Comparison of long-term postoperative sequelae in patients with tetralogy of Fallot versus isolated pulmonic stenosis.
Patients with tetralogy of Fallot (TOF) after complete repair and pulmonic stenosis (PS) after surgical valvotomy often develop significant pulmonic regurgitation (PR) that eventually requires valve replacement. Although criteria exist for the timing of pulmonary valve replacement in TOF, it remains less clear when to intervene in valvotomy patients and whether TOF recommendations can be applied. Our aim was to compare the structural and functional sequelae of valvotomy for PS with complete repair for TOF. We compared the clinical characteristics, electrocardiograms, echocardiograms, cardiac magnetic resonance imaging (MRI), and invasive hemodynamics of 109 adults (34 PS and 75 TOF) newly referred to a congenital heart disease center for evaluation of PR between 2005 and 2012. Both cohorts were similar in terms of baseline demographics and presenting New York Heart Association function class. Valvotomy patients had a slightly greater degree of PR by echocardiogram, although it was similar by cardiac MRI. Electrocardiography QRS width was greater in patients with TOF (114±27 vs 150±28 ms, p<0.001). MRI right ventricular ejection fraction (49±8 vs 41±11%, p=0.001) and left ventricular ejection fraction (59±7 vs 52±10%, p=0.002) were lower in patients with TOF. Pacemaker or defibrillator implantation was significantly greater in patients with TOF (3% vs 23%, p=0.011). In conclusion, patients postvalvotomy and complete repair present with similar degrees of PR and severity of symptoms. Biventricular systolic function and electrocardiography QRS width appear less affected, suggesting morphologic changes in TOF and its repair that extend beyond the effects of PR. These findings suggest the need for developing disease-specific guidelines for patients with PR postvalvotomy.


[Comparative evaluation of the effectiveness of various physical training methods with patients who have had a myocardial infarct].
A total of 180 men were examined 4 months after myocardial infarction. The patients of the main group were randomised into subgroups according to the nature of physical training (PT). B2 subgroup did in-door therapy exercises with elements of games; B3 subgroup was assigned the same exercises, but received 5,2 mg of nitrong 1 hour prior to PT; B4 subgroup practiced bicycle ergometry with stable load comprising 50% of individual exercise tolerance. In B5 subgroup the stable load was 75% and in B6 subgroup the load was gradually increased (50-75-90% of individual exercise tolerance). All the patients participating in PT showed a considerable increase of the main indices of physical capacity (threshold power, maximal oxygen consumption, double product), which was accompanied by an improvement of their state and functional class. PT with pre-exercise nitrong, and bicycle ergometry with the load constituting 50% of the individual threshold power yielded the best results.


Dynamic performance of duolayers at the air/water interface. 2. Mechanistic insights from all-atom simulations.
The novel duolayer system, comprising a monolayer of ethylene glycol monooctadecyl ether (C18E1) and the water-soluble polymer poly(vinylpyrrolidone) (PVP), has been shown to resist forces such as wind stress to a greater degree than the C18E1 monolayer alone. This paper reports all-atom molecular dynamics simulations comparing the monolayer (C18E1 alone) and duolayer systems under an applied force parallel to the air/water interface. The simulations show that, due to the presence of PVP at the interface, the duolayer film exhibits an increase in chain tilt, ordering, and density, as well as a lower lateral velocity compared to the monolayer. These results provide a molecular rationale for the improved performance of the duolayer system under wind conditions, as well as an atomic-level explanation for the observed efficacy of the duolayer system as an evaporation suppressant, which may serve as a useful guide for future development for thin films where resistance to external perturbation is desirable.


Label-free, real-time on-chip sensing of living cells via grating-coupled surface plasmon resonance.
The application of nanotechnologies to address biomedical questions is a key strategy for innovation in biomedical research. Among others, a key point consists in the availability of nanotechnologies for monitoring cellular processes in a real-time and label-free approach. Here, we focused on a grating-coupled Surface Plasmon Resonance (GC-SPR) sensor exploiting phase interrogation. This sensor can be integrated in a microfluidic chamber that ensures cell viability and avoids cell stress. We report the calibration of the sensor response as a function of cell number and its application to monitor cell adhesion kinetics as well as cell response to an external stimulus. Our results show that GC-SPR sensors can offer a valuable alternative to prism-coupled or imaging SPR devices, amenable for microfluidic implementation.


Serum creatine kinase MB isoenzyme activity in long-term hemodialysis patients.
Serum creatine kinase MB isoenzyme (CK-MB) activity was determined in 46 male long-term hemodialysis patients without evidence of myocardial infarction. Thirteen (28.3%) showed mild elevations. The abnormality persisted in seven of eight patients on repeated measurement at three- to eight-month intervals. There was a significant correlation between serum CK-MB and CK-MN activity, and the activity of both enzymes rose after intramuscular injection. The reason for the abnormality is not known. It is possible that skeletal muscle is the source of elevated enzyme activity. Caution should be exercised in the interpretation of serum CK-MB activity in the diagnosis of acute myocardial infarction in this patient population.


Attempted experimental infection of domestic goats with Ehrlichia chaffeensis.
Although white-tailed deer (WTD; Odocoileus virginianus ) are considered the primary natural reservoir host for Ehrlichia chaffeensis, the causative agent of human monocytotropic ehrlichiosis, the potential role of other vertebrates as reservoir hosts has not been fully explored. Because domestic goats are naturally infected in areas where E. chaffeensis is endemic in deer, we evaluated the susceptibility of domestic goats to experimental infection with E. chaffeensis. A total of 12 goats were inoculated with E. chaffeensis (15B-WTD-GA or Ark strain)-infected DH82 cells by one of three routes: intravenously, subcutaneously, or intradermally. White-tailed deer simultaneously inoculated with the same dose, route, and inoculum served as positive controls; additional goats and WTD were included as negative controls. Evidence of E. chaffeensis infection was evaluated in all animals by indirect fluorescent antibody assay, PCR, and cell culture isolation techniques. All goats exposed to E. chaffeensis seroconverted by 14 days post-infection (DPI), and E. chaffeensis was isolated from one goat on 3 DPI; however, molecular or cell culture evidence of active infection was not detected in goats later than 3 DPI. White-tailed deer exhibited serologic and molecular evidence of E. chaffeensis infection throughout both trials, and E. chaffeensis was reisolated in cell culture from all infected WTD on numerous days post-infection. Our results suggest that despite the occurrence of natural infection in goats, this animal may not be susceptible to experimental infection and thus may not serve as a suitable model of E. chaffeensis reservoir host infection.


Dystrophin stabilizes alpha 3- but not alpha 7-containing nicotinic acetylcholine receptor subtypes at the postsynaptic apparatus in the mouse superior cervical ganglion.
The nicotinic acetylcholine receptor (nAChR) subtypes were characterized in the superior cervical ganglion (SCG) of wild-type and dystrophin-lacking mdx mice. The binding of Epibatidine and alphaBungarotoxin, ligands for alpha3- and alpha7-containing receptors, respectively, revealed, for each ligand, a single class of high-affinity binding sites, with similar affinity in both wild-type and mdx mice. The Epibatidine-labeled receptors were immunoprecipitated by antibodies against the alpha3, beta2, and beta4 subunits. Immunocytochemistry showed that the percentage of alpha3-, beta2-, and beta4- but not of alpha7-immunopositive postsynaptic specializations was significantly lower in mdx than in wild-type mouse SCG. These observations suggest that the mouse SCG contains nAChRs, stabilized by dystrophin, in which the alpha3 subunit is associated with the beta2 and/or beta4 subunits. Conversely, dystrophin is not involved in the stabilization of the alpha7-containing nAChRs, as the percentage of alpha7-immunopositive synapses is similar in both wild-type and mdx mouse SCG.


Identification of ultrasound contrast agent dilution systems for ejection fraction measurements.
Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study.


Antitumor effects and the underlying mechanism of licochalcone A combined with 5-fluorouracil in gastric cancer cells.
Licochalcone A (LCA) is a flavonoid extracted from licorice root that has antiparasitic, antibacterial and antitumor properties. Previous studies have revealed that LCA may be a novel treatment for gastric cancer. The present study further assessed the potential antitumor effects of LCA alone or in combination with 5-fluorouracil (5-FU), and the underlying mechanisms responsible for those effects in gastric cancer cells. The effects of LCA alone or in combination with 5-FU on SGC7901 and MKN-45 gastric cancer cell lines were studied using Cell Counting Kit-8, cell cycle, apoptosis and western blot analyses of cell check points and apoptosis-associated proteins. The results revealed that LCA inhibited cell proliferation, blocked cell cycle progression at the G2/M transition and induced apoptosis. Western blot analysis demonstrated that LCA treatment increased the levels of tumor proteins 21 and 27, as well as mouse double minute 2 homolog in gastric cancer cells. In addition, LCA treatment increased the expression levels of Bax, cleaved-poly ADP ribose polymerase, tumor protein 53 and caspase 3, and decreased the expression levels of Bcl-2. Therefore, the present study demonstrated that LCA alone or in combination with 5-FU may have significant anticancer effects on gastric cancer cells, and may be a novel therapeutic for the treatment of gastric cancer in the future.


Effect of eccentric exercise on muscle oxidative metabolism in humans.
The purpose of this study was to evaluate the effects of eccentric exercise on muscle oxidative function. Thirteen subjects performed high-intensity eccentric cycling for 30 min. Muscle oxidative function in vastus lateralis was evaluated by measurements of respiration in permeabilized muscle fibers (skinned fibers) and from the kinetics of oxyhemoglobin (oxyHb) saturation measured with near infrared spectroscopy (NIRS). After eccentric cycling, all subjects reported extensive delayed onset muscle soreness (DOMS), but plasma markers of muscle damage (creatine kinase and beta-glucuronidase activity) were not significantly altered. The half time of oxyHb desaturation after circulatory occlusion (128 +/- 11 s, mean +/- SE) and oxyHb resaturation after restoration of blood flow (13.8 +/- 0.7 s) were not significantly changed after eccentric cycling (N = 7). Respiration in skinned muscle fibers measured in the absence of ADP and in the presence of a submaximal (0.1 mM) or maximal ADP concentration (1 mM) was not significantly changed after eccentric cycling (N = 6). The sensitivity of respiration to ADP was not significantly changed after eccentric cycling. Muscle oxidative function (maximal respiration and respiratory control by ADP) was not compromised after high-intensity eccentric cycle exercise. Furthermore, NIRS indicates that after eccentric cycling muscle oxygen utilization and local oxygen transport at rest are unchanged. It is concluded that eccentric cycling, although causing DOMS, does not negatively affect skeletal muscle oxidative function.


Positive Effects of α-Lactalbumin in the Management of Symptoms of Polycystic Ovary Syndrome.
To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of natural molecules like inositols, overcoming the inositol resistance. However, due to its own aminoacidic building blocks, α-LA is involved in various biological processes that can open new additional applications. A great portion of women with PCOS exhibit gastrointestinal dysbiosis, which is in turn one of the triggering mechanisms of the syndrome. Due to its prebiotic effect, α-LA can recover dysbiosis, also improving the insulin resistance, obesity and intestinal inflammation frequently associated with PCOS. Further observations suggest that altered gut microbiota negatively influence mental wellbeing. Depressive mood and low serotonin levels are indeed common features of women with PCOS. Thanks to its content of tryptophan, which is the precursor of serotonin, and considering the strict link between gut and brain, using α-LA contributes to preserving mental well-being by maintaining high levels of serotonin. In addition, considering women with PCOS seeking pregnancy, both altered microbiota and serotonin levels can induce later consequences in the offspring. Therefore, a deeper knowledge of potential applications of α-LA is required to transition to preclinical and clinical studies extending its therapeutic advantages in PCOS.


[Left ventricular diastolic properties in dilated cardiomyopathy, transmural myocardial infarction, and hypertrophic cardiomyopathy].
Left ventricular (LV) diastolic properties in dilated cardiomyopathy (DCM), transmural myocardial infarction (TMI), and hypertrophic cardiomyopathy (HCM) were evaluated. Radionuclide angiography and M-mode echocardiography were performed for 11 cases of DCM, 40 cases of TMI, 21 cases of HCM, and nine normal control subjects. In DCM, the peak filling rate (PFR) and filling fraction (FF) were significantly reduced, but the time to the peak filling rate (TPFR) was not prolonged. In TMI, both the PFR and FF were significantly reduced. Moreover, the TPFR was significantly prolonged in TMI as compared to DCM. Although depression of the PFR in HCM was not apparent, prolongation of the TPFR in HCM was marked. In DCM, there was good correlation between the PFR and left ventricular ejection fraction (EF) (r = 0.71, p less than 0.03). In TMI, there was a good correlation between the TPFR and the standard deviation of the LV phase angle histogram (SDP), indicating LV asynergy (r = 0.589, p less than 0.005). In HCM, both the FF and PFR correlated inversely with the LV wall thickness (r = -0.74, p less than 0.008; r = -0.581, p less than 0.03, respectively). These results indicate that various factors affect LV diastolic properties in heart disease, and that radionuclide angiography is a valuable technique for evaluating LV diastolic function.


Diagnostic and Prognostic Value of Circulating MicroRNAs for Esophageal Squamous Cell Carcinoma: a Systematic Review and Meta-analysis.
Background and Aim: MicroRNAs, dysregulated in the circulation of esophageal squamous cell carcinoma (ESCC) patient, have been assumed to be with great potential in the diagnosis and prognosis of esophageal cancer. We aimed to review previous articles on ESCC. Methods: A search of electronic databases was performed before Nov 12, 2017. We summarized the identification of microRNA imbalance in the blood of ESCC compared with the healthy controls, with the objective to evaluate the efficiency of microRNAs in diagnosing and forecasting ESCC. Results: A total of 35 studies investigating plasma or serum microRNAs were included in the meta-analysis. Based on the consequences of the quality assessment of each study, the articles involved were appropriate for quantitative synthesis. For diagnostic meta-analysis. The overall pooled sensitivity, specificity, and area under the curve of circulating microRNA is 0.794 (95% CI: 0.765 - 0.820), 0.779 (95%CI: 0.746 - 0.808), 0.86 (95%CI: 0.82 - 0.88). The diagnostic value of each microRNA was calculated respectively. For prognostic meta-analysis, the overall pooled hazard ratios of higher microRNA expression in circulation was 1.34 (95% CI: 1.14-1.58), which could significantly predict poorer survival in ESCC. Conclusions: Circulating microRNAs distinguish patients with ESCC from healthy controls with high sensitivity and specificity, compared to other invasive currently used screening methods. Simultaneously, there was prognostic value for the prognosis of ESCC.


Antifungal and antiovarian cancer properties of α Fe2O3 and α Fe2O3/ZnO nanostructures synthesised by Spirulina platensis.
Candida albicans (C. albicans) infection shows a growing burden on human health, and it has become challenging to search for treatment. Therefore, this work focused on the antifungal activity, and cytotoxic effect of biosynthesised nanostructures on human ovarian tetracarcinoma cells PA1 and their corresponding mechanism of cell death. Herein, the authors fabricated advanced biosynthesis of uncoated α-Fe2O3 and coated α-Fe2O3 nanostructures by using the carbohydrate of Spirulina platensis. The physicochemical features of nanostructures were characterised by UV-visible, high resolution transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The antifungal activity of these nanostructures against C. albicans was studied by the broth dilution method, and examined by 2', 7'-dichlorofluorescein diacetate staining. However, their cytotoxic effects against PA1 cell lines were evaluated by MTT and comet assays. Results indicated characteristic rod-shaped nanostructures, and increasing the average size of α-Fe2O3@ZnO nanocomposite (105.2 nm × 29.1 nm) to five times as compared to α-Fe2O3 nanoparticles (20.73nm × 5.25 nm). The surface coating of α-Fe2O3 by ZnO has increased its antifungal efficiency against C. albicans. Moreover, the MTT results revealed that α-Fe2O3@ZnO nanocomposite reduces PA1 cell proliferation due to DNA fragmentation (IC50 18.5 μg/ml). Continual advances of green nanotechnology and promising findings of this study are in favour of using the construction of rod-shaped nanostructures for therapeutic applications.


Radiation dose estimate in small animal SPECT and PET.
Calculations of radiation dose are important in assessing the medical and biological implications of ionizing radiation in medical imaging techniques such as SPECT and PET. In contrast, radiation dose estimates of SPECT and PET imaging of small animals are not very well established. For that reason we have estimated the whole-body radiation dose to mice and rats for isotopes such as 18F, 99mTc, 201Tl, (111)In, 123I, and 125I that are used commonly for small animal imaging. We have approximated mouse and rat bodies with uniform soft tissue equivalent ellipsoids. The mouse and rat sized ellipsoids had a mass of 30 g and 300 g, respectively, and a ratio of the principal axes of 1:1:4 and 0.7:1:4. The absorbed fractions for various photon energies have been calculated using the Monte Carlo software package MCNP. Using these values, we then calculated MIRD S-values for two geometries that model the distribution of activity in the animal body: (a) a central point source and (b) a homogeneously distributed source, and compared these values against S-value calculations for small ellipsoids tabulated in MIRD Pamphlet 8 to validate our results. Finally we calculated the radiation dose taking into account the biological half-life of the radiopharmaceuticals and the amount of activity administered. Our calculations produced S-values between 1.06 x 10(-13) Gy/Bq s and 2.77 x 10(-13) Gy/Bq s for SPECT agents, and 15.0 x 10(-13) Gy/Bq s for the PET agent 18F, assuming mouse sized ellipsoids with uniform source distribution. The S-values for a central point source in an ellipsoid are about 10% higher than the values obtained for the uniform source distribution. Furthermore, the S-values for mouse sized ellipsoids are approximately 10 times higher than for the rat sized ellipsoids reflecting the difference in mass. We reviewed published data to obtain administered radioactivity and residence times for small animal imaging. From these values and our computed S-values we estimated that the whole body dose in small animals ranges between 6 cGy and 90 cGy for mice and between about 1 cGy and 27 cGy for rats. The whole body dose in small animal imaging can be very high in comparison to the lethal dose to mice (LD50/30 approximately 7 Gy). For this reason the dose in small animal imaging should be monitored carefully and the administered activity should be kept to a minimum. These results also underscore the need of further development of instrumentation that improves detection efficiency and reduces radiation dose in small animal imaging.


Cloning of the ADPglucose pyrophosphorylase (glgC) and glycogen synthase (glgA) structural genes from Salmonella typhimurium LT2.
The structural genes of ADPglucose pyrophosphorylase (glgC) and glycogen synthase (glgA) from Salmonella typhimurium LT2 were cloned on a 5.8-kilobase-pair insert in the SalI site of pBR322. A single strand specific radioactive probe containing the N terminus of the Escherichia coli K-12 glgC gene in M13mp8 was used to hybridize against a S. typhimurium genomic library in lambda 1059. DNA from a plaque showing a positive hybridization signal was isolated, subcloned into pBR322, and transformed into E. coli K-12 RR1 and E. coli G6MD3 (a mutant with a deletion of the glg genes). Transformants were stained with iodine for the presence of glycogen. E. coli K-12 RR1 transformants stained dark brown, whereas G6MD3 transformants stained greenish yellow, and they both were shown to contain a 5.8-kilobase-pair insert in the SalI site of pBR322, designated pPL301. Enzyme assays of E. coli K-12 G6MD3 harboring pPL301 restored ADPglucose pyrophosphorylase and glycogen synthase activities. The specific activities of ADPglucose pyrophosphorylase and glycogen synthase in E. coli K-12 RR1(pPL301) were increased 6- to 7-fold and 13- to 15-fold, respectively. Immunological and kinetic studies showed that the expressed ADPglucose pyrophosphorylase activity in transformed E. coli K-12 G6MD3 cells was very similar to that of the wild-type enzyme.


[New methods of determination of the functional peculiarities of autoantibodies in various types of autoimmune reactions].
Anderson's method (with our modification of Jerne's method) was applied in experiments on 574 albino female mice; a study was made of the affinity of autoantibodies in three groups of animals: intact, gamma (Co60) irradiated in a dose of 600 r, and with stimulation of auto-immune reaction by injection of a complete adjuvant (0.05 ml subcutaneously) or injection of living E. coli cells (subcutaneously 300 million) or hemostimulation (subcutaneously 0.1--0.3 or 0.5 ml of homologous blood). The maximal autoantibody indices were obtained in the irradiated mice, the least -- in the intact animals. Apart from the plaque-formation inhibition phenomenon, there were observed two more phenomena; these were an immune erythrocyte adherence to the immunocompetent cells and a marked increase in the formation of plaques of autoimmune hemolysis in the preparation with addition of diluted (1:10) lysate of erythrocytes obtained from mice with the administration of an adjuvant or homologous blood.


Reorganizing medical education.
The education of doctors has not kept up with changes in medicine, medical technology and the organization of health services. Training at undergraduate and postgraduate level can be rigid and is at times inappropriate. Continuing medical education needs expansion. A review of the work and lifestyle of junior hospital doctors is needed.


Person transfer assist systems: a literature review.
Novel developments in the robotics field have produced systems that can support person wheelchair transfers, maximize safety and reduce caregiver burden. The purpose of this study was to identify and describe these systems, their usability (or satisfaction), the context for which they have been or can be used and how they have been evaluated to determine evidence for their effectiveness. Available research on Person Transfer Assist Systems (PTAS) was systematically gathered using similar standards to the PRISMA guidelines. The search terms were derived from common terms and via exploring similar review articles. Initial search terms displayed 1330 articles and by using the inclusion/exclusion criteria 96 articles were selected for abstract review. After full- text reviewing 48 articles were included. 29 articles concerned research in robotic transfer systems, 10 articles used both ceiling and floor-mounted lifts and 9 articles used only floor-mounted lifts as an intervention/control group. The results of this analysis identified a few usability evaluations for robotic transfer prototypes, especially ones comparing prototypes to existing marketed devices. Robotic device research is a recent development within assistive technology. Whilst usability evaluations provided evidence that a robotic device will provide better service to the user, the sample number of subjects used are minimal in comparison to any of the intervention/control group articles. Experimental studies between PTASs are required to support technological advancements. Caregiver injury risk has been the focus for most of the comparison articles; however, few articles focus on the implications to the person.IMPLICATIONS FOR REHABILITATIONCeiling mounted lifts are preferred over floor-based lifts due to lower injury rates.Many robotic transfer systems have been developed; however, there is a paucity of quantitative and qualitative studies.Based on the results of this review, rehabilitation settings are recommended to use ceiling over floor assist systems, and it is recommended to provide training on using devices to assist with patient transfers to lower the risk of injuries.


Genomic Data Reveal Conserved Female Heterogamety in Giant Salamanders with Gigantic Nuclear Genomes.
Systems of genetic sex determination and the homology of sex chromosomes in different taxa vary greatly across vertebrates. Much progress remains to be made in understanding systems of genetic sex determination in non-model organisms, especially those with homomorphic sex chromosomes and/or large genomes. We used reduced representation genome sequencing to investigate genetic sex determination systems in the salamander family Cryptobranchidae (genera Cryptobranchus and Andrias), which typifies both of these inherent difficulties. We tested hypotheses of male- or female-heterogamety by sequencing hundreds of thousands of anonymous genomic regions in a panel of known-sex cryptobranchids and characterized patterns of presence/absence, inferred zygosity, and depth of coverage to identify sex-linked regions of these 56 gigabase genomes. Our results strongly support the hypothesis that all cryptobranchid species possess homologous systems of female heterogamety, despite maintenance of homomorphic sex chromosomes over nearly 60 million years. Additionally, we report a robust, non-invasive genetic assay for sex diagnosis in Cryptobranchus and Andrias which may have great utility for conservation efforts with these endangered salamanders. Co-amplification of these W-linked markers in both cryptobranchid genera provides evidence for long-term sex chromosome stasis in one of the most divergent salamander lineages. These findings inform hypotheses about the ancestral mode of sex determination in salamanders, but suggest that comparative data from other salamander families are needed. Our results further demonstrate that massive genomes are not necessarily a barrier to effective genome-wide sequencing and that the resulting data can be highly informative about sex determination systems in taxa with homomorphic sex chromosomes.


Benign Breast Disease and Breast Cancer Risk in the Percutaneous Biopsy Era.
Benign breast disease (BBD) comprises approximately 75% of breast biopsy diagnoses. Surgical biopsy specimens diagnosed as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH) are associated with increasing breast cancer (BC) risk; however, knowledge is limited on risk associated with percutaneously diagnosed BBD. To estimate BC risk associated with BBD in the percutaneous biopsy era irrespective of surgical biopsy. In this retrospective cohort study, BBD biopsy specimens collected from January 1, 2002, to December 31, 2013, from patients with BBD at Mayo Clinic in Rochester, Minnesota, were reviewed by 2 pathologists masked to outcomes. Women were followed up from 6 months after biopsy until censoring, BC diagnosis, or December 31, 2021. Benign breast disease classification and multiplicity by pathology panel review. The main outcome was diagnosis of BC overall and stratified as ductal carcinoma in situ (DCIS) or invasive BC. Risk for presence vs absence of BBD lesions was assessed by Cox proportional hazards regression. Risk in patients with BBD compared with female breast cancer incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) program were estimated. Among 4819 female participants, median age was 51 years (IQR, 43-62 years). Median follow-up was 10.9 years (IQR, 7.7-14.2 years) for control individuals without BC vs 6.6 years (IQR, 3.7-10.1 years) for patients with BC. Risk was higher in the cohort with BBD than in SEER data: BC overall (standard incidence ratio [SIR], 1.95; 95% CI, 1.76-2.17), invasive BC (SIR, 1.56; 95% CI, 1.37-1.78), and DCIS (SIR, 3.10; 95% CI, 2.54-3.77). The SIRs increased with increasing BBD severity (1.42 [95% CI, 1.19-1.71] for NP, 2.19 [95% CI, 1.88-2.54] for PDWA, and 3.91 [95% CI, 2.97-5.14] for AH), comparable to surgical cohorts with BBD. Risk also increased with increasing lesion multiplicity (SIR: 2.40 [95% CI, 2.06-2.79] for ≥3 foci of NP, 3.72 [95% CI, 2.31-5.99] for ≥3 foci of PDWA, and 5.29 [95% CI, 3.37-8.29] for ≥3 foci of AH). Ten-year BC cumulative incidence was 4.3% for NP, 6.6% for PDWA, and 14.6% for AH vs an expected population cumulative incidence of 2.9%. In this contemporary cohort study of women diagnosed with BBD in the percutaneous biopsy era, overall risk of BC was increased vs the general population (DCIS and invasive cancer combined), similar to that in historical BBD cohorts. Development and validation of pathologic classifications including both BBD severity and multiplicity may enable improved BC risk stratification.


Gentle cyclic straining of human fibroblasts on electrospun scaffolds enhances their regenerative potential.
The extracellular matrix of fascia-like tissues is a resilient network of collagenous fibers that withstand the forces of daily life. When overstretched, the matrix may tear, with serious consequences like pelvic organ prolapse (POP). Synthetic implants can provide mechanical support and evoke a host response that induces new matrix production, thus reinforcing the fascia. However, there is considerable risk of scar formation and tissue contraction which result in severe complications. Matrix producing fibroblasts are both mechanosensitive and contractile; their behavior depends on the implant's surface texture and mechanical straining. Here we investigate the effect of both in a newly-designed experimental setting. Electrospun scaffolds of Nylon and PLGA/PCL and a non-porous PLGA/PCL film were clamped like a drumhead and seeded with fibroblasts of POP patients. Upon confluency, scaffolds were cyclically strained for 24 or 72 h at 10% and 0.2 Hz, mimicking gentle breathing. Non-loading condition was control. Strained fibroblasts loosened their actin-fibers, thereby preventing myofibroblastic differentiation. Mechanical loading upregulated genes involved in matrix synthesis (collagen I, III, V and elastin), matrix remodeling (α-SMA, TGF-β1, MMP-2) and inflammation (COX-2, TNF-α, IL8, IL1-β). Collagen genes were expressed earlier under mechanical loading and the ratio of I/III collagen increased. Matrix synthesis and remodeling were stronger on the electrospun scaffolds, while inflammation was more prominent on the non-porous film. Our findings indicate that mechanical straining enhances the regenerative potential of fibroblasts for the regeneration of fascia-type tissues and limit the risk of scar tissue formation. These effects are stronger on an electrospun texture. STATEMENT OF SIGNIFICANCE: Pelvic organ prolapsed is a dysfunctional disease in female pelvic floor that can reduce the quality of life women. Currently, trans-vaginal knitted meshes are used to anatomically correct the dysfunctional tissues. However, the meshes can create sever adverse complications in some patients (e.g. chronic pain) in longer-term. As an alternative, we developed nanofibrous matrices by electrospinning based on different materials. We designed an in-vitro culture system and subjected cell-seeded matrices to cyclic mechanical loading. Results revealed that gentle straining of POP-cells on electrospun matrices, advances their regenerative potential at morphological and gene expression levels. Our findings, provide a proof-of-concept for using electrospun matrices as an alternative implant for pelvic floor repair, given that the parameters are designed efficiently and safely.


Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.
The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.


Intraspecific genetic variability and diurnal activity affect environmental DNA detection in Japanese eel.
Environmental DNA (eDNA) analysis with species-specific primer/probe sets is promising as a tool to quantify fish abundance and distribution. Nevertheless, several factors could reduce the accuracy of this method. Here, we aimed to analyze whether intraspecific variability and diel activity rhythm affect eDNA detection in Japanese eels (Anguilla japonica). For this purpose, we performed tank experiments focusing on two points. First, we assessed the effects of base pair sequences with probe region polymorphism on eDNA detection. Next, we evaluated the influences of diel rhythm, activity, and individual differences in eDNA release rate on eDNA concentration. We examined the base pair sequences of the probe regions of 20 individuals and found genetic mismatches in two of them. The eDNA concentration was estimated to be much lower in these variants than it was in the other individuals. We conducted a rearing experiment on four non-variant individuals to explore the influences of diel activity and inter-individual differences in eDNA detection. Nocturnal eel activity was reflected in the eDNA detection but the inter-individual differences remained large. The observed weak positive correlations between eDNA concentration and activity suggest that eDNA emission is highly dependent on basal metabolism. The present study suggests that consideration of polymorphic sites at the probe region and diel activity rhythms should improve the accuracy and precision of abundance estimation through eDNA. Such fine-tuning is applicable not only for eels but also for other fishes to be targeted by eDNA technology.


The effects of Brazilian propolis on etiological agents of mastitis and the viability of bovine mammary gland explants.
The objective of this study was to evaluate in vitro the antimicrobial activity of Brazilian propolis from Urupema, São Joaquim, and Agua Doce (Santa Catarina State) and green propolis from Minas Gerais State, and the effects of propolis on bovine mammary gland explant viability. The propolis samples differed in flavonoid content and antioxidant activity. Green propolis showed the highest content of flavonoids, followed by the sample from São Joaquim. The propolis from Urupema showed the lowest flavonoid content along with the lowest antioxidant activity. The total phenolics were similar across all studied samples. Despite phytochemical differences, the propolis samples from Minas Gerais, São Joaquim, and Urupema presented the same level of antimicrobial activity against Staphylococcus aureus strains. The reduction in S. aureus growth was, on average, 1.5 and 4 log10 times at 200 and 500 μg/mL, respectively. At concentrations of 1,000 μg/mL, all propolis reduced bacterial growth to zero. On the other hand, when the propolis were tested against strains of Escherichia coli, the samples presented weak antimicrobial activity. Mammary explants were maintained in culture for 96h without a loss in viability, demonstrating the applicability of the model in evaluating the toxicity of propolis. The origin and chemical composition of the propolis had an effect on mammary explant viability. We encountered inhibitory concentrations of 272.4, 171.8, 63.85, and 13.26 μg/mL for the propolis from Água Doce, Urupema, São Joaquim, and Mina Gerais, respectively. A clear association between greater antimicrobial activity and toxicity for mammary explants was observed. Of all propolis tested, the Urupema sample was noteworthy, as it showed antimicrobial activity at less toxic concentrations than the other samples, reducing bacterial growth to an average of 9.3 × 10(2) cfu/mL after 6h of contact using 200 μg/mL of extract. The results demonstrate the potential for Brazilian propolis in the treatment of mastitis, although effectiveness is dependent on geographical origin and concentration. The results from the mammary gland explant assays are promising for the investigation of other natural products with antimicrobial and anti-inflammatory properties that can be used in the intramammary treatment of subclinical mastitis and during dry cow therapy.


Deregulated Long Non-Coding RNA HCG11 in Cerebral Atherosclerosis Serves as a Biomarker to Predict the Risk of Cerebrovascular Events.
Carotid artery stenosis (CAS) is one of the main risk factors of ischemic stroke (IS), which needs a screening and monitoring biomarker. The study focused on the clinical significance of long non-coding RNA (lncRNA) HCG11 in CAS patients aiming to identify a potential therapeutic target for CAS. Serum samples were collected from 70 CAS patients and 80 age- and gender-matched healthy people. HCG11 levels were measured via quantitative real-time PCR (qRT-PCR), and its significance in CAS identification and development prediction was also assessed. HCG11 was enriched in the serum of CAS patients, and serves as a possible biomarker for disease diagnosis with the area under the curve (AUC) of 0.930. Elevated expression of HCG11 was significantly correlated with hypertension, dyslipidemia, and degree of carotid stenosis. HCG11 was highly expressed in severe CAS cases compared to moderate ones, which was positively related to the disease severity. Cox regression analysis determined the close relationship of serum HCG11 with the occurrence of cerebral ischemia events. CAS patients with high HCG11 expression showed a high occurrence rate of cerebral ischemia events. The upregulation of HCG11 could serve as a potential diagnostic biomarker for CAS and is positively related to the disease severity. Serum HCG11 can independently predict the occurrence of following cerebral ischemia events.


Blastobotrys baotianmanensis sp. nov. and Blastobotrys xishuangbannaensis f.a., sp. nov., two novel yeast species associated with insects and rotting wood.
Five yeast strains were isolated from the gut of the groundbeetle Pterostichus gebleri and rotting wood, which were collected from two different localities in China. These strains were identified as representing two novel species of the genus Blastobotrys through comparison of sequences in the D1/D2 domains of the LSU rRNA gene and other taxonomic characteristics. Blastobotrys baotianmanensis sp. nov. produces two to three spherical ascospores per ascus, and is most closely related to the type strains of B. elegans, B. capitulata, B. arbuscula, and an undescribed species represented by strain BG02-7-20-006A-3-1. Blastobotrys baotianmanensis sp. nov. differed from these strains by 3.6-8.4 % divergence (21-46 substitutions and 0-4 gaps) in the D1/D2 sequences. Blastobotrys xishuangbannaensis f.a., sp. nov. is closely related to B. nivea, B. elegans and B. aristata but the formation of ascospores was not observed on various sporulation media, and it differed from its relatives by 6.2-8.5 % divergence (34-43 substitutions and 2-6 gaps) in the D1/D2 sequences. The holotype of Blastobotrys baotianmanensis sp. nov. is NYNU 1581 and the holotype of Blastobotrys xishuangbannaensis f.a., sp. nov. is NYNU 181030.


Effects of acupressure on menstrual distress in adolescent girls: a comparison between Hegu-Sanyinjiao matched points and Hegu, Zusanli single point.
To examine a comparison between Hegu and Sanyinjiao matched points and Hegu, Zusanli single point on adolescent girls' menstrual distress, pain and anxiety perception. Primary dysmenorrhoea is a major cause of temporary disability, with a prevalence ranging from 60-93%, depending upon the population and study. No one has yet compared the effects of single point and multiple point acupressures. Design. A single blind randomised experimental study was used. Adolescents (n = 134) randomly assigned to experimental groups Zusanli (n = 30), Hegu (n = 33) and Hegu-Sanyinjiao Matched Points (n = 36) received acupressure intervention protocol for 20 minutes, while the control group (n = 35) did not receive any acupressure intervention. Four instruments were used to collect data: (1) the Visual Analog Scale for Pain; (2) the Menstrual Distress Questionnaire Short Form; (3) the Short-Form McGill Pain Questionnaire and (4) the Visual Analog Scale for Anxiety. During the six-month follow-up, acupressure at matched points Hegu and Sanyinjiao reduced the pain, distress and anxiety typical of dysmenorrhoea. Acupressure at single point Hegu was found, effectively, to reduce menstrual pain during the follow-up period, but no significant difference for reducing menstrual distress and anxiety perception was found. Zusanli acupressure had no significant effects of reducing menstrual pain, distress and anxiety perception. This controlled trial provides preliminary evidence that six-month acupressure therapy provides female adolescents with dysmenorrhoea benefits. Acupressure is an effective and safe non-pharmacologic strategy for the treatment of primary dysmenorrhoea. We recommend the use of acupressure for self-care of primary dysmenorrhoea at Hegu and Sanyinjiao matched points and single point Hegu, as pressure placement at these points is easy for adolescent girls to learn and practice.


5'-Terminal nucleotide sequence of Escherichia coli lactose repressor mRNA: features of translational initiation and reinitiation sites.
In a sequence of 214 nucleotides at the 5' terminus of the I gene mRNA, which codes for the lactose repressor protein of Escherichia coli, (i) an untranslated leader sequence of 28 residues precedes the repressor coding region; (ii) a GUG initiates synthesis of the wild-type repressor; (iii) GUG and AUG are the functional initiators for the synthesis of restart polypeptides activated by early I gene amber mutations, confirming previous assignments for these residues based on protein sequencing data; and (iv) sequences complementary to 16S ribosomal RNA provide stronger potential mRNA.16S rRNA interaction at the wild-type initiation site than at the restart sites. When I mRNA is used to direct the formation of initiation complexes in vitro, ribosomes bind only to the wild-type initiator region.A striking feature of the I mRNA sequence is the presence of a number of in-phase GUGs that have not been observed to serve as initiation signals in vivo in the nonsense mutant strains examined. The selective use of potential initiator triplets in the I mRNA leads to the following conclusions. First, when presented with several neighboring initiator triplets at the wild-type initiator region, ribosomes select the one preceded by the strongest appropriately positioned complementarity to the 16S 3' end. Second, ribosomes do not restart after termination simply by moving to the next available initiator codon. Third, the formation of stable secondary structures predicted for the untranslated I mRNA beyond chain-terminating nonsense mutations may prevent ribosome access to some potential reinitiation sites.


A cost-minimisation analysis of lobectomy: thoracoscopic versus posterolateral thoracotomy.
Recent evidence suggests that lobectomy performed either through thoracoscopy (TL) or via a posterolateral thoracotomy (PLT) produces equivalent oncologic outcomes in appropriately selected patients. Advantages of thoracoscopic lobectomy include decreased postoperative pain, shorter length of stay, fewer postoperative complications and better compliance with adjuvant chemotherapy. This study evaluates the costs associated with lobectomy performed thoracoscopically or via thoracotomy. This is a retrospective analysis of actual costing and prospectively collected health-related quality of life (QOL) outcomes. Between 2002 and 2004, 113 patients underwent lobectomy (PLT: n=37; TL: n=76) and completed QOL assessments both preoperatively and 1-year postoperatively. Actual fixed and variable direct costs from the preoperative, hospitalisation and 30-day postoperative phases were captured using a T1 cost accounting system and were combined with actual professional collections. Cost-utility analysis was performed by transforming a global QOL measurement to an estimate of utility and calculating a quality-adjusted life year (QALY) for each patient. Baseline characteristics were similar in the two groups. Total costs (USD) were significantly greater for the strategy of PLT (USD 12,119) than for TL (USD 10,084; p=0.0012). Even when only stage I and II lung cancers were included (n=32 PLT, n=69 TL), total costs for PLT were still higher than that for TL (USD 11,998 vs USD 10,120; p=0.005). The mean QALY for the PLT group was 0.74+/-0.22 and for the TL group was 0.72+/-0.18 (p=0.68). In this retrospective analysis, TL was significantly less expensive than PLT from the preoperative evaluation through 30 days postoperatively, with overall savings of approximately USD 2000 per patient. In light of equivalent QALY outcomes, this cost-utility analysis supports increased adoption of TL as a cost-minimisation strategy. The use of TL for the 50,000 lobectomies performed in the United States each year would represent a savings of approximately USD 100 million.


Rationale and design of a patient-centered medical home intervention for patients with end-stage renal disease on hemodialysis.
In the U.S., more than 400,000 individuals with end-stage renal disease (ESRD) require hemodialysis (HD) for renal replacement therapy. ESRD patients experience a high burden of morbidity, mortality, resource utilization, and poor quality of life (QOL). Under current care models, ESRD patients receive fragmented care from multiple providers at multiple locations. The Patient-Centered Medical Home (PCMH) is a team approach, providing coordinated care across the healthcare continuum. While this model has shown some early benefits for complex chronic diseases such as diabetes, it has not been applied to HD patients. This study is a non-randomized quasi-experimental intervention trial implementing a Patient-Centered Medical Home for Kidney Disease (PCMH-KD). The PCMH-KD extends the existing dialysis care team (comprised of a nephrologist, dialysis nurse, dialysis technician, social worker, and dietitian) by adding a general internist, pharmacist, nurse coordinator, and a community health worker, all of whom will see the patients together, and separately, as needed. The primary goal is to implement a comprehensive, multidisciplinary care team to improve care coordination, quality of life, and healthcare use for HD patients. Approximately 240 patients will be recruited from two sites; a non-profit university-affiliated dialysis center and an independent for-profit dialysis center. Outcomes include (i) patient-reported outcomes, including QOL and satisfaction; (ii) clinical outcomes, including blood pressure and diet; (iii) healthcare use, including emergency room visits and hospitalizations; and (iv) staff perceptions. Given the significant burden that patients with ESRD on HD experience, enhanced care coordination provides an opportunity to reduce this burden and improve QOL.


Host protein interactions with the 3' end of bovine coronavirus RNA and the requirement of the poly(A) tail for coronavirus defective genome replication.
RNA viruses have 5' and 3' untranslated regions (UTRs) that contain specific signals for RNA synthesis. The coronavirus genome is capped at the 5' end and has a 3' UTR that consists of 300 to 500 nucleotides (nt) plus a poly(A) tail. To further our understanding of coronavirus replication, we have begun to examine the involvement of host factors in this process for two group II viruses, bovine coronavirus (BCV) and mouse hepatitis coronavirus (MHV). Specific host protein interactions with the BCV 3' UTR [287 nt plus poly(A) tail] were identified using gel mobility shift assays. Competition with the MHV 3' UTR [301 nt plus poly(A) tail] suggests that the interactions are conserved for the two viruses. Proteins with molecular masses of 99, 95, and 73 kDa were detected in UV cross-linking experiments. Less heavily labeled proteins were also detected in the ranges of 40 to 50 and 30 kDa. The poly(A) tail was required for binding of the 73-kDa protein. Immunoprecipitation of UV-cross-linked proteins identified the 73-kDa protein as the cytoplasmic poly(A)-binding protein (PABP). Replication of the defective genomes BCV Drep and MHV MIDI-C, along with several mutants, was used to determine the importance of the poly(A) tail. Defective genomes with shortened poly(A) tails consisting of 5 or 10 A residues were replicated after transfection into helper virus-infected cells. BCV Drep RNA that lacked a poly(A) tail did not replicate, whereas replication of MHV MIDI-C RNA with a deleted tail was detected after several virus passages. All mutants exhibited delayed kinetics of replication. Detectable extension or addition of the poly(A) tail to the mutants correlated with the appearance of these RNAs in the replication assay. RNAs with shortened poly(A) tails exhibited less in vitro PABP binding, suggesting that decreased interactions with the protein may affect RNA replication. The data strongly indicate that the poly(A) tail is an important cis-acting signal for coronavirus replication.


Lipophilic extracts from leaves, inflorescences and fruits of Prunus padus L. as potential sources of corosolic, ursolic and oleanolic acids with anti-inflammatory activity.
Chloroform extracts from leaves, inflorescences and fruits of Prunus padus were analysed for anti-inflammatory activity and accumulation of corosolic (CA), ursolic (UA) and oleanolic (OA) acids. The analytes were identified and quantified by GC-MS and UHPLC-PDA. Their total levels depend on plant material type and harvesting time, and varied from 0.25 mg/g DW in fruits, through 0.76-1.09 mg/g DW in flowers, to 1.41-4.54 mg/g DW in leaves. Significant variation in the leaf analytes contents was observed during vegetation with the peak amounts in autumn, which indicated the optimal harvesting season. The plant extracts inhibited pro-inflammatory enzymes (lipoxygenase and hyaluronidase) in a concentration-dependent manner, and their activity parameters correlated with the levels and activity of pure triterpene acids, especially CA and UA. The results of the comparison with the positive controls (heparin, indomethacin, dexamethasone) might partly support the application of P. padus in anti-inflammatory therapies, reported by traditional medicine.


Commentary: An Equitable Approach to Serving Structurally Marginalized Communities.
As the United States grapples with social injustices, greater attention is being placed on the historical lack of equity practices among health and social service organizations that serve marginalized and predominantly racially minoritized communities. We describe strategies health and social service organizations that partner with community-led organizations must take to ensure actionable equitable changes. The opportunity and promise are upon us to resolve health inequities and promote equity-oriented practices, policies, systems, and social-environmental changes.


BioGRID: A Resource for Studying Biological Interactions in Yeast.
The Biological General Repository for Interaction Datasets (BioGRID) is a freely available public database that provides the biological and biomedical research communities with curated protein and genetic interaction data. Structured experimental evidence codes, an intuitive search interface, and visualization tools enable the discovery of individual gene, protein, or biological network function. BioGRID houses interaction data for the major model organism species--including yeast, nematode, fly, zebrafish, mouse, and human--with particular emphasis on the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe as pioneer eukaryotic models for network biology. BioGRID has achieved comprehensive curation coverage of the entire literature for these two major yeast models, which is actively maintained through monthly curation updates. As of September 2015, BioGRID houses approximately 335,400 biological interactions for budding yeast and approximately 67,800 interactions for fission yeast. BioGRID also supports an integrated posttranslational modification (PTM) viewer that incorporates more than 20,100 yeast phosphorylation sites curated through its sister database, the PhosphoGRID.


An Analysis of Global Research Trends in Cardiology Over the Last two Decades.
Heart disease today is a major cause of morbidity and mortality plaguing mankind worldwide. The present research was undertaken to ascertain global research trends in clinical trials in Cardiology involving human subjects over the last two decades. Cross-sectional study. A detailed search strategy was employed in December 2013, using the PubMed database. All papers published in 1993-2013 were evaluated. The research trends of various cardiologic subspecialties in the United States and worldwide have been analysed and detailed statistical analysis was done. United States had maximum number of researches. Clinical trials involving infarction were maximum followed by coronary angiography and coronary angioplasty in that order. The year 2013 had the most researches. The United States was the top country and Boston was the top city. Author Christodoulos Stefanadis had the greatest number of researches in this field. American Journal of Cardiology was the most favored journal and Circulation was the journal with the highest impact factor. This effort may help funding agencies, prospective job seekers, fellowship applicants, policymakers and patients Conclusion: The research output in cardiology has increased and improved significantly over past decade. The publication per diplomat is more in transplant cardiology, Also more clinical trials involving coronary restenosis have to be done to know in depth to add to current knowledge and database.


Limb Rotation in Lower Extremity Fractures.
Fractures of the tibia and femur are common. Rotation of the limb can affect the outcome of the injury, both in the immediate term and the long term. Because plain radiographs are two dimensional, rotation is hard to assess radiographically. As a result, rotational malalignment is common. It is important to provide technical tips on the assessment of rotation preoperatively, intraoperatively, and postoperatively. The goal is to better assess rotation so that deformity can be minimized. This applies to fractures of the tibia and femur. Even after careful treatment, rotational deformities can occur. When they are symptomatic, correction should be considered. Techniques for correction of malrotation of both tibial and femoral fractures are presented.


Community Event-Based Surveillance for Ebola Virus Disease in Sierra Leone: Implementation of a National-Level System During a Crisis.
There are few documented examples of community networks that have used unstructured information to support surveillance during a health emergency. In January 2015, the Ebola Response Consortium rapidly implemented community event-based surveillance for Ebola virus disease at a national scale in Sierra Leone. Community event based surveillance uses community health monitors in each community to provide an early warning system of events that are suggestive of Ebola virus disease transmission. The Ebola Response Consortium, a consortium of 15 nongovernmental organizations, applied a standardized procedure to implement community event-based surveillance across nine of the 14 districts. To evaluate system performance during the first six months of operation (March to August 2015), we conducted a process evaluation. We analyzed the production of alerts, conducted interviews with surveillance stakeholders and performed rapid evaluations of community health monitors to assess their knowledge and reported challenges. The training and procurement of supplies was expected to begin in January 2015 and attain full scale by March 2015. We found several logistical challenges that delayed full implementation until June 2015 when the epidemic was past its peak. Community health monitors reported 9,131 alerts during this period. On average, 82% of community health monitors reported to their supervisor at least once per week. Most alerts (87%) reported by community health monitors were deaths unrelated to Ebola. During the rapid evaluations, the mean recall by community health monitors was three of the six trigger events. Implementation of the national system achieved scale, but three months later than anticipated. Community event based surveillance generated consistent surveillance information during periods of no- to low-levels of transmission across districts. We interpret this to mean that community health monitors are an effective tool for generating useful, unstructured information at the village level. However, to maximize validity, the triggers require more training, may be too many in number, and need increased relevance to the context of the tail end of the epidemic.


Intractable pain management with intravenous narcotic administration at home.
Administration of intravenous narcotics in a patient's home is a relatively new therapeutic method of controlling excruciating cancer-related pain. As with any new therapy, there are many questions and concerns related to administration and management. This article presents information derived from a literature review designed to improve understanding and technique.


Perceptions of primary care staff on a regional data quality intervention in Australian general practice: a qualitative study.
Technological advances in clinical data capturing and storage systems have led to recent attempts at disease surveillance and region specific population health planning through regularly collected primary care administrative clinical data. However the accuracy and comprehensiveness of primary care health records remain questionable. We aimed to explore the perceptions and experiences of general practice staff in maintaining accurate patient health data within clinical software used in primary care settings of regional NSW. Focus groups were conducted with general practitioners, practice nurses and practice administrative staff from 17 practices in the Illawarra-Shoalhaven region of the state of New South Wales (NSW) in Australia that had participated in the Sentinel Practices Data Sourcing (SPDS) project - a general practice based chronic disease surveillance and data quality improvement study. A total of 25 respondents that included 12 general practitioners (GPs) and 13 practice staff participated in the 6 focus groups. Focus groups were audio-recorded and transcribed verbatim. Thematic analysis of the data was undertaken. Five key themes emerged from the data. Firstly, the theme of resourcing data management raised issues of time constraints, the lack of a dedicated data management role and the importance of multidisciplinary involvement, including a data champion. The need for incentives was identified as being important to motivate ongoing commitment to maintaining data quality. However, quality of software packages, including coding issues and software limitations and information technology skills were seen as key barriers. The final theme provided insight into the lessons learnt from the project and the increased awareness of the importance of data quality amongst practice staff. The move towards electronic methods of maintaining general practice patient records offers significant potential benefits in terms of both patient care and monitoring of health status and health needs within the community. However, this study has reinforced the importance of human factors in the maintenance of such datasets. To achieve optimal benefits of electronic health and medical records for patient care and for population health planning purposes, it is extremely essential to address the barriers that clinicians and other staff face in maintaining complete and correct primary care patient electronic health and medical information.


Effects of erythromycin, tetracycline and ibuprofen on the growth of Synechocystis sp. and Lemna minor.
Pharmaceutically active substances have recently been recognised as an emerging environmental problem. Human and veterinarian therapeutic agents can contaminate aquatic ecosystems via sewage discharges (human and animal excretion), improper disposal or industrial waste. Very little is known on the effects of pharmaceutical pollutants on aquatic photosynthetic organisms. In this study the effects of erythromycin, tetracycline and ibuprofen on the growth of the cyanobacterium Synechocystis sp. PCC6803 and the duckweed Lemna minor FBR006 were studied at concentrations of 1-1000 microg l(-1). At dosage of 1 mg l(-1), erythromycin affected the growth of both Synechocystis and Lemna with a maximum inhibition of 70 and 20%, respectively. Tetracycline had inhibitory effects (20-22% reduction in growth) on Synechocystis at intermediate dosages. The same aminoglycoside antibiotic promoted growth in Lemna by 26% at 10 microg l(-1), while frond development was reduced at 1 mg l(-1) (tetracycline). The anti-inflammatory ibuprofen strongly stimulated the growth of Synechocystis at all concentrations tested (72% increase at 10 microg l(-1)) although inhibited Lemna in a linear dose-dependent manner with a 25% reduction over control levels at a dosage of 1 mg l(-1). The 7 days effective concentration (EC(50)) calculated for Lemna were 5.6, 1 and 4 g l(-1), respectively, for erythromycin, tetracycline and ibuprofen. Moreover, exposure to the three pharmaceuticals resulted in the production of the stress hormone, abscisic acid (ABA), in Lemna. Erythromycin and tetracycline were more effective in promoting ABA synthesis compared to ibuprofen. The effects shown by the three therapeutic drugs on Synechocystis and Lemna growth may have potential implications in the assessments of residual environmental risks associated with the presence of pharmaceuticals in freshwater ecosystems. Promotion of ABA synthesis in Lemna by the two antibiotics and by copper suggests that the plant hormone could be a suitable (additional) indicator for future evaluation of phytotoxicity that results in plant senescence.


Reaction Time and Visible White Matter Lesions in Subcortical Ischemic Vascular Cognitive Impairment.
Slowed behavioral reaction time is associated with pathological brain changes, including white matter lesions, the common clinical characteristic of subcortical ischemic vascular cognitive impairment (SIVCI). In the present study, reaction time (RT) employing Trails B of the Trail Making Test, with responses capped at 300 s, was investigated in SIVCI (n = 27) compared to cognitively healthy aging (CH) (n = 26). RT was significantly slowed in SIVCI compared to CH (Cohen's d effect size = 1.26). Furthermore, failure to complete Trails B within 300 s was also a characteristic of SIVCI although some ostensibly cognitively healthy older adults also failed to complete within this time limit. Within the SIVCI group, RT did not differ significantly with respect to whether the patients were classified as having moderate/severe or mild, periventricular white matter changes visible on their diagnostic CT/MRI scans. This, together with the high degree of overlap in RT between the two SIVCI subgroups, raises the possibility that using visible ratings scales in isolation may lead to the underestimation of disease level.


Differences between primary central nervous system lymphoma and glioblastoma: topographic analysis using voxel-based morphometry.
To evaluate the diagnostic feasibility of probabilistic analysis using voxel-based morphometry (VBM) in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma (GBM). In total, 118 patients with GBM (57 males, 61 females; mean [± standard deviation] age, 56.9±19.3 years; median, 61 years) and 52 patients with PCNSL (37 males, 15 females; mean age, 62±13.3 years, median, 66 years) were studied retrospectively. Each patient underwent preoperative contrast-enhanced T1-weighted imaging (CE-T1WI) using a 1.5 or 3 T magnetic resonance imaging (MRI) system. To assess preferential occurrence sites, images from CE-T1WI were co-registered and spatially normalised using the MNI152 T1 template. Subsequently, a region of interest (ROI) was placed in the centre of the enhancing tumour in normalised images with 1-mm isotropic resolution. The same ROI between normalised and T1 template images was set up using an ROI manager function in ImageJ software. A spherical volume of interest (VOI) with a radius of 10 mm was determined. A probability map was created by overlaying each image with the VOI. Each VOI was removed from T1 template images for VBM analysis. VBM analysis was performed using statistical parametric mapping (SPM) 12 software under default settings. VBM analysis showed significantly higher frequency in the splenium of the corpus callosum among PCNSL patients than among GBM patients (p<0.05; family-wise error correction). Topographic analysis using VBM provides useful information for differentiating PCNSL from GBM.


Recruitment patterns in the cervical paraspinal muscles during cervical forward flexion: evidence of cervical flexion-relaxation.
The phenomenon of lumbar paraspinal flexion-relaxation has been well established and its clinical significance to low back pain has been demonstrated. Conversely, cervical paraspinal flexion-relaxation has not been consistently observed. This may be attributable to the inappropriate use of trunk flexion motion used to observe the phenomenon in previous studies. This investigation reports on the observance of cervical flexion-relaxation when flexion is limited to the cervical spine. Results demonstrate the observance of cervical flexion-relaxation in ten of ten asymptomatic subjects when flexion is limited to the cervical region in the seated orthograde position.


High-level expression of the antimicrobial peptide plectasin in Escherichia coli.
Plectasin is a defensin-like antimicrobial peptide isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella. Plectasin showed marked antibacterial activity in vitro against Gram-positive bacteria, especially Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin could kill the sensitive strain as efficaciously as vancomycin and penicillin and without cytotoxic effects on mammalian cell viability. In order to establish a bacterium-based plectasin production system, in the present study, the coding sequence of plectasin was optimized, and then cloned into pET32a (+) vector and expressed as a thioredoxin (Trx) fusion protein in Escherichia coli. The soluble fusion protein collected from the supernatant of the cell lysate was separated by Ni(2+)-chelating affinity chromatography. The purified protein was then cleaved by Factor Xa protease to release mature plectasin. Final purification was achieved by Ni(2+)-chelating chromatography again. The recombinant plectasin exhibited the same antimicrobial activity as reported previously. This is the first study to describe the expression of plectasin in E. coli expression system, and these works might provide a significant foundation for the following production or study of plectasin, and contribute to the development and evolution of novel antimicrobial drugs in clinical applications.


[Monitoring sheet for the management of the diabetic patient in preparation for elective surgery].
Diabetes represents a risk factor for patients undergoing surgery, not only in emergency but also in elective situations. All efforts in such patients are addressed to the restoration of the most physiologic conditions in respect for glucose balance and glucose metabolism since the preoperative phase, and during all the perioperative period. As these patients have to observe a more or less long period of preoperative and perioperative fasting since the day preceding the operation, any oral anti-diabetic regimen has to be timely discontinued, and the use of insulin is necessary. The doses of insulin have to be defined preoperatively with respect of the metabolic needs of the patients in the days preceding the operation, and must be able meanwhile to reduce blood glucose among the physiologic values, in absence on any urinary glucose, to restore a correct metabolism. The simple management form introduced in the paper for this purpose, and in use in our department through many years, makes easier getting and keeping all this aim and is extremely useful not only for the residents but also for the nurse staff. Its main characteristic is to offer daily, and for the single meal, a direct visual comparison of insulin dose and blood glucose level, in respect of a correct and constant caloric alimentation.


Vitamin D3 Receptors and Metabolic Enzymes in Hen Reproductive Tissues.
In recent years, vitamin D3 has been revealed as an important regulator of reproductive processes in humans and livestock; however, its role in the female reproductive system of poultry is poorly known. The aim of this study was to examine vitamin D3 receptor (VDR and PDIA3) and metabolic enzyme (1α-hydroxylase and 24-hydroxylase) mRNA transcript and protein abundances, and protein localization within the hen ovary, oviductal shell gland, pituitary, liver, and kidney. We demonstrated, for the first time, the patterns of the relative mRNA and protein abundances of examined molecules in the ovary, dependent on follicle development and the layer of follicle wall, as well as in other examined organs. Immunohistochemically, PDIA3, 1α-hydroxylase, and 24-hydroxylase are localized in follicular theca and granulosa layers, luminal epithelium and tubular glands of the shell gland, pituitary, liver, and kidney. These results indicate that reproductive tissues have both receptors, VDR, primarily involved in genomic action, and PDIA3, probably participating in the rapid, non-genomic effect of vitamin D3. The finding of 1α-hydroxylase and 24-hydroxylase expression indicates that the reproductive system of chickens has the potential for vitamin D3 synthesis and inactivation, and may suggest that locally produced vitamin D3 can be considered as a significant factor in the orchestration of ovarian and shell gland function in hens. These results provide a new insight into the potential mechanisms of vitamin D3 action and metabolism in the chicken ovary and oviduct.


Branched-chain Fatty acids in sediments.
Branched-chain (iso and anteiso) fatty acids were isolated from marine sediments from several environments. The relatively high ratio of branched-chain to straight-chain fatty acids for the even-numbered carbon molecules suggests a bacterial origin for the branched-chain isomers. The branched-chain fatty acids are present in the Green River shale. Possible geochemical implications are suggested.


Cuticle deposition improves the biosecurity of eggs through the laying cycle and can be measured on hatching eggs without compromising embryonic development.
The cuticle is part of the egg's natural defense and it can be improved by genetic selection. Prior to adoption of this measurement in breeding programs, questions that need to be addressed are whether improved cuticle deposition will result in a reduced risk of eggs becoming contaminated and whether selection for this trait will have any unintended consequences on the incubation process. Bacterial penetration experiments were carried out using eggs from a pedigree line of broiler breeders (BB) and Rhode Island Red (RIR) layers. Within the natural variation in cuticle deposition in each line, a good cuticle was shown to reduce an egg's susceptibility to penetration by Escherichia coli (BB, P = 0.023) and Salmonella typhimurium (RIR, P < 0.001). Deglycosylation of cuticle proteins had little effect on their antimicrobial activity. The effect of bird age on cuticle deposition was also examined. Shell color decreased with age as anticipated; however, we found no evidence that cuticle deposition decreases with age, at least up to 50 wk. A thicker cuticle could affect the water vapor conductance (WPC) of hatching eggs. The WPC of eggs was, therefore, measured on eggs selected from the top and tail of the cuticle distribution, this time in a Lohmann Selected Leghorn (LSL) pedigree line. Broiler breeder eggs were also tested. No evidence of a relationship between cuticle deposition and WPC was found for LSL or BB eggs. Cuticle deposition measurements require eggs to be stained. Here, we show that this has no adverse effect on embryo development at d 12 of incubation. Thus, we conclude that cuticle deposition is important in preventing bacterial penetration of eggs in genetically divergent breeds of chicken and that the measurement can be practically incorporated into breeding programs. This will contribute to improving the biosecurity of eggs by reducing vertical and horizontal transmission of potentially zoonotic and pathogenic organisms from parent to offspring.


The impact of age on the art of mammography and how to adapt accordingly.
Breast cancer is increasingly a disease of the elderly, and combined with the NHS Breast Screening Extension means that more elderly patients are having mammography. Increasing age can make mammography more technically difficult. This is a technical note detailing the results of a local audit which may be of interest due to potential service implications. A retrospective audit of the first year of screening extension of The Shropshire Breast Screening Programme. Aims to collect data on patient demographics and describe the technical adaptations developed in Shropshire. Breast screening extension has increased by 2.5 times the number of women aged 70-74 screened, and doubled the overall numbers of women over 70 screened. Significantly more older patients are being screened to present technical challenges to a screening programme. Data was obtained from a month of screening showed that 29% of patients over 70 needed extra time for positioning. Reasons included 22% difficulty in obtaining adequate positioning and 15% needed a relative to aid with consent. In the Shropshire screening programme different technical adaptations have been developed and are key to ensuring adequate images. These include double appointments, two radiographers, thorough assessment, steeper angles, seated examinations, from-below imaging and pre-planning for subsequent screen. Significantly more older women are having breast screening due to the increasing incidence of breast cancer and the Breast Screening Programme extension. Increasing age can significantly increase time taken for adequate imaging and present technical challenges. Development of technical adaptations to art of mammography is key to achieve adequate images.


Significance of the interval between first and second transurethral resection on recurrence and progression rates in patients with high-risk non-muscle-invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guérin.
To evaluate the effect of the interval between the initial and second transurethral resection (TUR) on the outcome of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy. We reviewed the data of patients from 10 centres treated for high-risk NMIBC between 2005 and 2012. Patients without a diagnosis of muscle-invasive cancer on second TUR performed ≤90 days after a complete first TUR, and received at least 1 year of maintenance BCG were included in this study. The interval between first and second TUR in addition to other parameters were recorded. Multivariate logistic regression analysis was used to identify predictors of recurrence and progression. In all, 242 patients were included. The mean (sd, range) follow-up was 29.4 (22.2, 12-96) months. The 3-year recurrence- and progression-free survival rates of patients who underwent second TUR between 14 and 42 days and 43-90 days were 73.6% vs 46.2% (P < 0.001) and 89.1% vs 79.1% (P = 0.006), respectively. On multivariate analysis, the interval to second TUR was found to be a predictor of both recurrence [odds ratio (OR) 3.598, 95% confidence interval (CI) 1.885-8.137; P = 0.001] and progression (OR 2.144, 95% CI 1.447-5.137; P = 0.003). The interval between first and second TUR should be ≤42 days in order to attain lower recurrence and progression rates. To our knowledge, this is the first study demonstrating the effect of the interval between first and second TUR on patient outcomes.


[Eye's and excretory lacrimal apparatus' argyrosis: case report].
From March to November 2001, a case of eye's argyrosis was diagnosed based on clinical history, eye's biomicroscopy and histopathology. In the biomicroscopy exam, there were gray deposits of pigments in corneal stroma and conjunctiva. In the incisional biopsy of conjuctiva, lens, upper lacrimal canaliculi and lacrimal sac deposits of silver were found.


Stem cell properties of peripheral blood endothelial progenitors are stimulated by soluble CD146 via miR-21: potential use in autologous cell therapy.
Cell-based therapies constitute a real hope for the treatment of ischaemic diseases. One of the sources of endothelial progenitors for autologous cell therapy is Endothelial Colony Forming Cells (ECFC) that can be isolated from peripheral blood. However, their use is limited by their low number in the bloodstream and the loss of their stem cell phenotype associated with the acquisition of a senescent phenotype in culture. We hypothesized that adding soluble CD146, a novel endothelial growth factor with angiogenic properties, during the isolation and growth procedures could improve their number and therapeutic potential. Soluble CD146 increased the number of isolated peripheral blood ECFC colonies and lowered their onset time. It prevented cellular senescence, induced a partial mesenchymal phenotype and maintained a stem cell phenotype by stimulating the expression of embryonic transcription factors. These different effects were mediated through the induction of mature miR-21. When injected in an animal model of hindlimb ischaemia, sCD146-primed ECFC isolated from 40 ml of blood from patients with peripheral arterial disease were able to generate new blood vessels and restore blood flow. Treatment with sCD146 could thus constitute a promising strategy to improve the use of autologous cells for the treatment of ischaemic diseases.


Awareness of anti-malarial policy and malaria treatment practices of patent medicine vendors in three Nigerian states.
This paper assesses Patent Medicine Vendors' (PMVs) practices, awareness of new Nigerian Artemisinin Combination Therapy (ACT) policy, the anti-malarial drugs in stock and how the PMVs identify fake drugs. PMVs and medicine shops were selected through a multi-stage random sampling process, beginning with the purposive selection of three states that reflect major geographic and ethnolinguistic areas of Nigeria: Oyo (Southwest-Yoruba), Kaduna (Northcentral-Hausa), and Enugu (Southeast-Igbo). Local Government Areas (LGAs) in selected states were stratified into urban and rural strata, with two LGAs randomly sampled from each stratum in each state, and one ward (urban LGAs) or community (rural LGAs) randomly sampled from a list in each LGA. A complete listing of PMVs and drug shops was constructed at each site, yielding 111 PMVs and 106 medicine shops. Out of this number, a total of 110 PMVs consented to be interviewed. Some PMVs (43.1%) were aware of the 2005 government policy that changed the recommended first-line treatment for malaria from chloroquine (CQ) to ACT, but significant differences were found between states (p < 0.001). PMV shops stocked many brands of anti-malarial drugs (average 5.5 brands), with ACTs stocked in only 8.5% of the stores at a mean price of N504 ($4) per treatment, compared to sulfadoxine-pyrimethamine (92% of shops, mean price of N90 ($0.7) and even monotherapy artesunates (32% of shops, mean price of N39 ($0.3). The PMVs identify a drug not bearing the National Agency for Food & Drug Administration and Control (NAFDAC) identification number as being fake or counterfeit. PMVs need to be a part of the strategy to change treatment to ACTs if there are to be meaningful changes in the anti-malarial drugs that Nigerians receive.


Finding Integrative Medication for Neuroblastoma and Glioblastoma through Zebrafish as A Model of Organism.
As far as malignant tumors of the central nervous system are concerned, glioblastoma (GB) and neuroblastoma (NB) are the most prevalent, aggressive, and fatal forms in adult and pediatric populations, respectively. NB is the most prominent childhood extracranial compact neoplasm in pediatrics when the embryo develops from undifferentiated neural crest cells. Regarding malignant primary brain tumors, GB is the most lethal and difficult to treat. Currently, there are few effective treatments available for either condition. Research using zebrafish is relatively new in the field of animal cancer studies, and the first results show promise. In particular, integrated genomic investigations of NB and GB have revealed the potential of the zebrafish model in elucidating the roles of specific genetic changes in the development of this fatal childhood malignancy. Hence, this study examines the possibility of zebrafish as a model organism for discovering integrative medicines for these types of cancer. This model is an excellent animal model for study due to its transparency, ease of genetic modification, ethics and financial benefits, and preservation of the primary brain areas andbloodbrain barrier (BBB). This review provides recent developments in the zebrafish model of NB and GB to illustrate the benefits of using them in cancer studies as a model of the organism. This approach provides novel insights into delivering individualized treatment and enhancing outcomes for people coping with central nervous system malignancies.


On nonlinear amplification: improved quantum limits for photon counting.
We show that detection of single photons is not subject to the fundamental limitations that accompany quantum linear amplification of bosonic mode amplitudes, even though a photodetector does amplify a few-photon input signal to a macroscopic output signal. Alternative limits are derived for nonlinear photon-number amplification schemes with optimistic implications for single-photon detection. Four commutator-preserving transformations are presented: one idealized (which is optimal) and three more realistic (less than optimal). Our description makes clear that nonlinear amplification takes place, in general, at a different frequency ω' than the frequency ω of the input photons. This can be exploited to suppress thermal noise and dark counts past what is possible with linear amplification up to a fundamental limit imposed by nonlinear amplification into a single bosonic mode.


Systemic hemodynamic determinants of blood pressure in women: age, physical activity, and hormone replacement.
We tested the hypothesis that the age-related changes in systemic hemodynamic determinants of arterial blood pressure in healthy women are related to physical activity and hormone replacement status. We studied 66 healthy, normotensive premenopausal (21-35 yr) and postmenopausal (50-72 yr) sedentary and endurance-trained women under supine resting conditions. Mean blood pressure was 7 mmHg higher in sedentary post- compared with premenopausal women, which was associated with an 11-mmHg higher systolic blood pressure, a 25% lower stroke volume and cardiac output, and a 50% higher systemic vascular resistance (all P < 0.05). Absolute (ml) levels of total blood volume did not differ across age, but resting oxygen consumption was approximately 35% lower in the postmenopausal women (P < 0.05). The elevations in mean and systolic blood pressures with age were similar in endurance-trained runners, but, in contrast to the sedentary women, the elevations were not associated with significant age-related differences in cardiac output, stroke volume, or oxygen consumption, and only a modest (15%) increase in systemic vascular resistance (P = 0.06). Postmenopausal swimmers demonstrated the same systemic hemodynamic profile as that of postmenopausal runners, indicating a nonspecific influence of the endurance-trained state. Blood pressure and its systemic hemodynamic determinants did not differ in postmenopausal users compared with those of nonusers of hormone replacement therapy. Resting oxygen consumption was the strongest physiological correlate of cardiac output in the overall population (r = 0.65, P < 0.001). We conclude that 1) the increases in arterial blood pressure at rest with age in healthy normotensive women are not obviously related to habitual physical activity status; 2) the systemic hemodynamic determinants of the age-related elevations in blood pressure are fundamentally different in sedentary vs. active women, possibly due, in part, to an absence of decline in resting oxygen consumption in the latter; and 3) systemic hemodynamics at rest are not different in healthy normotensive postmenopausal users vs. nonusers of estrogen-based hormone replacement.


Fructoselysine 3-epimerase, an enzyme involved in the metabolism of the unusual Amadori compound psicoselysine in Escherichia coli.
The frl (fructoselysine) operon encodes fructoselysine 6-kinase and fructoselysine 6-phosphate deglycase, allowing the conversion of fructoselysine into glucose 6-phosphate and lysine. We now show that a third enzyme encoded by this operon catalyses the metal-dependent reversible interconversion of fructoselysine with its C-3 epimer, psicoselysine. The enzyme can be easily assayed through the formation of tritiated water from [3-3H]fructoselysine. Psicoselysine supports the growth of Escherichia coli, causing the induction of the three enzymes of the frl operon. No growth on fructoselysine or psicoselysine was observed with Tn5 mutants in which the putative transporter (FrlA) or fructoselysine 6-phosphate deglycase (FrlB) had been inactivated, indicating the importance of the frl operon for the metabolism of both substrates. The ability of E. coli to grow on psicoselysine suggests the occurrence of this unusual Amadori compound in Nature.


Responses of ventral respiratory group neurons of the cat to natural vestibular stimulation.
Stimulation of vestibular otolith afferents by fore-aft tilt (pitch) elicits changes in activity of nerves innervating respiratory muscles, including the diaphragm, abdominal muscles, and tongue musculature. To determine the role of ventral respiratory group (VRG) neurons in producing these vestibular-respiratory responses, the activity of VRG neurons was recorded during natural vestibular stimulation in multiple transverse planes. Only a small fraction of VRG neurons with inspiratory (I, 20 of 80 cells), expiratory (E, 11 of 59 cells), or phase spanning (4 of 16 cells) activity responded to tilts up to 15 degrees in amplitude delivered at frequencies from 0.02 to 2 Hz. In particular, responses were infrequent in VRG neurons with projections to the spinal cord (0 of 23 E cells and 2 of 15 degrees I cells), despite the fact that the tilts employed produced robust modulation of the activity of abdominal (expiratory) nerves. Furthermore, the characteristics of responses to tilt of the small fraction of VRG neurons with vestibular inputs did not match those of respiratory muscles. These data suggest that neurons in addition to those in the VRG must participate in generating vestibular-respiratory responses.


Stimulation of creatine kinase BB activity by parathyroid hormone and by prostaglandin E2 in cultured bone cells.
Bone cells in culture responded to parathyroid hormone (PTH) and prostaglandin E2 (PGE2) by a 2-fold increase in creatine kinase (CK) activity. Combined treatment resulted in a higher response than with PTH alone. Calcitonin (CT) failed to stimulate CK activity, did not affect the response of CK to PTH, but inhibited slightly the increase in CK activity by PGE2. Bone-cell cultures grown in low [Ca2+] (0.125 mM), enriched in PTH-responsive osteoblast-like cells, responded to PTH, but not to PGE2 or CT, by increased CK activity. In both normal and low-[Ca2+] cultures, 8-bromo cyclic AMP did not affect CK activity, nor did it change the response of the cells to PTH, PGE2 or CT. The increase in CK activity was time- and dose-dependent and inhibited both by cycloheximide and by actinomycin D. The isoenzyme of CK stimulated was the CKBB form, the isoenzyme induced by other hormones. This appears to be the first report of the stimulation of CK activity by a polypeptide hormone or a prostaglandin. We suggest that stimulation of CKBB can serve as a marker for the action of a variety of hormones and growth promoters.


[Inhibitory action of sensory transmission by inhalational anesthetics in the spinal cord].
This review article focuses on the suppression of sensory transmission by inhalational anesthetics at the spinal cord level. Volatile anesthetics (e.g. halothane and isoflurane) suppress neuronal responses evoked by both noxious and non-noxious stimuli. This suppression is mediated largely by activation of GABAA and glycine receptors systems in the spinal dorsal horn. Depression of spinal glutamate receptor systems is also probably involved. The analgesic action of nitrous oxide is produced by activation of supra-spinal descending inhibitory systems, not by direct action on the spinal cord. Activation of the descending inhibitory systems by nitrous oxide causes release of noradrenaline in the spinal dorsal horn, and activates alpha 2 adrenergic receptor systems, resulting in depression of neuronal responses evoked by noxious stimuli. GABAA and glycine receptor systems in the spinal dorsal horn are also important components of nitrous oxide anesthesia in depressing neuronal responses evoked by non-noxious stimuli. Although excitation or inhibition of GABAA, glycine, alpha 2 adrenergic and glutamate receptors systems is an important action of inhalational anesthetics, influence of inhalational anesthetics on interactions among these receptor systems has yet to be studied.


Phase II cancer prevention clinical trials.
The development of agents to prevent cancer requires an iterative process of target identification, preclinical testing, and early and late phase clinical trials to establish efficacy and safety. Since phase III definitive efficacy trials with cancer endpoints require a lengthy timeframe and considerable resources for completion, it is critical to first optimize agent delivery and trial design and to determine preliminary efficacy via the conduct of phase II trials. Phase II trials vary considerably in their endpoints, cohorts, and designs due to differences in the process of carcinogenesis and ability to sample tissues across different target organs. However, the goal of all such trials is to provide evidence of interference with the development of cancer and to identify safety signals that would limit the benefit from interventions.


Spectroscopic evidence of keto-enol tautomerism in deliquesced malonic acid particles.
Scanning transmission X-ray microscopy combined with near-edge X-ray absorption fine structure spectroscopy (STXM/NEXAFS) and optical microscopy coupled with Fourier transform infrared spectroscopy (micro-FTIR) have been applied to observe hygroscopic growth and chemical changes in malonic acid particles deposited on substrates. The extent of the hygroscopic growth of particles has been quantified in terms of the corresponding water-to-solute ratios (WSR) based on STXM/NEXAFS and micro-FTIR data sets. WSR values derived separately from two applied methods displayed a remarkable agreement with previous data reported in the literature. Comparison of NEXAFS and FTIR spectra acquired at different relative humidity (RH) shows efficient keto-enol tautomerization of malonic acid, with the enol form dominating at higher RH. The keto-enol equilibrium constants were calculated using relevant peak intensities in the carbon and oxygen K-edge NEXAFS spectra as a function of RH. We report strong dependence of the equilibrium constant on RH, with measured values of 0.18 ± 0.03, 1.11 ± 0.14, and 2.33 ± 0.37 corresponding to 2, 50, and 90% RH, respectively. Enols are important intermediates in aldol condensation reactions pertaining to formation and atmospheric aging of secondary organic aerosol (SOA). The present knowledge assumes that constituents of atmospheric deliquesced particles undergo aqueous chemistry with kinetic and equilibrium constants analogous to reactions in bulk solutions, which would estimate absolute dominance of the keto form of carboxylic acids. For instance, the keto-enol equilibrium constant of malonic acid in diluted aqueous solution is <10(-4). Our results suggest that in deliquesced micrometer-size particles, carboxylic acids may exist in predominantly enol forms that need to be explicitly considered in atmospheric aerosol chemistry.