weeks in addition to the regular therapy. The patients tolerated the programme well, and therapists rated the programme less strenuous compared to manually assisted treadmill training. Gait ability improved in all four patients; three patients could walk independently on the floor with the help of technical aids, and one required the help of one therapist after therapy; gait speed and endurance more than doubled, and the gastrocnemius activity increased in the patients with a central paresis. This combined technique allows intensive locomotor therapy in SCI subjects with reduced effort from the therapists. The patients' improved walking ability confirmed the potential of locomotor therapy in SCI subjects.


Behavior modification therapy in hyperactive children. Research and clinical implications.
One hundred fifty-seven studies employing behavior modification in the management of hyperactive and disruptive children were reviewed. The studies were analyzed against standards of scientific validity. The review found: (1) behavior modification was effective in alleviating problem behaviors; (2) token programs were the most commonly used; (3) both positive reinforcement and punishment were effective; positive reinforcement, however, had the advantage of improving self-esteem; (4) behavioral problems occurring in the home most likely require a home-based program; (5) behavior modification and stimulant medication can be used simultaneously, often with additive effects; and (6) long-term benefits beyond one year have not been assessed.


The impact of diet on disease activity in spondyloarthritis: A systematic literature review.
Our study aimed to systematically review the evidence about the effect of diet or dietary supplements on spondyloarthritis (SpA) disease activity. a systematic literature review (SLR) was conducted in MEDLINE, EMBASE, Cochrane and SCOPUS according to the "PEO" format (Population, Exposure, Outcome). The population was SpA (axial or peripheral, axSpA/pSpA, including Psoriatic Arthritis-PsA); the intervention any kind of diet/dietary supplement; the outcome disease activity. Inclusion criteria were: adult patients, Randomized Controlled Trials (RCTs) and longitudinal studies (so that a pre-and post-intervention assessment were available), papers in English. Risk of bias (RoB) was conducted with different tools according to the design of the study. Literature search yielded 1390 publications, of which 15 were finally inlcuded: 12 interventional and 3 observational studies. Among those with the lower RoB: a) 2 RCTs, one at unclear and one at low RoB, failed to show benefit of probiotics in SpA b) Two RCTs at unclear RoB provided evidence that weight loss, but not hypocaloric diet, was associated to MDA achievement in PsA. The remaining interventional studies were at high RoB. Among the observational studies, one study on Mediterranean diet demonstrated an association between diet adherence and a ≥ 20% decrease of ASDAS in axSpA. The other two observational studies were judged of poor quality. weight loss seem to be able to impact disease activity in PsA, while probiotics do not seem useful in SpA; evidence for dietary behaviors is scarce and heterogeneous.


Characterization of Specific RAPD Markers of Virulence in Trichomonas vaginalis Isolates.
As for human trichomoniasis the host-parasite relationship is very complex, and the broad ranges of clinical symptoms are unlikely be attributable to a single pathogenic mechanism. Specific Random Amplified Polymorphic DNA (RAPD) markers of 490 bp, 720 bp and 460 bp using the primers Tv-5, OPA-6 and OPA-11, respectively, were reported. This was the first description of possible genetic virulence markers of the infection by T. vaginalis. The aim of this study was to characterize the specific RAPD markers in order to elucidate their importance on virulence of this illness. The selected specific RAPD fragments were cloned and sequenced. The obtained sequences were compared by the BLAST algorithm. The nucleotide sequence of the Tv-5490 RAPD marker exhibited significant similarity to T. vaginalis hypothetical G3 leucine rich repeat (LRR) family protein (e-value: 6e-14) and Giardia lamblia leucine rich repeat protein 1 virus receptor protein (e-value: 6e-14 and 2e-12) ; however, the OPA-6720 and OPA-11460 showed no significant similarity with any coding published sequence. All the evaluated strains showed the presence of the LRR gene. These results demonstrate a possible role of this gene in the virulence of T. vaginalis and in the parasite infection with Trichomonas virus as a possible virus receptor. Further analysis of this gene and encoded protein will allow determining the role that they play in the isolates virus susceptible or resistant phenotypes.


Immunoautoradiographic and protein-A/gold labelling experiments for localization of pollen allergens using antisera from atopic human individuals.
Using serum from human atopic individuals with a sufficiently high titre of IgE and IgG antibodies to birch- or hazel-pollen allergens and antigens, the localization of IgE binding sites in birch- and hazel-pollen grains was determined by pre- and post-embedding electron microscopic immunoautoradiography with 125I-anti-IgE, whereas the IgG binding sites were localized in ultrathin sections of birch-pollen grains by the protein-A/gold technique. Concerning the distribution patterns of both IgE/IgG binding sites within the pollen grains, no difference could be observed in the dormant pollen grain: Labelling was found in the exine part of the pollen wall and throughout the highly condensed cytoplasm except for starch grains and lipid droplets. The intine part and the germination pores were almost completely unlabelled. In pollen grains which had been soaked in a hypotonic buffer for 15 min, however, IgE binding sites were predominantly localized within the intine and the germination pores. The specificity of the labelling reactions and the observed differences in the localization patterns are discussed.


Morphological aspects of the development of hydrocephalus in a mouse mutant (SUMS/NP).
The SUMS/NP is a mouse mutant with a recessive gene for congenital hydrocephalus. The condition is detectable outwardly at 3 days after birth and affected animals die soon after weaning. The heads of fetuses from 14 to 20 days gestation and at 1, 4, 5, 12 and 18 days after birth have been sectioned for light microscopy and the volume of the lateral ventricles measured in all but the three oldest ages. At 16 days gestation and earlier all fetuses had a relatively large lateral ventricle volume. Hydrocephalus was first detected from volume measurements at 18 days gestation and generally became progressively more severe with age. Hydrocephalic animals, in addition to lateral and third ventricle dilatation, always showed a reduction in the cross-sectional area of the cerebral aqueduct or a total absence of the aqueduct. All hydrocephalics, with the exception of two fetuses, also had cystic cavitation of the forebrain around the lateral ventricles. Electron microscopy of animals with a reduced aqueduct showed the ventral part to be absent in hydrocephalics.


Involvement of transient receptor potential vanilloid type 1 channels in the pro-convulsant effect of anandamide in pentylenetetrazole-induced seizures.
Anandamide, an endogenous agonist of CB(1) receptors, also activates TRPV1 but at a higher concentration. Studies demonstrate the anticonvulsant activity of anandamide via CB(1) receptors, while its action through TRPV1 is still ambiguous. Thus, the present study investigated the influence of anandamide on pentylenetetrazole-induced seizures in mice pretreated with TRPV1 or CB(1) receptor antagonists. Acute intracerebroventricular administration of low doses of anandamide (10, 20, or 40μg/mouse) produced anticonvulsant effect, while the pro-convulsant effect was evident at high doses (80 or 100μg/mouse). Interestingly, AM251 (2μg/mouse), a CB(1) antagonist pretreatment blocked the anticonvulsant effect, but augmented the pro-convulsant effect. Conversely, in the presence of inactive dose of capsazepine (1μg/mouse), a TRPV1 antagonist, anandamide exhibited significant anticonvulsant effect even at high doses with no change in its anticonvulsant effect. Moreover, mice treated with capsaicin, a TRPV1 agonist (10, or 100μg/mouse) exhibited pro-convulsant activity that was blocked by capsazepine pretreatment. However, capsazepine, per se at doses 10 or 100μg/mouse exhibited anticonvulsant effect. Like anandamide, the agents (AM404 and URB597), which increase its synaptic concentrations produced similar biphasic effects. Thus, these results indicate that anandamide exhibits both pro- and anticonvulsant activities by activating TRPV1 and CB(1) receptor respectively.


TAT-RasGAP317-326 Enhances Radiosensitivity of Human Carcinoma Cell Lines In Vitro and In Vivo through Promotion of Delayed Mitotic Cell Death.
The synthetic peptide TAT-RasGAP317-326 has been shown to potentiate the efficacy of anti-cancer drugs. In this study, we explored the action of TAT-RasGAP317-326 when combined with radiation by investigating its radiosensitizing activity in vitro and in vivo. To investigate the modulation of intrinsic radiosensitivity induced by TAT-RasGAP317-326, clonogenic assays were performed using four human cancer cell lines, HCT116 p53+/+ (ATCC: CCL-247), HCT116 p53-/-, PANC-1 (ATCC: CRL-1469) and HeLa (ATCC: CCL-2), as well as one nontumor cell line, HaCaT (CLS: 300493). Next, to investigate tumor growth delay after irradiation, HCT116 cell lines were selected and xenografted onto nude mice that were then treated with TAT-RasGAP317-326 alone or in combination with radiation or cisplatin. Afterwards, cell cycle and death modulation were investigated by quantification of micronuclei and apoptosis-related protein array. TAT-RasGAP317-326 radiosensitized all four human carcinoma cell lines tested but displayed no effect on normal cells. It also displayed no effect when administered as monotherapy. This radiosensitizing effect was confirmed in vivo in both p53-positive and p53-negative HCT116 xenografts. TAT-RasGAP317-326 combined with radiation enhanced the number of cells in S phase and subsequently delayed cell death, but had almost no effect on major apoptosis-related proteins. TAT-RasGAP317-326 is a radiosensitizing agent that acts on carcinoma cells and its radiosensitizing effect might be mediated, at least in part, by the enhancement of mitotic cell death.


Improving recognition of depression in primary care: a study of evidence-based quality improvement.
Depression's high prevalence and large amount of potentially modifiable morbidity make it an excellent candidate for quality improvement (QI) techniques. Yet there is little evidence on how to promote adherence to evidence-based guidelines. A locally run research and QI project that was part of a larger National Institute of Mental Health-funded study to implement depression guidelines was implemented by a primary care team at a Department of Veterans Affairs (VA) ambulatory care center in 1997 and 1998. DEVELOPMENT OF THE QI INTERVENTION: The plan to improve screening and recognition entailed systematically screening all patients attending the primary care clinic; sending computer reminders to clerical staff, nursing assistants, and primary care providers; and auditing team performance with monthly feedback. Once the intervention was in place, nearly all patients were screened. The primary care provider documented the assessment of whether a patient was depressed for nearly all patients who screened positive. Few resources were needed to maintain the project once it was implemented. An evidence-based QI intervention led to profound and lasting changes in primary care providers' recognition of depression or depressive symptoms. The QI implementation continued for one year after the intervention's end, but a new VA computerized medical record system uses similar computer-generated reminders.


Decline of a sylvatic focus of Schistosoma mansoni in Guadeloupe (French West Indies) following the competitive displacement of the snail host Biomphalaria glabrata by Ampullaria glauca.
Grand Etang lake in Guadeloupe is a focus of intestinal schistosomiasis characterized by the virtual absence of human contact and the presence of a heavily infested rat population. The lake, with a surface area of 0.03 km2, is situated in rain forest at an altitude of 450 m. Originally it contained an extensive belt of the floating plant Pistia stratiotes which provided a favourable habitat for Biomphalaria glabrata, the intermediate host snail of Schistosoma mansoni. In 1974 and 1975, a low prevalence (about 3%) of S. mansoni was observed in B. glabrata while a high prevalence (about 60%) was recorded in rats. The rat population was infected with another trematode, Ribeiroia guadeloupensis, which requires two intermediate hosts, B. glabrata and the fish Tilapia mossambica. In 1976, the prosobranch snail, Ampullaria glauca, was accidentally introduced into the lake. By 1980, this snail had spread over half of the lake and had caused marked regression of the P. stratiotes layer. Concomitantly, the population of B. glabrata declined to such a point that in 1985 only a small colony remained in the northern section of the lake. The consequences of these changes are reflected in a rapid decline of S. mansoni in the rat population from 61.3% in 1980 to 34.8% in 1981, 6.5% in 1982, 2.8% in 1983, 11.6% in 1984, and 0% in 1985 and 1986.


Effect of calcium and magnesium on binding of beta, gamma-methylene ATP to sarcoplasmic reticulum.
Isolated sarcotubular membranes (SR) from skeletal muscle bound 3.7 nmol of beta, gamma-methylene [8-3H]ATP (AMP-PCP) per mg of membrane protein. Only one class of binding site was identified and the dissociation constant (K) for this site was 1.5 X 10(-5) M. Addition of 0.05% Triton X-100 increased the number of binding sites to 5.7 nmol/mg. ATP and ADP competitively inhibited AMP-PCP binding. The dissociation constants for ATP and ADP were 3.5 X 10(-5) M and 3.3 X 10(-6) M, respectively. Since this data was obtained in the presence of 5 mM EDTA, it was established that the sarcoplasmic reticulum has a high affinity for the metal free forms of ATP, ADP, and AMP-PCP. Magnesium concentrations in excess of 1 X 10(-4) M inhibited AMP-PCP binding. Lower concentrations of magnesium had little effect on AMP-PCP binding. The effect of calcium on AMP-PCP binding was biphasic. Calcium concentration between 1 X 10(-6) and 1 X 10(-4) M inhibited AMP-PCP binding. Inhibition was maximal at 1 X 10(-5) M. Calcium concentration above 1 X 10(-4) M facilitated analogue binding. Possible sites of magnesium and calcium actions are discussed.


Evidence that enzymatic conversion of N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, a specific inhibitor of endopeptidase 24.15, to N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala is necessary for inhibition of angiotensin converting enzyme.
N-[1(R,S)-Carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) is a potent, substrate-related, specific inhibitor of endopeptidase 24.15, an enzyme involved in the metabolism of bioactive peptides including bradykinin, neurotensin, and proenkephalin, and prodynorphin-derived enkephalin precursors. The observation that this inhibitor causes a pronounced decrease in blood pressure after intravenous infusion into normotensive rats posed the question of the mechanism of this hypotensive response. It was suggested previously that cFP-AAF-pAB is an inhibitor of angiotensin converting enzyme (ACE) and that this function can account for the hypotensive response to the inhibitor. We present here evidence that cFP-AAF-pAB has no intrinsic ACE-inhibitory activity. The previously observed inhibition is shown to be dependent on cleavage of the Ala-Phe bond in the inhibitor by endopeptidase 24.11 (enkephalinase, EC 126.96.36.199), a contaminant of some ACE preparations.


Novel approaches to microalgal and cyanobacterial cultivation for bioenergy and biofuel production.
Growing demand for energy and food by the global population mandates finding water-efficient renewable resources. Microalgae/cyanobacteria have shown demonstrated capacity to contribute to global energy and food security. Yet, despite proven process technology and established net energy-effectiveness and cost-effectiveness through co-product generation, microalgal biofuels are not a reality. This review outlines novel biofilm cultivation strategies that are water-smart, the opportunity for direct energy conversion via anaerobic digestion of N2-fixing cyanobacterial biomass and integrative strategies for microalgal biodiesel and/or biocrude production via supercritical methanol-direct transesterification and hydrothermal liquefaction, respectively. Additionally, fermentation of cyanobacterial biofilms could supply bioethanol to feed wet transesterification to biodiesel conversion for on-site use in remote locations.


Relationship between ventilatory function and age in master athletes and a sedentary reference population.
Ageing is accompanied with a decline in respiratory function. It is hypothesised that this may be attenuated by high physical activity levels. We performed spirometry in master athletes (71 women; 84 men; 35-86 years) and sedentary people (39 women; 45 men; 24-82 years), and calculated the predicted lung age (PLA). The negative associations of age with forced expiratory volume in 1 s (FEV1; 34 mL·year(-1)) and other ventilatory parameters were similar in controls and master athletes. FEV1pred was 9 % higher (P < 0.005) and PLA 15 % lower (P = 0.013) in athletes than controls. There were no significant differences between endurance and power athletes and sedentary people in maximal inspiratory and expiratory pressure. Neither age-graded performance nor weekly training hours were significantly related to lung age. Life-long exercise does not appear to attenuate the age-related decrease in ventilatory function. The better respiratory function in master athletes than age-matched sedentary people might be due to self-selection and attrition bias.


Biweekly dose-dense gemcitabine-oxaliplatin and dexamethasone for relapsed/refractory aggressive non-Hodgkin lymphoma: A multicenter, single-arm, phase II trial.
We performed a phase II study to evaluate the efficacy of combination chemotherapy consisting of gemcitabine, dexamethasone and oxaliplatin (GemDOx) as a biweekly regimen and salvage therapy in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Gemcitabine (1000 mg/m(2) ) and oxaliplatin (85 mg/m(2) ) were administered intravenously on days 1 and 15, and dexamethasone (40 mg) was administered orally on days 1-4. Twenty-nine patients were enrolled, and most patients had diffuse large B-cell lymphoma (n = 18). The median age of the patients and median prior number of chemotherapy cycles were 53 (range, 26-74) years and 1 (range, 1-4) cycle, respectively. Only 17 (58.6%) and 9 (31.0%) patients completed two or more and four or more cycles, respectively, and the median number of received cycles was two (range, 1-8). Overall response rates were 27.6% (complete response in 13.8%) among intent-to-treat patients and 47.1% (complete response in 23.5%) among patients who had received at least two GemDOx cycles. Median progression-free survival and median overall survival were 3.9 and 20.5 months, respectively. The most-frequent grade 3 or 4 toxicity was neutropenia (22.9%), and no grade 3 or 4 peripheral neurotoxicity was noted. GemDOx chemotherapy, therefore, showed modest activity against relapsed or refractory aggressive NHL, although toxicities were acceptable.


Fight or flight? Dream content during sleepwalking/sleep terrors vs. rapid eye movement sleep behavior disorder.
Dreams enacted during sleepwalking or sleep terrors (SW/ST) may differ from those enacted during rapid eye movement sleep behavior disorder (RBD). Subjects completed aggression, depression, and anxiety questionnaires. The mentations associated with SW/ST and RBD behaviors were collected over their lifetime and on the morning after video polysomnography (PSG). The reports were analyzed for complexity, length, content, setting, bizarreness, and threat. Ninety-one percent of 32 subjects with SW/ST and 87.5% of 24 subjects with RBD remembered an enacted dream (121 dreams in a lifetime and 41 dreams recalled on the morning). These dreams were more complex and less bizarre, with a higher level of aggression in the RBD than in SW/ST subjects. In contrast, we found low aggression, anxiety, and depression scores during the daytime in both groups. As many as 70% of enacted dreams in SW/ST and 60% in RBD involved a threat, but there were more misfortunes and disasters in the SW/ST dreams and more human and animal aggressions in the RBD dreams. The response to these threats differed, as the sleepwalkers mostly fled from a disaster (and 25% fought back when attacked), while 75% of RBD subjects counterattacked when assaulted. The dreams setting included their bedrooms in 42% SW/ST dreams, though this finding was exceptional in the RBD dreams. Different threat simulations and modes of defense seem to play a role during dream-enacted behaviors (e.g., fleeing a disaster during SW/ST, counterattacking a human or animal assault during RBD), paralleling and exacerbating the differences observed between normal dreaming in nonrapid eye movement (NREM) vs rapid eye movement (REM) sleep.


Genetic variation in brown trout Salmo trutta across the Danube, Rhine, and Elbe headwaters: a failure of the phylogeographic paradigm?
Brown trout Salmo trutta have been described in terms of five major mtDNA lineages, four of which correspond to major ocean basins, and one, according to some authors, to a distinct taxon, marbled trout Salmo marmoratus. The Atlantic and Danubian lineages of brown trout meet in a poorly documented contact zone in Central Europe. The natural versus human mediated origin of the Atlantic lineage in the upper Danube is a question of both theoretical and practical importance with respect to conservation management. We provide a comprehensive population genetic analysis of brown trout in the region with the aim of evaluating the geographic distribution and genetic integrity of these two lineages in and around their contact zone. Genetic screening of 114 populations of brown trout across the Danube/Rhine/Elbe catchments revealed a counter-intuitive phylogeographic structure with near fixation of the Atlantic lineage in the sampled portions of the Bavarian Danube. Along the Austrian Danube, phylogeographic informative markers revealed increasing percentages of Danube-specific alleles with downstream distance. Pure Danube lineage populations were restricted to peri-alpine isolates within previously glaciated regions. Both empirical data and simulated hybrid comparisons support that trout in non-glaciated regions north and northeast of the Alps have an admixed origin largely based on natural colonization. In contrast, the presence of Atlantic basin alleles south and southeast of the Alps stems from hatchery introductions and subsequent introgression. Despite extensive stocking of the Atlantic lineage, little evidence of first generation stocked fish or F1 hybrids were found implying that admixture has been established over time. A purely phylogeographic paradigm fails to describe the distribution of genetic lineages of Salmo in Central Europe. The distribution pattern of the Atlantic and Danube lineages is extremely difficult to explain without invoking very strong biological mechanisms.The peri-alpine distribution of relict populations of pure Danubian lineage brown trout implies that they colonized headwater river courses post-glacially ahead of the expansion of the Atlantic lineage. The recognition of natural as opposed to anthropogenic introgression of the Atlantic lineage into Danubian gene pools is of fundamental importance to management strategies.


The relocation and road transfer of intensive care patients to a new hospital in Bristol: Our experiences.
In May 2014, North Bristol NHS Trust merged its two existing hospitals - Southmead and Frenchay - into a new, purpose-built building. The project involved the movement of 540 patients, many over a distance of several miles. We describe the planning process and transfer of 24 level two and three patients from two intensive care units into the new hospital. These transfers were performed successfully, without significant incident and under intense scrutiny from the Trust, the patients and the media. In this paper, we reflect upon our experiences of this process, which may be of benefit to those encountering a similar move in the future.


Need for frequent dilations after magnetic sphincter augmentation: an assessment of associated factors and outcomes.
Dysphagia is the most common complaint after magnetic sphincter augmentation (MSA), with nearly one-third of patients requiring at least one dilation following MSA. A subset of patients require frequent dilations, but there is a paucity of data on the characteristics of this population. This study aimed to identify predictors of the need for frequent dilations within the first year after implant and to assess these patients' outcomes. This is a retrospective review of prospectively collected data of patients who underwent MSA over an 8-year period. Frequent dilations were defined as 2 or more dilations within 1 year of surgery. Patients completed baseline and 1-year postoperative GERD-HRQL questionnaires and objective physiology testing. Baseline demographic, clinical characteristics, and objective testing data were compared between patients who did and did not require frequent dilations. A total of 697 (62.7% female) patients underwent MSA, with 62 (8.9%) patients requiring frequent dilation. At a mean (SD) of 12.3 (3.4) months follow-up, the frequent dilation group had higher median GERD-HRQL total scores (21.0 vs. 5.0, p < 0.001), PPI use (20.8% vs.10.1%, p = 0.023), dissatisfaction (46.7% vs. 11.6%, p < 0.001), and device removal (25.8% vs. 2.2%, p < 0.001) rates. Acid normalization was comparable (p = 0.997). Independent predictors of frequent dilation included preoperative odynophagia (OR 2.85; p = 0.001), IRP > 15 mmHg (OR 2.88; p = 0.006), and > 30% incomplete bolus clearance (OR 1.94; p = 0.004). At a mean (SD) of 15.7 (10.7) months, 28 (45.1%) patients underwent device removal after frequent dilation. Independent predictors of device removal after frequent dilation within 5 years of surgery were preoperative odynophagia (OR 7.18; p = 0.042), LES resting pressure > 45 mmHg (OR 28.5; p = 0.005), and ≥ 10% failed swallows (OR 23.5; p < 0.001). The need for frequent dilations after MSA is a marker for poor symptom control, dissatisfaction, and device removal. Patients with preoperative odynophagia, high LES pressures, and poor esophageal motility should be counseled of their risk for these poor outcomes.


Development and evaluation of high-resolution melting curve analysis for rapid detection and subtyping of Blastocystis and comparison the results with sequencing.
Blastocystis is a prevalent parasite that has a wide distribution. In order to design HRM real-time PCR, primers were selected from SSU rRNA gene to amplify specific fragment with different melting temperatures for each subtype of Blastocystis. Subsequently, HRM real-time PCR was performed and melting curve analysis was done by Rotor-Gene Q software. The results of HRM real-time PCR was then compared with sequence results of "barcoding region" of SSU rRNA gene of Blastocystis. To evaluate sensitivity of test, 10-fold serial dilutions of the parasite were prepared from ~ 106 to 1 parasite per mL of stool sample and were investigated by HRM real-time PCR. In order to determine specificity of method, HRM real-time PCR was done for some microorganisms and Blastocystis-negative stool samples. In silico analysis showed that all seventeen subtypes of Blastocystis were distinguish. In vitro analysis revealed that the test discriminated subtypes with specific melting temperatures.


Clinical characteristics of patients with takotsubo syndrome recurrence: An observational study with long-term follow-up.
Research investigating takotsubo syndrome (TTS) recurrence yielded conflicting results. Aim of the present study is to describe clinical characteristics of patients with TTS recurrence in a cohort with available long-term follow-up. The study population included 234 TTS patients enrolled in a prospective multicenter registry, median follow-up of 1328 (407, 2526) days. To investigate factors associated with TTS recurrence, we analyzed patients with recurrence (Group A) in comparison with a subgroup of TTS patients within the whole population (group B) who had similar age, sex and median follow-up length (Group A 2280 days vs Group B 2361 days). We observed 9 TTS recurrences affecting 8 patients, all women, with a rate of 0.9% patients/year. Median time to first recurrence was 1593 days (interquartile range: 950, 2516). We detected no significant differences between patients with and without recurrences regarding cardiovascular risk factors, symptoms, ECG and echocardiographic findings at presentation, discharge therapy. Physical trigger and chronic obstructive pulmonary disease (COPD) were more prevalent in patients who experienced a recurrence (75% vs 27% and 50% vs 14% with p = 0.01 and p = 0.022 respectively). Univariable Cox regression analysis identified physical trigger and history of COPD to be both associated with TTS recurrence [hazard ratio (HR) 11.4, 95% confidence interval (CI) 2.29-56.8, p = 0.003 and HR 4.94, 95% CI 1.16-20.99 p = 0.031 respectively]. TTS recurrence is relatively uncommon. Association with physical trigger and COPD would suggest a closer follow-up in this subgroup of patients.


Body Mass Index, the Most Widely Used But Also Widely Criticized Index: Would a Criterion Standard Measure of Total Body Fat Be a Better Predictor of Cardiovascular Disease Mortality?
To examine whether an accurate measure (using a criterion standard method) of total body fat would be a better predictor of cardiovascular disease (CVD) mortality than body mass index (BMI). A total of 60,335 participants were examined between January 1, 1979, and December 31, 2003, and then followed-up for a mean follow-up period of 15.2 years. Body mass index was estimated using standard procedures. Body composition indices (ie, body fat percentage [BF%], fat mass index [FMI], fat-free mass [FFM], and FFM index [FFMI]) were derived from either skinfold thicknesses or hydrostatic weighing. For exact comparisons, the indices studied were categorized identically using sex-specific percentiles. Compared with a medium BMI, a very high BMI was associated with a hazard ratio (HR) of 2.7 (95% CI, 2.1-3.3) for CVD mortality, which was a stronger association than for BF% or FMI (ie, HR, 1.6; 95% CI, 1.3-1.9 and HR, 2.2; 95% CI, 1.8-2.7, respectively). Compared with a medium FFMI, a very high FFMI was associated with an HR of 2.2 (95% CI, 1.7-2.7) for CVD mortality, with these estimates being markedly smaller for FFM (ie, HR, 1.2; 95% CI, 0.9-1.6). When the analyses were restricted only to the sample assessed with hydrostatic weighing (N=29,959, 51.7%), the results were similar, with even slightly larger differences in favor of BMI (ie, HR, 3.0; 95% CI, 2.2-4.0) compared with BF% and FMI (ie, HR, 1.5; 95% CI, 1.2-1.9 and HR, 2.1; 95% CI, 1.6-2.7, respectively). We estimated Harrell's c-index as an indicator of discriminating/predictive ability of these models and observed that the c-index for models including BMI was significantly higher than that for models including BF% or FMI (P<.005 for all). The simple and inexpensive measure of BMI can be as clinically important as, or even more than, total adiposity measures assessed using accurate, complex, and expensive methods. Physiological explanations for these findings are discussed.


Clot Lysis Time Predicts Stroke During Anticoagulant Therapy in Patients with Atrial Fibrillation.
Formation of dense fibrin clots has been reported in both atrial fibrillation (AF) and ischemic stroke. We have previously demonstrated that such clot properties can predict thromboembolism and major bleeding in AF patients treated with vitamin K antagonists (VKAs). In this longitudinal cohort study, we evaluated whether impaired fibrinolysis is associated with clinical outcomes in AF. In 236 patients with AF receiving VKAs, we measured ex vivo plasma clot lysis time (CLT), a measure of global fibrinolysis along, with von Willebrand factor antigen (vWF), plasminogen activator inhibitor 1 antigen (PAI-1), and other fibrinolysis modulators. The primary outcome were ischemic cerebrovascular events. Secondary end points were death and major bleeding. During a median follow-up time of 4.3 (interquartile range 3.7-4.8) years, annual rates of death, ischemic cerebrovascular events, and major bleeding were 1.48%, 2.96%, and 3.45%, respectively. Patients with CLT in the fourth quartile (> 115 min) had 8-fold higher stroke or transient ischemic attack (TIA) rates compared with the other patients (8.67% vs 1.1%; P < 0.0001). CLT correlated with PAI-1 and vWF (r = 0.59; P < 0.0001 for both). In the multivariate Cox regression analysis adjusted for potential confounders, the independent predictors of stroke or TIA were CLT > 115 minutes (hazard ratio [HR] 7.67, 95% confidence interval [CI] 2.78-21.17; P < 0.0001), PAI-1 (HR 1.16, 95% 1.05-1.28; P = 0.003), and CHA2DS2-VASc score ≥3 (HR 5.18, 95% 1.76-15.29; P = 0.003). CLT was not associated with death or major and minor bleeding events. Impaired fibrinolysis may predict thromboembolic events in AF patients receiving VKA.


Liquids with High Compressibility.
Compressibility is a fundamental property of all materials. For fluids, that is, gases and liquids, compressibility forms the basis of technologies such as pneumatics and hydraulics and determines basic phenomena such as the propagation of sound and shock waves. In contrast to gases, liquids are almost incompressible. If the compressibility of liquids could be increased and controlled, new applications in hydraulics and shock absorption could result. Here, it is shown that dispersing hydrophobic porous particles into water gives aqueous suspensions with much greater compressibilities than any normal liquids such as water (specifically, up to 20 times greater over certain pressure ranges). The increased compressibility results from water molecules being forced into the hydrophobic pores of the particles under applied pressure. The degree of compression can be controlled by varying the amount of porous particles added. Also, the pressure range of compression can be reduced by adding methanol or increased by adding salt. In all cases, the liquids expand back to their original volume when the applied pressure is released. The approach shown here is simple and economical and could potentially be scaled up to give large amounts of highly compressible liquids.


Application of thiazole dyes to amyloid under conditions of direct cotton dyeing: correlation of histochemical and chemical data.
The fluorescent brightening agent Phorwhite (Blankophor) BBU imparts intense selective fluorescence to amyloid, but this modern reagent is no longer readily available on the biological dye market. Conventional Thioflavine S and T stains require differentiation and are not specific. To improve selectivity, direct and cationic thiazole dyes were substituted in the alkaline Congo Red and the Phorwhite BBU procedure. With the former technic Diphenyl Brilliant Yellow 8G, Clayton Yellow, Thiazol Yellow, Thioflavine T and Seto Flavine T imparted strong to intense selective fluorescence to amyloid. Under the conditions of the Phorwhite BBU reaction these dyes were suitable only for formalin-fixed amyloid. Several thiazole dyes did not fluoresce. Fluorescence is a function of the molecular orbital system, the thiazole rings per se cannot induce fluorescence. Paper chromatograms indicated two or more fractions in the dyes studied. Different samples of the same dye can vary significantly in their staining and fluorescence properties. This heterogeneity is inherent in the mode of synthesis. In some cases the cationic thiazole dyes rendered certain amyloid deposits, e.g. in vessel walls, intensely fluorescent; other amyloid deposits in the same sections showed only weak fluorescence. Further studies are required to correlate these peculiar patterns with immunological data on amyloid types.