Emotion expressivity in the Dutch: Validation of the Dutch translation of the Berkeley Expressivity Questionnaire.
When examining emotions and emotion regulation, we discriminate between emotion experience and emotion expressivity. Research shows that the two are modestly related. The Berkeley Expressivity Questionnaire (BEQ) was designed to assess positive and negative expressivity, as well as the intensity of the expressive behavior. The current article reports on 2 studies that examined the reliability and validity of the Dutch translation of the BEQ. In Study 1, we performed a confirmatory factor analysis of the BEQ items in two samples that differed in age (young adults and adults), correlated the facet and total scores with measures of behavioral control, affective response tendencies, and emotion regulation strategies, and examined sex differences. Results confirmed the three-factor structure and further showed that factors were correlated, and two items loaded on all factors. Internal consistency was good, and test-retest reliability was excellent. As expected, emotion expression was larger in women. Convergent and divergent validity were confirmed. Behavioral control measures were inversely related to emotion expression. Although neuroticism and depression were associated with negative expressivity, extraversion, openness, and agreeableness were associated with positive expressivity. Emotion regulation strategies generally showed association patterns in the expected directions. In Study 2, we report on the predictive value of the BEQ facet scores for the emotional response to acute social evaluative stress. Results showed that only expression intensity was significantly associated with a larger emotional stress response. In conclusion, the Dutch version of Berkeley Expressivity Questionnaire is a reliable and valid instrument to be used in the Dutch setting. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Cell viability and proteins release during ultrasound-assisted yeast lysis of light lees in model wine.
Light lees that spent more than one year in barrels were used for ultrasound-assisted yeast lysis (22W/L, 18°C) in a model wine. For comparison, a classical yeast autolysis at mild temperature (25°C) was performed. The effect of ultrasound on lees was evaluated by analysing the release of proteins and polysaccharides to the model wine, and the viability of the yeasts contained in the lees. Under conditions tested, ultrasound-assisted yeast lysis increased the concentrations of proteins and polysaccharides in the model wine due to the release of these compounds from yeasts. Unlike the classical autolysis, ultrasound led to a high cell disruption, and after 20h of ultrasonic treatment, viable cells were hardly found. Furthermore, the final cell concentration for the ultrasound-assisted yeast lysis was much lower than that for the classical autolysis. The inactivation rate constant of ultrasound-assisted yeast lysis was 2.54×10(-5)s(-1). Finally, the morphological changes in cells were examined by scanning electron microscopy to verify the effect of ultrasound on yeast cells.


Rhamnose-coated superparamagnetic iron-oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity.
Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.


Use of compression bone plate after metatarsal nonunion.
In summary, slow union can be caused from impaired blood supply, delayed union by inadequate immobilization, whether external or internal, and infection. Nonunion as well as delayed union may be caused by prolonged movement and interposition of soft tissue. Slow union and delayed union with too early cessation of immobilization cause nonunion. It may be said that if a fracture has not united within 4 months, delayed union is occurring. After 8 months, nonunion or pseudoarthrosis occurs (4).


Liposomes as gene carriers: efficient transformation of mouse L cells by thymidine kinase gene.
Stable transformation of mouse L cells deficient in thymidine kinase was achieved by liposome-mediated transfer of a recombinant plasmid carrying the thymidine kinase gene. Ten percent of the recipient cells expressed thymidine kinase activity. The transformed phenotype (for example, 200 out of 10(6) cells) was stable under selective and nonselective conditions. The liposome technique is compared with other methods currently used for gene transfer.


Soluble tumor necrosis factor receptor 2 is associated with progressive diabetic kidney disease in patients with type 2 diabetes mellitus.
Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes. A total of 364 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests. Seventy-three patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria. Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.63, 95% confidence interval 0.57-0.70, p < 0.001), yielding a sensitivity of 75.3% and a specificity of 51.2%. The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 2.27, 95% confidence interval 1.23-4.20, p = 0.009) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers. Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.


Suppression of radiation-induced testicular germ cell apoptosis by 2,5-hexanedione pretreatment. III. Candidate gene analysis identifies a role for fas in the attenuation of X-ray-induced apoptosis.
Germ cell apoptosis directly induced by x-radiation (x-ray) exposure is stage specific, with a higher incidence in stage II/III seminiferous tubules. A priming exposure to the Sertoli cell toxicant 2,5-hexanedione (HD) results in a marked reduction in x-ray-induced germ cell apoptosis in these affected stages. Because of the stage specificity of these responses, examination of associated gene expression in whole testis tissue has clear limitations. Laser capture microdissection (LCM) of specific cell populations in the testis is a valuable technique for investigating the responses of different cell types following toxicant exposure. LCM coupled with quantitative real-time PCR was performed to examine the expression of apoptosis-related genes at both early (3 h) and later (12 h) time points after x-ray exposure, with or without the priming exposure to HD. The mRNAs examined include Fas, FasL, caspase 3, bcl-2, p53, PUMA, and AEN, which were identified either by literature searches or microarray analysis. Group 1 seminiferous tubules (stages I-VI) exhibited the greatest changes in gene expression. Further analysis of this stage group (SG) revealed that Fas induction by x-ray is significantly attenuated by HD co-exposure. Selecting only for germ cells from seminiferous tubules of the most sensitive SG has provided further insight into the mechanisms involved in the co-exposure response. It is hypothesized that following co-exposure, germ cells adapt to the lack of Sertoli cell support by reducing the Fas response to normal FasL signals. These findings provide a better understanding and appreciation of the tissue complexity and technical difficulties associated with examining gene expression in the testis.


Disruption of Sensorimotor Cortical Oscillations by Visual Interference Predicts the Altered Motor Performance of Persons with Cerebral Palsy.
Emerging evidence indicates that aberrations in sensorimotor cortical oscillations likely play a key role in uncharacteristic motor actions seen in cerebral palsy. This interpretation is largely centered on the assumption that the aberrant cortical oscillations primarily reflect the motor aspects, with less consideration of possible higher-order cognitive connections. To directly probe this view, we examined the impact of cognitive interference on the sensorimotor cortical oscillations seen in persons with cerebral palsy using magnetoencephalography. Persons with cerebral palsy (N = 26, 9-47 years old) and controls (N = 46, 11-49 years) underwent magnetoencephalographic imaging while completing an arrow-based version of the Eriksen flanker task. Structural equation modeling was used to evaluate the relationship between the extent of interference generated by the flanker task and the strength of the sensorimotor cortical oscillations and motor performance. Our results indicated that the impact of cognitive interference on beta and gamma oscillations moderated the interference effect on reaction times in persons with cerebral palsy, above and beyond that seen in controls. Overall, these findings suggest that alterations in sensorimotor oscillatory activity in those with cerebral palsy at least partly reflects top-down control influences on the motor system. Thus, suppression of distracting stimuli should be a consideration when evaluating altered motor actions in cerebral palsy.


Mechanical behavior of thermo-responsive orthodontic archwires.
This investigation was conducted to describe the mechanical behavior of thermo-responsive nitinol archwires in flexure at 5 degrees and 37 degrees C. Four same-sized (but different force level) rectangular archwires were examined using a three-point bend test. Samples were tested at 5 degrees and 37 degrees C. Linear regressions were fit to different segments of the load-deflection plots. Regression parameters of the segments and other properties were statistically analyzed. Superelastic behavior was exhibited by all wires tested at 37 degrees but not at 5 degrees C. Permanent deformation was greater at 5 degrees than 37 degrees. The initial slope of the load-deflection data averaged 1230 g/mm at 37 degrees, which was significantly different from the average at 5 degrees (500 g/mm). Loads at the apparent yield point and the loads at 1, 2, and 3 mm of deflection were greater at 37 degrees C than at 5 degrees. While the slope and length of the superelastic region were not judged to be clinically significantly different, the average load of the superelastic region was significantly different: F300 (340 g) > F200 (250 g) > F100 (180 g) and Bioforce (180 g). When loaded at 5 degrees and then unloaded at 37 degrees, the mechanical hysteresis of the wires tested at 37 degrees and the permanent deformation of the wires tested at 5 degrees were reduced for all wires. Nitinol wires are available with a variety of mechanical properties. The different mechanical properties of thermo-responsive wires at 5 degrees and 37 degrees C result in clinically useful shape-memory behavior. Utilizing the superelastic and shape-memory features of thermo-responsive wires has clinical advantages.


Binge drinking among U.S. active-duty military personnel.
Binge drinking (drinking on a single occasion >or=5 drinks for men or >or=4 drinks for women) is a common risk behavior among U.S. adults that is associated with many adverse health and social consequences. However, little is known about binge drinking among active-duty military personnel (ADMP). The objectives of this study were to quantify episodes of binge drinking, to characterize ADMP who binge-drink, and to examine the relationship between binge drinking and related harms. The prevalence of binge drinking and related harms was assessed from responses to the 2005 Department of Defense Survey of Health Related Behaviors Among Military Personnel (n=16,037), an anonymous, self-administered survey. The data were analyzed in 2007 after the release of the public-use data. In 2005, a total of 43.2% of ADMP reported past-month binge drinking, resulting in 29.7 episodes per person per year. In all, 67.1% of binge episodes were reported by personnel aged 17-25 years (46.7% of ADMP), and 25.1% of these episodes were reported by underage youth (aged 17-20 years). Heavy drinkers (19.8% of ADMP) were responsible for 71.5% of the binge-drinking episodes and had the highest number of annual per-capita episodes of binge drinking (112.6 episodes). Compared to nonbinge drinkers, binge drinkers were more likely to report alcohol-related harms, including job performance problems (AOR=6.5; 95% CI=4.65, 9.15); alcohol-impaired driving (AOR=4.9; 95% CI=3.68, 6.49); and criminal justice problems (AOR=6.2; 95% CI=4.00, 9.72). Binge drinking is common among ADMP and is strongly associated with adverse health and social consequences. Effective interventions (e.g., the enforcement and retainment of the minimum legal drinking age) to prevent binge drinking should be implemented across the military and in conjunction with military communities to discourage binge drinking.


Effect of dietary protein content on nalidixic acid disposition in chickens.
The effect of a diet high in protein (HP) (26%) or low protein (LP) (15%) content on kidney function and pharmacokinetic of nalidixic acid was studied in chickens. Nalidixic acid was given intravenously and orally in a dose of 25 mg/kg b. wt. with 15 days rest period between treatments. Nalidixic acid was determined by microbiological assay. The serum nalidixic acid concentrations were consistently higher in chickens that received a LP diet. The intravenous pharmacokinetics could be described by two compartments model with a t0.5(alpha) 0.13 +/- 0.008 hours and 0.17 +/- 0.008 hours; t0.5(beta) 3.07 +/- 0.07 hours and 2.56 +/- 0.05 hours; Cltot. 0.51 +/- 0.005 ml/kg/min and 0.59 +/- 0.01 ml/kg/min; Vdss 0.349 +/- 0.008 L/kg and 0.462 +/- 0.01 L/kg in LP and HP respectively. This suggests that the protein content of the diet modifies the distribution of body water and kidney function. Also, the results cleared higher recoveries of nalidixic acid in HP chickens.


Nucleation of microtubules from mitotic centrosomes is modulated by a phosphorylated epitope.
At the onset of mitosis a class of proteins appears that possess a phosphorylated epitope recognized by the monoclonal antibody MPM-2. Immunofluorescence staining shows that a subset of these proteins is associated with the centrosomes of the mitotic apparatus. The appearance of these proteins coincides with the increased microtubule nucleating capacity of the centrosomes. We have tested whether growth of microtubules from mitotic centrosomes in a lysed cell model is dependent on the availability of the phosphorylated epitope by blocking the epitope with a specific antibody or by modifying it by removal of the phosphate. Centrosomes incubated with purified tubulin nucleate microtubule asters. However, preincubating the centrosomes with MPM-2 blocks all microtubule nucleation. Pretreating mitotic centrosomes with alkaline phosphatase also inhibits nucleation. These data suggest that the phosphorylated epitope recognized by MPM-2 is important for microtubule nucleation.


Eosinophil-epithelial cell interaction augments cysteinyl leukotrienes synthesis.
Eosinophils accumulation in the airways and sustained eosinophil-derived cysteinyl leukotrienes production represent key elements of the inflammatory response seen in asthma. However, it is not known whether activated epithelial cells influence cysteinyl leukotrienes production by eosinophils from healthy valunteers. The aim of the present study was therefore to analyse the effects of interactions between non-atopic eosinophils and epithelial cells on cysteinyl leukotrienes production in vitro. We measured cysteinyl leukotrienes released by phorbol 12-myristate 13-acetate (PMA) -activated human eosinophils or epithelial cells (human bronchial epithelial cell line -BEAS-2B) cultured alone or together. While activated BEAS-2B cells barely formed leukotrienes (1.39 pg/ml +/- 0.2) (n=32), activated eosinophils produced considerable amount of them (62.25 pg/ml +/- 10.29) (n=32). Interestingly, when activated eosinophils and epithelial cells were co-incubated, production of cysteinyl leukotrienes increased substantially (571.1 pg/ml +/- 80.9) (n=32). Thus, eosinophil-epithelial cell interactions, when occur, are associated with increased biosythesis of cysteinyl leukotrienes.


[MR coronary angiography with MS-325, a blood pool contrast agent: comparison of an inversion recovery steady-state free precession with an inversion recovery fast low angle shot sequence in volunteers].
To compare the signal-to-noise and contrast-to-noise ratio as well as the image quality of 3D inversion recovery steady-state free precession (IR-SSFP) and 3D inversion recovery fast low angle shot (IR-FLASH) sequences for contrast-enhanced breath-hold MRCA. 24 healthy volunteers (10 female, 14 male, mean age 29.8 +/- 6.1 years) were involved in this study. All examinations were performed on a 1.5 T MR scanner (Magnetom Sonata, Siemens, Germany) after injection of 0.05 mmol/kg body weight MS-325 (EPIX Pharmaceuticals, Cambridge, MA and Schering AG, Berlin, Germany). MRCA was performed using IR-SSFP (TR 3.8 ms, TE 1.6 ms, FA 65 degrees , 35 phase encoded steps, bandwidth 540 Hz/pixel, slice thickness 1.5 mm, in-plane resolution 1.2 x 0.9 - 1.4 x 1.0 mm) and IR-FLASH (TR 3.8 ms, TE 1.6 ms, FA 25 degrees , bandwidth 490 Hz/pixel, slice thickness 1.5 mm, in-plane resolution 1.2 x 0.9 - 1.4 x 1.0 mm) sequences. For all scans the inversion time was set to null the signal intensity of the myocardium. Signal-to-noise ratio (SNR) as well as contrast-to-noise ratio (CNR) measurements (blood versus myocardium) were performed. The image quality was assessed based on a 5-point scale ranging from 1 (excellent) to 5 (non-diagnostic) by two radiologists in consensus. The mean signal-to-noise ratio of blood (27.7 +/- 4.7 vs. 22.6 +/- 4.9, P < 0.0001) and the contrast-to-noise ratio (21.0 +/- 4.3 vs. 15.8 +/- 4.3, P < 0.0001) showed significantly higher values for IR-SSFP sequences. The mean image quality scores were significantly higher for SSFP (3.6 +/- 0.7) than FLASH (2.8 +/- 0.9) sequences (P < 0.05). IR-SSFP sequences show a considerable overall improvement in image quality compared to IR-FLASH sequences for MRCA after injection of a gadolinium-based blood pool contrast agent.


Information fusion: application to data and model fusion for ultrasound image segmentation.
Nowadays, information fusion constitutes a challenging research topic. Our study proposes to achieve the fusion of several knowledge sources. This, in order to detect the esophagus inner wall from ultrasound medical images. After a brief description of information fusion concepts, we propose a system architecture including both model and data fusion. The data fusion is accomplished using fuzzy modeling, which can be seen as a monosensor/multiple sources data fusion system. The model fusion is performed using a full-adapted snake theory, which projects the fuzzy decision into the binary decision space.


ASSOCIATION AMONG HISTOLOGICAL FINDINGS SUGGESTIVE OF PAPILLOMA VIRUS ON HEMORRHOIDECTOMY SPECIMENS.
Many researchers studied human Papillomavirus infection in the anal area supposing it represents a risk factor for precursor lesions of anal cancer. To study the association between histological findings suggestive of injury by the virus in hemorrhoidectomy specimens. Prevalence study was carried out based on histopathological analysis of hemorrhoidectomy specimens to find viral cytopathic effects. These findings were compared with anal condyloma acuminata that had no relationship with hemorrhoidectomy for microscopic comparison. Of the 91 hemorroidectomies analyzed, eight had findings suggestive of viral cytopathic effects, with the presence of irregular acanthosis in 63%, koilocytes in 50% and other indirect viral cytopathic effects, such as hyperkeratosis (38%), parakeratosis (25% ) and papillomatosis (13%). This study was unable to conclude that there is an association between these two pathologic entities.


Human rabies encephalomyelitis.
Seven weeks after he was bitten on the lip by a puppy in the Gambia a patient showed symptons of rabies. Passive and active immunisation was begun three days after the onset of symptons. The evidence indicated that death was a direct consequence of the central nervous system disease rather than any associated complication. Our inability to alter the course of the illness appreciably emphasises the importance of immediate postexposure immunisation in rabies and draws attention to the present lack of effective means of preventing virus replication within the central nervous system.


Probiotic-Guided CAR T cells Promote Antigen-Agnostic Solid Tumor Cytotoxicity.
The ProCAR platform was developed in which tumor-colonizing probiotics label tumor tissue for CAR T-cell lysis.


Treatment adherence and outcomes in the management of convulsive status epilepticus in the emergency room.
According to published literature status epilepticus (SE) is associated with 7-39% mortality. Timely management is one variable that potentially influences the outcome. We sought to review the process of acute management of SE at the University of Alberta Hospital and correlate outcome with adherence to a recommended treatment protocol. We identified 86 patients 18 years of age or older who presented with convulsive SE to our emergency room between 2000 and 2004. We defined SE as continuous convulsive activity for 30 or more minutes or >or= 2 convulsions with incomplete recovery in the interim. Information was collected pertaining to etiology, epidemiology, and management. We then reviewed the relationship of the treatment protocol in terms of mortality and morbidity. Forty five patients were included. There were 18 males and 27 females with a mean age of 45 years; 80% were known to have epilepsy. Sub-therapeutic drug levels were found in the majority 60%; benzodiazepines (diazepam 81% and lorazepam 19%) were the first line agent in 93.3% mostly initiated by paramedics (EMS); 48.9% of patients required intubation and 26.7% required admission to intensive care. Four patients died. Control of convulsive SE was obtained sooner for patients in whom therapy was administered according to the recommended time frame (p <or= 0.02). The presence of strict treatment protocols for SE made readily available for the treating staff could potentially improve the outcome of patients. Despite the lack of standardized treatment protocols among various physicians, most patients are treated according to generally recommended sequence and time frames. Analysis of this data will help devise prospective treatment protocols.


High precision semi-automated vertebral height measurement using computed tomography: A phantom study.
The measurement of vertebral heights is necessary for the evaluation of many disorders affecting the spine. High precision is particularly important for longitudinal studies where subtle changes are to be detected. Computed tomography (CT) is the modality of choice for high precision studies. Radiography and dual emission X-ray absorptiometry (DXA) use 2D images to assess 3D structures, which can result in poor visualization due to the superimposition of extraneous anatomical objects on the same 2D space. We present a semi-automated computer algorithm to measure vertebral heights in the 3D space of a CT scan. The algorithm segments the vertebral bodies, extracts their end plates and computes vertebral heights as the mean distance between end plates. We evaluated the precision of our algorithm using repeat scans of an anthropomorphic vertebral phantom. Our method has high precision, with a coefficient of variation of only 0.197% and Bland-Altmann 95% limits of agreement of [-0.11, 0.13] mm. For local heights (anterior, middle, posterior) the algorithm was up to 4.2 times more precise than a manual mid-sagittal plane method.


Apical surgical margins status in robot-assisted laparoscopic radical prostatectomy does not depend on disease characteristics.
Positive surgical margins (PSM) during robot-assisted laparoscopic radical prostatectomy (RALP) are generally considered an adverse event. We attempted to identify the factors associated with PSM and their location. Records of patients undergoing RALP between 2003 and 2009 were retrospectively reviewed. We collected demographic (age, race, body mass index [BMI]), cumulative surgical experience (years from RALP introduction at our center), clinical (prostate-specific antigen [PSA] levels, and biopsy Gleason sums), nerve-sparing technique (yes/no), and pathological variables, including stage (organ-confined vs. non), Gleason sums, prostate weight, status, and location of the surgical margins. Multivariate regression models were constructed to identify the factors associated with PSM at prostate apex, periphery, proximal, and all locations. A total of 560 patients were analyzed. Median age was 60.1 (interquartile range [IQR] 55.1-64.7), 19% were African-Americans, median BMI was 28.1 (25.8-30.8 kg/m(2)), PSA levels were 5.3 (3.9-7.1 ng/mL), and prostate weight was 45.2 (36.8-57.0 g). Gleason sums were as follows: ≤6 in 42.5%, 7 in 53.4%, and >7 in 3.1%. Overall, PSM were reported in 130 (23.2%), including 58 (44.6%) apical, 81 (62.3%) peripheral, and 20 (15.4%) proximal. The overall rate of PSM was associated with surgical experience, PSA, prostate weight, and Gleason sums. Apical PSM were independently associated only with surgical experience. Peripheral PSM were associated with PSA, stage, Gleason sums, and prostate weight. Finally, proximal margin status showed an association with PSA levels only. While peripheral, proximal, and overall PSM are largely associated with inherent disease biology (grade, PSA levels, etc.), apical margin status is independently associated only with cumulative surgical experience. These results suggest that a lower rates of positive apical margins may be obtained as the cumulative center experience grows, suggesting a potential role of a "teaching learning curve," independently from disease characteristics.


Diagnosis and Treatment of Slipping Rib Syndrome.
(1) To investigate the clinical presentation, diagnosis, and treatment of slipping rib syndrome in athletes; (2) to investigate the hooking maneuver for diagnosis of slipping rib syndrome. Retrospective chart review of 362 athletes with rib pain. Pediatric-based sports medicine clinic between January 1, 1999, and March 1, 2014. Costochondritis, Tietze, fractures, rib tip syndrome, and unclear diagnoses were excluded. Athletes were included who had a palpable rib subluxation, mechanical rib symptom, positive hooking maneuver, or resolution of pain after the resection of a slipping rib segment. Slipping rib syndrome is associated with athletic performance. Fifty-four athletes were diagnosed with slipping rib syndrome, of which 38 (70%) were females. Mean age at presentation was 19.1 years (range 4-40 years). Mean number of previous specialist consultations per athlete was 2.3 and mean time from symptom onset to diagnosis was 15.4 months. The hooking maneuver was attempted 21 times (38.9%). Unilateral symptoms presented in 49 athletes (90.7%). The most symptomatic rib was the 10th, affecting 24 athletes (44.4%), eighth and ninth were affected in 17 athletes (31.5%) each. Most, 39 (72.2%), reported insidious onset of symptoms. Running, rowing, lacrosse, and field hockey were frequently associated activities. Twelve athletes had psychiatric diagnoses (22.2%), 10 (19.2%) were hypermobile. Sixty-six total imaging studies were performed. The most successful treatment options included: osteopathic manipulative treatment (71.4%), surgical resection (70%), and diclofenac gel (60%). Most athletes with slipping rib syndrome were active females with insidious onset of unilateral pain, a high prevalence of hypermobility and prolonged pain. The hooking maneuver was underused.


Effects of Eplerenone on Resistance to Antihypertensive Medication in Patients with Primary or Secondary Hyperaldosteronism.
Resistant hypertension is an important problem; nearly half of diagnosed hypertensives are not controlled to target blood pressure levels, and approximately 90% of strokes occur among patients with resistant hypertension. Primary aldosteronism accounts for approximately 20% of resistant hypertension, but the role of secondary hyperaldosteronism in resistant hypertension is seldom considered. We assessed the effects of eplerenone in patients with hypertension and either primary or secondary hyperaldosteronism. Patients with a history of resistant hypertension and a supine plasma aldosterone level ≥ 360 pmol/L were randomized to eplerenone versus placebo in a fully blinded study for one year. A medication intensity score was developed to assess the resistance of hypertension to medication (blood pressure × medication intensity). We assessed the effects of eplerenone on blood pressure and on resistance to concomitant medication. Final results were available in 37 patients (19 on eplerenone and 18 on placebo). Resistance to medication, as assessed by the intensity of concomitant medication required to maintain blood pressure control, was markedly reduced by eplerenone: medication intensity scores declined by -0.50 ± 1.04 (SD) on placebo versus -2.11 ± 1.45 with eplerenone (P = 0.0001), the Systolic Resistance Score declined by -80.00 ± 122.93 on placebo versus -334.05 ± 21.73 on eplerenone (P = 0.0001), and the Diastolic Resistance Score increased by 1.28 ± 31.65 on placebo and declined by -40.74 ± 57.08 on eplerenone (P = 0.009). Eplerenone significantly reduced resistance to concomitant antihypertensive medication in both primary and secondary hyperaldosteronism.


Long-Term Mortality Trends After Revision Total Knee Arthroplasty.
Long-term mortality following primary total knee arthroplasty (TKA) is lower than the general population. However, it is unknown whether this is true in the setting of revision TKA. We examined long-term mortality trends following revision TKA. This retrospective study included 4907 patients who underwent 1 or more revision TKA between 1985 and 2015. Patients were grouped by surgical indications and followed until death or October 2017. The observed number of deaths was compared to the expected number of deaths using standardized mortality ratios (SMR) and Poisson regression models. Compared to the general population, patients who underwent revision TKA for infection (SMR, 1.45; 95% confidence interval [CI], 1.33-1.57; P < .0001) and fracture (SMR, 1.16; 95% CI, 1.00-1.34; P = .04) experienced a significantly higher mortality risk. Patients who underwent revision TKA for infection and fracture experienced excess mortality soon after surgery which became more pronounced over time. In contrast, the mortality risk among patients who underwent revision TKA for loosening and/or bearing wear was similar to the general population (SMR, 0.95; 95% CI, 0.89-1.02; P = .16). Aseptic loosening and/or wear and instability patients had improved mortality initially; however, there was a shift to excess mortality beyond 5 years among instability patients, and beyond 10 years among aseptic loosening and/or wear patients. Mortality is elevated soon after revision TKA for infection and fracture. Mortality is lower than the general population after revision TKA for loosening and/or bearing wear but gets worse than the general population beyond the first postoperative decade.


Streptomyces harenosi sp. nov., a home for a gifted strain isolated from Indonesian sand dune soil.
A polyphasic study was undertaken to establish the position of a Streptomyces strain, isolate PRKS01-65T, recovered from sand dune soil collected at Parangkusumo, Yogyakarta Province, Java, Indonesia. A combination of chemotaxonomic, cultural and morphological properties confirmed its position in the genus of Streptomyces. Comparative 16S rRNA gene sequence analyses showed that the isolate was most closely related to Streptomyces leeuwenhoekii C34T (99.9 % similarity) and loosely associated with the type strains of Streptomyces chiangmaiensis (98.7 % similarity) and Streptomyces glomeratus (98.9 % similarity). Multilocus sequence analyses based on five conserved housekeeping gene alleles confirmed the close relationship between the isolate and S. leeuwenhoekii C34T, although both strains belonged to a well-supported clade that encompassed the type strains of S. glomeratus, Streptomyces griseomycini, Streptomyces griseostramineus, Streptomyces labedae, Streptomyces lomondensis and Streptomyces spinoverrucosus. A comparison of the draft genome sequence generated for the isolate with corresponding whole genome sequences of its closest phylogenomic neighbours showed that it formed a well-separated lineage with S. leeuwenhoekii C34T. These strains can also be distinguished using a combination of phenotypic properties and by average nucleotide identity and digital DNA-DNA hybridization similarities of 94.3 and 56 %, values consistent with their classification in different species. Based on this wealth of data it is proposed that isolate PRKS01-65T (=NCIMB 15211T=CCMM B1302T=ICEBB-03T) be classified as Streptomyces harenosi sp. nov. The genome of the isolate contains several biosynthetic gene clusters with the potential to produce new natural products.


Triplex-directed recognition of a DNA nanostructure assembled by crossover strand exchange.
DNA has been widely exploited for the self-assembly of nanosized objects and arrays that offer the potential to act as scaffolds for the spatial positioning of molecular components with nanometer precision. Methods that allow the targeting of components to specific locations within these structures are therefore highly sought after. Here we report that the triplex approach to DNA recognition, which relies on the specific binding of an oligonucleotide within the major groove of double-helical DNA, can be exploited to recognize specific loci within a DNA double-crossover tile and array, a nanostructure assembled by crossover strand exchange. The oligonucleotide can be targeted to both crossover and non-crossover strands and, surprisingly, across the region spanning the crossover junction itself. Moreover, by attaching biotin to the end of the oligonucleotide, we show that streptavidin molecules can be recruited to precise locations within a DX array, with an average spacing of 31.9 (±1.3) nm. This is a promising approach that could be exploited to introduce other components compatible with oligonucleotide synthesis into the wide variety of DNA nanostructures assembled by crossover strand exchange, such as those generated by DNA origami.


BuMP-ing up insulin secretion by pancreatic beta cells.
While several transcription factors are known to increase insulin production and secretion, their therapeutic potential for treatment of type 2 diabetes remains unrealized. In this issue, Goulley et al. (2007) show that BMP signaling specifically regulates genes involved in insulin production and secretion and demonstrate that exogenous BMP4 administration augments glucose-stimulated insulin secretion in vivo.


Coevolutionary dynamics of genetic traits and their long-term extended effects under non-random interactions.
Organisms continuously modify their living conditions via extended genetic effects on their environment, microbiome, and in some species culture. These effects can impact the fitness of current but also future conspecifics due to non-genetic transmission via ecological or cultural inheritance. In this case, selection on a gene with extended effects depends on the degree to which current and future genetic relatives are exposed to modified conditions. Here, we detail the selection gradient on a quantitative trait with extended effects in a patch-structured population, when gene flow between patches is limited and ecological inheritance within patches can be biased towards offspring. Such a situation is relevant to understand evolutionary driven changes in individual condition that can be preferentially transmitted from parent to offspring, such as cellular state, micro-environments (e.g., nests), pathogens, microbiome, or culture. Our analysis quantifies how the interaction between limited gene flow and biased ecological inheritance influences the joint evolutionary dynamics of traits together with the conditions they modify, helping understand adaptation via non-genetic modifications. As an illustration, we apply our analysis to a gene-culture coevolution scenario in which genetically-determined learning strategies coevolve with adaptive knowledge. In particular, we show that when social learning is synergistic, selection can favour strategies that generate remarkable levels of knowledge under intermediate levels of both vertical cultural transmission and limited dispersal. More broadly, our theory yields insights into the interplay between genetic and non-genetic inheritance, with implications for how organisms evolve to transform their environments.


Heart rate control in diabetic rabbits: blunted response to isoproterenol.
To study the effects of chronic diabetes on heart rate and adrenergic responsiveness we compared unanesthetized diabetic rabbits, 10-13 mo after alloxan monohydrate injection, to age-matched controls. There were no significant differences found between groups for body or heart weight. Both resting and intrinsic heart rate (the latter obtained after atropine sulfate and propranolol HCl) were similar. In addition, serum and left ventricular epinephrine and norepinephrine concentrations as well as left ventricular beta-receptor density and affinity were unchanged in diabetic animals. Heart rate responses to isoproterenol were blunted in diabetics at the three highest doses. Base-line mean blood pressure was modestly lower in diabetic rabbits, and parallel declines in pressure for both groups were observed in response to isoproterenol. The diminished heart rate response to isoproterenol in diabetic rabbits may be due to diminished myocardial sensitivity to catecholamines, possibly combined with altered baroreceptor reflexes. These experiments may provide an explanation for the blunted heart rate response to exercise described in human diabetics.


Validation of heavy-water stable isotope probing for the characterization of rapidly responding soil bacteria.
Rapid responses of bacteria to sudden changes in their environment can have important implications for the structure and function of microbial communities. In this study, we used heavy-water stable isotope probing (H2(18)O-SIP) to identify bacteria that respond to soil rewetting. First, we conducted experiments to address uncertainties regarding the H2(18)O-SIP method. Using liquid chromatography-mass spectroscopy (LC-MS), we determined that oxygen from H2(18)O was incorporated into all structural components of DNA. Although this incorporation was uneven, we could effectively separate 18O-labeled and unlabeled DNAs derived from laboratory cultures and environmental samples that were incubated with H2(18)O. We found no evidence for ex vivo exchange of oxygen atoms between DNA and extracellular H2O, suggesting that 18O incorporation into DNA is relatively stable. Furthermore, the rate of 18O incorporation into bacterial DNA was high (within 48 to 72 h), coinciding with pulses of CO2 generated from soil rewetting. Second, we examined shifts in the bacterial composition of grassland soils following rewetting, using H2(18)O-SIP and bar-coded pyrosequencing of 16S rRNA genes. For some groups of soil bacteria, we observed coherent responses at a relatively course taxonomic resolution. Following rewetting, the relative recovery of Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria increased, while the relative recovery of Chloroflexi and Deltaproteobacteria decreased. Together, our results suggest that H2(18)O-SIP is effective at identifying metabolically active bacteria that influence soil carbon dynamics. Our results contribute to the ecological classification of soil bacteria while providing insight into some of the functional traits that influence the structure and function of microbial communities under dynamic soil moisture regimes.


Assessment of the viscosity of the pulmonary artery wall.
Large artery wall viscosity reduces the efficiency of heart/vessel coupling. The aim of the present study was to assess pulmonary artery wall viscosity through comparison of the static (Dst) and dynamic distensibility (Ddyn) of the vessel wall. Right pulmonary artery pressure and diameter was measured in 13 patients and eight healthy volunteers. Ddyn was calculated as the relative change in end-diastolic diameter induced by the pressure pulse, and Dst as the relative change in mean diameter induced by the change in mean pressure during steady-state exercise. Dst did not differ significantly from Ddyn (mean+/-SD 22.8+/-19.2 versus 21.0+/-18.3 10(-3) mmHg(-1)), as tested by paired t-test and analysis of covariance, with age as covariant. End-diastolic diameter increased, whereas Dst and Ddyn decreased as a function of age (r=-0.69 and -0.67, respectively; p<0.01 for both). Ddyn did not change from rest to exercise in spite of a 23+/-16-beats-min(-1) increase in cardiac frequency. Pulmonary artery wall viscosity was negligible and no increase in wall viscosity occurred during cardioacceleration.


[ROC curves: general characteristics and their usefulness in clinical practice].
The use of diagnostic tests to determine the presence or absence of a disease is essential in clinical practice. The results of a diagnostic test may correspond to numerical estimates that require quantitative reference parameters to be transferred to a dichotomous interpretation as normal or abnormal and thus implement actions for the care of a condition or disease. For example, in the diagnosis of anemia it is necessary to define a cut-off point for the hemoglobin variable and create two categories that distinguish the presence or absence of anemia. The method used for this process is the preparation of diagnostic performance curves, better known by their acronym in English as ROC (Receiver Operating Characteristic). The ROC curve is also useful as a prognostic marker, since it allows defining the cut-off point of a quantitative variable that is associated with greater mortality or risk of complications. They have been used in different prognostic markers in COVID-19, such as the neutrophil/lymphocyte ratio and D-dimer, in which cut-off points associated with mortality and/or risk of mechanical ventilation were identified. The ROC curve is used to evaluate the diagnostic performance of a test in isolation, but it can also be used to compare the performance of two or more diagnostic tests and define which one is more accurate. This article describes the basic concepts for the use and interpretation of the ROC curve, the interpretation of an area under the curve (AUC) and the comparison of two or more diagnostic tests.


Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum.
The neurological effects of organophosphate (OP) pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here, we characterized the effects of the broadly used insecticide chlorpyrifos (CPF) on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. CPF potentiated protein kinase A (PKA)-dependent phosphorylation of the striatal protein dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) and the glutamate receptor 1 (GluR1) subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide N,N-diethyl-meta-toluamide (DEET). This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle-associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus, consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration.


Cardiac differentiation of pluripotent stem cells.
The ability of human pluripotent stem cells to differentiate towards the cardiac lineage has attracted significant interest, initially with a strong focus on regenerative medicine. The ultimate goal to repair the heart by cardiomyocyte replacement has, however, proven challenging. Human cardiac differentiation has been difficult to control, but methods are improving, and the process, to a certain extent, can be manipulated and directed. The stem cell-derived cardiomyocytes described to date exhibit rather immature functional and structural characteristics compared to adult cardiomyocytes. Thus, a future challenge will be to develop strategies to reach a higher degree of cardiomyocyte maturation in vitro, to isolate cardiomyocytes from the heterogeneous pool of differentiating cells, as well as to guide the differentiation into the desired subtype, that is, ventricular, atrial, and pacemaker cells. In this paper, we will discuss the strategies for the generation of cardiomyocytes from pluripotent stem cells and their characteristics, as well as highlight some applications for the cells.


Evaluation of Curcumin Capped Copper Nanoparticles as Possible Inhibitors of Human Breast Cancer Cells and Angiogenesis: a Comparative Study with Native Curcumin.
Synthesis of metal nanoparticles for improving therapeutic index and drug delivery is coming up as an attractive strategy in the mainstream of cancer therapeutic research. In the present study, curcumin-capped copper nanoparticles (CU-NPs) were evaluated as possible inhibitors of in vivo angiogenesis, pro-angiogenic cytokines involved in promoting tumor angiogenesis along with inhibition of cell proliferation and migration of breast cancer cell line MDA-MB-231. The antiangiogenic potential was assessed using in vivo chorioallantoic membrane (CAM) model. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)-based cytotoxicity assay was used to assess the effect of CU-NPs against proliferation of breast cancer cell line. The wound healing migration assay was used to evaluate the effects of CU-NPs on the migration ability of breast cancer cell line. Native curcumin (CU) was used as a reference compound for comparison purpose. The result of the present investigation indicates that CU-NPs could not demonstrate impressive antiangiogenic or anticancer activities significantly as compared to native CU. The possible mechanisms of experimental outcomes are discussed in the light of the methods of nanoparticle synthesis in concert with the current state of the art literature.


[The clinico-laboratory effects of acupuncture in patients with glomerulonephritis].
As many as 104 patients with different clinical forms and variants of glomerulonephritis were examined and treated with acupuncture. This mode of treatment was found out to positively influence the level of hemoglobin, ESR, eosinophilia, making for diminution of proteinuria and erythrocyturia, returning hemostasis and blood biochemical spectrum (proteinogrammes, levels of cholesterol, uric acid) to normal, with the level of arterial pressure being normalized in patients with mild hypertension or reduced in those with moderately severe to severe hypertension. Acupuncture is recommended as a monotherapeutic modality in the treatment of uric syndrome with a hematuric component in a combined treatment of nephrotic syndrome and hypertension, which attempt will, we believe, help in preventing side effects of the drugs employed.


Temperature and oxygen regulation of oleate desaturation in developing sunflower (Helianthus annuus) seeds.
The effect of low (10 degrees C) and high (30 degrees C) temperature on in vivo oleate desaturation has been studied in developing sunflower (Helianthus annuus L.) seeds under conditions of different oxygen availability (capitulum, detached achenes or peeled seeds). In seeds remaining in the capitulum, only a part of the oleate newly synthesized at high temperature was desaturated to linoleate, whereas more oleate than that synthesized de novo was desaturated at low temperature. Achenes were only able to significantly desaturate oleate at low temperatures. In contrast, oleate desaturation was detected in peeled seeds incubated at low and high temperatures, showing the highest rate at 20 degrees C. Hull removing dramatically increased the activity of the microsomal oleate desaturase (FAD2, EC 126.96.36.199) at all studied temperatures, although a long-term inactivation of the enzyme was observed at high temperatures. Low oxygen concentration (1-2%) obtained by respiration of peeled seeds incubated in sealed vials, brought about the inactivation of the enzyme. All these data suggest that temperature regulates oleate desaturation controlling the amount of oleate and the FAD2 activity. In addition, this enzyme seems to be also regulated by the availability of oxygen, which is affected inside the achene by its diffusion through the hull, and the competition with respiration, both factors being temperature-dependent.


Potential of Microbial Communities to Perform Dehalogenation Processes in Natural and Anthropogenically Modified Environments-A Metagenomic Study.
Halogenated organic compounds (HOCs) pose a serious problem for the environment. Many are highly toxic and accumulate both in soil and in organisms. Their biological transformation takes place by dehalogenation, in which the halogen substituents are detached from the carbon in the organic compound by enzymes produced by microorganisms. This increases the compounds' water solubility and bioavailability, reduces toxicity, and allows the resulting compound to become more susceptible to biodegradation. The microbial halogen cycle in soil is an important part of global dehalogenation processes. The aim of the study was to examine the potential of microbial communities inhabiting natural and anthropogenically modified environments to carry out the dehalogenation process. The potential of microorganisms was assessed by analyzing the metagenomes from a natural environment (forest soils) and from environments subjected to anthropopression (agricultural soil and sludge from wastewater treatment plants). Thirteen genes encoding enzymes with dehalogenase activity were identified in the metagenomes of both environments, among which, 2-haloacid dehalogenase and catechol 2,3-dioxygenase were the most abundant genes. Comparative analysis, based on comparing taxonomy, identified genes, total halogens content and content of DDT derivatives, demonstrated the ability of microorganisms to transform HOCs in both environments, indicating the presence of these compounds in the environment for a long period of time and the adaptive need to develop mechanisms for their detoxification. Metagenome analyses and comparative analyses indicate the genetic potential of microorganisms of both environments to carry out dehalogenation processes, including dehalogenation of anthropogenic HOCs.


Corticosteroid therapy for nephrotic syndrome in children.
In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. About 70% of children experience a relapsing course with recurrent episodes of oedema and proteinuria. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus and osteoporosis. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. The aim of this systematic review is to assess the benefits and harms of corticosteroid therapy in treating children with nephrotic syndrome. To determine the benefits and harms of different corticosteroid regimes in preventing relapse in children with steroid responsive nephrotic syndrome (SRNS). Published and unpublished randomised controlled trials were identified from the Cochrane Controlled Trials Register, Medline, Embase, reference lists of articles, abstracts from proceedings and contact with known investigators in the area. Randomised trials were included if they were carried out in children (aged three months to 18 years) in their initial or subsequent episode of SRNS, if they compared different durations, total doses or other dose strategies using prednisone or other corticosteroid agent and if they had outcome data at six months or more. Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality and extracted data. The principle outcome measure was the number of children with and without relapse after six and 12-24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk RR, risk difference RD) after testing for heterogeneity. Meta-regression was used to explore potential between-study differences due to the baseline risk of relapse, study quality and types of interventions used. Twelve trials were identified. A meta-analysis of five trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 - 24 months (relative risk 0.73; 95% CI 0.60,0.89) without an increase in adverse events. There was an inverse linear relationship (RR = 1.382 (SE 0.215) - 0.133 duration (SE 0.048); r2 = 0.66; p = 0.05) between the duration of treatment and risk of relapse. The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR 0.44; 95% CI 0.25, 0.78). From this meta-analysis of randomised controlled trials it can be concluded that children in their first episode of nephrotic syndrome should be treated for at least three months with an increase in benefit being demonstrated for up to seven months of treatment. In a population with a baseline risk for relapse following the first episode of 60% with two months of prednisone, daily prednisone for four weeks followed by alternate day therapy for six months would be expected to reduce the number of children experiencing a relapse by about 40%. In children who relapse frequently, deflazacort deserves further study.


Transglutaminase activity changes during the hypersensitive reaction, a typical defense response of tobacco NN plants to TMV.
The occurrence of glutamyl polyamines (PAs) and changes in activity and levels of transglutaminase (TGase, EC 18.104.22.168), the enzyme responsible for their synthesis, are reported during the progression of the hypersensitive reaction (HR) of resistant NN tobacco plants (Nicotiana tabacum L. cv. Samsun) to tobacco mosaic virus (TMV). Mature leaves of tobacco were collected over 0-72 h after inoculation with TMV or phosphate buffer (mock). In vivo synthesis of polyamine glutamyl derivatives (glutamyl PAs), catalyzed by TGase activity, was evaluated after supplying labeled putrescine (Pu, a physiological substrate of TGase) to leaves. Results show that, starting from 24 h, mono-(gamma-glutamyl)-Pu and bis-(gamma-glutamyl)-Sd were recovered in TMV-inoculated samples but not in mock-inoculated ones; 2 days later, in the former, the amount of glutamyl derivatives further increased. An in vitro radiometric assay showed that, in TMV-inoculated leaves, TGase activity increased from 24 h onwards relative to mock controls. An immunoblot analysis with AtPng1p polyclonal antibody detected a 72-kDa protein whose amount increased at 72 h in TMV-inoculated leaves and in the lesion-enriched areas. A biotin-labeled cadaverine incorporation assay showed that TGase activity occurred in S1 (containing soluble proteins), S2 (proteins released by both cell walls and membranes) and S3 (membrane intrinsic proteins) fractions. In S3 fraction, where changes were the most relevant, TGase activity was enhanced in both mock-inoculated and TMV-inoculated samples, but the stimulation persisted only in the latter case. These data are discussed in the light of a possible role of TGase activity and glutamyl PAs in the defense against a viral plant pathogen.


Benchmarking treatment of schizophrenia: a comparison of service delivery by the national government and by state and local providers.
This study compared treatment of schizophrenia in two types of organization: a national, government-operated health care system, the Department of Veterans Affairs (VA), and in hospitals and clinics operated by state and local providers. Between 1994 and 1996, 746 male patients with a clinical diagnosis of schizophrenia residing in two states in the Southeast and Midwest were surveyed: 192 VA inpatients were compared with 96 non-VA inpatients, and 274 VA outpatients were compared with 184 non-VA outpatients. VA patients were older and had higher incomes than non-VA patients but did not differ significantly on measures of clinical status, satisfaction with providers, or community adjustment. VA outpatients were more likely to have been hospitalized during the previous year than non-VA outpatients and were less likely to have received services from a day hospital, from a case manager or social worker, or to have received crisis intervention services. On 5 of 26 Schizophrenic Patient Outcomes Research Team treatment recommendations, a smaller proportion of VA than non-VA patients adhered to standards. Four of these reflected reduced access among VA patients to psychosocial services such as work therapy, job training, or case management services. Cross-sectional surveys can be used to compare quality of care across service systems. VA care was associated with similar satisfaction and clinical outcomes but greater reliance on hospital treatment and less use of community-based psychosocial services.


Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): A Prospective Study to Improve Diagnostic Precision.
Acute kidney injury (AKI) is associated with poor outcomes in critically ill children. Recent international consensus panels recommend standardized classification systems to improve the precision of AKI diagnosis, but there is a paucity of data to enable this refinement, particularly in pediatric critical care. This is a prospective observational study. We anticipate collecting data from more than 5500 critically ill children admitted to 32 pediatric intensive care units (PICUs) across the world, during the calendar year of 2014. Data will be collected continuously for three months at each center on all children older than 90 days and younger than 25 years admitted to the ICU. Demographic, resuscitative, and daily physiological and lab data will be captured at individual centers using MediData Rave™, a commercial system designed to manage and report clinical research data. Kidney specific measured variables include changes in serum creatinine and urine output, cumulative fluid overload (%), serum creatinine corrected for fluid balance, and KDIGO AKI stage. Urinary AKI biomarkers to be measured include: urinary neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). Biomarker combinations will be created from different pairs and triplets of urinary biomarkers. The primary analysis will compare the discrimination of these panels versus changes in creatinine for prediction of severe AKI by Day 7 of ICU admission. Secondary analysis will investigate the prediction of biomarkers for injury 'time based phenotypes': duration (>2 days), severity (KDIGO stage, use of renal replacement therapy), reversibility (time to return of serum creatinine to baseline), association with fluid overload > 10%, and disease association (sepsis, hypovolemia, hypoxemia, or nephrotoxic). The Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) study will be the largest ever prospective study of any disease process in pediatric critical care. Data from AWARE will enable refinement of AKI classification. AWARE creates the largest ever all-cause pediatric AKI data warehouse and biologic sample repository, providing a broad and invaluable resource for critical care nephrologists seeking to study risk factors, prediction, identification, and treatment options for a disease syndrome with high associated morbidity affecting a significant proportion of hospitalized children. Improving the precision of AKI diagnosis using biomarker combinations provides a foundation for targeted, personalized therapy for different injury phenotypes. NCT01987921.


Questioning patient engagement: research scientists' perceptions of the challenges of patient engagement in a cardiovascular research network.
Patient engagement in research is a dominant discourse in clinical research settings as it is seen as a move toward sustainable and equitable health care systems. In Canada, a key driver is the Strategy for Patient-Oriented Research of the Canadian Institutes of Health Research, which asserts that meaningful patient engagement can only be fostered when stakeholders understand its value. This study assessed researchers' perceptions of the meaning and value of patient engagement in research within a Canadian cardiovascular research network. In doing so, the secondary aim was to inform the development of a structured patient engagement initiative by identifying potential challenges and related mitigation strategies. We employed a multi-method strategy involving electronic surveys and semi-structured telephone interviews with network research scientists across Canada. Interview data were analyzed using thematic and content analysis. Survey data were analyzed using descriptive statistics. Thirty-eight electronic surveys (response rate =33%) and 16 interviews were completed with network members. Some participants were uncertain about the meaning and value of patient engagement. While voicing guarded support, four challenges relating to patient engagement were identified from the interviews: 1) identification of representative and appropriate patients, 2) uncertainty about the scope of patients' roles given concerns about knowledge discrepancies, 3) a perceived lack of evidence of the impact of patient engagement, and 4) the need for education and culture change as a prerequisite for patient engagement. Research scientists were largely concerned that patients untrained in science and tasked with conveying an authentic patient experience and being a conduit for the voices of others might unsettle a traditional model of conducting research. Concerns about patient involvement in research were related to a lack of clarity about the meaning, process, and impact of involvement. This study highlights the need for education on the meaning of patient engagement, evidence of its impact, and guidance on practical aspects of implementation within this research community.


Augmentation of cardiopulmonary baroreflex control of forearm vascular resistance in borderline hypertension.
Arterial baroreflex control of heart rate is impaired in young men with borderline or mild hypertension. Despite this impairment, these subjects often have exaggerated increases in vascular resistance during orthostatic stress. We considered the possibility that this exaggerated reflex vasoconstriction might reflect augmented cardiopulmonary baroreflex control of vascular resistance in borderline hypertension (BHT). Accordingly, we studied cardiopulmonary baroreflex control of forearm vascular resistance in nine BHT men with blood pressure intermittently above 150/90 mm Hg and in seven normotensive (NT) men. Cardiopulmonary baroreceptor input was reduced with lower body negative pressure (LBNP-5 to-20 mm HG), which decreases cardiac filling pressures. Baseline mean arterial pressure was 99 /+- 3 mm Hg (mean /+- SE) in BHT vs 83 /+- 2 mm Hg in NT (p less than 0.05). Baseline forearm resistance was also higher in BHT than in NT: 19 /+- 2 vs 13 /+-1 mm Hg/ml/min/100 ml or units (p less than 0.05). Reflex increases in forearm resistance during LBNP were greater (p less than 0.05) in BHT than in NT 8.6 /+- 1.7 vs 4.5 /+- 1.1 units during LBNP-20). Increases in arterial pressure and forearm resistance during a cold pressor test were not significantly different in the two groups. Thus, the augmented response to LBNP could not be attributed to a nonspecific influence of increased baseline resistance or a generalized abnormality in reflex control. In summary, the results of this study suggest that there is augmentation of the tonic inhibitory influence of cardiopulmonary baroreceptors in humans with BHT.


Maxillary protraction and vertical control utilizing skeletal anchorage for midfacial-maxillary deficiency.
The efficacy and efficiency of early treatment of skeletal Class III patients with facemask therapy are well-documented; however, very few cases for adolescents or adults were reported. The aim of this case report was to demonstrate skeletal and dental correction of a post-pubertal-growth-spurt patient whose malocclusion consisted of a skeletal Class III with slight transverse deficiency, a high mandibular plane angle, and a retrusive maxillary complex. A 13-year-5-months old Hispanic female was diagnosed as a retrognathic maxilla and mandible, a high mandibular plane angle, open bite pattern, a bilateral Angle Class I molar relationship with an anterior crossbite on the maxillary lateral incisors. A TAD-supported Haas rapid palatal expander was utilized for maxillary protraction combined with a facemask, vertical control, and maxillary molar distalization with fixed appliance. The total treatment time was 26 months. An improved facial profile with maxillary lip support and more prominent cheeks was established. Adequate vertical control prevented a change in the mandibular plane angle even though facemask treatment can increase the vertical dimension. After the 18-month retention, excellent stability of the treatment results was shown. With skeletal anchorage and facemask treatment, orthodontists have the ability of expanding and protracting the maxilla without tipping maxillary molars buccally and without the risk of unfavorable periodontal consequences. A TAD-supported Haas rapid palatal expander allowed to control the vertical dimension and distalize molars, while minimizing undesired consequences.


Multispecies coalescent delimits structure, not species.
The multispecies coalescent model underlies many approaches used for species delimitation. In previous work assessing the performance of species delimitation under this model, speciation was treated as an instantaneous event rather than as an extended process involving distinct phases of speciation initiation (structuring) and completion. Here, we use data under simulations that explicitly model speciation as an extended process rather than an instantaneous event and carry out species delimitation inference on these data under the multispecies coalescent. We show that the multispecies coalescent diagnoses genetic structure, not species, and that it does not statistically distinguish structure associated with population isolation vs. species boundaries. Because of the misidentification of population structure as putative species, our work raises questions about the practice of genome-based species discovery, with cascading consequences in other fields. Specifically, all fields that rely on species as units of analysis, from conservation biology to studies of macroevolutionary dynamics, will be impacted by inflated estimates of the number of species, especially as genomic resources provide unprecedented power for detecting increasingly finer-scaled genetic structure under the multispecies coalescent. As such, our work also represents a general call for systematic study to reconsider a reliance on genomic data alone. Until new methods are developed that can discriminate between structure due to population-level processes and that due to species boundaries, genomic-based results should only be considered a hypothesis that requires validation of delimited species with multiple data types, such as phenotypic and ecological information.


The efficacy of amitraz against cattle ticks in Tanzania.
The efficacy of amitraz on cattle ticks was assessed by susceptibility tests, spraying and dipping trials. Tests on the susceptibility of three tick species, Rhipicephalus appendiculatus, Amblyomma variegatum and Boophilus decoloratus to amitraz (technical grade-purity 98.6% w/w) showed all 15 tick strains tested to be highly susceptible, with LC50 ranging between 0.001% and 0.03%, and LC99, between 0.01% and 0.07%. Spraying trials were carried out on calves infested with R. appendiculatus, A. variegatum and B. decoloratus. Amitraz wettable powder [as Taktic total replacement (TR)] was tested against B. decoloratus, and amitraz emulsifiable concentrate (as Taktic EC) against the other two species. Both formulations showed instant action, with ticks detaching from the calves between 30 min and 8 h after spraying. More than 50% of the detached engorged females failed to lay eggs. The remainder laid few eggs, and these had a low hatching rate of 0-2%, compared with 90-98% in the controls. The detached nymphs failed to moult, and the males and non-engorged females also detached, were immobilized and finally died. In the dipping trials, cattle heavily infested with ticks (mean tick counts of about 800) were dipped once weekly in amitraz (Taktic TR). Weekly tick counts showed that the reinfestation rate was reduced to zero after the ninth dipping. The results of the three trials complement each other, showing that amitraz is at present effective in the control of African tick species on cattle in Tanzania.


Dopamine beta-hydroxylase and its genetic variants in human health and disease.
Dopamine beta-hydroxylase (DβH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DβH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DβH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DβH protein by genetic polymorphisms may result in DβH becoming rate-limiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DβH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DβH and its role in health and disease.


The role of ethnic matching between patient and provider on the effectiveness of brief alcohol interventions with Hispanics.
Evaluating the effectiveness of treatments such as brief alcohol interventions among Hispanics is essential to effectively addressing their treatment needs. Clinicians of the same ethnicity as the client may be more likely to understand the culture-specific values, norms, and attitudes and, therefore, the intervention may be more effective. Thus, in cases in which Hispanic patients were provided intervention by a Hispanic clinician improved drinking outcomes were expected. Patients were recruited from an urban Level I Trauma following screening for an alcohol-related injury or alcohol problems. Five hundred thirty-seven Hispanics were randomly assigned to brief intervention or treatment as usual. Hierarchical linear modeling was used to determine the effects of ethnic match on drinking outcomes including volume per week, maximum amount, and frequency of 5 or more drinks per occasion. Analyses controlled for level of acculturation and immigration status. For Hispanics who received brief motivational intervention, an ethnic match between patient and provider resulted in a significant reduction in drinking outcomes at 12-month follow-up. In addition, there was a tendency for ethnic match to be most beneficial to foreign-born Hispanics and less acculturated Hispanics. As hypothesized, an ethnic match between patient and provider significantly enhanced the effectiveness of brief intervention among Hispanics. Ethnic concordance between patient and provider may have impacted the effectiveness of the intervention through several mechanisms including cultural scripts, ethnic-specific perceptions pertaining to substance abuse, and ethnic-specific preferred channels of communication.


[Paramecium test for toxic substances in the blood of humans exposed to conditions simulating weightlessness].
The Paramecium test was for the first time used to measure the build-up of toxic substances in the healthy man exposed to simulated weightlessness. The most distinct changes were seen on bed rest days 3 and 7-8 in all test subjects (41 subjects). After bed rest day 8 the parameter reached a plateau, the toxicity level stopped to increase, but the Paramecium test time remained shorter than normal. It can therefore be suggested that the prognosis of any disease that may develop in this situation will be worse. In view of this it is important to improve the prophylaxis and treatment of endogenous and exogenous intoxications during space flight and to provide active detoxication based on the purification of biological fluids by sorption.


Renewal of the intestinal epithelium: new aspects as indicated by recent ultrastructural observations.
This article is a summary of our work of several years on the renewal of the intestinal epithelium. A combination of ultrastructural, radioautographic, and light microscopic analyses was carried out using normal tissue and tissue affected by inhibitors of RNA and protein synthesis. Measuring protein synthesis by 3H-leucine radioautography showed that the life span of the columnar (absorptive) cells in the rat small intestine was divisible into two main phases: differentiation (from stem to functional cell) and maturation (from functional to extruding cell), each phase and its subdivisions being well defined morphologically. Differentiation involved a linear rise in the rate of protein synthesis per cell and showed at the same time heterochromatinization and silencing of RNA transcription. Data from various experiments indicated that the cells functioned from stored information (RNA), part of which came from the nucleolus, which underwent marked and characteristic ultrastructural changes. Although transcription from rDNA ceased, the nucleolus released its ribosomal material, which added to the existing protein synthesis, presumably by recruiting excess stored mRNAs. Maturation involved a nearly linear decrease of the rate of protein synthesis per cell to a characteristic low value at which extrusion took place. A gradual exhaustion of the stored RNA was indicated to be the key factor in this decrease. Ultrastructurally, maturation was associated with a gradually increasing vesiculation of rER and Golgi. The results thus imply a regulatory role of cellular protein synthesis level in renewal. This would be an epigenetic response after the genes are silenced. The nucleolus seems to play a central role in this process, and this in turn is reflected in its characteristic ultrastructural changes. The work also included new observations on the epithelium of the rat ascending colon describing a hitherto unrecognized deep crypt mucus-secretory ("DCS") cell which is a nongoblet mature cell type apparently arising from midcrypt mitoses. In between the DCS cells, occasional slender columnar cells were seen which displayed the ultrastructural features of stem cells. These were probably reserve stem cells. We also observed nongoblet deep crypt mucous cells in the human right colon although fewer in number than in the rat. Nucleolar regulation and the presence of reserve stem cells represent new dimensions in our understanding of renewal. Electron microscopy is an essential tool in this investigation.


What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis.
BACKGROUND Frozen-thawed embryo transfer (FET) enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred at a later date. In recent years the number of FET cycles performed has increased due to transferring fewer embryos per transfer and improved laboratory techniques. Currently, there is little consensus on the most effective method of endometrium preparation prior to FET. METHODS Using both MEDLINE and EMBASE database a systematic review and meta-analysis of literature was performed. Case-series, case-control studies and articles in languages other than English, Dutch or Spanish were excluded. Those studies comparing clinical and ongoing pregnancy rates as well as live birth rates in (i) true natural cycle FET (NC-FET) versus modified NC-FET, (ii) NC-FET versus artificial cycle FET (AC-FET), (iii) AC-FET versus artificial with GnRH agonist cycle FET and (iv) NC-FET versus artificial with GnRH agonist cycle FET were included. Forest plots were constructed and relative risks or odds ratios were calculated. RESULTS A total of 43 publications were selected for critical appraisal and 20 articles were included in the final review. For all comparisons, no differences in the clinical pregnancy rate, ongoing pregnancy rate or live birth rate could be found. Based on information provided in the articles no conclusions could be drawn with regard to cancellation rates. CONCLUSIONS Based on the current literature it is not possible to identify one method of endometrium preparation in FET as being more effective than another. Therefore, all of the current methods of endometrial preparation appear to be equally successful in terms of ongoing pregnancy rate. However, in some comparisons predominantly retrospective studies were included leaving these comparisons subject to selection and publication bias. Also patients' preferences as well as cost-efficiency were not addressed in any of the included studies. Therefore, prospective randomized studies addressing these issues are needed.


The rational clinical examination. Does this infant have pneumonia?
Acute lower respiratory tract illness is common among children seen in primary care. We reviewed the accuracy and precision of the clinical examination in detecting pneumonia in children. Although most cases are viral, it is important to identify bacterial pneumonia to provide appropriate therapy. Studies were identified by searching MEDLINE from 1982 to 1995, reviewing reference lists, reviewing a published compendium of studies of the clinical examination, and consulting experts. Observer agreement is good for most signs on the clinical examination. Each study was reviewed by 2 observers and graded for methodologic quality. There is better agreement about signs that can be observed (eg, use of accessory muscles, color, attentiveness; kappa, 0.48-0.66) than signs that require auscultation of the chest (eg, adventitious sounds; kappa, 0.3). Measurements of the respiratory rate are enhanced by counting for 60 seconds. The best individual finding for ruling out pneumonia is the absence of tachypnea. Chest indrawing, and other signs of increased work of breathing, increases the likelihood of pneumonia. If all clinical signs (respiratory rate, auscultation, and work of breathing) are negative, the chest x-ray findings are unlikely to be positive. Studies are needed to assess the value of clinical findings when they are used together.


Laser absorption spectroscopy at 2 µm inside revolver-type anti-resonant hollow core fiber.
In this paper, we present a laser-based sensing inside anti-resonant hollow core fiber. A distributed feedback laser diode operating near 2004 nm and a 1.35-m-long silica-based fiber are used to demonstrate carbon dioxide detection with sensitivity down to ~5 ppmv. Gas exchange time as low as 5 seconds is obtained. This performance was achieved in a very simple optical configuration, without any mirrors or lenses in the setup.


Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases.
While an age-associated diminution in myocardial contractile response to beta-adrenergic receptor (beta-AR) stimulation has been widely demonstrated to occur in the context of increased levels of plasma catecholamines, some critical mechanisms that govern beta-AR signaling must still be examined in aged hearts. Specifically, the contribution of beta-AR subtypes (beta1 versus beta2) to the overall reduction in contractile response with aging is unknown. Additionally, whether G protein-coupled receptor kinases (GRKs), which mediate receptor desensitization, or adenylyl cyclase inhibitory G proteins (Gi) are increased with aging has not been examined. Both these inhibitory mechanisms are upregulated in chronic heart failure, a condition also associated with diminished beta-AR responsiveness and increased circulatory catecholamines. In this study, the contractile responses to both beta1-AR and beta2-AR stimulation were examined in rat ventricular myocytes of a broad age range (2, 8, and 24 mo). A marked age-associated depression in contractile response to both beta-AR subtype stimulation was observed. This was associated with a nonselective reduction in the density of both beta-AR subtypes and a reduction in membrane adenylyl cyclase response to both beta-AR subtype agonists, NaF or forskolin. However, the age-associated diminutions in contractile responses to either beta1-AR or beta2-AR stimulation were not rescued by inhibiting Gi with pertussis toxin treatment. Further, the abundance or activity of beta-adrenergic receptor kinase, GRK5, or Gi did not significantly change with aging. Thus, we conclude that the positive inotropic effects of both beta1- and beta2-AR stimulation are markedly decreased with aging in rat ventricular myocytes and this is accompanied by decreases in both beta-AR subtype densities and a reduction in membrane adenylate cyclase activity. Neither GRKs nor Gi proteins appear to contribute to the age-associated reduction in cardiac beta-AR responsiveness.


Weekly and daily cycle of alcohol use among the U.S. general population.
Studies such on alcohol and injuries have defined alcohol-related injury as an injury with a positive self-report of alcohol consumption in the 6h prior to the event. However, there is very limited data on the pattern of alcohol use over time of day and day of week among the general population. The aim of this study is to estimate the rate of alcohol use by time of day, and day of week for the U.S. general adult (≥ 18 years) population. This study employed the design of a retrospective cohort study using data collected from three waves (2005-06, 2007-08, 2009-10) of the National Health and Nutrition Examination Survey (NHANES). Incidence rates of overall drinking (≥ 10 g of alcohol) and incidence rates of heavy drinking (≥ 40 g of alcohol) were estimated for day of week, and time of day (in hours). Multivariable Poisson regression models were used to investigate the difference between weekend nights and weekday nights. The incidence rates (95% confidence interval) of all drinking episodes were 30.5 (29.2-32.0) per 100 person-days and 24.4 (22.8-26.2) per 100 person-days for weekend and the rest of the week, respectively. The incidence rates of heavy drinking episodes were 11.0 (10.2-11.9) and 7.7 (6.8-8.7) for weekend and the rest of the week. Multivariable analysis indicated that risks of overall drinking and heavy drinking were significantly higher (18% and 34%, respectively) during the weekend nights when compared to weekday nights. It was also observed young adults (18-29 years old) were more likely to increase their alcohol use during weekend nights compared to older age groups. The general US population, especially young adults are exposed to alcohol and its acute effects at a much higher level during the night, and this in-turn increases the risk of alcohol-related injuries during that time.


Effects of a plant cyclotide on conformational dynamics and destabilization of β-amyloid fibrils through molecular dynamics simulations.
Aggregation of β-amyloid (Aβ) peptide is one of the hallmarks of Alzheimer's disease (AD) which results in chronic and progressive neurodegeneration of the brain. A recent study by our group have shown the ability of cyclic disulfide-rich peptides ("cyclotides") isolated from a medicinal plant, Clitoria ternatea, to inhibit the aggregation of Aβ peptides and reduce oxidative stress caused by reactive oxygen species using in vivo models of transgenic Caenorhabditis elegans. In the present study, through extensive computational docking and multi-ns molecular dynamics (MD) simulation, we evaluated if cyclotides can stably bind to Aβ molecules and/or destabilize the Aβ fibril by preventing conformational changes from α-helical to β-sheet rich structures. We demonstrate that cyclotides bind effectively and stably to different forms of Aβ structures via hydrogen bonding and hydrophobic interactions. One of the conserved hydrophobic interface residues, Tyr10 was mutated to Ala and the impact of this virtual mutation was estimated by additional MD simulations for the wild-type (WT) and mutant protein-peptide complexes. A detailed MD simulation analyses revealed that cyclotides form hydrogen bonds with the toxic amyloid assemblies thereby weakening the inter-strand hydrogen bonds between the Aβ peptide. The φ-ѱ distribution map of residues in the cyclotide binding pocket that ideally adopt β-sheet conformation show deviation towards right-handed ɑ-helical (ɑR) conformation. This effect was similar to that observed for the Tyr10Ala mutant and doubly so, for the cyclotide bound form. It is therefore possible to hypothesise that the opening up of amyloid β-sheet is due to an unfolding process occurring in the Aβ caused by cyclotide binding and inhibition. Our current findings provide novel structural insights on the mode of interaction between cyclotides and Aβ fibrils and describe their anti-amyloid aggregation potential. This sheds light on the future of cyclotide-based drug design against protein aggregation, a hallmark event in many neurodegenerative diseases.


Comparative splanchnic blood flow effects of various vasodilator compounds.
We examined the visceral blood flow distribution during infusion of three vasodilators at doses that produced similar depression of systemic arterial pressure. The studies were performed in pentobarbital-anesthetized dogs using the radioactive microspheres technique. Minoxidil did not alter renal, total visceral, or visceral organ flow distribution with the exception of a modest increase in relative stomach blood flow. Nitroprusside increased the percentage of total visceral flow to the spleen and the hepatic artery. Dopamine increased blood flow to the stomach, intestine, and kidney. After phenoxybenzamine, the augmentation of stomach blood flow by dopamine was greatly increased, while blood flow to the splenic, pancreatic, and hepatic arteriolar vascular beds decreased. The decreases in blood flows may be due to decreased perfusion pressure in the absence of active vasodilation or to myogenic or metabolic autoregulation. Thus, at equivalent hypotensive responses, the vasodilator compounds that we studied produced markedly different patterns of visceral blood flow.


Mendelian and non-Mendelian regulation of gene expression in maize.
Transcriptome variation plays an important role in affecting the phenotype of an organism. However, an understanding of the underlying mechanisms regulating transcriptome variation in segregating populations is still largely unknown. We sought to assess and map variation in transcript abundance in maize shoot apices in the intermated B73 × Mo17 recombinant inbred line population. RNA-based sequencing (RNA-seq) allowed for the detection and quantification of the transcript abundance derived from 28,603 genes. For a majority of these genes, the population mean, coefficient of variation, and segregation patterns could be predicted by the parental expression levels. Expression quantitative trait loci (eQTL) mapping identified 30,774 eQTL including 96 trans-eQTL "hotspots," each of which regulates the expression of a large number of genes. Interestingly, genes regulated by a trans-eQTL hotspot tend to be enriched for a specific function or act in the same genetic pathway. Also, genomic structural variation appeared to contribute to cis-regulation of gene expression. Besides genes showing Mendelian inheritance in the RIL population, we also found genes whose expression level and variation in the progeny could not be predicted based on parental difference, indicating that non-Mendelian factors also contribute to expression variation. Specifically, we found 145 genes that show patterns of expression reminiscent of paramutation such that all the progeny had expression levels similar to one of the two parents. Furthermore, we identified another 210 genes that exhibited unexpected patterns of transcript presence/absence. Many of these genes are likely to be gene fragments resulting from transposition, and the presence/absence of their transcripts could influence expression levels of their ancestral syntenic genes. Overall, our results contribute to the identification of novel expression patterns and broaden the understanding of transcriptional variation in plants.


Driving speed of young novice and experienced drivers in simulated hazard anticipation scenes.
In this study, we aimed to demonstrate analysis methods that are sensitive to speed-related differences between experienced and young novice drivers. These differences may be linked to determining which group is better at anticipating hazards. Awareness of hazardous situations, especially potential ones, is a major discriminator between experienced and young novice drivers who tend to misidentify potential hazards in the traffic environment. Experienced and young novice drivers were asked to drive a sequence of 14 scenarios in a driving simulator. Scenarios were created in two city areas, residential and business district, and included various types of hazards. Group homogeneity of speed for each group of drivers was computed for each scenario, and two business district scenarios were subjected to piecewise linear regression analysis. Group homogeneity analysis showed consistent and significant experience-based differences across all scenarios, revealing that the experienced drivers as a group were more homogenous in choosing their driving speed. Differences between groups were larger in the business district where speed was less restricted. Piecewise linear regression analysis revealed that experienced drivers approached uncontrolled intersections by slowing down and responded earlier to materialized events. Young novice drivers were more likely than experienced drivers to choose diverse values of speed at any given road section, presumably due to their poor awareness of potential and hidden hazards. Unlike other analysis methods, it is argued that group homogeneity of speed is a more sensitive measurement to reveal these gaps. Speed management could be the basis of future hazard anticipation simulator assessments.


Status survey on enema reduction of paediatric intussusception in China.
Intussusception is a common paediatric abdominal emergency in infants. The first-line treatment of choice in uncomplicated paediatric intussusception is enema reduction. The study aim was to provide an overview of the current national practice of enema reduction of paediatric intussusception in China. A questionnaire on enema reduction of paediatric intussusception was sent to respondents (members of the Pediatric Anorectal Group, the Neonatal Group, the Society of Pediatric Surgery and the China Medical Association). Data from 128 questionnaires were analysed. Of these, 78.1% (100/128) reported the use of fluoroscopy, 17.2% (22/128) use of ultrasound monitoring, 78.9% (101/128) use of air and 17.9% (23/128) use of normal saline. A total of 78.9% (101/128) reported a success rate of 90%, 25.8% (33/128) reported that a paediatric surgeon managed the reduction, 18.8% (24/128) that a radiologist managed the reduction and 44.5% (57/128) that a paediatric surgeon and radiologist jointly managed the reduction. There is large variation in the techniques of enema reduction of intussusception in China. Fluoroscopy-guided air enema reduction is mainly used. Enema reduction of uncomplicated cases of paediatric intussusception in China lacks standardization of equipment and personnel involvement.


Plasma leptin levels in rats with pancreatitis.
Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12 ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.