The Stiff Joint: Comparative Evaluation of Monotherapy and Combination Therapy With Urate Lowering Agents in Managing Acute Gout.
Gout, an extremely painful form of arthritis, is triggered by the innate immune system's response to the accumulation of monosodium urate crystals in specific joints and surrounding tissues. This condition is characterized by recurring episodes of excruciating arthritis flares, interspersed with periods of disease quiescence. Over time, gout can result in disability, tophi formation, and severe pain. The treatment of gout is centered around two main objectives: alleviating inflammation and pain during acute gout attacks and long-term management to reduce serum urate levels and mitigate the risk of future attacks. Addressing inflammation and pain during acute attacks is often complicated by various factors, including underlying health conditions commonly associated with gout, such as hypertension, chronic kidney disease, cardiovascular disease, and diabetes mellitus. Moreover, gout patients are frequently older and have multiple coexisting health issues, necessitating complex medication regimens. Given the rising prevalence of gout and its associated comorbidities, there's a growing demand for improved treatment options. While existing treatments effectively manage gout in some patients, a significant portion, particularly those with comorbidities, face contraindications to these treatments and require alternative approaches. Innovative medications are required to enhance gout treatment, especially for individuals with concurrent health conditions. These considerations underscore the importance of reviewing both monotherapy and combination therapy approaches for acute gout treatment.


Carhart v. Stenberg.
The Eighth Circuit Court of Appeals affirmed a lower court decision that had held Nebraska's statute banning partial-birth abortion to be unconstitutional under the Fourteenth Amendment to the U.S. Constitution. The lower court had permanently enjoined enforcement of the statute. Nebraska's Partial-Birth Abortion Act prohibited "an abortion procedure in which the person performing the abortion partially delivers vaginally a living unborn child before killing the unborn child and completing the delivery." A physician who performs abortions had challenged this statute as being vague and overly broad. The lower court had ruled that the statute was unconstitutional under the Fourteenth Amendment since it banned the common dilation and evacuation (D&E) procedure thereby creating an undue burden for women seeking to terminate a pregnancy before the fetus becomes viable.


The effect of positive inotropes on the failing human myocardium.
Heart failure is associated with pathobiochemical changes that can reduce the responsiveness of the myocardium to positive inotropic agents. We studied the contractile effects of a range of inotropic agents on papillary muscle strips from healthy and failing human hearts. Specimens were obtained from patients with different grades of heart failure. These included individuals undergoing mitral valve replacement (New York Heart Association Class II-III) or receiving heart transplantation (New York Heart Association Class IV). Heart failure was associated with attenuation of myocardial contractile responses to dobutamine, histamine, 3-isobutyl-1-methylxanthine, and the phosphodiesterase inhibitors, milrinone and pimobendan. However, pretreatment of the papillary muscle with isoprenaline augmented the positive inotropic effect observed with the phosphodiesterase inhibitors. The contractile response to ouabain was not influenced by the presence of heart failure. We conclude that, unlike beta-adrenoceptors, cardiac glycoside receptors in the myocardium are not down regulated in the presence of heart failure.


Orofacial rhabdomyosarcoma: report of a case and review of the literature.
Rhabdomyosarcomas (RMS) are among the most common soft-tissue tumors in children. These tumors are derived from mesenchymal tissue with a tendency toward myogenic differentiation that probably originates from immature and highly invasive satellite cells associated with the embryogenesis of skeletal muscle. Some of these tumors are associated with high rates of recurrence and metastasis. The diagnosis is made by microscopic analysis and auxiliary techniques such as immunohistochemistry, electron microscopy, cytogenetic analysis, and molecular biology. We report here a case of orofacial RMS in a 4- year-old child and provide an updated review of the literature, focusing mainly on the clinicopathological aspects, diagnosis and treatment of RMS of the head and neck.


Average entanglement entropy of midspectrum eigenstates of quantum-chaotic interacting Hamiltonians.
To which degree the average entanglement entropy of midspectrum eigenstates of quantum-chaotic interacting Hamiltonians agrees with that of random pure states is a question that has attracted considerable attention in the recent years. While there is substantial evidence that the leading (volume-law) terms are identical, which and how subleading terms differ between them is less clear. Here we carry out state-of-the-art full exact diagonalization calculations of clean spin-1/2 XYZ and XXZ chains with integrability breaking terms to address this question in the absence and presence of U(1) symmetry, respectively. We first introduce the notion of maximally chaotic regime, for the chain sizes amenable to full exact diagonalization calculations, as the regime in Hamiltonian parameters in which the level spacing ratio, the distribution of eigenstate coefficients, and the entanglement entropy are closest to the random matrix theory predictions. In this regime, we carry out a finite-size scaling analysis of the subleading terms of the average entanglement entropy of midspectrum eigenstates when different fractions ν of the spectrum are included in the average. We find indications that, for ν→0, the magnitude of the negative O(1) correction is only slightly greater than the one predicted for random pure states. For finite ν, following a phenomenological approach, we derive a simple expression that describes the numerically observed ν dependence of the O(1) deviation from the prediction for random pure states.


Fructosamine--an underutilized tool in diabetes management: case report and literature review.
Glucose binds irreversibly to a variety of structures, including hemoglobin and proteins, by non-enzymatic glycosylation. Glycosylated Hemoglobin A1c (HbA1c) measures the blood glucose control over the lifespan of the RBCs. The importance of routinely assessing HbA1c in diabetic patients is well established. Both individual and institutional performance in the diabetes arena may be judged by the number of patients reaching target HbA1c values. In some patients, however, the HbA1c does not accurately portray glycemic control and may delay treatment for poorly-controlled diabetes. We report on a patient in whom the HbA1c values were falsely low as a result of hemolytic anemia associated with Myelodysplastic syndrome. The patient had consistent elevation of glucose values. Fructosamine measurement was able to confirm poorly-controlled diabetes and assist in improving diabetes control. Fructosamine is unaffected by disorders of red blood cells, which have a profound potential influence on HbA1c. Fructosamine also has the advantage of accurately reflecting shorter-term changes in glycemia that correspond to the half-life of albumin. In diabetic patients with HbA1c values below the lower limit of normal, a routine Fructosamine level should be performed. We recommend a Fructosamine level should be considered in all patients with red blood cell disorders or with discrepancies between glucose measurements and HbAlc values. Fructosamine, an inexpensive assay, is currently underused in the clinical practice. A guideline for using Fructosamine levels is included and some of the pitfalls in relying solely on the HbAlc are discussed.


Tree gum stabilised selenium nanoparticles: characterisation and antioxidant activity.
Selenium nanoparticles (Se NPs) were synthesised using sodium borohydride as a reductant and gum kondagogu as a stabiliser. Plant gum serves as a renewable, non-toxic, non-immunogenic, biopolymer based feedstock. Role of gum on synthesis and mean particle size was studied using ultraviolet-visible spectroscopy and dynamic light scattering. NP generation was visualised with orange red colouration and NPs exhibited a surface plasmon resonance peak at 250 nm. Formed NPs were amorphous, polydisperse and spherical. NPs showed a bimodal distribution, size varied from 44.4 to 200 nm and mean particle size was 105.6 nm. NP solution exhibited a zeta potential of -39.9 mV, confirming the superior stability. In comparison to ionic Se, the gum capped Se NPs exhibited superior 1, 1-diphenyl-2-picrylhydrazyle and 2, 2-azinobis-(3-ethylbenzthinzoline-6-sulphonic acid) radial scavenging activities of 73.2 and 92.2%, respectively, at 25 µg/ml. Antibacterial potential of NPs was checked with well diffusion assay. NPs exhibited growth inhibition activity against Gram-positive bacteria only. Bacillus subtilis and Micrococcus luteus showed respective inhibition zones of 6.3 and 8.6 mm at 12 µg. Thus, the present study demonstrates the applicability of tree gum stabilised Se NPs as a potent antioxidant nutrition supplement at a much lower dose, in comparison with ionic Se.


Evolution of chromosome 6 of Solanum species revealed by comparative fluorescence in situ hybridization mapping.
Comparative genetic linkage mapping using a common set of DNA markers in related species is an important methodology in plant genome research. Here, we demonstrate a comparative fluorescence in situ hybridization (FISH) mapping strategy in plants. A set of 13 bacterial artificial chromosome clones spanning the entire length of potato chromosome 6 was used for pachytene chromosome-based FISH mapping in seven distantly related Solanum species including potato, tomato, and eggplant. We discovered one paracentric inversion and one pericentric inversion within specific lineages of these species. The comparative FISH mapping data revealed the ancestral structure of this chromosome. We demonstrate that comparative FISH mapping is an efficient and powerful methodology to study chromosomal evolution among plant species diverged for up to 12 million years.


Mid-term success rate of single stage hybrid ablation of persistent and long-term persistent atrial fibrillation.
Single stage thoracoscopic radiofrequency ablation (RFA) is a treatment method for persistent and long-term persistent atrial fibrillation (AF) offering the possibility for patients otherwise inconsolable by conventional catheter RFA. We present a pilot group of patients after the introduction of the new method at our clinical center. Patients group: A total of 52 patients aged 61.82 ± 9.7 years underwent single stage hybrid ablation (thoracoscopic isolation of pulmonary veins and box lesion followed by catheter verification of the surgical procedure effectivness) for symptomatic persistent and long-term persistent AF with significantly dilated left atrium 57.9 ± 11.0mm in the period September 2016-March 2019. The median duration of the procedure was 232 minutes and the median duration of hospitalization was 10 days. At discharge, 52 patients (100%) had sinus rhythm. 48 of 52 patients (92.3%) had a 6-month follow-up. 41 of 48 (85.4%) and 38 of 44 (86.4%) of patients were AF free at 3-month and 6-month follow-up, respectively. Acute complications were: one left atrial perforation resolved successfully by suture and one transient ischaemic attack without permanent sequelae. Late complications involved one massive pulmonary embolization and an atrioesophageal fistula. There was no periprocedural myocardial infarction or stroke with permanent sequelae. Hybrid thoracoscopic-catheter ablation performed during one procedure is an effective and relatively safe mini-invasive method of treatment for long-term persistent atrial fibrillation.


Suitability of melanoma FFPE samples for NGS libraries: time and quality thresholds for downstream molecular tests.
The use of NGS in clinical practice for precision diagnosis requires a quality starting material. Despite the broadly established use of formalin-fixed paraffin-embedded (FFPE) samples in molecular testing, these usually have low-quality DNA. We established a method to determine the suitability of melanoma FFPE samples for an amplicon-based NGS custom panel analysis. DNA was extracted from unstained melanoma samples and wide local excision samples. Amplicon-based libraries were constructed and tested using time and quality parameters as variables. Time elapsed from sample retrieval >7 years, a quality control value > 5.63 and a DNA integrity value < 2.05 indicated samples were not suitable. A decision tree is provided with rate of samples suitable for analysis according to the combination of these parameters.


A comparison of wood density between classical Cremonese and modern violins.
Classical violins created by Cremonese masters, such as Antonio Stradivari and Giuseppe Guarneri Del Gesu, have become the benchmark to which the sound of all violins are compared in terms of their abilities of expressiveness and projection. By general consensus, no luthier since that time has been able to replicate the sound quality of these classical instruments. The vibration and sound radiation characteristics of a violin are determined by an instrument's geometry and the material properties of the wood. New test methods allow the non-destructive examination of one of the key material properties, the wood density, at the growth ring level of detail. The densities of five classical and eight modern violins were compared, using computed tomography and specially developed image-processing software. No significant differences were found between the median densities of the modern and the antique violins, however the density difference between wood grains of early and late growth was significantly smaller in the classical Cremonese violins compared with modern violins, in both the top (Spruce) and back (Maple) plates (p = 0.028 and 0.008, respectively). The mean density differential (SE) of the top plates of the modern and classical violins was 274 (26.6) and 183 (11.7) gram/liter. For the back plates, the values were 128 (2.6) and 115 (2.0) gram/liter. These differences in density differentials may reflect similar changes in stiffness distributions, which could directly impact vibrational efficacy or indirectly modify sound radiation via altered damping characteristics. Either of these mechanisms may help explain the acoustical differences between the classical and modern violins.


Mitochondrial complex V expression and activity in cystinotic fibroblasts.
Alterations in ATP metabolism have been proposed to be involved in the pathogenesis of cystinosis, the most common form of inherited Fanconi syndrome. A recent study showed normal activity of respiratory chain complexes I-IV with decreased ATP levels in cystinotic fibroblasts. Here, we show normal complex V expression and activity in mitochondria of cystinotic fibroblasts. This indicates that alterations in mitochondrial oxidative phosphorylation enzymes are not responsible for ATP decrease in cystinotic fibroblasts.


Detection of antibodies against African swine fever virus using infected monolayers and monoclonal antibodies.
Three monoclonal antibodies, specific for porcine IgG, IgM and IgA, were used to develop isotype-specific immunoperoxidase monolayer assays for the detection of antibodies against African swine fever virus. A mixture of anti-IgM and anti-IgG monoclonal antibodies was used in an assay designed for screening sera. This test was compared with a commercially available ELISA by using experimental sera and field sera obtained after an outbreak of African swine fever on two farms in the Netherlands in 1986. Although the ELISA was less sensitive than the immunoperoxidase monolayer assay on sera taken early after infection, the tests were equally useful for screening purposes. The isotype-specific assays gave epizootiological information about the stage of infection on the two farms.


The Usefulness of Intraoperative Circumferential Frozen-Section Analysis of Lumpectomy Margins in Breast-Conserving Surgery.
Intraoperative frozen-section analysis of the lumpect-omy margin during breast-conserving surgery (BCS) is an excellent method in obtaining a clear resection margin. This study aimed to investigate the usefulness of intraoperative circumferential frozen-section analysis (IOCFS) of lumpectomy margin during BCS for breast cancer, and to find factors that increase the conversion into mastectomy. From 2007 to 2011, 509 patients with breast cancer underwent IOCFS during BCS. The outer surfaces of the shaved lumpectomy margins were evaluated. A negative margin was defined as no ink on the tumor. All margins were evaluated using the permanent section analysis. Among the 509 patients, 437 (85.9%) underwent BCS and 72 (14.1%) finally underwent mastectomy. Of the 483 pathologically confirmed patients, 338 (70.0%) were true-negative, 24 (5.0%) false-negative, 120 (24.8%) true-positive, and 1 (0.2%) false-positive. Twenty-four patients (4.7%) among total 509 patients had undetermined margins as either atypical ductal hyperplasia or ductal carcinoma in situ in the first IOCFS. The IOCFS has an accuracy of 94.8% with 83% sensitivity, 99.7% specificity, 93.4% negative predictive value, and 99.2% positive predictive value. Sixty-three cases (12.4%) were converted to mastectomy, the first intraoperatively. Of the 446 (87.6%) patients who successfully underwent BCS, 64 patients received additional excisions and 32 were reoperated to achieve clear margin (reoperation rate, 6.3%). Twenty-three of the reoperated patients underwent re-excisions using the second intraoperative frozen section analysis, and achieved BCS. Nine cases were additionally converted to mastectomy. No significant differences in age, stage, and biological factors were found between the BCS and mastectomy cases. Factors such as invasive lobular carcinoma, multiple tumors, large tumor, and multiple excisions increased the conversion to mastectomy. The IOCFS analysis during BCS is useful in evaluating lumpectomy margins and preventing reoperation.


Cell lines with heterogeneous phenotypes result from a single isolation of albumin-sv40 T-antigen transgenic rat hepatocytes.
Several immortalized cell lines were established from the livers of two transgenic rats expressing the simian virus protein large T antigen under the control of the albumin promoter. Hepatocytes from transgenic rats were isolated by a two-step perfusion procedure from a normal-appearing liver and from a liver that contained a single neoplasm. Cells were also isolated from the dissociated liver neoplasm. After 5 weeks in culture, cell colonies were isolated and subcloned as individual cell lines. Electron microscopy revealed that all cell lines had a high nuclear-to-cytoplasmic ratio compared with normal hepatocytes. The cytoplasm contained numerous organelles, including smooth and rough endoplasmic reticulum, Golgi, mitochondria, peroxisomes, and annulate lamellae. However, the lines exhibited a variety of different cell morphologies. All cell lines, including those derived from neoplastic cells, exhibited a similar doubling time of 26 hours and the ability to grow in soft agar. Northern blot analysis revealed that the cell lines differentially expressed hepatocyte markers. Large T antigen was expressed in the cultured cell lines at much higher levels than was observed in transgenic hepatocytes in vivo. This suggests that the viral protein is required to maintain cell viability in culture. In addition, the tumor suppressor proteins, p53 and Rbp105, were detected in all cultured cell lines. In contrast, these same proteins were not detected by Western blot in transgenic hepatocytes in vivo. All cell lines expressed the oncogene c-myc, yet growth factor-dependent and independent growth were observed. The data presented show for the first time the establishment and characterization of a number of cell lines derived from hepatocytes isolated from an alb-SV40 large T-antigen transgenic rat. These cell lines exhibited varied morphological and biochemical hepatocellular characteristics in vitro, suggesting that the expression of the transgene in hepatocytes leads to considerable phenotypic diversity analogous to that seen in hepatocellular carcinomas induced by chemical carcinogenesis.


Unusual foreign body in the urethra.
Numerous cases of intraurethral foreign bodies of great variety and unusual nature have been reported. Such foreign bodies are usually introduced for sexual stimulation and/or during an intoxicated or confused state. Resulting symptoms usually involve the urinary frequency, dysuria, nocturia, hematuria, gross bleeding per urethra, difficulty in voiding, or complete urinary retention. Depending on the type of foreign body and its location, various methods of removal have been described, including meatotomy, cystoscopy, internal or external urethrotomy, suprapubic cystostomy, Fogarty catheterization, and injection of solvents. The most frequent complications are urethritis, urethral tear with periurethral abscess and/or fistula, hemorrhage, and urethral diverticuli. We report a case of an intraurethral fishhook with its complications and treatment. The diagnosis should be considered in high-risk patients with lower and urinary tract signs and symptoms.


Gold crescent nanodisk array for nanoantenna-enhanced sensing in subwavelength areas.
Benefitting from the antenna effect and localized surface plasmon resonance (LSPR), a metal nanoparticle with a designed morphology has the amazing ability to confine light energy into the required extremely small volume, whose refractive index largely affects the optical properties of the whole metal nanoparticle. In this work, the optical spectra and near-field distribution of a gold nanocrescent array were investigated both experimentally and theoretically. To find out the LSPR wavelength and the enhancement using different morphologies of sharp tips, the spectra of gold nanocrescent arrays with different waist widths (d) were first measured, which were then confirmed and analyzed using the finite difference time-domain method and the hybridization theory. At last, the LSPR of this array with 100 nm diameter dielectric nanodisks was studied for sensing in subwavelength areas. Our results showed that because of its giant nanoantenna-enhanced electromagnetic field at the two tips, this gold nanocrescent array could be a suitable local senor to sense the variation of a local medium in a subwavelength area.


Synthesis of a library of complex macrodiolides employing cyclodimerization of hydroxy esters.
The synthesis of complex macrodiolides involving microwave-accelerated transesterification of chiral, nonracemic, hydroxy esters is described. Methodology development studies indicate that both microwave power and reaction temperature play an important role in the efficiency of cyclodimerizations. Hydroxy ester monomer pairs were evaluated using an analytical rehearsal leading to the preparation of a 127-member library of highly diverse and stereochemically well-defined macrodiolides. Preliminary assays identified a novel macrodiolide antagonist of the kappa opioid receptor.


Transformation of cell-derived microparticles into quantum-dot-labeled nanovectors for antitumor siRNA delivery.
Cell-derived microparticles (MPs) have been recently recognized as critical intercellular information conveyors. However, further understanding of their biological behavior and potential application has been hampered by the limitations of current labeling techniques. Herein, a universal donor-cell-assisted membrane biotinylation strategy was proposed for labeling MPs by skillfully utilizing the natural membrane phospholipid exchange of their donor cells. This innovative strategy conveniently led to specific, efficient, reproducible, and biocompatible quantum dot (QD) labeling of MPs, thereby reliably conferring valuable traceability on MPs. By further loading with small interference RNA, QD-labeled MPs that had inherent cell-targeting and biomolecule-conveying ability were successfully employed for combined bioimaging and tumor-targeted therapy. This study provides the first reliable and biofriendly strategy for transforming biogenic MPs into functionalized nanovectors.


Prognostic classification in myelodysplastic syndromes.
Factors for predicting the prognosis of myelodysplastic syndromes (MDS) have been widely used over the last few years. The proportion of bone marrow blasts, number and severity of cytopenias, and cytogenetic abnormalities are the main prognostic factors and can be used in combination to determine prognostic scores capable of predicting the outcome with fairly high accuracy. Molecular biology parameters, such as RAS and p53 mutations, can also be of assistance in establishing a prognosis. Factors that predict responsiveness to therapy are usually the same as those that predict survival. Current prognostic scores are unable to identify the minority of patients who will have very long survivals and therefore require no treatment.


Physiological fluid shear alters the virulence potential of invasive multidrug-resistant non-typhoidal Salmonella Typhimurium D23580.
Salmonella enterica serovar Typhimurium strains belonging to sequence type ST313 are a major cause of fatal bacteremia among HIV-infected adults and children in sub-Saharan Africa. Unlike "classical" non-typhoidal Salmonella (NTS), gastroenteritis is often absent during ST313 infections and isolates are most commonly recovered from blood, rather than from stool. This is consistent with observations in animals, in which ST313 strains displayed lower levels of intestinal colonization and higher recovery from deeper tissues relative to classic NTS isolates. A better understanding of the key environmental factors regulating these systemic infections is urgently needed. Our previous studies using dynamic Rotating Wall Vessel (RWV) bioreactor technology demonstrated that physiological levels of fluid shear regulate virulence, gene expression, and stress response profiles of classic S. Typhimurium. Here we provide the first demonstration that fluid shear alters the virulence potential and pathogenesis-related stress responses of ST313 strain D23580 in a manner that differs from classic NTS.


Preparation of MoS2 Nanospheres using a Hydrothermal Method and Their Application as Ammonia Gas Sensors Based on Delay Line Surface Acoustic Wave Devices.
An ammonia sensor based on a delay-line surface acoustic wave (SAW) device is developed in this study by coating the delay line area of the device with a nano-structured molybdenum disulfide (MoS2) sensitive material. A SAW device of 122 MHz was designed and fabricated with a pair of interdigital transducers (IDTs) defined on a 128° y-cut LiNbO3 substrate using photolithography technologies, and the aluminum IDT electrodes were deposited by a DC magnetron sputtering system. By adjusting the pH values of precursor solutions, molybdenum disulfide (MoS2) nanospheres were prepared with various structures using a hydrothermal method. Finally, an NH3 gas sensor with high sensitivity of 4878 Hz/ppm, operating at room temperature, was successfully obtained. The excellent sensitivity performance may be due to the efficient adsorption of NH3 gas molecules on the surfaces of the nanoflower-like MoS2, which has a larger specific surface area and provides more active sites, and results in a larger change in the resonant frequency of the device due to the mass loading effect.


Efficient induction of dopaminergic neurons from embryonic stem cells for application to Parkinson's disease.
For cell replacement therapy of neurodegenerative diseases such as Parkinson's disease (PD), methods for efficiently generating midbrain dopaminergic (DA) neurons from embryonic stem (ES) cells have been investigated. Two aspects of DA neuron generation are considered: genetic modification and manipulation of culture conditions. A transcription factor known as critical for development of DA neurons, Nurr1, was introduced into ES cells to see how they facilitate the generation of DA neurons from ES cells. Also, two culture procedures, the 5-stage method and stromal cell-derived inducing activity (SDIA) method, were used for ES cell differentiation. Using the 5-stage method, we and others previously demonstrated that Nurr1-overexpressing ES cells, under treatment of signaling molecules such as SHH and FGF8 followed by treatment of ascorbic acid, can differentiate into DA neurons with a high efficiency (> 60% of TH+/Tuj1+ neurons). Furthermore, using the SDIA method with treatment of signaling molecules, we found that Nurr1-overexpressing ES cells can differentiate to DA neurons with the highest efficiency ever reported (approximately 90% of TH+/Tuj1+ neurons). Importantly, our semi-quantitative and real-time PCR analyses demonstrate that all known DA marker genes (e.g., TH, AADC and DAT) were up-regulated in Nurr1- overexpressing ES cells when compared to the na ve ES cells. These cells produced increased dopamine compared to na ve D3 cells after differentiation. In the in vivo context after transplantation, the genetically modified ES cells also showed the highly increased dopaminergic neuronal phenotypes. Thus, the combination of genetic engineering and appropriate culture conditions provides a useful tool to generate a good cell source from ES cells for cell replacement therapy of degenerative diseases such as PD.


A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes.
To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse-coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs -0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364).


Developmental expression of Rab11, a small GTP-binding protein in Drosophila epithelia.
Intracellular membrane trafficking regulates a wide variety of developmental processes, including cell and tissue morphogenesis. Here we report developmental expression of Drosophila Rab11, a small GTP-binding protein, required for both endocytic recycling and exocytosis. Rab11 is expressed in the epithelial cell types of diverse lineages at all developmental stages, beginning from the cellular blastoderm in early embryos to adult primordia and adult tissues, like the columnar epithelia lining male ejaculatory bulb. A robust expression of Rab11 is seen both in the amnioserosa and in the lateral epidermis during embryonic dorsal closure, a morphogenetic event that involves spreading and fusion of the contra-lateral sides of epidermis. Rab11 mutant embryos fail to display the characteristic morphological changes in these two epithelial tissues during dorsal closure, providing a strong basis to dissect the role of Rab11 in coordinated epithelial sheet movements. genesis 47:32-39, 2009. (c) 2008 Wiley-Liss, Inc.


Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.
Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.


Potential neuroprotective effects of acamprosate.
This article represents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers were Barbara J. Mason and George F. Koob. Anita M. Goodman served as chair. The presentations were (1) Acamprosate inhibits alcohol withdrawal-induced neurotoxicity in organotypic hippocampal cultures, by John Littleton; (2) Acamprosate alteration of NMDA receptor-dependent synaptic transmission and synaptic plasticity, by George R. Siggins; (3) Acamprosate and glutamate during ethanol withdrawal, by Philippe De Witte; (4) Clinical evidence of protective CNS effects of acamprosate in alcohol-dependent individuals, by Barbara J. Mason.


Comparison of 3D Conformal Proton Therapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Photon Therapy for Retroperitoneal Sarcoma.
External beam radiation therapy (RT) for retroperitoneal sarcoma often requires treatment of large target volumes close to critical normal tissues. Radiation may be limited by adjacent organs at risk (OAR). Intensity-modulated radiation therapy has been shown to improve target coverage and reduce doses to OAR. To compare target coverage and dose to OAR with 3D conformal proton therapy (3D CPT), intensity-modulated proton therapy (IMPT), and intensity-modulated photon therapy (IMXT). We performed a comparative study of treatment plans with 3D CPT, IMPT, and IMXT for ten patients with retroperitoneal sarcomas. RT was delivered to 50.4 Gy to the clinical target volume (CTV), the structures considered at risk for microscopic disease. CTVs ranged from 74 to 357 cc (mean 188 cc). Dose conformity was improved with IMPT, while 3D CPT provided better dose homogeneity. Mean dose to the liver, small bowel, and stomach was reduced with IMPT compared with 3D CPT or IMXT. IMPT, 3D CPT, and IMXT provide excellent target coverage for retroperitoneal sarcomas. OAR dose is lower with IMPT and 3D CPT, and IMPT achieves the closest conformity. These techniques offer the opportunity for further dose escalation to areas with positive margins.


Effects of pond draining on biodiversity and water quality of farm ponds.
Farm ponds have high conservation value because they contribute significantly to regional biodiversity and ecosystem services. In Japan pond draining is a traditional management method that is widely believed to improve water quality and eradicate invasive fish. In addition, fishing by means of pond draining has significant cultural value for local people, serving as a social event. However, there is a widespread belief that pond draining reduces freshwater biodiversity through the extirpation of aquatic animals, but scientific evaluation of the effectiveness of pond draining is lacking. We conducted a large-scale field study to evaluate the effects of pond draining on invasive animal control, water quality, and aquatic biodiversity relative to different pond-management practices, pond physicochemistry, and surrounding land use. The results of boosted regression-tree models and analyses of similarity showed that pond draining had little effect on invasive fish control, water quality, or aquatic biodiversity. Draining even facilitated the colonization of farm ponds by invasive red swamp crayfish (Procambarus clarkii), which in turn may have detrimental effects on the biodiversity and water quality of farm ponds. Our results highlight the need for reconsidering current pond management and developing management plans with respect to multifunctionality of such ponds. Efectos del Drenado de Estanques sobre la Biodiversidad y la Calidad del Agua en Estanques de Cultivo.


A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma.
To determine the maximum tolerated dose (MTD) of erlotinib when administered concurrently with twice weekly gemcitabine and radiation therapy (RT) for locally advanced pancreatic cancer, assess the safety and toxicity profile of this combination and secondarily evaluate response, time to tumor progression and overall survival. Patients with untreated locally advanced pancreas cancer were treated with daily erlotinib in combination with gemcitabine 40 mg/m(2)/30 min twice weekly and RT delivered at 180 cGy/day in 28 fractions over 5.5 weeks for a total of 5040 cGy. Erlotinib was dose escalated in successive cohorts (100 mg, 125 mg). When the MTD was determined, the cohort was expanded to better define toxicity and preliminarily efficacy. All patients were surgically staged. After chemoradiation, patients received maintenance weekly gemcitabine 1000 mg/m(2) on days 1 and 8 of a 21 day cycle and daily erlotinib for four cycles. Three patients were treated at dose level 1 (erlotinib 100 mg) without limiting toxicity. Two of six patients at dose level 2 (erlotinib 125 mg) had dose-limiting toxicities, neutropenia and thrombocytopenia, causing dose delay and elevated liver enzymes. The MTD for erlotinib in combination with twice weekly gemcitabine-based chemoradiation was 100 mg/day. Eleven additional patients were treated at dose level 1. All twenty patients were assessable for toxicity. Seventeen patients were assessable for response. The partial response rate was 35% and 53% had stable disease. The median survival for all patients was 18.7 months. In combination with fixed dose gemcitabine at 40 mg/m(2) twice weekly and radiation at 180 cGy/day, the MTD of erlotinib was found to be 100 mg/day. This is a relatively well tolerated, biologically active combination in a poor prognostic cancer.


A Braided Hetero[2](3)rotaxane.
A novel braided hetero[2](3)rotaxane is demonstrated by integrating the braided structure and mechanically interlocked rotaxane, in which a heterotritopic linear tris(dialkylammonium) guest penetrates a heterotritopic tris(crown ether) host, resulting in the formation of braided pseudohetero[2](3)rotaxane with different crossing and threading points. Then a braided hetero[2](3)rotaxane is constructed through the "CuAAC" click reaction.


Neural correlates of retaliatory and prosocial reactions to social exclusion: Associations with chronic peer rejection.
Social exclusion is a distressing experience and can lead to both retaliatory and prosocial reactions toward the sources of exclusion. The way people react to social exclusion has been hypothesized to be shaped through chronic exposure to peer rejection. This functional Magnetic Resonance Imaging study examined associations between chronic peer rejection and retaliatory (i.e. punishing) and prosocial (i.e. forgiving) reactions to social exclusion and the neural processes underlying them. Chronically rejected (n=19) and stably highly accepted adolescents (n=27) distributed money between themselves and unknown others who previously included or excluded them in a virtual ball-tossing game (Cyberball). Decreasing the excluders' monetary profits (i.e., punishment) was associated with increased activity in the ventral striatum, dorsolateral prefrontal cortex (PFC) and parietal cortex in both groups. Compared to stably highly accepted adolescents, chronically rejected adolescents exhibited higher activity in the dorsal striatum and lateral prefrontal cortex - brain regions implicated in cognitive control - when they refrained from punishment and shared their money equally with (i.e. forgave) the excluders. These results provide insights into processes that might underlie the maintenance of peer rejection across development, such as difficulties controlling the urge to retaliate after exclusion.


Elevated resting [Ca(2+)](i) in myotubes expressing malignant hyperthermia RyR1 cDNAs is partially restored by modulation of passive calcium leak from the SR.
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered in susceptible individuals by inhalation anesthetics and depolarizing skeletal muscle relaxants. This syndrome has been linked to a missense mutation in the type 1 ryanodine receptor (RyR1) in more than 50% of cases studied to date. Using double-barreled Ca(2+) microelectrodes in myotubes expressing wild-type RyR1 ((WT)RyR1) or RyR1 with one of four common MH mutations ((MH)RyR1), we measured resting intracellular Ca(2+) concentration ([Ca(2+)](i)). Changes in resting [Ca(2+)](i) produced by several drugs known to modulate the RyR1 channel complex were investigated. We found that myotubes expressing any of the (MH)RyR1s had a 2.0- to 3.7-fold higher resting [Ca(2+)](i) than those expressing (WT)RyR1. Exposure of myotubes expressing (MH)RyR1s to ryanodine (500 microM) or (2,6-dichloro-4-aminophenyl)isopropylamine (FLA 365; 20 microM) had no effects on their resting [Ca(2+)](i). However, when myotubes were exposed to bastadin 5 alone or to a combination of ryanodine and bastadin 5, the resting [Ca(2+)](i) was significantly reduced (P < 0.01). Interestingly, the percent decrease in resting [Ca(2+)](i) in myotubes expressing (MH)RyR1s was significantly greater than that for (WT)RyR1. From these data, we propose that the high resting myoplasmic [Ca(2+)](i) in (MH)RyR1 expressing myotubes is due in part to a related structural conformation of (MH)RyR1s that favors "passive" calcium leak from the sarcoplasmic reticulum.


Cirsimaritin, a lung squamous carcinoma cells (NCIH-520) proliferation inhibitor.
Cirsimaritin is a dimethoxy flavone, which is present in Ocimum sanctum, Microtea debilis, Artemisia judaica, Cirsium japonicum, and Lithocarpus dealbatus. Its antiproliferative potential has been explored in breast and gall bladder cancer cell lines. However, no reports are available on skin and squamous lung carcinoma. Also, the complete mode of action is unknown. Therefore, in the present study, the anticancer potential of cirsimaritin is explored in organ-specific cell lines by using MTT assay. Further, the inhibitory potential and binding interaction with the selected targets were analyzed through in vitro and in-silico analysis. Cirsimaritin showed selective anticancer activity against NCIH-520 cell-line (IC50 23.29 µM), also inhibited the proliferation of other cell-lines up to 48% at 100 µM. In NCIH-520 cell-line, cirsimaritin significantly increased the apoptosis of the cells at both the tested concentrations (10 and 100 µM), which was confirmed by Annexin-V signifying the induction of late apoptosis. Besides, an increase in the ROS levels of 1.6 fold (10 µM) and 1.8 fold (100 µM), circimaritin also inhibits the activity of ODC and CATD with the IC50 57.30 and 68.22 µM respectively. It exhibited a good binding score with the selected targets, follow Lipinski's rule of five and non-mutagenic. Hence, cirsimaritin is a potent molecule, which inhibits the proliferation of lung squamous cell lines by inducing apoptosis. It also inhibited the activity of ODC and CATD responsible for the progression phase in the cancer cells. Communicated by Ramaswamy H. Sarma.


Impact of Video Technology on the Comprehension of Patients With First Insulin Injection and the Efficiency of Nurse Education.
This study aims to compare the effectiveness of video and paper materials used for teach-back education on the first insulin injection for patients with diabetes. The study enrolled 110 patients hospitalized for diabetes who had received education on their first insulin injection in the endocrinology department. The patients were divided into an intervention group (n = 55) and a control group (n = 55) using convenience sampling. Video materials were employed for the teach-back education of the intervention group, while paper materials were employed for the teach-back education of the control group. We compared cases who answered correctly to the common parts (selection and management of injection devices, selection and rotation of injection sites, proper use of injection angles and pinching, insulin storage, injection-related complications and their prevention, selection of the correct needle length, and safe disposal of needles after use) for the first time, the number of educational sessions and total education duration between the two groups and employed the "My View on Insulin" questionnaire to survey the two groups before and 28 days after the intervention. The intervention group had a shorter total education duration than the control group, a difference that was statistically significant (p < .001). The intervention group had more advantages over the control group in terms of rotation education at the injection site (p < .05). There was no statistically significant difference in the questionnaire scores between the two groups after the intervention (p > .05); however, both groups scored significantly higher than before the intervention, a difference that was statistically significant (p < .001). The teach-back method combined with video materials applied for educating patients on their first insulin injection could reduce the education duration by healthcare providers and improve the patients' psychological insulin resistance. The key to successfully teaching patients to self-administer insulin, and allowing them to master the steps involved, is to focus on "why" rather than "what" to do.


Treatment of chronic osteomyelitis of the femur with combined technique.
Treatment of chronic osteomyelitis of the long bones is challenging due to infection and bone resection. The aim of this case presentation is to report an alternative method for chronic osteomyelitis of the femur. We aimed to provide acute and rapid shortening at the resected site, and lengthening from the metaphyseal bone of a 22-year-old male patient who applied with pain and discharge in the right thigh due to chronic osteomyelitis, and who had undergone three surgical procedures previously. A two-stage treatment was planned. At the first stage, bone resection, antibiotic-impregnated cement rod, and external fixator were applied. At the second stage, intramedullary femoral nail was applied, compression was continued to achieve the docking side in the resection area, and lengthening was performed to eliminate shortness. At the final follow-up, excellent bone and functional scores were obtained. The distraction-compression technique described here can provide successful results in the treatment of chronic osteomyelitis of the long bones.


The Role of Short-Chain Fatty Acids in Acute Pancreatitis.
Acute pancreatitis (AP) is a digestive emergency and can develop into a systematic illness. The role of the gut in the progression and deterioration of AP has drawn much attention from researchers, and areas of interest include dysbiosis of the intestinal flora, weakened intestinal barrier function, and bacterial and endotoxin translocation. Short-chain fatty acids (SCFAs), as one of the metabolites of gut microbiota, have been proven to be depleted in AP patients. SCFAs help restore gut homeostasis by rebuilding gut flora, stabilizing the intestinal epithelial barrier, and regulating inflammation. SCFAs can also suppress systematic inflammatory responses, improve the injured pancreas, and prevent and protect other organ dysfunctions. Based on multiple beneficial effects, increasing SCFAs is an essential idea of gut protective treatment in AP. Specific strategies include the direct use of butyrate or indirect supplementation through fiber, pre/pro/synbiotics, or fecal microbiota transplantation as a promising adjective therapy to enteral nutrition.


Improving the quality of cancer pain management in an academic medical center emergency department.
The impact and outcomes of the implementation of a pain management guideline and pain assessment standard operating procedure (SOP) in a cancer-specific emergency department are evaluated in this article. After implementation of the SOP, the number of pain assessments conducted per patient during hospitalization increased, as did the percentage of patients who underwent a pain assessment at admission, within one hour after analgesic medication was administered, and at regular intervals.


Effects of ambient PM2.5 and particle-bound metals on the healthy residents living near an electric arc furnace: A community- based study.
Fine particulate matter (PM2.5) emitted from electric arc furnaces (EAFs) poses health concerns. However, little research has been done on the impact of EAF on the health of community residents. This cross-sectional study conducted a PM2.5 exposure assessment and health examination of community residents living near an EAF. A total of 965 residents aged 40-90 years were recruited. The residents' exposure to PM2.5 was categorized according to the distance of their residence from the EAFs (<500, 500-1000, 1000-1500, 1500-2000, and > 2000 m). Average ambient PM2.5 concentrations were estimated using a hybrid kriging/land-use regression (LUR) model. In addition, we selected two air-sampling sites to monitor the 2-year levels of PM2.5 and particle-bound metals. A spot urine sample and blood samples were collected and ten heavy metal concentrations in the blood were analyzed. Inflammation- and oxidative stress-related biomarkers were measured. The associations between environmental factors and a biochemical examination were estimated using a generalized linear model. Active air sampling and hybrid kriging/LUR model simulation indicated increased levels of PM2.5 near the EAF. The metal concentrations in PM2.5 included Fe, Pb, Mn, Ni, As, Cu, Ni, Zn, and Al, which also significantly increased near the EAF. PM2.5 levels were significantly associated with an increased total cholesterol-high-density lipoprotein (TC/HDL) ratio. High levels of PM2.5 and malondialdehyde were associated with a 1.72-fold increased risk of TC/HDL ratio ≥ 4 (95% CI: 1.12-2.65) after adjusting for potential confounding factors. Blood Pb levels were significantly associated with increased systolic and diastolic blood pressure and decreased estimated glomerular filtration rate but negatively associated with distance from the EAF. The results show that people living near EAFs should pay more attention to adverse health problems, including atherogenic dyslipidemia, hypertension, and chronic kidney disease associated with exposure to PM2.5 and particle-bound metals.


Removal of heavy metals from aqueous solution by sawdust adsorption.
The adsorption of lead, cadmium and nicel from aqueous solution by sawdust of walnut was investigated. The effect of contact time, initial metal ion concentration and temperature on metal ions removal has been studied. The equilibrium time was found to be of the order of 60 min. Kinetics fit pseudo first-order, second-order and intraparticle diffusion models, hence adsorption rate constants were calculated. The adsorption data of metal ions at temperatures of 25, 45 and 60 degrees C have been described by the Freundlich and Langmuir isotherm models. The thermodynamic parameters such as energy, entropy and enthalpy changes for the adsorption of heavy metal ions have also been computed and discussed. Ion exchange is probably one of the major adsorption mechanisms for binding divalent metal ions to the walnut sawdust. The selectivity order of the adsorbent is Pb(II) approximately Cd(II)>Ni(II). From these results, it can be concluded that the sawdust of walnut could be a good adsorbent for the metal ions from aqueous solutions.


Interactions between oxidative stress and inflammation in salt-sensitive hypertension.
The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-kappaB (NF-kappaB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H(2)O(2) and O(2)(*-) release and renal NF-kappaB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-alpha by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-kappaB, and arterial pressure and improved renal function and damage.


Noise analysis of the fiber-based vibration detection system.
Detecting seismic events using a fiber-based CW laser interferometer attracts wide attention. To make the detection more effective, we analyze the system's noise level by setting up two vibration detection systems. By changing the fiber length (0∼100 km) and laser noise level, respectively, we detect the minor phase change caused by a 160 µm-fiber-length vibration. Furthermore, we use three indicators, Power Spectral Density, Background Noise Level, and Signal-to-Noise Ratio to analyze the noise level of the whole system. The relation between the system's background noise and corresponding detection result is carried out. This quantitative research can serve as a reference and help people to realize the most efficient vibration detection system.


Release of O2- and LTC4 by murine eosinophils: role of intra- and extracellular calcium.
Using an experimental model of mouse peritoneal eosinophilia, we investigated the role of Ca2+ in the in vitro activation of these cells challenged with specific Mesocestoides corti antigen. We have detected LTC4, a metabolite derived from arachidonic acid by way of 5'lipo-oxygenase and superoxide anion from the oxidative burst, as inflammatory mediators produced by activated eosinophils. Preincubation with hyperimmune mice serum increases the amount of LTC4 and superoxide anion in response to the antigenic extract. Release of O2- is inhibited by Verapamil (a voltage-gated calcium channel) and Quin 2 (an intracellular trapped chelator of calcium). Also, LTC4 produced by preincubated eosinophils challenged with M. corti is dramatically inhibited by Quin 2. Our results suggest an intact mechanism for calcium control for the release of these inflammatory mediators by eosinophils, after specific antigenic stimulation.


Hongyacha, a Naturally Caffeine-Free Tea Plant from Fujian, China.
Hongyacha (HYC) is a type of new wild tea plant discovered in Fujian Province, China. This tea is helpful to the healing or prevention of disease in its original growing area. However, research on this tea is limited. Our results showed that HYC displayed obvious differences in its morphological characteristics compared with Cocoa tea ( Camellia ptilophylla Chang), a famous caffeine-free tea plant in China. Theobromine and trans-catechins, but not caffeine and cis-catechins, were the dominant purine alkaloids and catechins detected in HYC. HYC might contain abundant gallocatechin-(4 → 8)-gallocatechin gallate, 1,3,4,6-tetra- O-galloyl-β-d-glucopyranose, and (-)-gallocatechin-3,5-di- O-gallate, which were not detected in regular tea. We also found that the TCS1 of HYC was distinct, and the responding recombinant protein exhibited only theobromine synthase activity. The obtained results showed that HYC is a new kind of caffeine-free tea plant and may be used for scientific protection and efficient utilization in the future.


Life inside and out: making and breaking protein disulfide bonds in Chlamydia.
Disulphide bonds are widely used among all domains of life to provide structural stability to proteins and to regulate enzyme activity. Chlamydia spp. are obligate intracellular bacteria that are especially dependent on the formation and degradation of protein disulphide bonds. Members of the genus Chlamydia have a unique biphasic developmental cycle alternating between two distinct cell types; the extracellular infectious elementary body (EB) and the intracellular replicating reticulate body. The proteins in the envelope of the EB are heavily cross-linked with disulphides and this is known to be critical for this infectious phase. In this review, we provide a comprehensive summary of what is known about the redox state of chlamydial envelope proteins throughout the developmental cycle. We focus especially on the factors responsible for degradation and formation of disulphide bonds in Chlamydia and how this system compares with redox regulation in other organisms. Focussing on the unique biology of Chlamydia enables us to provide important insights into how specialized suites of disulphide bond (Dsb) proteins cater for specific bacterial environments and lifecycles.


[Central venous oxygen saturation monitoring was useful in two cases of hepatectomy with massive bleeding].
To maintain adequate hepatic oxygen supply during intra-operative period is very important to prevent post-operative liver failure after hepatectomy. One of the most useful monitors is hepatic venous oxygen saturation. In the same way, central venous oxygen saturation can evaluate balance between oxygen supply and demand, and its cannulation is easier and safer than that for hepatic and mixed venous oxygen saturation. Two cases of hepatectomy performed with the monitoring of continuous central venous oxygen saturation using PreSep Central Venous Oximetry Catheter (Edwards Lifesciences) suffered from massive bleeding. For the management of the circulation and organ oxygenation, the monitoring of continuous central venous oxygen saturation was very simple and useful in these cases.


Long-term associations of modeled and self-reported measures of exposure to air pollution and noise at residence on prevalent hypertension and blood pressure.
Air pollution, traffic noise and noise annoyance are suggested to be associated with hypertension and blood pressure (BP); however, the evidence remains inconsistent. Our study examined the long-term associations of modeled and self-reported measures of air pollution and traffic noise on prevalent hypertension and BP. We analyzed cross-sectional data from 2552 participants aged 31-72years from the KORA F4 (2006-2008) study conducted in the region of Augsburg, Germany. Land-use regression models were used to estimate residential long-term exposure to particulate matter <2.5μm (PM2.5), soot content of PM2.5 (PM2.5abs) and nitrogen dioxide (NO2). Road traffic noise levels at the facade of the dwellings were estimated for the participants' residences. Participants filled-in a questionnaire on noise annoyance and heavy traffic passing their residence. Linear and logistic regression models adjusting for confounders were used to assess the association between exposure measures and hypertension and BP. An interquartile increase in annual mean PM2.5 (1μg/m3) was significantly associated with 15% higher prevalence of hypertension, without (95% CI: 2.5; 28.0%) and with (95% CI: 0.7; 30.8%) adjustment for traffic noise. Diastolic blood pressure (DBP) was associated with air pollutants and traffic noise with percent increases in mean of 0.7 (95% CI: 0.2; 1.2), 0.6 (95% CI: 0.1; 1.1) and 0.3 (95% CI: 0.0; 0.7) for an interquartile increase in PM2.5 (1μg/m3) and PM2.5abs (0.2∗10-5/m), and 5dB(A) increase in 24-hour road traffic noise, respectively. Associations of PM2.5abs and NO2 with hypertension or DBP were stronger in men and diabetic individuals. No clear associations were seen with systolic BP or noise annoyance. In conclusion, self-reported measures of air pollution or noise did not perform better than the objective measures. Our findings provide further evidence for a link between air pollution, noise and cardiovascular disease and indicate a stronger association for men and diabetic individuals.


A review of schizophrenia research in malaysia.
Research in schizophrenia has advanced tremendously. One hundred and seventy five articles related to Schizophrenia were found from a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. This project aims to examine published research articles, in local and international journals in order to provide a glimpse of the research interest in Malaysia with regards to schizophrenia. Single case study, case series report, reviews and registry reports were not included in this review. Medication trial, unless it concerned a wider scope of psychopharmacology was also excluded from this review. A total of 105 articles were included in this review. Despite numerous genetics studies conducted and published, a definitive conclusion on the aetiology or mechanism underlying schizophrenia remains elusive. The National Mental Health - Schizophrenia Registry (NMHR) proved to be an important platform for many studies and publications. Studies stemmed from NMHR have provided significant insight into the baseline characteristic of patients with schizophrenia, pathway to care, and outcomes of the illness. International and regional collaborations have also encouraged important work involving stigma and discrimination in schizophrenia. Ministry of Health's hospitals (MOH) are the main research sites in the country with regards to schizophrenia research. Numbers of schizophrenia research are still low in relation to the number of universities and hospitals in the country. Some of the weaknesses include duplication of studies, over-emphasising clinical trials and ignoring basic clinical research, and the lack of publications in international and regional journals.


Comparison of two question sequences for assessing pregnancy intentions.
Unintended pregnancies can have serious health, social, and economic consequences. Such pregnancies may be unwanted (a baby is not wanted at any time) or mistimed, yet wanted (a baby is wanted eventually). Intended pregnancies are those conceived when desired. Reproductive health survey respondents' understanding of these concepts and validity of survey results may be affected by question order and wording. Using a randomized crossover design, National Survey of Family Growth (NSFG) and Demographic and Health Survey (DHS) intendedness questions were asked in a 1993 survey of Arizona women aged 18-44 years. Of 2,352 ever-pregnant respondents, 25% gave discordant responses to DHS and NSFG questions about the most recent pregnancy. Age, marital status, household income, education, parity, time since pregnancy, and outcome of pregnancy were significantly predictive of discordant responses. DHS and NSFG questions yielded similar prevalence estimates of intendedness and wantedness; but young, unmarried respondents gave more "mistimed" responses on whichever question was asked later. Classifying pregnancies as intended, mistimed, or unwanted may be a problem for women who have not decided on lifetime reproductive preferences. Approaches to improving survey validity include addressing ambivalence, clarifying the definition of "unwanted," and, for young, unmarried women, not attempting to classify unintended pregnancies as mistimed or unwanted.


Ubiquitin-mediated degradative pathway degrades the extracellular but not the intracellular form of amyloid beta-protein precursor.
The presence of ubiquitin and ubiquitin conjugates has been detected in patients affected by neurodegenerative diseases such as Alzheimer's disease. We investigated the role of ubiquitin in the degradation of amyloid beta-protein precursor (APP) and its participation in the process of amyloid beta-protein formation. APP was tested as a substrate for ubiquitin-mediated degradation, using both the extracellular and the intracellular forms of APP770, APP751 and APP695. The intracellular APP forms did not show appreciable ubiquitin-mediated degradation. In contrast, the three extracellular forms of APP were degraded in vitro by this proteolytic pathway, with similar degradation rates. Our results suggest a potential regulatory role for the ubiquitin-dependent degradation mechanism in the in vivo APP metabolic pathway.


TARP γ-8 glycosylation regulates the surface expression of AMPA receptors.
TARP [transmembrane AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor regulatory protein] γ-8 is an auxiliary subunit of AMPA receptors that is widely distributed in the hippocampus. It has been shown that TARP γ-8 promotes surface expression of AMPA receptors; however, how TARP γ-8 regulates the expression of AMPA receptors remains unclear. In the present study, we examined the effect of TARP glycosylation on AMPA receptor trafficking. We first showed that TARP γ-8 is an N-glycosylated protein, which contains two glycosylation sites, Asn53 and Asn56, and compared this with the glycosylation of TARP γ-2 and the AMPA receptor auxiliary protein CNIH-2 (cornichon homologue 2). We next examine the effect of TARP glycosylation on TARP trafficking and also on AMPA receptor surface expression. We find that TARP γ-8 glycosylation is critical for surface expression of both TARP γ-8 and GluA1 in heterologous cells and neurons. Specifically, knockdown of TARP γ-8 causes a decrease in both total and surface AMPA receptors. We find that the expression of unglycosylated TARP γ-8 in cultured neurons is unable to restore GluA1 expression fully. Furthermore, when the maturation of TARP γ-8 is impaired, a large pool of immature GluA1 is retained intracellularly. Taken together, our data reveal an important role for the maturation of TARP γ-8 in the trafficking and function of the AMPA receptor complex.


Thiopurine Methyltransferase Intermediate Metabolizer Status and Thiopurine-Associated Toxicity During Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia.
Mercaptopurine is a cornerstone of maintenance chemotherapy in childhood acute lymphoblastic leukemia (ALL). Its cytotoxic effects are mediated by 6-thioguanine nucleotides (TGNs) incorporation into lymphocyte DNA. Thiopurine methyltransferase (TPMT) inactivates mercaptopurine, and deficiency resulting from genetic variants increases TGN exposure and hematopoietic toxicity. Although mercaptopurine-dose reduction reduces toxicity risk without compromising relapse rate in patients with TPMT deficiency, dosing recommendations for those with moderately reduced activity (intermediate metabolizer (IM)) are less clear and their clinical impacts have yet to be established. This cohort study assessed the effect of TPMT IM status on mercaptopurine-associated toxicity and TGN blood exposure in pediatric patients with ALL initiated on standard dose mercaptopurine. Of 88 patients studied (mean age 4.8 years), 10 (11.4%) were TPMT IM, and all had undergone ≥ 3 cycles of maintenance therapy (80% completed). A larger proportion of TPMT IM than normal metabolizers (NM) had febrile neutropenia (FN) during the first two cycles of maintenance, reaching significance in the second cycle (57% vs. 15%, respectively; odds ratio = 7.33, P < 0.05). Compared to NM, FN events occurred more frequently and with prolonged duration in IM in cycles 1 and 2 (adjusted P < 0.05). IM had a 2.46-fold increased hazard ratio for FN, and about twofold higher TGN level than NM (P < 0.05). Myelotoxicity was more common in IM than NM (86% vs. 42%, respectively) during cycle 2 (odds ratio = 8.2, P < 0.05). TPMT IM initiated at a standard mercaptopurine dose are at greater risk for FN during early cycles of maintenance therapy, thus our findings support genotype-guided dose adjustment to reduce toxicity.


Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations.
The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN), and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn (-/-) mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcn (flox/flox)). The reintroduction of tumor-associated FLCN mutants (FLCN ΔF157, FLCN 1-469 or FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.


FXYD5 is a Marker for Poor Prognosis and a Potential Driver for Metastasis in Ovarian Carcinomas.
Ovarian cancer (OC) is a leading cause of cancer mortality, but aside from a few well-studied mutations, very little is known about its underlying causes. As such, we performed survival analysis on ovarian copy number amplifications and gene expression datasets presented by The Cancer Genome Atlas in order to identify potential drivers and markers of aggressive OC. Additionally, two independent datasets from the Gene Expression Omnibus web platform were used to validate the identified markers. Based on our analysis, we identified FXYD5, a glycoprotein known to reduce cell adhesion, as a potential driver of metastasis and a significant predictor of mortality in OC. As a marker of poor outcome, the protein has effective antibodies against it for use in tissue arrays. FXYD5 bridges together a wide variety of cancers, including ovarian, breast cancer stage II, thyroid, colorectal, pancreatic, and head and neck cancers for metastasis studies.


Severe preeclampsia and delivery outcomes: is immediate cesarean delivery beneficial?
This study was designed to determine whether immediate cesarean delivery for patients with severe preeclampsia confers any benefit to the mother or neonate. This retrospective chart review included all deliveries complicated by severe preeclampsia between July 1, 1999, and June 30, 2000. Cesarean deliveries performed for malpresentation, previous classic incision, multiple gestation, placenta previa, and herpetic outbreak were not included. Demographic variables, maternal outcomes, and neonatal outcomes were collected. Of 114 patients, 93 had an option regarding route of delivery. Thirty-four had an immediate cesarean section and 59 had induction of labor. Thirty-seven of 59 were delivered vaginally and 22 of 59 underwent cesarean delivery. Pulmonary complications in the mother and neonate were more common in cesarean delivery (P <.05). No morbidity was decreased by cesarean delivery. Bishop score and gestational age did not affect the labor induction success rate. Immediate cesarean delivery confers no benefit to patients with severe preeclampsia.


A Rare Case of Benign Metastasizing Leiomyoma Causing T11 Spinal Cord Compression: A Report and Literature Review.
Diagnosis of uterine smooth muscle tumors depends upon histologic characteristics as both benign and malignant share clinical features such as metastases. A benign metastasizing leiomyoma is a rare benign smooth muscle tumor that metastasizes to extrauterine sites with simultaneous uterine leiomyoma or previously biopsy-proven leiomyoma during myomectomy or hysterectomy. Benign metastasizing leiomyoma metastasizes outside the uterus, predominantly to the lungs and lymph nodes. However, the involvement of other organs, such as the heart, liver, spine, and soft tissue, is also reported. Here, we present a case of a 42-year-old woman with a history of uterine leiomyoma with prior myomectomy and hysterectomy, who presented with worsening back pain and lower extremity weakness and was found to have an acute cord compression, a serious complication caused by mass effect and a medical emergency that requires prompt attention to prevent permanent spinal cord damage. Sacral soft tissue biopsy and T11 spinal bone biopsy both demonstrated leiomyoma with immunostains positive for desmin, smooth muscle actin, and positive estrogen and progesterone receptors. No atypia, necrosis, and mitosis were identified. The patient had hepatic and pulmonary metastasis on imaging. The final diagnosis was benign metastasizing leiomyoma. There is no standard treatment for benign metastasizing leiomyoma. Both surgical and pharmacological approaches are employed. Although most cases are benign, there is a possibility for life-threatening complications. Benign metastasizing leiomyomas can be considered when multiple soft tissue tumors are found in premenopausal women with a history of uterine leiomyomas. Multidisciplinary discussion between oncologists, gynecologists, and relevant specialists is crucial in the optimal evaluation and treatment of benign metastasizing leiomyoma.


Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
Missense mutations in the α-galactosidase A (GLA) gene comprising the majority of mutations responsible for Fabry disease result in heterogeneous phenotypes ranging from the early onset severe "classic" form to the "later-onset" milder form. To elucidate the molecular basis of Fabry disease from the viewpoint of structural biology, we comprehensively examined the effects of different substitutions at the same residue in the amino acid sequence of GLA on the structural change in the enzyme molecule and the clinical phenotype by calculating the number of atoms affected and the root-mean-square-distance value, and by coloring of the atoms influenced by the amino acid replacements. The results revealed that the severity of the structural change influences the disease progression, i.e., a small structural change tends to lead to the later-onset form and a large one to the classic form. Furthermore, the study revealed the residues important for expression of the GLA activity, i.e., residues involved in construction of the active site, a disulfide bond or a dimer. Structural study from such a viewpoint is useful for elucidating the basis of Fabry disease.


Chemical Genomics, Structure Elucidation, and in Vivo Studies of the Marine-Derived Anticlostridial Ecteinamycin.
A polyether antibiotic, ecteinamycin (1), was isolated from a marine Actinomadura sp., cultivated from the ascidian Ecteinascidia turbinata. 13C enrichment, high resolution NMR spectroscopy, and molecular modeling enabled elucidation of the structure of 1, which was validated on the basis of comparisons with its recently reported crystal structure. Importantly, ecteinamycin demonstrated potent activity against the toxigenic strain of Clostridium difficile NAP1/B1/027 (MIC = 59 ng/μL), as well as other toxigenic and nontoxigenic C. difficile isolates both in vitro and in vivo. Additionally, chemical genomics studies using Escherichia coli barcoded deletion mutants led to the identification of sensitive mutants such as trkA and kdpD involved in potassium cation transport and homeostasis supporting a mechanistic proposal that ecteinamycin acts as an ionophore antibiotic. This is the first antibacterial agent whose mechanism of action has been studied using E. coli chemical genomics. On the basis of these data, we propose ecteinamycin as an ionophore antibiotic that causes C. difficile detoxification and cell death via potassium transport dysregulation.


Ginsenoside Rb1 enhanced immunity and altered the gut microflora in mice immunized by H1N1 influenza vaccine.
Influenza is an acute infectious respiratory disease caused by the influenza virus that seriously damages human health, and the essential way to prevent influenza is the influenza vaccine. Vaccines without adjuvants produce insufficient specific antibodies and therefore require adjuvants to boost antibody titers. Microbes and hosts are a community that needs to "promote bacteria," which could provide new value for the immune effect. (1) The H1N1 influenza vaccine, in combination with Ginsenoside Rb1, was co-injected into mice intraperitoneally (I.P.). Then, immunoglobulin G and antibody subtype levels were tested by enzyme-linked immunosorbent assay (ELISA). Moreover, mice were infected with a lethal dose of the H1N1 influenza virus (A/Michigan/45/2015), and survival status was recorded for 14 days. Lung tissues were stained by hematoxylin and eosin (H&E), and ELISA detected inflammatory factor expression levels. (2) Mice were immunized with Ginsenoside Rb1 combined with quadrivalent influenza inactivated vaccine(IIV4), and then IgG levels were measured by ELISA. (3) Fresh stool was collected for fecal 16S rDNA analysis. Ginsenoside Rb1 boosted IgG and antibody subtypes in the H1N1 influenza vaccine, improved survival of mice after virus challenge, attenuated lung histopathological damage, and reduced inflammatory cytokines expression in IL-6 and TNF-α. The results of 16S rDNA showed that Rb1 decreased species diversity but increased species richness compared to the PBS group and increased the abundance of Akkermansiaceae and Murbaculaceae at the Family and Genus levels compared with the HA+Alum group. Ginsenoside Rb1 has a boosting effect on the immune efficacy of the H1N1 influenza vaccine and is promising as a novel adjuvant to regulate the microecological balance and achieve an anti-infective effect.


Chinese version of the separation-individuation inventory.
The importance of the separation-individuation process in object relations theory is well known in disciplines of psychology, counseling, and human development. Based on the Separation-Individuation Inventory of Christenson and Wilson, which measures the manifestations of disturbances in this process, a Chinese version of the inventory was developed. For college students Cronbach coefficient alpha was .89, and test-retest reliability over 28 days was .77. The scores of the inventory had positive correlations with both the number of borderline personality characteristics and the Individualism-Collectivism Scale, respectively. Also, the mean score on the inventory of patients diagnosed with borderline personality disorder was significantly higher than that of the two normal control groups (ns = 564). Thus the inventory possessed satisfactory construct validity. Cultural differences regarding the separation-individuation process need to be investigated further.


Developing a research mentoring partnership in Israel.
A relationship begun in 1985 between the University of Pennsylvania School of Nursing and the Henrietta Szold Hadassah/Hebrew University has included a student exchange program and a faculty mentoring partnership. The student exchange focused on maternal-child nursing and led to the development of the faculty mentoring program. The goals of the latter program are to increase the expertise of the Israeli nursing faculty in the development of grant applications, publications, and abstracts and to develop a National Institutes of Health-supported research project with an Israeli nursing faculty as principal investigator.


Efficacy of an acceptance-based behavior therapy for generalized anxiety disorder: evaluation in a randomized controlled trial.
Generalized anxiety disorder (GAD) is a chronic anxiety disorder, associated with comorbidity and impairment in quality of life, for which improved psychosocial treatments are needed. GAD is also associated with reactivity to and avoidance of internal experiences. The current study examined the efficacy of an acceptance-based behavioral therapy aimed at increasing acceptance of internal experiences and encouraging action in valued domains for GAD. Clients were randomly assigned to immediate (n = 15) or delayed (n = 16) treatment. Acceptance-based behavior therapy led to statistically significant reductions in clinician-rated and self-reported GAD symptoms that were maintained at 3- and 9-month follow-up assessments; significant reductions in depressive symptoms were also observed. At posttreatment assessment 78% of treated participants no longer met criteria for GAD and 77% achieved high end-state functioning; these proportions stayed constant or increased over time. As predicted, treatment was associated with decreases in experiential avoidance and increases in mindfulness.


NITRILASE1 regulates the exit from proliferation, genome stability and plant development.
Nitrilases are highly conserved proteins with catabolic activity but much less understood functions in cell division and apoptosis. To elucidate the biological functions of Arabidopsis NITRILASE1, we characterized its molecular forms, cellular localization and involvement in cell proliferation and plant development. We performed biochemical and mass spectrometry analyses of NITRILASE1 complexes, electron microscopy of nitrilase polymers, imaging of developmental and cellular distribution, silencing and overexpression of nitrilases to study their functions. We found that NITRILASE1 has an intrinsic ability to form filaments. GFP-NITRILASE1 was abundant in proliferating cells, distributed in cytoplasm, in the perinuclear area and associated with microtubules. As cells exited proliferation and entered differentiation, GFP-NITRILASE1 became predominantly nuclear. Nitrilase silencing dose-dependently compromised plant growth, led to loss of tissue organization and sustained proliferation. Cytokinesis was frequently aborted, leading to enlarged polyploid cells. In reverse, independently transformed cell lines overexpressing GFP-NITRILASE1 showed slow growth and increased rate of programmed cell death. Altogether, our data suggest that NITRILASE1 homologues regulate the exit from cell cycle and entry into differentiation and simultaneously are required for cytokinesis. These functions are essential to maintain normal ploidy, genome stability and tissue organization.


Evaluation of the predatory mite, Neoseiulus californicus, for spider mite control on greenhouse sweet pepper under hot arid field conditions.
The efficacy of Neoseiulus californicus (a generalist predatory mite) for the biological control of Tetranychus urticae, was compared to release of Phytoseiulus persimilis (a specialist predatory mite) and an acaricide treatment in sweet pepper plants grown in greenhouse tunnels in a hot and arid climate. To ensure uniform pest populations, spider mites were spread on pepper plants in two seasons; a natural infestation occurred in one season. Predators were released prophylactically and curatively in separate tunnels when plants were artificially infested with spider mites, and at low and moderate spider mite populations when infestations occurred naturally. Although spider mite populations did not establish well the first year, fewer spider mites were recovered with release of N. californicus than with all other treatments. In the second year, spider mites established and the prophylactic release of N. californicus compared favorably with the acaricide-treated plants. In the course of monitoring arthropod populations, we observed a significant reduction in western flower thrips (Frankliniella occidentalis) populations in tunnels treated with N. californicus as compared with non-treated control tunnels. Our field trials validate results obtained from potted-plant experiments and confirm that N. californicus is a superior spider mite predator at high temperatures and low humidities.


Generation of Recombinant Ebola Viruses Using Reverse Genetics.
Reverse genetics systems encompass a wide array of tools aimed at recapitulating some or all of the virus life cycle. In their most complete form, full-length clone systems allow us to use plasmid-encoded versions of the ribonucleoprotein (RNP) components to initiate the transcription and replication of a plasmid-encoded version of the complete viral genome, thereby initiating the complete virus life cycle and resulting in infectious virus. As such this approach is ideal for the generation of tailor-made recombinant filoviruses, which can be used to study virus biology. In addition, the generation of tagged and particularly fluorescent or luminescent viruses can be applied as tools for both diagnostic applications and for screening to identify novel countermeasures. Here we describe the generation and basic characterization of recombinant Ebola viruses rescued from cloned cDNA using a T7-driven system.


Obstructive sleep apnea in amyloidosis treated with nasal continuous positive airway pressure.
Obstructive sleep apnea can occur in patients with a variety of upper airway anatomic abnormalities including macroglossia. We present a case of macroglossia secondary to amyloidosis causing obstructive sleep apnea that was successfully treated with low pressures of nasal continuous positive airway pressure (5 cm of water).


Brain-derived neurotrophic factor in arterial baroreceptor pathways: implications for activity-dependent plasticity at baroafferent synapses.
Functional characteristics of the arterial baroreceptor reflex change throughout ontogenesis, including perinatal adjustments of the reflex gain and adult resetting during hypertension. However, the cellular mechanisms that underlie these functional changes are not completely understood. Here, we provide evidence that brain-derived neurotrophic factor (BDNF), a neurotrophin with a well-established role in activity-dependent neuronal plasticity, is abundantly expressed in vivo by a large subset of developing and adult rat baroreceptor afferents. Immunoreactivity to BDNF is present in the cell bodies of baroafferent neurons in the nodose ganglion, their central projections in the solitary tract, and terminal-like structures in the lower brainstem nucleus tractus solitarius. Using ELISA in situ combined with electrical field stimulation, we show that native BDNF is released from cultured newborn nodose ganglion neurons in response to patterns that mimic the in vivo activity of baroreceptor afferents. In particular, high-frequency bursting patterns of baroreceptor firing, which are known to evoke plastic changes at baroreceptor synapses, are significantly more effective at releasing BDNF than tonic patterns of the same average frequency. Together, our study indicates that BDNF expressed by first-order baroreceptor neurons is a likely mediator of both developmental and post-developmental modifications at first-order synapses in arterial baroreceptor pathways.


A systematic review of the frequency, duration, type and effect of involuntary treatment for people with anorexia nervosa, and an analysis of patient characteristics.
Involuntary treatment of anorexia nervosa is controversial and costly. A better understanding of the conditions that determine involuntary treatment, as well as the effect of such treatment is needed in order to adequately assess the legitimacy of this model of care. The aim of the present study was to investigate the frequency and duration of involuntary treatment, the characteristics of this group of patients, the kind of involuntary actions that are applied and the effect of such actions. Relevant databases were systematically searched for studies investigating the involuntary treatment of individuals diagnosed with anorexia nervosa. The studies included in the review contained people treated in an inpatient setting for severe or severe and enduring anorexia nervosa. People that were treated involuntarily were characterised by a more severe psychiatric load. The levels of eating disorder pathology between involuntary and voluntary groups were similar and the outcome of involuntary treatment was comparable in terms of symptom reduction to that of voluntary treatment. Despite inconsistent findings, the comparable levels of eating disorder pathology observed between involuntary and voluntary patient-groups together with findings of higher co-morbidity, more preadmissions, longer duration of illness and more incidences of self-harm for involuntary patients suggest that involuntary treatment is not a reaction to the severity of eating disorder symptoms alone, but is most likely a response to the complexity of the patient's situation as a whole.


Source control review in clinical trials of anti-infective agents in complicated intra-abdominal infections.
In clinical trials of complicated intra-abdominal infections, assessment of adequacy of the initial surgical approach to the management of the infection is of considerable importance in determining outcome. Antibiotic therapy would not be expected to adequately treat the infection if the surgical procedure was inadequate with respect to source control. Inclusion of such cases in an efficacy analysis of a particular therapeutic antibiotic may confound the results. We analyzed the source control review process used in double-blind clinical trials of antibiotics in complicated intra-abdominal infections identified through systematic review. We searched MEDLINE (PubMed) and ClinicalTrials.gov databases to identify relevant articles reporting results from double-blind clinical trials that used a source control review process. Eight prospective, randomized, double-blind, multicenter, clinical trials of 5 anti-infective agents in complicated intra-abdominal infections used a source control review process. We provide recommendations for an independent, adjudicated source control review process applicable to future clinical trials.


Comparison of two methods for assessing diabetes risk in a pharmacy setting in Australia.
Since 2007, the Australian Know your numbers (KYN) program has been used in community settings to raise awareness about blood pressure and stroke. In 2011, the program was modified to include assessment for type 2 diabetes risk. However, it is unclear which approach for assessing diabetes risk in pharmacies is best. We compared two methods: random (non-fasting) blood glucose testing (RBGT); and the Australian type 2 diabetes risk assessment tool (AUSDRISK); according to 1) identification of 'high risk' participants including head-to-head sensitivity and specificity; 2) number of referrals to doctors; and 3) feasibility of implementation. 117 Queensland pharmacies voluntarily participated and were randomly allocated to RBGT and AUSDRISK or AUSDRISK only. Although discouraged, pharmacies were able to change allocated group prior to commencement. AUSDRISK is a validated self-administered questionnaire used to calculate a score that determines the 5-year risk of developing type 2 diabetes. AUSDRISK (score 12+) or RBGT (≥5.6 mmol/I) indicates a high potential risk of diabetes. Median linear regression was used to compare the two measures. Staff from 68 pharmacies also participated in a semi-structured interview during a site visit to provide feedback. Data were submitted for 5,483 KYN participants (60% female, 66% aged >55 years, 10% history of diabetes). Approximately half of the participants without existing diabetes were identified as 'high risk' based on either RBGT or AUSDRISK score. Among participants who undertook both measures, 32% recorded a high RBGT and high AUSDRISK. There was a significant association between RBGT and AUSDRISK scores. For every one point increase in AUSDRISK score there was a half point increase in RBGT levels (coefficient 0.55, 95% CI: 0.28, 0.83). Pharmacy staff reported that AUSDRISK was a simple, low cost and efficient method of assessing diabetes risk compared with RBGT, e.g. since management of sharps is not an issue. In a large, community-based sample of Australians about half of the participants without diabetes were at 'high risk 'of developing diabetes based on either AUSDRISK or RBGT results. AUSDRISK was considered to be an acceptable method for assessing the risk of diabetes using opportunistic health checks in community pharmacies.


Investigation of factors affecting crystallization of cyclopentane clathrate hydrate.
We report the results of systematic investigations of the influence of thermal history and other factors on crystallization of a model clathrate hydrate (cyclopentane hydrate) studied as water-in-oil and oil-in-water emulsions to remove the nucleation influence of substrates other than ice and hydrates. Hydrate and ice seem to form simultaneously under the conditions of these experiments, with ice forming preferentially. Thermal treatment, melting the ice, and leaving only the hydrate, promotes further hydrate formation. Not all the hydrate formed can be accounted for by the recrystallization of water freed by melting ice.


The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.
Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.