0-π phase-controllable thermal Josephson junction.
Two superconductors coupled by a weak link support an equilibrium Josephson electrical current that depends on the phase difference ϕ between the superconducting condensates. Yet, when a temperature gradient is imposed across the junction, the Josephson effect manifests itself through a coherent component of the heat current that flows opposite to the thermal gradient for |ϕ| < π/2 (refs 2-4). The direction of both the Josephson charge and heat currents can be inverted by adding a π shift to ϕ. In the static electrical case, this effect has been obtained in a few systems, for example via a ferromagnetic coupling or a non-equilibrium distribution in the weak link. These structures opened new possibilities for superconducting quantum logic and ultralow-power superconducting computers. Here, we report the first experimental realization of a thermal Josephson junction whose phase bias can be controlled from 0 to π. This is obtained thanks to a superconducting quantum interferometer that allows full control of the direction of the coherent energy transfer through the junction. This possibility, in conjunction with the completely superconducting nature of our system, provides temperature modulations with an unprecedented amplitude of ∼100 mK and transfer coefficients exceeding 1 K per flux quantum at 25 mK. Then, this quantum structure represents a fundamental step towards the realization of caloritronic logic components such as thermal transistors, switches and memory devices. These elements, combined with heat interferometers and diodes, would complete the thermal conversion of the most important phase-coherent electronic devices and benefit cryogenic microcircuits requiring energy management, such as quantum computing architectures and radiation sensors.


Using an online viewing system for Parent-Child Interaction therapy consulting with professionals.
Parent-Child Interaction Therapy (PCIT) training was provided to therapists working with parents of children with disruptive behavior problems. Therapists uploaded video-recordings of selected sessions using a web-based tool for video sharing and review, the Video Analysis Tool (VAT). Trainers utilized the VAT for consultation to improve treatment fidelity. Clinical practice benefits include the ability to provide targeted, specific feedback to the trainees soon after a session and to disseminate PCIT to a larger, global audience.


Off-site determinations of effective renal plasma flow using technetium-99m-MAG3 and single blood sampling.
This study evaluated the feasibility of determining effective renal plasma flow (ERPF) at an off-site central laboratory by transferring blood samples from the on-site laboratory. Blood samples were obtained from 66 patients referred for renal imaging with 99mTc-MAG3. ERPF values were determined using the single blood sample method (BSM) at both on- and off-site laboratories. The ERPF values were classified clinically as normal or abnormal. Both the ERPF values and clinical classification were compared between on- and off-site laboratories. The off-site ERPF overestimated those on-site by 2.8% (paired Student's t-test p < 10(-5)). However, off-site ERPF values highly correlated with the values obtained on-site (r = 0.99; p < 10(-5)). In addition, the clinical classification for each patient determined at each site was identical. ERPF can be determined accurately off-site. This method should allow many nuclear medicine departments access to the ERPF determination by the BSM at a central off-site laboratory.


Characterization of a novel mouse model of multiple myeloma and its use in preclinical therapeutic assessment.
To aid preclinical development of novel therapeutics for myeloma, an in vivo model which recapitulates the human condition is required. An important feature of such a model is the interaction of myeloma cells with the bone marrow microenvironment, as this interaction modulates tumour activity and protects against drug-induced apoptosis. Therefore NOD/SCIDγc(null) mice were injected intra-tibially with luciferase-tagged myeloma cells. Disease progression was monitored by weekly bioluminescent imaging (BLI) and measurement of paraprotein levels. Results were compared with magnetic resonance imaging (MRI) and histology. Assessment of model suitability for preclinical drug testing was investigated using bortezomib, melphalan and two novel agents. Cells engrafted at week 3, with a significant increase in BLI radiance occurring between weeks 5 and 7. This was accompanied by an increase in paraprotein secretion, MRI-derived tumour volume and CD138 positive cells within the bone marrow. Treatment with known anti-myeloma agents or novel agents significantly attenuated the increase in all disease markers. In addition, intra-tibial implantation of primary patient plasma cells resulted in development of myeloma within bone marrow. In conclusion, using both myeloma cell lines and primary patient cells, we have developed a model which recapitulates human myeloma by ensuring the key interaction of tumour cells with the microenvironment.


[Combined therapy of psoralen plus ultraviolet A followed by narrow band ultraviolet B photochemotherapy for early stage mycosis fungoides].
Only a few clinical reports in the treatment of early mycosis fungoides (MF)(IA, IB, IIA stage) are available in the literature. The purpose of this study was to compare the efficacy and safety of narrow-band UVB and psoralen plus ultraviolet A (PUVA) photochemoterapy in 24 patients with early-stage MF, and explore a new approach for the treatment of early mycosis fungoides. A total of 24 identified early mycosis fungoides patients received PUVA, NB-UVB and a combined therapy of PUVA followed by NB-UVB (n = 9/6/9) irradiation. A retrospective study was carried out to analyze the sex, age of onset, TNM stage, treatment, and duration of treatment, and times of treatment, duration of maintenance treatment, effective and recurrence in these patients. The data were analyzed using SPSS 17.0 and a two-sided test at the α = 0.05 level of significance was conducted. Of the 24 patients studied, the average treatment was 104.5 (95% CI, 75.71-133.29) times. The average duration of treatment was 12.88 (95% CI, 9.90-15.85) months. The average maintenance treatment time was 11.08 (95% CI, 2.13-20.04) months. The effective rate (CR+PR) of PUVA treatment was 88.9%, recurrence rate was 11.1% (n = 9). In the NB-UVB treatment group, the effective rate was 100.0%, and the recurrence rate was 33.3% (n = 6). In the PUVA followed by NB-UVB (combination therapy) treatment group, the effective rate was 77.8% and the recurrence rate was 55.6% (n = 9). There were no significant differences among the three groups in terms of number of treatments, treatment duration, maintenance treatment duration, effective rate and recurrence rate (P > 0.05). PUVA and NB-UVB are effective and safe in the targeted therapy of early stage mycosis fungoides. The combined therapy of PUVA followed by NB-UVB can reduce the total PUVA dose and risk of developing skin cancer.


[Primary malignant melanoma of the esophagus].
We report two cases of primary malignant melanoma of the esophagus. Both were female, 83 and 68 years of age. Both had metastatic spread of the disease at the time of first treatment, either in regional lymph nodes or organ involvement. One patient underwent resection of the tumor (partial esophagectomy). The second patient is alive 22 months postoperatively with metastatic tumor (12/1989), the first died one year after diagnosis. Prognosis of primary melanoma of the esophagus is poor. Though, resection of the tumor is the most promising therapy.


Heterozygote galactocerebrosidase (GALC) mutants have reduced remyelination and impaired myelin debris clearance following demyelinating injury.
Genome-wide association studies are identifying multiple genetic risk factors for several diseases, but the functional role of these changes remains mostly unknown. Variants in the galactocerebrosidase (GALC) gene, for example, were identified as a risk factor for Multiple Sclerosis (MS); however, the potential biological relevance of GALC variants to MS remains elusive. We found that heterozygote GALC mutant mice have reduced myelin debris clearance and diminished remyelination after a demyelinating insult. We found no histological or behavioral differences between adult wild-type and GALC +/- animals under normal conditions. Following exposure to the demyelinating agent cuprizone, however, GALC +/- animals had significantly reduced remyelination during recovery. In addition, the microglial phagocytic response and elevation of Trem2, both necessary for clearing damaged myelin, were markedly reduced in GALC +/- animals. These altered responses could be corrected in vitro by treatment with NKH-477, a compound discovered as protective in our previous studies on Krabbe disease, which is caused by mutations in both GALC alleles. Our data are the first to show remyelination defects in individuals with a single mutant GALC allele, suggesting such carriers may have increased vulnerability to myelin damage following injury or disease due to inefficient myelin debris clearance. We thus provide a potential functional link between GALC variants and increased MS susceptibility, particularly due to the failure of remyelination associated with progressive MS. Finally, this work demonstrates that genetic variants identified through genome-wide association studies may contribute significantly to complex diseases, not by driving initial symptoms, but by altering repair mechanisms.


Experience Within the Emergency Department and Improved Productivity for First-Year Residents in Emergency Medicine and Other Specialties.
Resident productivity is an important educational and operational measure in emergency medicine (EM). The ability to continue effectively seeing new patients throughout a shift is fundamental to an emergency physician's development, and residents are integral to the workforce of many academic emergency departments (ED). Our previous work has demonstrated that residents make gains in productivity over the course of intern year; however, it is unclear whether this is from experience as a physician in general on all rotations, or specific to experience in the ED. This was a retrospective cohort study, conducted in an urban academic hospital ED, with a three-year EM training program in which first-year residents see new patients ad libitum. We evaluated resident shifts for the total number of new patients seen. We constructed a generalized estimating equation to predict productivity, defined as the number of new patients seen per shift, as a function of the week of the academic year, the number of weeks spent in the ED, and their interaction. Off-service residents' productivity in the ED was analyzed in a secondary analysis. We evaluated 7,779 EM intern shifts from 7/1/2010 to 7/1/2016. Interns started at 7.16 (95% confidence interval [CI] [6.87 - 7.45]) patients per nine-hour shift, with an increase of 0.20 (95% CI [0.17 - 0.24]) patients per shift for each week in the ED, over 22 weeks, leading to 11.5 (95% CI [10.6 - 12.7]) patients per shift at the end of their training in the ED. The effects of the week of the academic year and its interaction with weeks in the ED were not significant. We evaluated 2,328 off-service intern shifts, in which off-service residents saw 5.43 (95% CI [5.02 - 5.84]) patients per nine-hour shift initially, with 0.46 additional patients per week in the ED (95% CI [0.25 - 0.68]). The weeks of the academic year were not significant. Intern productivity in EM correlates with time spent training in the ED, and not with experience on other rotations. Accordingly, an EM intern's productivity should be evaluated relative to their aggregate time in the ED, rather than the time in the academic year.


Parental burnout among Somali mothers: Associations with mental health, perceived social support, and sociodemographic factors.
Parenthood can be defined by the contradiction that it is one of the most satisfying yet stressful experiences in life. Many parents experience stress during parenthood, and some to the extent that they display symptoms of parental burnout. Nevertheless, research on parental burnout is scant and many studies have only examined the condition in Western settings. The aim of this study was to examine parental burnout among Somali mothers in Mogadishu, Somalia, and its association with certain psychological, psychosocial, and sociodemographic factors. In this cross-sectional study, questionnaire data were collected through the measurements Parental Burnout Assessment and Patient Health Questionnaire 9, as well as through social and demographic questions. A total of 882 Somali mothers in Mogadishu participated. The analysis methods used were univariate, bivariate, and multiple linear regression analysis. The results revealed that the mean parental burnout score was low in the sample. Additionally, a significant association was found between higher levels of parental burnout and higher levels of depression, perceived lack of social support, being unmarried, having a low monthly household income, and when the youngest child was of school-age.


Comprehensive taxonomic, faunistic, biological, and geographic inventory and analysis of the Sciomyzidae (Diptera: Acalyptratae) of the Delmarva region and nearby states in eastern North America.
Genera and species of Sciomyzidae known from the Delmarva region (Delaware, the District of Columbia, Maryland, Virginia, and West Virginia) and nearby states are reviewed taxonomically, faunistically, biologically, and geographically. Although restricted to the taxa in that area, this work amounts to a revision of the sciomyzid fauna of that portion of the Nearctic region. Treated are 91 species in 19 genera, i.e. 46% of the 199 species and all but four of the 23 genera of Sciomyzidae known from the Nearctic Region. Included are 67 species in 16 genera from Delmarva and 24 other species in 10 genera from nearby states. Euthycera flavescens (Loew) is resurrected; Renocera cressoni Mathis and Knutson sp. nov. is described from eastern North America; R. amanda Cresson is given new status as a junior synonym of R. longipes (Loew); and Chaetomacera brevis Cresson, R. cyathiformis Melander, R. pacifica Curran, and R. bergi Steyskal are given new status as junior synonyms of R. striata (Meigen). Newly diagnosed are taxonomic categories ranging from family to species level, including the first diagnoses of abdomens of females of many species, where known. Provided for each genus and species are annotated taxonomic/nomenclatorial catalogs of all North American references to all species, with generic combinations noted, with previously unrecorded synonymies as well as North American literature references, illustrations, and information on natural history and morphology of immature stages. Results of cross-mating studies of Dictya are reported and discussed. Provided are label data from examined specimens, lists of Canadian provinces and U.S. states from which reviewed species have been recorded, and detailed maps of geographical distribution of species in Delmarva, with references to previously published maps.


Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells.
Stem cells drive embryonic and fetal development. In several adult tissues, they retain the ability to self-renew and differentiate into a variety of specialized cells, thus contributing to tissue homeostasis and repair throughout life span. Alcohol consumption is associated with an increased risk for several diseases and conditions. Growing and developing tissues are particularly vulnerable to alcohol's influence, suggesting that stem- and progenitor-cell function could be affected. Accordingly, recent studies have revealed the possible relevance of alcohol exposure in impairing stem-cell properties, consequently affecting organ development and injury response in different tissues. Here, we review the main studies describing the effects of alcohol on different types of progenitor/stem cells including neuronal, hepatic, intestinal and adventitial progenitor cells, bone-marrow-derived stromal cell, dental pulp, embryonic and hematopoietic stem cells, and tumor-initiating cells. A better understanding of the nature of the cellular damage induced by chronic and episodic heavy (binge) drinking is critical for the improvement of current therapeutic strategies designed to treat patients suffering from alcohol-related disorders.


Novel technology for the preparation of sterile alginate-poly-l-lysine microcapsules in a bioreactor.
The purpose of this study was to develop a method that may be suitable for the commercial manufacture of sterile alginate-polylysine-alginate microcapsules in a bioreactor. A Turbotak atomizing device in conjunction with a Bellco Bioreactor was used to prepare sterile microcapsules. Aseptic procedures were followed using sterilized equipment and materials. Sodium alginate solution was sprayed into calcium chloride solution using the Turbotak, with nitrogen as the atomizing gas. The resultant gelled alginate microcapsules were coated with polylysine and alginate to produce alginate-poly-l-lysine microcapsules. In-process contamination of the atomizing gas and microcapsules was investigated using modified USP sterility tests. Microcapsule size was determined using a light blockage technique (Accusizer) which measures both number and volume weighted mean diameters. The microcapsules prepared passed a modified USP sterility test, and the Bellco Bioreactor was found to minimize the possibilities of environmental contamination and therefore enhanced operator safety. The flow rate of the atomizing gas was determined to significantly alter number and volume weighted mean microcapsule diameters. Statistical analysis indicated that the number weighted mean diameters in conjunction with the volume weighted mean diameters can be used to detect batch-to-batch changes in microcapsule diameters. In conclusion, the modified Bellco Bioreactor offers a novel approach for producing sterile alginate-polylysine microcapsules on a laboratory scale.


Gingerol activates noxious cold ion channel TRPA1 in gastrointestinal tract.
TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies. The intracellular calcium and secretion of serotonin or cholecystokinin were measured by fura-2/AM and ELISA. Stimulation of those cells with gingerol increased intracellular calcium levels and the serotonin or cholecystokinin secretion. The gingerol-induced intracellular calcium increase and secretion (serotonin or cholecystokinin) release were completely blocked by ruthenium red, EGTA, and TRPA1-specific siRNA. In summary, our results suggested that gingerol derived from ginger might improve the digestive function through secretion releasing from endocrine cells of the gut by inducing TRPA1-mediated calcium influx.


Role Of Clamping Tube Thoracostomy Prior To Removal In Non-Cardiac Thoracic Trauma.
The frequently encountered thoracic trauma in surgical emergencies is a major cause of mortality and morbidity. Eighty percent of thoracic trauma can be managed by simple insertion of tube thoracostomy. Though guidelines for insertion are comprehensively explained in literature, an ideal algorithm for discontinuation is not available. A standard and safe defined protocol would eliminate hesitancy in confident removal among general surgeons. The objective of this study was to determine role of clamping trial prior to removal in terms of frequency of recurrent pneumothorax. This study was conducted in department of Surgery Combined military hospital/Military Hospital Rawalpindi from April 2013 to March 2014. Total 180 patients with blunt or penetrating thoracic trauma were included in the study. Chest tube (28-36 Fr) was inserted in Trauma centre under strict asepsis. Tubes were then connected to under water seal for minimum six hours. Patients were randomly divided in two equal groups (90 in each). In Group A, Clamping trial was given before attempting removal while in Group B, tube was removed immediately without clamping trial. Patients of both groups were observed two hourly for development of recurrent pneumothorax. Data was analysed using SPSS-18. The comparison of frequency of recurrent pneumothorax in Group A (9 patients, 10%) and in Group B (4 patients, 4.5%) was not found to be statistically significant. (p-value 2.073). Clamping trial is unnecessary prior to removal of tube thoracostomy in blunt and penetrating non-cardiac thoracic trauma in terms of recurrent pneumothorax.


Anomalous 3D nanoscale photoconduction in hybrid perovskite semiconductors revealed by tomographic atomic force microscopy.
While grain boundaries (GBs) in conventional inorganic semiconductors are frequently considered as detrimental for photogenerated carrier transport, their exact role remains obscure for the emerging hybrid perovskite semiconductors. A primary challenge for GB-property investigations is that experimentally they need to be performed at the top surface, which is not only insensitive to depth-dependent inhomogeneities but also could be susceptible to topographic artifacts. Accordingly, we have developed a unique approach based on tomographic atomic force microscopy, achieving a fully-3D, photogenerated carrier transport map at the nanoscale in hybrid perovskites. This reveals GBs serving as highly interconnected conducting channels for carrier transport. We have further discovered the coexistence of two GB types in hybrid perovskites, one exhibiting enhanced carrier mobilities, while the other is insipid. Our approach reveals otherwise inaccessible buried features and previously unresolved conduction pathways, crucial for optimizing hybrid perovskites for various optoelectronic applications including solar cells and photodetectors.


Generation and preclinical characterization of an antibody specific for SEMA4D.
Semaphorin 4D (SEMA4D or CD100) is a member of the semaphorin family of proteins and an important mediator of the movement and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. Blocking the binding of SEMA4D to its receptors can result in physiologic changes that may have implications in cancer, autoimmune, and neurological disease. To study the effects of blocking SEMA4D, we generated, in SEMA4D-deficient mice, a panel of SEMA4D-specific hybridomas that react with murine, primate, and human SEMA4D. Utilizing the complementarity-determining regions from one of these hybridomas (mAb 67-2), we generated VX15/2503, a humanized IgG4 monoclonal antibody that is currently in clinical development for the potential treatment of various malignancies and neurodegenerative disorders, including multiple sclerosis and Huntington's disease. This work describes the generation and characterization of VX15/2503, including in vitro functional testing, epitope mapping, and an in vivo demonstration of efficacy in an animal model of rheumatoid arthritis.


The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing.
The E6-AP gene (UBE3A) encodes an E3 ubiquitin-protein ligase that binds the human papillomavirus E6 oncoprotein and catalyzes the ubiquitination of p53. Recent studies have also established that mutations in E6-AP are the genetic basis of the Angelman syndrome in humans. In this study we present the genomic structure of the coding region of E6-AP and an analysis of a set of five E6-AP mRNAs with the potential to encode three protein isoforms of the E6-AP protein (isoforms I, II, and III) that differ at their extreme amino-termini. These transcripts were expressed in a variety of different cell lines examined.


Association between maternal depression and maternal sensitivity from birth to 12 months: a meta-analysis.
Maternal sensitivity plays a central role in shaping children's development across a number of domains, and may be disrupted by depression. The current meta-analysis quantified the magnitude of the association between depression and maternal sensitivity, defined broadly as timely, contingent, and appropriate responding to infants' cues, from birth to 12 months. Across k = 48 studies and n = 4,934 mother-infant dyads, the aggregate effect size between depression and maternal sensitivity was r = -.16, p < .0001, indicating that mothers with higher depression levels were less sensitive than mothers with lower depression levels. Studies that compared a depressed group with a nondepressed/control group had larger effect sizes (r = -.35, p < .0001) than studies that examined depression within a single sample of either unselected cases or clinical-only cases (r = -.11, p < .001), suggesting that clinical levels of depression may pose a particular threat to sensitive parenting. Clinical implications (e.g. screening, prevention) are discussed.


Discontinuity of the basement membrane in fibrosing basocellular carcinomas and basosquamous carcinomas of the skin: an immunohistochemical study with human laminin and type IV collagen antibodies.
Thirteen basocellular carcinomas (BCC) of different histologic types and 5 basosquamous carcinomas (BSC) of the skin were stained for laminin and type IV collagen with rabbit antibodies against the human basement membrane (BM) proteins, using an immunoperoxidase technique. The BM around the tumor aggregates contained both laminin and type IV collagen, and was continuous and distinct in all the nonfibrosing BCCs but indistinct or interrupted in the fibrosing BCCs and BSCs. The BM was not influenced by the focal adnexal differentiation of the BCC cells. The disintegrity of the BM in the fibrosing BCCs and BSCs may reflect some kind of disturbance in the interaction between the neoplastic epithelium and the connective tissue stroma, and be connected with the more aggressive nature of these tumors compared with ordinary BCCs. Thus local aggressive behavior seems to be accompanied by defects in the BM.


Dynamics study of the OH + O3 atmospheric reaction with both reactants vibrationally excited.
The dynamics of the title five-atom atmospheric reaction is studied by the quasiclassical trajectory method for vibrational states of OH over the range 2 < or = v < or = 9 and initial vibrational energies of O3 between 9 and 21 kcal mol-1 using a previously reported double many-body expansion potential energy surface for HO4(2A). The results show that the reaction is controlled by both capture- and barrier-type mechanisms, with the rate constants depending strongly on the reactants' internal energy content. Also suggested from the magnitude of the calculated rate coefficients is that the title processes may not be ignorable when studying the stratospheric ozone budget.


Effect of prostaglandin E1 infusion on leukocyte traffic and fibrosis in acute lung injury induced by bleomycin in hamsters.
To determine whether the iv infusion of prostaglandin E1 (PGE1) could modify the early influx of neutrophils into bleomycin-injured lungs and if that would affect subsequent development of inflammation and fibrosis. In vivo controlled animal study performed in a university hospital pulmonary research laboratory. Male Syrian golden hamsters (100- to 110-g body weight) were divided into four treatment groups: a) No treatment; b) intratracheal bleomycin plus PGE1 infusion; c) bleomycin plus saline infusion; d) PGE1 infusion only. PGE1 (180 ng/hr.100 g) or saline were infused iv 3 to 25 hr after intratracheal instillation of bleomycin sulfate (0.5 U/0.5 mL.100 g). Total and differential counts of cells recovered by lavage, lavage fluid protein, and lung total protein and hydroxyproline levels were measured from 6 hr to 30 days later. PGE1 infusion reduced the influx of neutrophils 6 hr after bleomycin injury by 53% compared with saline infusion (p less than .0001), but increased inflammatory cell traffic after 24 hr for 15 days. At 4 days, protein recovered in lung lavage fluid was also decreased in PGE1-treated, bleomycin-injured animals, reflecting reduced injury to lung permeability barriers. Accumulation of lung collagen in the PGE1-treated, bleomycin-instilled hamsters tended to be lower than in the bleomycin-injured, saline-infused group at 15 and 30 days, although these differences did not achieve statistical significance. Despite this fact, greater than 33% of the animals in the PGE1-treated group died, possibly indicating an increased risk of sepsis in these animals. PGE1 infusion can decrease early neutrophil traffic and reduce injury to the lung permeability barriers. However, this treatment augments late inflammatory events and does not significantly alter the development of fibrosis.


[Lipid-lipoprotein serum profile of the newborn and its birth weight].
The sixty-seven newborns were investigated. The umbilical cord blood samples were used to determine following indices: total cholesterol, LDL, HDL2, HDL3-cholesterol, total phospholipids, LDL, HDL-phospholipids, triglycerides and apolipoprotein B. The chi 2 test indicated correlations between increased levels of triglycerides, phospholipids LDL and cholesterol HDL2 and decreased level of cholesterol LDL in the group of newborns with the lowest delivery body mass.


Demand failures occurring during permanent pacing in patients with serious heart disease.
Demand failures during permanent cardiac pacing were studied in four patients with coronary heart disease and cardiomyopathies, by means of in vivo and in vitro analyses of the pacemaker system. A common feature of the electrogram analyses (except during a second replacement in one patient), was extremely low values of amplitudes (0.77-4.36 mV) and maximum derivatives (0.16-1.06 V/sec). In spite of low electrogram amplitudes, the myocardial threshold values were low in all patients. An attempt in one patient at unipolarizing a bipolar system made the adaptation between electrogram and pulse generator more difficult. Autopsy showed that the tip of the bipolar electrode was positioned in a fibrotic area of the myocardium. The signal available for the sensing circuit will also be reduced because of voltage division between the electrode/tissue interface impedance and the input impedance of the pulse generator. Although the pulse generators used had a high input impedance (10-50 K omega), the tissue interface impedance may have caused a further reduction in the electrogram amplitude of 10-30%. This may have contributed to demand failure. In vitro studies confirmed that test pulses with characteristics similar to those of the electrograms found in this investigation, were inadequate for pacemaker inhibition. Special care should be taken during electrogram recordings in patients with severe myocardial disease. One should consider the implantation of a high sensitivity pulse generator or the recently introduced sensitivity programmable pulse generators as first choice for this group of patients.


Mycophenolate mofetil and atherosclerosis: results of animal and human studies.
The immunosuppressive agent mycophenolate mofetil (MMF) has beneficial effects in cardiac transplant patients beyond the suppression of tissue rejection. Patients with regimens containing MMF experience diminished intimal thickening and cardiac allograft vasculopathy compared to patients treated with azathioprine. Studies have shown that diet-induced atherosclerosis (a related vasculopathy) is a chronic inflammatory process, and so MMF has also been used to reduce atherosclerosis in a rabbit model of hyperlipidemia. These data hold out the intriguing possibility that MMF might be a viable primary or secondary preventive agent in people at significant risk for atherosclerosis.


The modelling of heating a tissue subjected to external electromagnetic field.
The boundary element method (BEM) is used to solve the coupled problem connected with the biological tissue heating. The tissue treated as a non-homogeneous domain (healthy tissue and tumor region) is subjected to external electromagnetic field. The thermal effect is produced by electrodes that touches the skin surface. External electromagnetic field generates the internal temperature field, which can be modelled by using the volumetric internal heat sources in the tissue domain (this source function constitutes one of components of the Pennes equation). In the paper, both BEM application to coupled bioheat transfer problems and numerical results of computations are theoretically considered. The successive examples show the different input data determining the electromagnetic field parameters.


Difficult airway and one lung ventilation.
The number of indications for lung collapse during different procedures is rising. Difficult upper airway is more often encountered with the need for single lung ventilation. In patients with difficult airway, the safest approach is by placing a single-lumen endotracheal tube with the aid of a flexible fiberoptic bronchoscope. Lung isolation in these patients is then achieved by means of a bronchial blocker. An alternative technique is exchanging the single-lumen for a double-lumen tube using an airway exchange catheter. When there is a tracheostomy in place, an independent bronchial blocker is recommended.


Outcomes of Human Papilloma Virus Vaccination in a Private Women Health Clinic in Lebanon.
The study aims to report on the feasibility and associated adverse events of HPV-Vaccination (HPVV) in a private clinic setting in Lebanon and, when available, the results of subsequent cervical cancer screening. Opportunistic HPV vaccination is offered at the Women's Health Center of the AUBMC. We retrospectively reviewed the patients' demographic data, the incidence of adverse events, and their cytological screening. A cohort of healthy women (n = 1013) aged 26.2 years (12-54 years) were opportunistically vaccinated with one of two HPV vaccines; 845 (83.4%) received the quadrivalent vaccine (Q4V), and 151 (14.1%) received the bivalent vaccine (B2V). The majority (75.8%) received three doses while 16% received two doses. Out of these women, 26.3% (267) became sexually active postvaccination (NS2), whereas 17% (174) were sexually active prior to vaccination (SA) and the rest 57% (572) reported no sexual activity (NS1). Among the SA group, 26% (46/147) presented with abnormal cytology at time of vaccination. As for the NS2 women, 5% (14/267) had subsequently abnormal screening within 37 (12-103) months following vaccination. In this observational study, we report the successful introduction of HPVV with negligible adverse events. The incidence of abnormal cervical cytology was low among our patients.


Giant pyogenic granuloma in a patient with chronic lymphocytic leukemia.
Pyogenic granuloma, also known as lobular capillary hemangioma, is a common benign vascular proliferative lesion that can present at any age on the skin or mucous membranes. Most lesions do not exceed 2 cm, but there are a handful of giant cutaneous pyogenic granulomas that have been reported, often in individuals with underlying immune dysfunction. Here, we report the first giant pyogenic granuloma in a patient with a hematological malignancy, chronic lymphocytic leukemia.


Aerosol infection of calves and mice with Salmonella typhimurium.
The likelihood of airborne spread and infection by Salmonella typhimurium was studied in calves and mice. S typhimurium survived in air sufficiently long to present a significant hazard of airborne spread. In a dry climate (32 per cent relative humidity) its predicted viability five minutes after aerosolization was 4 per cent relative to its initial value. This increased to 24.8 per cent in a humid atmosphere (72 per cent relative humidity). Inhalation of S typhimurium by mice caused disease and death at times dependent upon the dose. Even the lowest dose of about 150 colony forming units (cfu) produced disease. Inoculation of approximately 10(4) to 10(6) cfu S typhimurium by either 'mouth and nose only' or 'whole body' aerosol exposure caused infection in calves. The consequences for the control of salmonellosis in intensive calf husbandry are discussed in the light of this demonstration that airborne transmission can be a primary mode of infection of S typhimurium.


Appraisal of guidelines for pre-operative body wash.
The pre-operative body wash is a strategy for reducing post-operative infection. However, there is a lack of knowledge about its importance. The purpose of the present study was to evaluate the quality of guidelines for the pre-operative body wash using the AGREE instrument--35 guidelines containing instructions for the pre-operative body wash or preparation were included. The AGREE instrument was employed to establish a quality assessment framework that facilitated a comparison of the guidelines. The results were based on the six domains of the AGREE instrument, all of which were found to have low adherence. Descriptive statistics were used to present the assessment score. The AGREE instrument is useful for evaluating the quality of clinical guidelines. The development of evidence-based guidelines must include clinical activities. Further research is required to clarify the pre-operative body wash process and how it should be performed to reduce post-operative infection.


Map-based cloning and characterization of a gene controlling hairiness and seed coat color traits in Brassica rapa.
A glabrous, yellow-seeded doubled haploid (DH) line and a hairy, black-seeded DH line in Chinese cabbage (B. rapa) were used as parents to develop a DH line population that segregated for both hairiness and seed coat color traits. The data showed that both traits completely co-segregated each other, suggesting that one Mendelian locus controlled both hairiness and seed coat color in this population. A fine genetic map was constructed and a SNP marker that was located inside a Brassica ortholog of TRANSPARENT TESTA GLABRA 1 (TTG1) in Arabidopsis showed complete linkage to both the hairiness and seed coat color gene, suggesting that the Brassica TTG1 ortholog shared the same gene function as its Arabidopsis counterpart. Further sequence analysis of the alleles from hairless, yellow-seeded and hairy, black-seeded DH lines in B. rapa showed that a 94-base deletion was found in the hairless, yellow-seeded DH lines. A nonfunctional truncated protein in the hairless, yellow-seeded DH lines in B. rapa was suggested by the coding sequence of the TTG1 ortholog. Both of the TTG1 homologs from the black and yellow seeded B. rapa lines were used to transform an Arabidopsis ttg1 mutant and the results showed that the TTG1 homolog from the black seeded B. rapa recovered the Arabidopsis ttg1 mutant, while the yellow seeded homolog did not, suggesting that the deletion in the Brassica TTG1 homolog had led to the yellow seeded natural mutant. This was the first identified gene in Brassica species that simultaneously controlled both hairiness and seed coat color traits.


Do sodium channel proteolytic fragments regulate sodium channel expression?
The cardiac voltage-gated sodium channel (gene: SCN5A, protein: NaV1.5) is responsible for the sodium current that initiates the cardiomyocyte action potential. Research into the mechanisms of SCN5A gene expression has gained momentum over the last few years. We have recently described the transcriptional regulation of SCN5A by GATA4 transcription factor. In this addendum to our study, we report our observations that 1) the linker between domains I and II (LDI-DII) of NaV1.5 contains a nuclear localization signal (residues 474-481) that is necessary to localize LDI-DII into the nucleus, and 2) nuclear LDI-DII activates the SCN5A promoter in gene reporter assays using cardiac-like H9c2 cells. Given that voltage-gated sodium channels are known targets of proteases such as calpain, we speculate that NaV1.5 degradation is signaled to the cell transcriptional machinery via nuclear localization of LDI-DII and subsequent stimulation of the SCN5A promoter.


Potential endocrine disruption of sexual development in free ranging male northern leopard frogs (Rana pipiens) and green frogs (Rana clamitans) from areas of intensive row crop agriculture.
Intensive row crop agriculture (IRCA) for corn and soybean production is predominant in eastern and central North America. IRCA relies heavily on pesticide and nutrient inputs to maximize production under conventional systems. In 2003-2005, we assessed the occurrence of a suite of potential endocrine effects in amphibians inhabiting farm ponds and agricultural drains in IRCA areas of southwestern Ontario. Effects were compared to amphibians from two agricultural reference sites as well as four non-agricultural reference sites. Pesticide and nutrient concentrations were also determined in water samples from those sites. Atrazine and metolachlor were detected in most samples, exceeding 1 microg L(-1) at some sites. Blood samples were taken from northern leopard frogs (Rana pipiens) and green frogs (Rana clamitans) for analysis of circulating sex steroids and vitellogenin-like protein (Vtg-lp), a biomarker of exposure to environmental estrogens. Gonads were histologically examined for evidence of abnormalities. Some evidence of exposure to endocrine disrupting compounds was apparent from the data. The occurrence of testicular ovarian follicles (TOFS) in male R. pipiens was significantly higher (42%; p<0.05) at agricultural sites, particularly those in Chatham county compared to frogs from reference sites (7%). There was no difference in circulating sex steroid levels between frogs from agricultural and reference sites and sex steroid levels did not correlate with pesticide concentrations in the environment. No differences were detected in the gonadosomatic indices or stage of spermatogenesis between frogs from agricultural and non-agricultural regions (p>0.05). Plasma Vtg-lp was detected in only one male R. pipiens from an agricultural site. Neither gonad size, gonad maturity nor sex steroid levels differed between normal males and those with testicular oocytes. Although the proportion of testicular oocytes did not correlate directly with atrazine concentrations, it did correlate with a mixture of pesticides and nutrients, particularly atrazine and nitrate, while the number of pesticides detected at each site was also important.


Reliability of 2-Dimensional Video Analysis in Adolescent Runners.
The literature on the reliability of qualitative and quantitative measures for running video analysis in the adolescent population is limited. Reliability of 2-dimensional (2D) video analysis has been reported in adult runners, but these findings may not apply to youth runners. We sought to determine the intra-rater and inter-rater reliability of sagittal and frontal plane kinematics using 2D video analysis in healthy adolescent runners. High-definition (1080p) videos were recorded of 10 healthy runners between 14 and 18 years old running on a treadmill at self-selected speed with markers attached to the cervical spine, pelvis, and lower extremities. Kinematic variables in the sagittal and frontal planes were measured using Dartfish Motion Analysis Software by 3 raters (2 sports medicine physical therapists and a research assistant). Intra- and inter-rater reliability were calculated using intraclass correlation coefficients (ICCs). Of the 10 runners, 4 (40%) were male and the mean age was 16 ± 1.5 years. The intra-rater ICC for all kinematic variables ranged from 0.574 to 0.999 for the experienced physical therapist, and 0.367 to 0.973 for the inexperienced research assistant. The inter-rater ICC for all raters ranged from -0.01 to 0.941. Eleven kinematic variables showed substantial agreement and 4 showed almost perfect agreement. Step width and foot progression showed fair and poor agreement, respectively. Running analysis using 2D video can be performed reliably in adolescents on all kinematic variables except for step width and foot progression. Inexperienced raters can be properly trained in the video analysis of running kinematics to consistently assess the same runner.


Suction detection for the MicroMed DeBakey Left Ventricular Assist Device.
The MicroMed DeBakey Ventricular Assist Device (MicroMed Technology, Inc., Houston, TX) is a continuous axial flow pump designed for long-term circulatory support. The system received CE approval in 2001 as a bridge to transplantation and in 2004 as an alternative to transplantation. Low volume in the left ventricle or immoderate pump speed may cause ventricular collapse due to excessive suction. Suction causes decreased flow and may result in patient discomfort. Therefore, detection of this critical condition and immediate adaptive control of the device is desired. The purpose of this study is to evaluate and validate system parameters suitable for the reliable detection of suction. In vitro studies have been performed with a mock loop allowing pulsatile and nonpulsatile flow. Evidence of suction is clearly shown by the flow waveform reported by the implanted flow probe of the system. For redundancy to the implanted flow probe, it would be desirable to use the electronic motor signals of the pump for suction detection. The continuously accessible signals are motor current consumption and rotor/impeller speed. The influence of suction on these parameters has been investigated over a wide range of hydrodynamic conditions, and the significance of the respective signals individually or in combination has been explored. The reference signal for this analysis was the flow waveform of the ultrasonic probe. To achieve high reliability under both pulsatile and nonpulsatile conditions, it was determined that motor speed and current should be used concurrently for suction detection. Using the amplified differentiated current and speed signals, a suction-detection algorithm has been optimized, taking into account two different working points, defined by the value of the current input. The safety of this algorithm has been proven in vitro under pulsatile and nonpulsatile conditions over the full spectrum of possible speed and differential pressure variations. The algorithm described herein may be best utilized to provide redundancy to the existing flow based algorithm.


Practice patterns for herpes simplex keratitis: A survey of ophthalmologists in Gulf Coast countries.
Herpes simplex is a common cause of visual disability, and there are published evidence-based guidelines for therapy. This survey aims to determine the preferred practice patterns of ophthalmologists in Gulf Coast Countries regarding herpetic eye disease, as well as identify areas of controversy or barriers to acceptance of evidence-based protocols. Anonymous web-based survey of ophthalmologists in Saudi Arabia, Bahrain, the United Arab Emirates, and Oman. There were 48 responses to the survey. For a first episode of epithelial dendritic keratitis, 28.2% reported "observation" rather than specific therapy. The majority of respondents utilize oral or topical antiviral for epithelial keratitis, with oral antiviral being the most popular (43.6%). The majority also included a corticosteroid with antiviral for stromal keratitis (83.9%) or iritis (70.3%). Over 90% prescribe a prophylactic antiviral after keratoplasty for herpetic eye disease, although the length of therapy ranged widely from <6 months to indefinite. The perceived risk of recurrent disease was ranked as the most important factor when considering antiviral prophylaxis, followed by risk of adverse effects. Topical cyclosporine was utilized "never or almost never" by 76.9% of respondents. Most respondents report following evidence-based guidelines. There was less consensus in areas where there are remaining knowledge gaps, such as the length of antiviral prophylaxis after keratoplasty and the potential role for topical cyclosporine.


In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life.
Soluble amyloid-beta (Abeta) peptide converts to structures with high beta-sheet content in Alzheimer's disease (AD). Soluble Abeta is released by neurons into the brain interstitial fluid (ISF), in which it can convert into toxic aggregates. Because assessment of ISF Abeta levels may provide unique insights into Abeta metabolism and AD, an in vivo microdialysis technique was developed to measure it. Our Abeta microdialysis technique was validated ex vivo with human CSF and then in vivo in awake, freely moving mice. Using human amyloid precursor protein (APP) transgenic mice, we found that, before the onset of AD-like pathology, ISF Abeta in hippocampus and cortex correlated with levels of APP in those tissues. After the onset of Abeta deposition, significant changes in the ISF Abeta40/Abeta42 ratio developed without changes in Abeta1-x. These changes differed from changes seen in tissue lysates from the same animals. By rapidly inhibiting Abeta production, we found that ISF Abeta half-life was short ( approximately 2 hr) in young mice but was twofold longer in mice with Abeta deposits. This increase in half-life, without an increase in steady-state levels, suggests that inhibition of Abeta synthesis reveals a portion of the insoluble Abeta pool that is in dynamic equilibrium with ISF Abeta. This now measurable in vivo pool is a likely target for new diagnostic and therapeutic strategies.


The Competitive Absorption by the Gut Microbiome Suggests the First-Order Absorption Kinetics of Caffeine.
In the literature archive, the intestinal microbiome is now considered as a discrete organ system. Despite living symbiotically with the human body, the gut microbiome is represented as potential drug targets because of its ability to modify the pharmacokinetics of orally administered drugs. Structural biology analysis indicates the existence of homology between transport proteins of microbial cells and membranes of enterocytes. It is speculated that structural similarity in the protein transporters may provoke an unwanted phenomenon of drug uptake by the gut microbiome present in the small intestine of the host. Considering this hypothesis, we analyzed the absorbance of orally administered caffeine by the gut microbiota in in vivo albino rat model through the RP-HPLC-UV approach. Microbiome absorbed the caffeine maximally at 2 hours and minimally at 5 hours post-drug administration following first-order absorption kinetics in a nonlinear way. Drug absorbance of microbial pellet and percent dose recovery was found significantly higher (P ≤ .05) at 2 hours post-administration as compared to all other groups. As speculated, our findings advocated the phenomenon that the gut microbiome influences the absorption of caffeine molecules. Members of the gut microbiome exhibited grouped behavior following first-order absorption kinetics in a nonlinear pattern.


Metabolic heterogeneity of nuclear poly (A)-containing RNA in mouse liver.
The analysis by the approach to equilibrium labeling method has shown that the poly(A)+ fraction of liver hnRNA is not a uniform class of molecules, but is comprised of two distinct subclasses with half-lives of 5 and 60 min, while the poly(A)- hnRNA was metabolically homogeneous and turned over with a rather uniform half-life of 30 min. The results suggest that (a) poly(A) synthesis and addition is not limiting for the rate of hnRNA processing, and (b) there is a correlation between the kinetics of mRNA appearance in the cytoplasm and kinetic behavior of their possible nuclear precursors.


The effects of smooth pursuit adaptation on the gain of visuomotor transmission in monkeys.
Smooth pursuit eye movements are supported by visual-motor systems, where visual motion information is transformed into eye movement commands. Adaptation of the visuomotor systems for smooth pursuit is an important factor to maintain pursuit accuracy and high acuity vision. Short-term adaptation of initial pursuit gain can be produced experimentally using by repeated trials of a step-ramp tracking with two different velocities (double-step paradigm) that step-up (10-30°/s) or step-down (20-5°/s). It is also known that visuomotor gain during smooth pursuit is regulated by a dynamic gain control mechanism by showing that eye velocity evoked by a target perturbation during pursuit increases bidirectionally when ongoing pursuit velocity is higher. However, it remains uncertain how smooth pursuit adaptation alters the gain of visuomotor transmission. Therefore, a single cycle of sinusoidal motion (2.5 Hz, ± 10°/s) was introduced during step-ramp tracking pre- and post-adaptation to determine whether smooth pursuit adaptation affects the perturbation response. The results showed that pursuit adaptation had a significant effect on the perturbation response that was specific to the adapted direction. These results indicate that there might be different visuomotor mechanisms between adaptation and dynamic gain control. Furthermore, smooth pursuit adaptation altered not only the gain of the perturbation response, but also the gain slope (regression curve) at different target velocities (5, 10 and 15°/s). Therefore, pursuit adaptation could affect the dynamic regulation of the visuomotor gain at different pursuit velocities.


Effects of sewage sludge-fertilized corn fed to growing swine.
Swine (2 groups) fed a ration containing 79% corn from sewage sludge-fertilized plots for 8 weeks may have had a modest performance advantage over swine fed corn from plots heavily fertilized with commercial nitrogen. Sludge-fertilized corn feeding-related deviations from population normals for electroencephalograms, electrocardiograms, clinical chemistry, or histopathology were not observed; however, swine fed sludge-fertilized corn differed significantly from the control swine for certain physiologic and biological characteristics, indicating possible interference with glucose metabolism and microsomal mixed-function oxidase activity. Control swine had mild microcytic anemia associated with parasitism, but swine in the principal groups were less adversely affected, probably due to higher iron intake. Corn heavily fertilized with sewage sludge from an urban-industrial complex can be safely fed to swine, based on these results, but it might be advantageous to feed on a short-term or intermittent schedule. Residues of heavy metals in the animal products must be examined.


Histone variants expression in peripheral blood mononuclear cells of patients with rheumatoid arthritis.
The purpose of the present study was to analyze the expression of four histone variants, implicated in the regulation of gene expression, in peripheral blood mononuclear cell (PBMC) samples of patients with rheumatoid arthritis and healthy controls. We analyzed the expression of three genes encoding histone variants H3.3, H2A.Z, macroH2A1.1 and macroH2A1.2 in PBMC samples of 50 patients with RA, diagnosed according to American College of Rheumatology (ACR) criteria, and 51 matched healthy controls using SYBR green real-time polymerase chain reaction. Mann-Whitney U-test and Spearman correlation were used for data analysis. The expression of H2A.Z was increased by 1.51-fold (P < 0.001) and the expression of H3.3 was increased by 1.13-fold (P = 0.048) in PBMCs of patients with RA compared to healthy controls. Furthermore, we found a positive correlation between Disease Activity Score (DAS-28) based on erythrocyte sedimentation rate and the expression of H2A.Z. Given the role of H3.3 and H2A.Z in nucleosome positioning, chromatin structure and transcription regulation, we suggest that lymphocytes and monocytes, the main cell subtypes in PBMCs of RA patients, possess a more accessible chromatin.


Characteristics and Ethnic Distribution of Aortic Aneurysms in a Caribbean Cohort.
There is a paucity of data regarding relationships between patient demographics and aneurysm characteristics in the West Indies. With this in mind, a retrospective cross-sectional review was conducted analyzing the computed tomography aortogram reports/images of 273 aortic aneurysms. Data were collected and analyzed on ethnicity, size, type, morphology, presence and maximum size of thrombus and aneurysm location, demographics, and clinical presentation with correlations. There were 273 patients with aortic aneurysms giving an incidence rate of 4.33 per 100,000 people per annum. Statistically significant associations were noted with age, gender, and ethnicity. All false aneurysms were male (p = 0.004). The average size of aortic aneurysms being 0.7 cm larger in males than females (p < 0.001). Females were more likely to present with rupture (p = 0.001). Thrombus was more likely in males, Black and mixed races, and in the 8th decade (p < 0.001). Mean age of presentation was the highest in East Indians at 78 than the other ethnicities (Chinese: 65, Black: 70, mixed: 71, White: 73). Aortic aneurysmal disease is increasing in Trinidad and the Caribbean. Infrarenal fusiform aneurysms are the most common types with many significant differences based on age, gender, and ethnicity in the Caribbean population.


Economic analysis of clinical positron emission tomography of the heart with rubidium-82.
This report describes a cost analysis for clinical positron emission tomography (PET) of the heart using generator produced rubidium-82 (82Rb). Considered sequentially are the clinical problem, current noninvasive radionuclide methods, positron emission tomograph, and the cost of PET per study. Also analyzed are the costs of PET versus thallium imaging in the management of chest pain, for screening asymptomatic men at high risk for coronary artery disease and for evaluating myocardial viability after myocardial infarction or thrombolytic therapy. Noninvasive assessment of coronary artery stenosis and myocardial ischemia/viability in symptomatic or asymptomatic subjects remains a major medical problem because the sensitivity and specificity of thallium imaging are only 70-85% and 50-70%, respectively, in recent studies. Cardiac positron imaging has an accuracy for noninvasive diagnosis of coronary artery disease in symptomatic or asymptomatic patients with a sensitivity and specificity of 95-98%. It can also be used for assessing physiologic stenosis severity, for imaging myocardial infarction and viability, for assessing effects of interventions such as thrombolysis, percutaneous transluminal coronary angioplasty (PTCA) or bypass surgery on myocardial perfusion, metabolism or coronary flow reserve, for assessing collateral function noninvasively in man, and for diagnosing cardiomyopathy not due to coronary artery disease. Although the cost for cardiac PET with 82Rb may be modestly higher than for 201Tl, the greater diagnostic yield of PET results in comparable or lower overall medical management costs than no diagnostic tests/interventions and lower overall costs compared to thallium imaging for evaluating patients with chest pain, asymptomatic high risk males, and patients after acute myocardial infarction/thrombolysis for myocardial viability.


Effect of Surgery Versus Observation: Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study).
Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm2 and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p < 0.001) and CTX-1 (p < 0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm2 ) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p < 0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p < 0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm2 ) for all compartments (FN, p < 0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p < 0.001) with the exception of the LS, where BMD was stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT. © 2017 American Society for Bone and Mineral Research.


Gold clusters on Nb-doped SrTiO3: effects of metal-insulator transition on heterogeneous Au nanocatalysis.
Doping induced metal-insulator transition (MIT) in transition-metal (TM) oxides has been the topic of continued interest outside the field of catalysis chemistry. In this paper, via ab initio (GGA+U) calculations, we show that Nb-doping induced MIT in SrTiO(3) causes a dimensionality crossover of supported Au clusters, and at the same time, greatly enhances the stability and catalytic activity of these clusters. Underlying the predicted high catalytic activity of Au clusters towards the CO oxidation is the MIT induced interaction between the O(2) antibonding 2π* orbital and Au conduction bands, leading to a shift in the population of electrons from Au to the antibonding orbital and the activation of the O(2) molecule. We expect these results to provide a new methodology for the control of catalytic performance of TM-oxide supported Au nanoclusters.


Compatibility of butorphanol and droperidol in 0.9% sodium chloride injection.
The compatibility and stability of butorphanol tartrate and droperidol in polyvinyl chloride (PVC) bags and glass bottles stored at 4°C and 25°C for up to 15 days were studied. Admixtures were assessed initially and for 15 days after preparation in PVC bags and glass bottles using 0.9% sodium chloride injection as a diluent and stored at 4°C and 25°C. The initial drug concentrations were 0.08 mg/mL for butorphanol tartrate and 0.05 mg/mL for droperidol. Samples were withdrawn from each container immediately after preparation and at predetermined intervals (2, 4, 8, 24, 48, 72, 120, 168, 240, and 360 hours after preparation). The solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using a validated high-pressure liquid chromatography method. After 15 days of storage, all formulations tested retained >98% of the initial concentrations of both drugs. The drug mixtures were clear in appearance, and no color change or precipitation was observed. Throughout this period, pH values remained stable. Admixtures of butorphanol tartrate 0.08 mg/mL and droperidol 0.05 mg/mL in 0.9% sodium chloride injection were stable for at least 360 hours when stored in PVC bags or glass bottles at 4°C and 25°C and protected from light.


Positive results of clinical educational support in situations of psychological distress.
Education is a complex process that involves the individual in the course of his entire life and leads to the maturation and the overall development of his personality. The educational process involves the complete growth of each and completes the infinite possibilities that every child has potential since birth. Education also is a necessity for the human being, as only adequate environmental stimulation causes the mental processes to begin. In fact, the higher intellectual functions, such as language, thought, memory, emerge only from social and educational experiences of the child. The educational surgery creates experiences and learning that allow the person to change by improving the efficiency of synaptic connections. Clinical pedagogy has developed in Italy in the last decades of the twentieth century with the aim of research and experimenting educational purposes suitable for different situations in order to provide each subject with appropriate development opportunities. Clinical pedagogical support is offered in the form of artistic or bodily activities and represents for the individual a positive environment that allows the development of different brain areas and the potential inherent in them. The various methods are suitable for any situation of existential discomfort, which are understood as moments of personal growth.


Multiple system atrophy with remarkable frontal lobe atrophy.
The autopsy findings of a multiple system atrophy (MSA) patient with remarkable frontal lobe atrophy are described. The patient was a 65-year-old woman with a 13-year history of untreatable parkinsonism, dysautonomia and progressive motor aphasia. The brain weight was 810 g, and there was remarkable atrophy of the cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum. Microscopic examination revealed a preserved cortical structure with laminar gliosis in the sixth layer of the precentral and superior frontal gyri of the frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal lobe. The second layer of the cortices of these regions were also revealed to be in a spongy state, and mild cell loss was seen in the fifth and six layers. The frontal lobe white matter showed a mild loss of myelinated fibers and axons, and mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the deep layer of the cortex in the regions mentioned above, and were more abundant in the white matter of the frontal and parietal lobes, callosal body, and internal, external and extreme capsules. There was severe degeneration in the olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of the brain. No Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or significant amounts of neurofibrillary tangles were detected. There were no vascular changes. Thus, this was a verified MSA patient with progressive aphasia and remarkable frontal lobe atrophy. We indicate a possible involvement of the cerebral lobes in MSA.


Near-Theoretical Thermal Conductivity Silver Nanoflakes as Reinforcements in Gap-Filling Adhesives.
The rapid development of highly integrated microelectronic devices causes urgent demands for advanced thermally conductive adhesives (TCAs) to solve the interfacial heat-transfer issue. Due to their natural 2D structure and isotropic thermal conductivity, metal nanoflakes are promising fillers blended with polymer to develop high-performance TCAs. However, achieving corresponding TCAs with thermal conductivity over 10 W m-1 K-1 at filler content below 30 vol% remains challenging so far. This longstanding bottleneck is mainly attributed to the fact that most current metal nanoflakes are prepared by "bottom-up" processes (e.g., solution-based chemical synthesis) and inevitably contain lattice defects or impurities, resulting in lower intrinsic thermal conductivities, only 20-65% of the theoretical value. Here, a "top-down" strategy by splitting highly purified Ag foil with nanoscale thickness is adopted to prepare 2D Ag nanoflakes with an intrinsic thermal conductivity of 398.2 W m-1 K-1 , reaching 93% of the theoretical value. After directly blending with epoxy, the resultant Ag/epoxy exhibits a thermal conductivity of 15.1 W m-1 K-1 at low filler content of 18.6 vol%. Additionally, in practical microelectronic cooling performance evaluations, the interfacial heat-transfer efficiency of the Ag/epoxy achieves ≈1.4 times that of the state-of-the-art commercial TCA.


Solvent-sensitive signs and magnitudes of circularly polarised luminescence and circular dichroism spectra: probing two phenanthrenes as emitters endowed with BINOL derivatives.
A C2-symmeric binaphthyl framework bearing phenanthrene as the emitter exhibited circularly polarised luminescence (CPL) in dilute solutions. The CPL and circular dichroism signs of the luminophores were altered by solvents (chloroform, methanol, acetonitrile, and dimethylformamide). DFT and TD-DFT calculations indicated that the dihedral angle between the phenanthrene and naphthyl rings was responsible for the apparent sign inversion. The role of solvent molecules in the ground and photoexcited states was discussed based on Hansen solubility parameters (δ, δd, δp and δh).


HLA-DQ and risk gradient for celiac disease.
Celiac disease (CD) is a rare example of multifactorial disorder in which a genetic test is of great clinical relevance, as the disease rarely develops in the absence of specific HLA alleles. We typed DR-DQ genes in 437 Italian children with celiac disease, 834 first-degree relatives, and 551 controls. Of patients, 91% carried DQ2 and/or DQ8 heterodimers, 6% only had beta2 chain, 2% was alpha5 positive, and four were DQ2/DQ8/beta2/alpha5 negative. Only the presence of alpha5 resulted negatively associated to disease (p = 2 x 10(-4)), whereas we confirmed the effect of the beta half of DQ2 dimer on CD predisposition (p = 4 x 10(-12)). Considering 1:100 disease prevalence, we obtained a risk gradient ranging from 1:7 for DQ2 and DQ8 individuals down to 1:2518 for subjects lacking all predisposing factors. The DQB1*02 and DQB1*0302 concurrence (p = 9 x 10(-4)), besides the DQB1*02/*02 homozygosity, had an additional role in disease genetic determination. The CD prevalence rose to 17.6% in sisters, 10.8% in brothers, and 3.4% in parents. In the three groups, the subjects carrying high-risk HLA molecules were 57%, 71%, and 58%; among them, 29%, 15%, and 6% respectively had CD. Those siblings and parents with no susceptible factors were not affected. These findings indicate the impact of the HLA test for CD in clinical practice.


Sublethal effects of methylmercury on fecal metabolites of testosterone, estradiol, and corticosterone in captive juvenile white ibises (Eudocimus albus).
Methylmercury (MeHg) is a globally distributed neurotoxin, endocrine disruptor, and teratogen, and its effects on birds are poorly understood, especially within an environmentally relevant exposure range. In an effort to understand the potential causal relationship between MeHg exposure and endocrine development, we established four dietary exposure groups (0 [control], 0.05, 0.1, and 0.3 mg/kg wet wt/d of MeHg) of postfledging white ibises (Eudocimus albus) in a divided, free-flight aviary that spanned the estimated range of environmental exposure for this species. Fecal samples were collected from individually identified ibises over six months in 2005 and processed for hormone evaluation. Significant sex-related differences in fecal estradiol concentrations, though unpredicted in direction, suggest that this steroid could be related to juvenile development in this species. Using repeated-measures general linear models, we tested a set of candidate models to explain variation in endocrine expression. We found that MeHg exposure led to significant differences in fecal estradiol concentrations between the control and medium-dose groups, whereas differences in fecal corticosterone concentrations were observed between the control and both the low- and high-dose groups. These results suggest highly nonlinear dose-response patterns for MeHg. Many endocrine-disrupting contaminants are theorized to affect multiple endpoints in a nonlinear manner, making results difficult to interpret using a traditional toxicological approach. The evidence presented here suggests that endocrine effects of MeHg exposure could behave similarly.


Antifungal activity of chlorhexidine containing mouthrinses. An in vitro study.
Oral candidosis has emerged as an increasing problem in immunocompromised patients because oral cavity represents an important port of entry for systemic fungal infections. The aim of the present study was to investigate the in vitro antifungal activity of 5 commercial mouthrinses containing chlorhexidine (CHX). The Minimum Fungicidal Concentration (MFC) against six species of yeasts was determined by a broth macrodilution method. The kill-time of mouthrinses at half the concentration of the commercial formulations was also determined. MFCs were achieved with each mouthrinses against all the organisms under test. However, significant differences in MFC values were found for Ebur Os in comparison with Dentosan, Corsodyl and Plak out (p < 0.001). Kill-times of Corsodyl and Dentosan were less than or equal to 120 sec with all the species of yeasts, except Torulopsis glabrata. Significant differences were found in kill-time values between Dentosan and Broxo Din only (p < 0.001). These results suggest that CHX-containing mouthrinses may represent an appropriate alternative to conventional antifungal drugs in the management of oral candidosis. Effectiveness in preventing systemic fungal infections in immunocompromised patients requires further in vivo studies.


IL-17 enhancement of the IL-6 signaling cascade in astrocytes.
Astrocytes have important physiological roles in CNS homeostasis and serve as a bridge between the CNS and immune system. IL-17 and IL-6 are important in many CNS disorders characterized by neuroinflammation. We examined the role of IL-17 on the IL-6 signaling cascade in primary astrocytes. IL-17 functioned in a synergistic manner with IL-6 to induce IL-6 expression in astrocytes. The synergistic effect involved numerous signaling pathways including NF-kappaB, JNK MAPK, and p38 MAPK. The NF-kappaB pathway inhibitor BAY-11, JNK inhibitor JNKi II, and p38 inhibitor SB203580 suppressed the synergistic effect of IL-6 and IL-17 on IL-6 expression. IL-17 synergized with IL-6 to enhance the recruitment of activated NF-kappaB p65, c-Fos, c-Jun, and the histone acetyltransferases CREB-binding protein and p300 to the IL-6 promoter in vivo to induce IL-6 transcription. This was accompanied by enhanced acetylation of histones H3 and H4 on the IL-6 promoter. Moreover, we elucidated an important role for suppressor of cytokine signaling (SOCS) 3 in IL-17 enhancement of IL-6 signaling in astrocytes. SOCS3 small interfering RNA knockdown and SOCS3 deletion in astrocytes augmented the synergistic effect of IL-6 and IL-17 due to an enhancement of activation of the NF-kappaB and MAPK pathways. These results indicate that astrocytes can serve as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 functions in the CNS as a negative feedback regulator.


Variation in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume, and patient characteristics.
The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) demonstrated the efficacy of carotid endarterectomy (CEA) in reducing the risk of stroke and death in selected patients when surgery was performed in institutions whose participation depended on demonstrated excellence. Thirty-day mortality rates in the trials were very low: 0.6% in NASCET and 0.1% in ACAS. To assess perioperative mortality among Medicare patients undergoing CEA in all nonfederal institutional settings. Retrospective national cohort study. All 113300 Medicare patients undergoing CEA during 1992 and 1993 in "trial hospitals" (those participating in NASCET and ACAS, n=86) and "nontrial hospitals" (all other nonfederal institutions performing CEAs, n=2613). Nontrial hospitals were stratified into terciles based on volume of CEAs performed. Crude and adjusted perioperative (30 day) mortality rates. The perioperative mortality rate was 1.4% (95% confidence interval [CI], 1.2%-1.7%) at trial hospitals; mortality in nontrial hospitals was higher: 1.7% (95% CI, 1.6%-1.8%) (high volume); 1.9% (95% CI, 1.7%-2.1 %) (average volume); 2.5% (95% CI, 2.0%-2.9%) (low volume); (P for trend, <.001). In multivariate modeling, patients undergoing their procedures at trial hospitals had a mortality risk reduction of 15% (95% CI, 0%-31%) compared with high-volume nontrial hospitals, 25% (95% CI, 7%-40%) compared with average-volume hospitals, and 43% (95% CI, 25%-56%) compared with low-volume hospitals (P for trend, <.001). Medicare patients' perioperative mortality following CEA is substantially higher than that reported in the trials, even in those institutions that participated in the randomized studies. Caution is advised in translating the efficacy of carefully controlled studies of CEA to effectiveness in everyday practice.


Novel phacB-encoded cytochrome P450 monooxygenase from Aspergillus nidulans with 3-hydroxyphenylacetate 6-hydroxylase and 3,4-dihydroxyphenylacetate 6-hydroxylase activities.
Aspergillus nidulans catabolizes phenylacetate (PhAc) and 3-hydroxy-, 4-hydroxy-, and 3,4-dihydroxyphenylacetate (3-OH-PhAc, 4-OH-PhAc, and 3,4-diOH-PhAc, respectively) through the 2,5-dihydroxyphenylacetate (homogentisic acid) catabolic pathway. Using cDNA subtraction techniques, we isolated a gene, denoted phacB, which is strongly induced by PhAc (and its hydroxyderivatives) and encodes a new cytochrome P450 (CYP450). A disrupted phacB strain (delta phacB) does not grow on 3-hydroxy-, 4-hydroxy-, or 3,4-dihydroxy-PhAc. High-performance liquid chromatography and gas chromatography-mass spectrum analyses of in vitro reactions using microsomes from wild-type and several A. nidulans mutant strains confirmed that the phacB-encoded CYP450 catalyzes 3-hydroxyphenylacetate and 3,4-dihydroxyphenylacetate 6-hydroxylations to generate 2,5-dihydroxyphenylacetate and 2,4,5-trihydroxyphenylacetate, respectively. Both of these compounds are used as substrates by homogentisate dioxygenase. This cytochrome P450 protein also uses PhAc as a substrate to generate 2-OH-PhAc with a very low efficiency. The phacB gene is the first member of a new CYP450 subfamily (CYP504B).


Testis-specific protein Y-encoded copy number is correlated to its expression and the field fertility of Canadian Holstein bulls.
Testis-specific protein Y-encoded (TSPY) is present in varying copy number in both human (20-76 copies) and cattle (37-200 copies), and some studies have linked this variation to semen quality in men. The purpose of this study was to determine if TSPY copy number is associated with fertility in bulls by using adjusted non-return rates, a commonly used measure of field fertility in Canada. In addition, we investigated the associations between TSPY copy number and its expression as well as specific semen parameters, such as average sperm concentration, sperm count, ejaculate volume, and motility. In 2 independent trials, TSPY copy number was shown to be positively correlated to adjusted non-return rates (trial #1: Spearman r = 0.34, p < 0.05; trial #2: Spearman r = 0.77, p < 0.01). Furthermore, TSPY copy number was inversely correlated to TSPY mRNA expression in the testis (Pearson r = -0.71, p < 0.0001). There were no correlations of TSPY copy number or expression with the semen parameters measured. Therefore, TSPY copy number might represent a potential marker of bull fertility, but its mechanism does not appear to be directly related to the semen characteristics analyzed as part of this study.


Adenosine and other mast cell preformed mediators.
Earlier studies of adenosine as a modulator of mast cell secretory functions have demonstrated that addition of exogenous adenosine to rat peritoneal mast cells has appeared to be a pro-inflammatory molecule in allergic reactions. More recent investigative studies with mouse bone-marrow mast cells have confirmed the role of adenosine as a potent augmenter of mast cell mediator release. Ongoing investigation is centered on characterization of an adenosine subtype in mast cells and biochemical mechanisms by which adenosine may effect bronchoconstrictor response in allergen-sensitive individuals.


An unusual case of hamartomatous polyposis with malignancy complication in a patient with ulcerative colitis treated with golimumab.
We report an unusual case of hamartomatous polyposis with malignant complications in a patient with ulcerative colitis on golimumab and previous thiopurine therapy. This patient was evaluated for iron deficiency anemia and underwent hemicolectomy for extensive right-side predominant inflammatory pseudopolyps. Anemia persisted post-colectomy and subsequent gastroscopy showed a fungating polypoid lesion along with numerous carpet-like strawberry appearing polyps in the stomach extending from the gastro-esophageal junction to the distal part of the antrum, necessitating a gastrectomy. Histology showed extensive hamartomatous-like polyps with adenocarcinoma and nodal metastases. Presence of alopecia totalis and hamartomas in this patient raise the possibility of Cronkhite-Canada Syndrome although this may also represent an undescribed hamartomatous polyposis associated with ulcerative colitis. Even though thiopurine analogue and anti-tumor necrosis factor agents have not been associated with increased risk of solid tumors, immunosuppression in patients with extensive polyposis should be cautiously used due to the potential accelerated malignancy risk. This case also highlights the importance of performing additional imaging of the gastrointestinal tract, in inflammatory bowel disease patients with anemia, particularly if the severity is incongruent with disease activity.


Transmastoid labyrinthectomy: surgical management of vertigo in the nonserviceable hearing ear. A five-year experience.
We have continued to employ transmastoid labyrinthectomy since reporting our results for the first 15 patients. Further experience has confirmed our earlier findings that the vestibular system rapidly accommodates to complete unilateral surgical vestibular ablation, regardless of age and vestibular activity of the ear operated upon as measured by bithermal caloric testing. Patients are able to ambulate in one to three days and typically return home three to eight days postoperatively. Only 7 percent of sixty patients retained occasional unsteadiness and only two individuals stated that they suffered constant unsteadiness. Once compensated, there was no instance in which vertigo or unsteadiness returned during the follow-up period. In the individual with unilateral sensorineural hearing loss and incapacitating dysequilibrium, the ear with the hearing loss can be reliably implicated as the one producing the vertigo, regardless of the vestibular activity in that ear as measured by the bithermal caloric test. As we gain more experience, this has continued to be a valid assumption. No individual has lost hearing in the contralateral ear during the period of observation. Dysequililbrium with all its variants--rotary vertigo, instability, veering , ataxia, and lightheadedness--is one of man's most disabling and incapacitating afflictions and affects an individual's ability to pursue normal life and work. We continue to be impressed with the length of time many individuals have borne this incapacitation; one-third of our patients have been incapacitated for over five years.(ABSTRACT TRUNCATED AT 250 WORDS)


Pretreatment with cholera or pertussis toxin differentially modulates morphine- and beta-endorphin-induced antinociception in the mouse formalin test.
The present study was designed to examine the possible involvement of supraspinal CTX- and PTX-sensitive G-proteins in an opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed near-maximal inhibitory effects against the formalin response in the first (0-5 min) and the second (20-40 min) phases. CTX (0.1-0.5 microg) pretreated i.c.v. produced antinociceptive effects in both phases of the formalin responses. Its effect was more pronounced in the first phase. However, PTX (0.05-0.5 microg) injected i.c.v produced the antinociceptive effect only in the first, but not the second, phase. Both CTX (0.5 microg) and PTX (0.5 microg), at the dose which had no intrinsic effect, significantly reversed the beta-endorphin-induced antinociceptive effect observed during the second, but not the first, phase. However, the antinociceptive effect by morphine failed to be affected by the same dose of treatment with CTX or PTX. Our results indicate that, at the supraspinal level, CTX- and PTX-sensitive G-proteins appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin pain model.


Triggered EMG (T-EMG) Values of Pedicle Screws with a Powered Screwdriver vs A Standard Probe in Adolescent Idiopathic Scoliosis Do Not Agree: A Prospective Validation Study.
Triggered electromyography (t-EMG) is a common technique used during spinal instrumentation in surgery for adolescent idiopathic scoliosis. This study tests the validity of t-EMG values obtained with a standard ball-tipped probe after completion of screw placement versus t-EMG values obtained during screw insertion with a powered screwdriver. t-EMG values were collected for screws spanning T7-L5 using both a standard probe and a powered screwdriver. A power analysis determined that a sample size of 300 screws would provide enough precision to estimate limits of agreement within ±2 mA. A monopolar constant current stimulation technique (0.2 ms duration and 3.11 Hz stimulation rate) was used at each level. EMG was acquired with placement of bipolar pairs of subdermal needle electrodes. A Bland-Altman plot was used to assess agreement between threshold readings from the two techniques. Twenty-nine patients were enrolled in this study with 305 screws. t-EMG values measured using a powered screwdriver were on average 1 mA lower than values from a standard probe. When readings less than or equal to 20 mA were considered, the limits of agreement were approximately 4 and 7 mA overall. In total, 28/305 (9%) screws were removed and reinserted, 9/305 (3%) screws were redirected, and 3/305 (1%) screws were aborted based on t-EMG readings. Despite a small overall difference in t-EMG value between the standard probe and screwdriver, there was still large variability in agreement between the two techniques. t-EMG values obtained with a powered screwdriver during screw insertion are not interchangeable with values measured by a probe.


Essential hypertension: an approach to its etiology and neurogenic pathophysiology.
Essential hypertension, a rise in blood pressure of undetermined cause, includes 90% of all hypertensive cases and is a highly important public health challenge that remains, however, a major modifiable cause of morbidity and mortality. This review emphasizes that, from an evolutionary point of view, we are adapted to ingest and excrete <1 g of sodium (2.5 g of salt) per day and that essential hypertension develops when the kidneys become unable to excrete the amount of sodium ingested, unless blood pressure is increased. The renal-mean arterial pressure set-point model is briefly described to explain that a shift of the pressure natriuresis relationship toward abnormally high pressure levels is a pathophysiological characteristic of essential hypertension. Evidence indicating that this anomaly in the pressure natriuresis relationship arises from a sympathetic nervous system dysfunction is briefly formulated, and the most widely accepted pathophysiologic proposal to explain the development of this sympathetic dysfunction is described, with commentaries about novel action mechanisms of some drugs currently used in essential hypertension treatment.


A ternary composite based on graphene, hemin, and gold nanorods with high catalytic activity for the detection of cell-surface glycan expression.
A novel graphene-family ternary composite with high catalytic activity has been developed by using simple synthetic methods. The graphene-based ternary composite has abundant positively charged Au NRs, which greatly improved the catalytic properties of the graphene-family of peroxidase mimetics, because of the high electron-transfer rate of graphene and the synergistic interaction of three components. Sensitive detection of glycan expression on K562 cell surface can be achieved with a low detection limit of 10 cells. This finding constitutes a novel graphene-family hybrid nanomaterials-based peroxidase mimetic that is expected to be applied widely in the construction of simple, sensitive, and selective biosensors for nucleic acids and proteins both inside and outside of cells through catalytic reaction of H2 O2 .


Experimental Identification of Non-Abelian Topological Orders on a Quantum Simulator.
Topological orders can be used as media for topological quantum computing-a promising quantum computation model due to its invulnerability against local errors. Conversely, a quantum simulator, often regarded as a quantum computing device for special purposes, also offers a way of characterizing topological orders. Here, we show how to identify distinct topological orders via measuring their modular S and T matrices. In particular, we employ a nuclear magnetic resonance quantum simulator to study the properties of three topologically ordered matter phases described by the string-net model with two string types, including the Z_{2} toric code, doubled semion, and doubled Fibonacci. The third one, non-Abelian Fibonacci order is notably expected to be the simplest candidate for universal topological quantum computing. Our experiment serves as the basic module, built on which one can simulate braiding of non-Abelian anyons and ultimately, topological quantum computation via the braiding, and thus provides a new approach of investigating topological orders using quantum computers.


Elucidation of the role of peptide linker in calcium-sensing receptor activation process.
Family 3 G-protein-coupled receptors (GPCRs), which includes metabotropic glutamate receptors (mGluRs), sweet and "umami" taste receptors (T1Rs), and the extracellular calcium-sensing receptor (CaR), represent a distinct group among the superfamily of GPCRs characterized by large amino-terminal extracellular ligand-binding domains (ECD) with homology to bacterial periplasmic amino acid-binding proteins that are responsible for signal detection and receptor activation through as yet unresolved mechanism(s) via the seven-transmembrane helical domain (7TMD) common to all GPCRs. To address the mechanism(s) by which ligand-induced conformational changes are conveyed from the ECD to the 7TMD for G-protein activation, we altered the length and composition of a 14-amino acid linker segment common to all family 3 GPCRs except GABA(B) receptor, in the CaR by insertion, deletion, and site-directed mutagenesis of specific highly conserved residues. Small alterations in the length and composition of the linker impaired cell surface expression and abrogated signaling of the chimeric receptors. The exchange of nine amino acids within the linker of CaR with the homologous sequence of mGluR1, however, preserved receptor function. Ala substitution for the four highly conserved residues within this amino acid sequence identified a Leu at position 606 of the CaR critical for cell surface expression and signaling. Substitution of Leu(606) for Ala resulted in impaired cell surface expression. However, Ile and Val substitutions displayed strong activating phenotypes. Disruption of the linker by insertion of nine amino acids of a random-coiled structure uncoupled the ECD from regulating the 7TMD. These data are consistent with a model of receptor activation in which the peptide linker, and particularly Leu(606), provides a critical interaction for the CaR signal transmission, a finding likely to be relevant for all family 3 GPCRs containing this conserved motif.


Chronic achilles paratenonitis. An immunohistologic study of fibronectin and fibrinogen.
Pathological alterations in chronic Achilles paratenonitis were studied histologically and using immunofluorescence techniques for fibronectin and fibrinogen in tissue samples obtained operatively from 11 athletes with this complaint and from 4 male cadavers serving as controls. The average duration of the paratenonitis was 20.4 months. The paratendineal fatty areolar tissue was clearly thickened and edematous, showing widespread fat necrosis and considerable connective tissue proliferation. The blood vessels were often obliterated and degenerated. Fibronectin and fibrinogen were commonly found in the proliferating connective tissue areas and in the vascular walls. Exudates rich in fibrinogen and fibronectin were seen in the inflamed paratendineal tissues, but not in the controls. The results indicate that increased vascular permeability and fibrin formation still persist in chronic Achilles paratenonitis and that marked obliterative and degenerative alterations of the blood vessels are frequent. The presence of fibronectin and fibrinogen points to an immature nature of scar tissue in chronic paratenonitis.


Transplantation of murine bone marrow stromal cells under the kidney capsule to secrete coagulation factor VIII.
Ectopic cell transplantation has been studied as an alternative to whole organ transplantation or as a method to produce secretable proteins for genetic disorders. In this study, bone marrow stromal cells isolated from C57Bl/6 mice were genetically modified to express either lacZ- or B-domain-deleted human factor VIII. In vitro modification of the isolated bone marrow stromal cells was initially performed by transducing increased doses of VSV-G pseudotyped lentiviral vectors expressing lacZ. At a MOI of 25, all of the bone marrow stromal cells were X-gal positive, which maintained their ability to expand and differentiate prior to transplantation into mice. Extremely poor engraftment was observed in the liver, but transplantation of the bone marrow stromal cells expressing lacZ under the kidney capsule resulted in long-term viable X-gal-positive cells for at least 8 weeks (length of study). In vitro expression of human factor VIII was detected in a dose-dependent manner following bone marrow stromal cell with a factor VIII-expressing lentiviral vector. Transplantation of the factor VIII-expressing bone marrow stromal cells under the kidney capsule led to long-term therapeutic expression in the mouse plasma (1-3 ng/ml; n = 4-5 mice/group) for 8 weeks. This study demonstrated that ectopic transplantation of bone marrow stromal cells under the kidney capsule can be effective as a method to express secretable proteins in vivo.


Dioxygen activation with stable N-heterocyclic carbenes.
Dioxygen activation with both cyclic (amino)(alkyl)carbenes and di(amino)carbenes at ambient temperature is described. Theoretical studies suggest that electron rearrangement from the doubly filled σ orbital of carbene carbon to its vacant p orbital through the π* antibonding orbital of 3O2 can be considered for Ccarbene-O bond formation.