An Empirical Bayes Mixture Model for Effect Size Distributions in Genome-Wide Association Studies.
Characterizing the distribution of effects from genome-wide genotyping data is crucial for understanding important aspects of the genetic architecture of complex traits, such as number or proportion of non-null loci, average proportion of phenotypic variance explained per non-null effect, power for discovery, and polygenic risk prediction. To this end, previous work has used effect-size models based on various distributions, including the normal and normal mixture distributions, among others. In this paper we propose a scale mixture of two normals model for effect size distributions of genome-wide association study (GWAS) test statistics. Test statistics corresponding to null associations are modeled as random draws from a normal distribution with zero mean; test statistics corresponding to non-null associations are also modeled as normal with zero mean, but with larger variance. The model is fit via minimizing discrepancies between the parametric mixture model and resampling-based nonparametric estimates of replication effect sizes and variances. We describe in detail the implications of this model for estimation of the non-null proportion, the probability of replication in de novo samples, the local false discovery rate, and power for discovery of a specified proportion of phenotypic variance explained from additive effects of loci surpassing a given significance threshold. We also examine the crucial issue of the impact of linkage disequilibrium (LD) on effect sizes and parameter estimates, both analytically and in simulations. We apply this approach to meta-analysis test statistics from two large GWAS, one for Crohn's disease (CD) and the other for schizophrenia (SZ). A scale mixture of two normals distribution provides an excellent fit to the SZ nonparametric replication effect size estimates. While capturing the general behavior of the data, this mixture model underestimates the tails of the CD effect size distribution. We discuss the implications of pervasive small but replicating effects in CD and SZ on genomic control and power. Finally, we conclude that, despite having very similar estimates of variance explained by genotyped SNPs, CD and SZ have a broadly dissimilar genetic architecture, due to differing mean effect size and proportion of non-null loci.


Na+-K+-ATPase-dependent sodium flux in cortical collecting tubule.
The instantaneous rate of efflux of intracellular Na was studied in rabbit isolated cortical collecting tubules (CCT) as a function of temperature and intracellular Na concentration ([Na]i). [Na]i of microdissected CCT was increased by cold and K-free exposure in the presence of 22Na and the extracellular tracer [3H] sorbitol. [Na]i rose rapidly to 40 mM at 30 min, after which it rose more slowly, reaching 120-140 mM at 6 h. Kinetics of Na efflux were studied after rapid rewarming, using a special device allowing measurements at 20-s intervals. Under control conditions, the total Na load was extruded in less than 8 min, whereas, in the presence of 10(-4) M ouabain, only 50% of the load was extruded during this period of time. Ouabain-sensitive Na efflux was first evident at 13 degrees C and gradually increased between 13 and 35 degrees C. At 37 degrees C, Na+-K+-ATPase-dependent Na efflux was dependent on [Na]i. This efflux gradually increased, from 0.05 to 0.5 peq.nl tubular volume-1.s-1 as a function of [Na]i and reached a plateau at 70 mM [Na]i. It is concluded that [Na]i is a major modulator of the pump activity in CCT; at normal levels of [Na]i, the pump is operating at only a small fraction of its total capacity.


Cell class-specific regulation of neocortical dendrite and spine growth by AMPA receptor splice and editing variants.
Glutamatergic transmission converging on calcium signaling plays a key role in dendritic differentiation. In early development, AMPA receptor (AMPAR) transcripts are extensively spliced and edited to generate subunits that differ in their biophysical properties. Whether these subunits have specific roles in the context of structural differentiation is unclear. We have investigated the role of nine GluA variants and revealed a correlation between the expression of flip variants and the period of major dendritic growth. In interneurons, only GluA1(Q)-flip increased dendritic length and branching. In pyramidal cells, GluA2(Q)-flop, GluA2(Q)-flip, GluA3(Q)-flip and calcium-impermeable GluA2(R)-flip promoted dendritic growth, suggesting that flip variants with slower desensitization kinetics are more important than receptors with elevated calcium permeability. Imaging revealed significantly higher calcium signals in pyramidal cells transfected with GluA2(R)-flip as compared with GluA2(R)-flop, suggesting a contribution of voltage-activated calcium channels. Indeed, dendritic growth induced by GluA2(R)-flip in pyramidal cells was prevented by blocking NMDA receptors (NMDARs) or voltage-gated calcium channels (VGCCs), suggesting that they act downstream of AMPARs. Intriguingly, the action of GluA1(Q)-flip in interneurons was also dependent on NMDARs and VGCCs. Cell class-specific effects were not observed for spine formation, as GluA2(Q)-flip and GluA2(Q)-flop increased spine density in pyramidal cells as well as in interneurons. The results suggest that AMPAR variants expressed early in development are important determinants for activity-dependent dendritic growth in a cell type-specific and cell compartment-specific manner.


Three-Dimensional Fast Spin-Echo Imaging without Fat Suppression of the Knee: Diagnostic Accuracy Comparison to Fat-Suppressed Imaging on 1.5T MRI.
To evaluate the diagnostic performance of three-dimensional fast spin-echo (3D FSE-Cube) without fat suppression (NFS) for detecting knee lesions, using comparison to 3D FSE-Cube with fat suppression (FS). One hundred twenty-four patients who underwent 1.5T knee magnetic resonance imaging (MRI) scans and 25 subsequent arthroscopic surgeries were retrospectively reviewed. Using arthroscopic results and two-dimensional images as reference standards, diagnostic performances of 3D FSE-Cube-NFS and FS imaging about lesions of ligament, meniscus, subchondral bone marrow edema (BME), and cartilage were compared. Scan parameters of 3D FSE-Cube imaging were previously optimized by a porcine knee phantom. No significant differences were observed between detection rates of NFS and FS imaging for detecting lesions of meniscus and cartilage (p>0.05). However, NFS imaging had lower sensitivity for detection of medial collateral ligament (MCL) tears, and lower sensitivity and specificity for detection of BME lesions, compared to FS imaging (p<0.05). 3D FSE-Cube-NFS imaging showed similar diagnostic performance for detecting lesions of meniscus or cartilage compared to FS imaging, unlike MCL or BME lesions.


Effect of SWCNT volume fraction on the viscosity of water-based nanofluids.
Nanofluids have received a great deal of interest in recent years because of their various unique features. According to the findings, the addition of nanotubes to the base materials can drastically alter their properties. In the present work, the viscosity of a typical water-based nanofluid containing single-walled carbon nanotubes is estimated using the molecular dynamics simulation for different volume fractions ranging between 0.557 and 3% at two temperatures (298 K and 313 K). The temperature of the systems is controlled using a Nose-Hoover thermostat. For calculating viscosity, the Green-Kubo equilibrium method is used. The enthalpy, potential, kinetic, and total energies are calculated to determine the system's stability. In addition, the influence of molecular mass on these energies is studied. The nanotube under investigation is an armchair(6,6)-type single-walled carbon nanotube. The results highlight the promise of the molecular dynamics simulation technique as a powerful tool in the prediction of nanofluid properties besides the experimental results. The value of viscosity will decrease as the temperature rises, much like the base fluid. Furthermore, it is shown that the viscosity is proportional to the volume fraction of water-SWCNT nanofluid. According to the results, a new viscosity relationship for volume fractions in the range of ϕ ≤ 3% is proposed. The viscosity, temperature, and volume fraction are all linked together in this equation.


Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction.
To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.


Influence of auditory and audiovisual stimuli on the right-left prevalence effect.
When auditory stimuli are used in two-dimensional spatial compatibility tasks, where the stimulus and response configurations vary along the horizontal and vertical dimensions simultaneously, a right-left prevalence effect occurs in which horizontal compatibility dominates over vertical compatibility. The right-left prevalence effects obtained with auditory stimuli are typically larger than that obtained with visual stimuli even though less attention should be demanded from the horizontal dimension in auditory processing. In the present study, we examined whether auditory or visual dominance occurs when the two-dimensional stimuli are audiovisual, as well as whether there will be cross-modal facilitation of response selection for the horizontal and vertical dimensions. We also examined whether there is an additional benefit of adding a pitch dimension to the auditory stimulus to facilitate vertical coding through use of the spatial-musical association of response codes (SMARC) effect, where pitch is coded in terms of height in space. In Experiment 1, we found a larger right-left prevalence effect for unimodal auditory than visual stimuli. Neutral, non-pitch coded, audiovisual stimuli did not result in cross-modal facilitation, but did show evidence of visual dominance. The right-left prevalence effect was eliminated in the presence of SMARC audiovisual stimuli, but the effect influenced horizontal rather than vertical coding. Experiment 2 showed that the influence of the pitch dimension was not in terms of influencing response selection on a trial-to-trial basis, but in terms of altering the salience of the task environment. Taken together, these findings indicate that in the absence of salient vertical cues, auditory and audiovisual stimuli tend to be coded along the horizontal dimension and vision tends to dominate audition in this two-dimensional spatial stimulus-response task.


Acute effects of transcranial direct current stimulation on cycling and running performance. A systematic review and meta-analysis.
Transcranial direct current stimulation (tDCS) has been proven to induce positive effects on athletic performance. The present study aimed to analyse the effect of anodal-tDCS on endurance (time to exhaustion [TTE] or endurance time trial [ETT]) and sprint performance during cycling and running tasks. We performed a systematic literature review in the databases Medline (via PubMed), SPORTDiscus and Science Direct. We included only randomised controlled trials conducted with healthy individuals in which an anodal-tDCS protocol was applied prior to cycling or running tests. The effect of anodal-tDCS (experimental condition) was compared against sham stimulation (control condition). A total of 15 interventions from 13 studies were included. The sub-group analysis revealed a positive effect of anodal-tDCS on TTE (standardised mean differences [SMD] = 0.37; 90% confidence interval [CI] = 0.13, 0.61; p = 0.01), but not on ETT (SMD = 0.00; 90% CI = -0.29, 0.30; p = 1.00) or sprint performance (SMD = 0.19; 90% CI = -0.23, 0.60; p = 0.46). The current meta-analysis suggests that the effect of anodal-tDCS on whole-body dynamic exercises (running and cycling) could be task dependent. Specifically, anodal-tDCS enhance running and cycling time to exhaustion performance during TTE tasks but not ETT or sprint tasks. The increase in cortical excitability induced by anodal-tDCS may lead to lower ratings of perceived exertion by reducing the input required to perform the physical task. Task should be taken into account, because it is probably influencing the result obtained by anodal-tDCS.


Mass-forming cholangiocarcinoma and adenocarcinoma of unknown primary: can they be distinguished on liver MRI?
To determine MR features suggestive of mass-forming cholangiocarcinoma (CCA) or liver metastases of adenocarcinoma of unknown primary (AUP), and to compare the ability of two experienced radiologists to establish the correct diagnosis. 61 patients with CCA or AUP, with MRIs were placed into two groups: population 1, 28 patients with certain diagnosis of either CCA or AUP; and population 2, 33 patients with uncertain diagnosis. Using population 1 with known diagnosis, two investigators formulated imaging criteria for CCA or AUP, which represented phase 1 of the study. In phase 2, two independent radiologists categorized the patients in populations 1 and 2 as CCA or AUP using the formulated criteria. This categorization was compared with the patient medical records and pathologist review. Findings were tested for statistical significance. In phase 1, solitary lesion, multifocal lesions with dominant lesion, capsule retraction, and porta hepatis lymphadenopathy were features of CCA; multifocal lesions with similar size, and ring enhancement were features of AUP. The number of lesions, capsule retraction, and early tumor enhancement pattern were observed to be significant features (P < 0.05). In phase 2, agreement between the two radiologists was good (k = 0.663). For population 1, the agreement was good (k = 0.659), and was fair for population 2 (k = 0.293). Concordance between the two radiologists, medical record, and the pathologist was found in 41/61 (67%) patients. Distinctive features of CCA and AUP are identifiable on MRI images, which may aid the radiologist to establish the correct diagnosis.


Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer. National Cancer Institute Bladder Tumor Marker Network.
A cohort of 109 patients with primary transitional cell carcinomas, stages T2-T3, grade 2 or higher, was identified and further divided into two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a minimum of 5 years of follow-up after cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were sectioned and distributed to different laboratories to be analyzed. Immunohistochemistry on deparaffinized tissue sections was conducted for evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular counts (factor VIII-related antigen). DNA content/ploidy studies were performed on material obtained from thick sections. A double-blinded strategy was used for the evaluation of laboratory data versus clinical parameters. The cutoff value for p53 nuclear overexpression was > or =20% of tumor cells displaying nuclear staining. The median values for MIB1 (> or =18% of tumor nuclear cell staining) and microvascular counts (> or =40 microvessels/area screened) were used as cutoff points for these two variables. The assessment of DNA content was conducted by classifying cases as diploid, tetraploid, or aneuploid. Statistical analyses were performed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlation with the end point of the study, i.e., the presence of lymph node metastatic disease, in the cohort of patients studied, although an obvious trend for p53 was noted. It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not strongly associated with lymph node status in patients affected with high-stage, high-grade bladder cancer.


Options on obesity.
Obesity is a major problem, putting increasing pressure on specialists services. Weight-loss programmer provided by multidisciplinary teams and based in hospitals or the community are achieving considerable success, with some candidates for bariatric surgery losing so much weight they no longer seek surgery. Nurses take an important and rewarding role in these services.


Impact of surgical margin status on prostate-cancer-specific mortality.
Study Type--Diagnostic (exploratory cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Surgical margin status at radical prostatectomy (RP) has been shown to be a predictor of disease progression and the strongest predictor of benefit from adjuvant therapy, but the impact of a positive surgical margin (PSM) on long-term prostate-cancer-specific survival is unknown. The PSM rate is dependent on the pathological stage of the cancer. In a recent multicentre nomogram for 15-year prostate-cancer-specific mortality (PCSM) after RP, PSM was not significantly associated with PCSM, while Gleason score and pathological stage were the only significant predictors. This has not been validated in a single centre, and PSM has been shown to vary greatly with surgical technique. This is the first study on the impact of PSM on PCSM in a single surgeon's cohort. In other centres, the decision to administer adjuvant therapy may be influenced by surgical margin status. In this cohort, men routinely did not receive adjuvant therapy, affording the unique opportunity to study the long-term implications of a PSM. • To examine the relative impact of a positive surgical margin (PSM) and other clinicopathological variables on prostate-cancer-specific mortality (PCSM) in a large retrospective cohort of patients undergoing radical prostatectomy (RP). • Between 1982 and 2011, 4569 men underwent RP performed by a single surgeon. • Of the patient population, 4461 (97.6%) met all the inclusion criteria. • The median (range) age was 58 (33-75) years and the median prostate-specific antigen (PSA) was 5.4 ng/mL; RP Gleason score was ≤ 6 in 2834 (63.7%), 7 in 1351 (30.3%), and 8-10 in 260 (6.0%) patients; PSMs were found in 462 (10.4%) patients. • Cox proportional hazards models were used to determine the impact of a PSM on PCSM. • At a median (range) follow-up of 10 years (1-29), 187 men (4.3%) had died from prostate cancer. • The 20-year prostate-cancer-specific survival rate was 75% for those with a PSM and 93% for those without. • Compared with those with a negative surgical margin, men with a PSM were more likely to be older (median age 60 vs 58 years) and to have undergone RP in the pre-PSA era (36.6% vs 11.8%). Additionally, they were more likely to have a higher PSA level (median 7.6 vs 5.2 ng/mL), a Gleason score of ≥ 7 (58.7% vs 33.7%), and a non-organ-confined tumour (90.9% vs 30.6% [P < 0.001 for all]). • In a univariate model for PCSM, PSM was highly significant (hazard ratio [HR] 5.0, 95% confidence interval [CI] 3.7-6.7, P < 0.001). • In a multivariable model, adjusting for pathological variables and RP year, PSM remained an independent predictor of PCSM (HR 1.4, 95% CI 1.0-1.9, P = 0.036) with a modest effect relative to RP Gleason score (HR 5.7-12.6) and pathological stage (HR 2.2-11.0 [P < 0.001]). • Although a PSM has a statistically significant adverse effect on prostate-cancer-specific survival in multivariable analysis, Gleason grade and pathological stage were stronger predictors.


Retinal Vascular Reactivity as Assessed by Optical Coherence Tomography Angiography.
The vascular supply to the retina has been shown to dynamically adapt through vasoconstriction and vasodilation to accommodate the metabolic demands of the retina. This process, referred to as retinal vascular reactivity (RVR), is mediated by neurovascular coupling, which is impaired very early in retinal vascular diseases such as diabetic retinopathy. Therefore, a clinically feasible method of assessing vascular function may be of significant interest in both research and clinical settings. Recently, in vivo imaging of the retinal vasculature at the capillary level has been made possible by the FDA approval of optical coherence tomography angiography (OCTA), a noninvasive, minimal risk and dyeless angiography method with capillary level resolution. Concurrently, physiological and pathological changes in RVR have been shown by several investigators. The method shown in this manuscript is designed to investigate RVR using OCTA with no need for alterations to the clinical imaging procedures or device. It demonstrates real time imaging of the retina and retinal vasculature during exposure to hypercapnic or hyperoxic conditions. The exam is easily performed with two personnel in under 30 min with minimal subject discomfort or risk. This method is adaptable to other ophthalmic imaging devices and the applications may vary based on the composition of the gas mixture and patient population. A strength of this method is that it allows for an investigation of retinal vascular function at the capillary level in human subjects in vivo. Limitations of this method are largely those of OCTA and other retinal imaging methods including imaging artifacts and a restricted dynamic range. The results obtained from the method are OCT and OCTA images of the retina. These images are amenable to any analysis that is possible on commercially available OCT or OCTA devices. The general method, however, can be adapted to any form of ophthalmic imaging.


Low-Frequency Raman Spectroscopy: An Exceptional Tool for Exploring Metastability Driven States Induced by Dehydration.
The use of low-frequency Raman spectroscopy (LFRS; ω < 150 cm-1) is booming in the pharmaceutical industry. Specific processing of spectra is required to use the wealth of information contained in this spectral region. Spectra processing and the use of LFRS for analyzing phase transformations in molecular materials are detailed herein from investigations on the devitrification of ibuprofen. LFRS was used to analyze the dehydration mechanism of two hydrates (theophylline and caffeine) of the xanthine family. Two mechanisms of solid-state transformation in theophylline were determined depending on the relative humidity (RH) and temperature. At room temperature and 1% RH, dehydration is driven by the diffusion mechanism, while under high RH (>30%), kinetic laws are typical of nucleation and growth mechanism. By increasing the RH, various metastability driven crystalline forms were obtained mimicking successive intermediate states between hydrate form and anhydrous form achieved under high RH. In contrast, the dehydration kinetics of caffeine hydrate under various RH levels can be described by only one master curve corresponding to a nucleation mechanism. Various metastability driven states were achieved depending on the RH, which can be described as intermediate between forms I and II of anhydrous caffeine.


Serum Erythropoietin level in anemia of elderly with unclear etiology.
Anemia is a common condition, but its causes are often unclear, especially in elderly adults. Erythropoietin (EPO) levels are known to be elevated in myelodysplastic syndrome and hematologic malignancies, but decreased in chronic benign anemia. This study aimed to investigate whether EPO levels could be used to identify underlying bone marrow diseases including malignancies, among elderly anemic patients with unclear etiology. This single centered retrospective study included patients presented with isolated anemia and had their EPO levels measured at their first visit. Patients were divided into two groups: bone marrow disease and benign etiologic anemia, based on observation and bone marrow test results. Out of 1180 patients reviewed, 81 patients with anemia of unclear etiology were identified, including 67 with benign anemia and 14 with bone marrow disease. Statistically significant difference in EPO levels between these two groups (P < 0.001) were observed. The receiver operating characteristic curve analysis showed that an EPO cut-off value of 36.4 mU/mL had a sensitivity and specificity of 92.8% and 94.0% for detecting underlying bone marrow disease, respectively. We suggest measuring serum EPO levels can aid in the early detection of benign anemia from bone marrow disease, including malignancies, with high sensitivity and specificity.


Flexible sigmoidoscopy as a colorectal cancer screening test in the general population: recruitment phase results of a randomized controlled trial in Lombardia, Italy.
A two arm multicentre randomized controlled trial is in progress to evaluate the efficacy of flexible sigmoidoscopy (FS) as a screening test for colorectal cancer in the general population. To determine the acceptance rate and feasibility of FS as a colorectal cancer screening test in average-risk asymptomatic volunteers. Average-risk, asymptomatic subjects, aged 55-64 years and assisted by 244 general practitioners (GPs) in Lombardy, Italy, were invited by postal questionnaire (PQ) to enter a study for the prevention of colorectal cancer and asked to indicate their interest in, and willingness to undergo, screening: those responding positively were randomized to the intervention or control arms. GPs were trained in colorectal cancer screening and proposed free FS to their patients randomized to the intervention arm. All sigmoidoscopies were performed by experienced endoscopists. Small polyps were removed at FS. Colonoscopy was indicated for high risk polyps (size more than 5 mm, more than two adenomas, villous histology, severe dysplasia or malignancy). 40,945 subjects were invited. 667 PQs were returned undelivered due to postal failure. 7,892 (19.59%) subjects responded, 2,116 of whom (26.81%) were not included, presenting 1 or more exclusion criteria. We randomized 5,778 volunteers and performed 1,582 sigmoidoscopies out of 2,885 subjects in the intervention arm (54.84% acceptance rate). Although the screening procedure had a good attendance rate in the intervention group, involvement of the people invited was lower than expected. Future FS screening programmes will require a keener focus on recruitment strategies, mainly with participation of GPs.


Narcea-an unknown, ancient cultivated rose variety from northern Spain.
The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias (northern Spain). The variety is here given the name Narcea. The majority of roses currently cultivated belong to the so-called group of 'Modern Roses', all of which were obtained after 1867 via artificial crosses and improvement programmes. All are destined for ornamental use. Until the 19th century, the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics, or had medicinal uses. Rosa damascena and Rosa centifollia are still grown and used by the French and Bulgarian perfume industries. The Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75% of the wild members of the genus Rosa, but until now there was no evidence that this area was home to ancient cultivated roses. A complete botanical description is here provided for a discovered ancient rose. It is also characterised according to a series of sequence tagged microsatellite sites, and its agronomic features are reported. In addition, a histological description (optical and scanning electronic microscope studies) of the petals is offered, along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass spectroscopy. The results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry.


Effects of 10 days of endurance exercise training on the suppression of whole body and regional lipolysis by insulin.
The aim of this study was to evaluate in premenopausal women (10 sedentary obese women) the effects of 10 days of exercise on the suppression of whole body and regional lipolysis by insulin. Lipolysis was determined using 2H5-glycerol infusion and microdialysis of sc adipose tissue during a two-stage hyperinsulinemic-euglycemic clamp [10 (LO) and 20 (MO) mU/m x min]. Microdialysis probes were positioned in abdominal and femoral sc adipose tissue to monitor interstitial glycerol and blood flow. Basal plasma glycerol was 86.7 +/-17.0 and 100.3 +/- 19.8 micromol/L before and after training, respectively (P < 0.05). Plasma glycerol was suppressed to a greater extent after [to 47 +/- 5% (LO) and 42 +/- 5% (MO) of basal] than before [to 62 +/- 8% (LO) and 55 +/- 8% (MO) of basal] training. The rate of appearance of glycerol was suppressed to 49 +/- 7% and 40 +/- 5% of basal during LO and to 38 +/- 5% and 30 +/- 4% of basal during MO (P < 0.05) before and after training, respectively. There were no differences in the suppression of lipolysis in abdominal as well as femoral sc adipose tissue as evidenced by similar reductions in dialysate glycerol levels before and after training in each of these tissues. The results indicate that the antilipolytic response to insulin can be improved through endurance exercise training. Intraabdominal adipose tissue or skeletal muscle may be the site of improved antilipolytic response to insulin after training, as improvement was not evident in abdominal or femoral sc adipose tissue.


Molecular analysis of WNT4 gene in four adolescent girls with mullerian duct abnormality and hyperandrogenism (atypical Mayer-Rokitansky-Küster-Hauser syndrome).
In a collaborative study, we investigated four 46,XX adolescent girls with Mayer-Rokitansky-Küster-Hauser syndrome and hyperandrogenism. Molecular analysis of the WNT4 gene permitted us to identify a new mutation (p.A233T). Functional studies revealed partial repression of steroidogenic enzymes (normal repression of HSD3B2) contrasting with the abnormal reexpression of CYP17A1 enzyme in the OVCAR3 cell line. This fourth new WNT4 mutation confirms that this signaling molecule is involved in mullerian development and androgen biosynthesis repression in the ovary. Interestingly, this mutant partially lacks the capability to repress ovarian steroidogenic enzymes, with abnormal expression of 17α- hydroxylase.


House fire injury prevention update. Part II. A review of the effectiveness of preventive interventions.
To evaluate and summarize the house fire injury prevention literature. MEDLINE (1983 to March 1997) was searched by keyword: fire, burn, etiology, cause, prevention, epidemiology, and smoke detector/alarm. ERIC (1966 to March 1997) and PSYCLIT (1974 to June 1997) were searched by keyword: as above, and safety, skills, education, and training. Other sources included references of retrieved publications, review articles, and books; Injury Prevention hand search; government documents; and internet sources. Sources relevant to residential fire injury prevention were selected, evaluated, and summarized. Forty three publications were selected for review, including seven randomized controlled trials, nine quasiexperiments, two natural experiments, 21 prospective cohort studies, two cross sectional surveys, one case report, and one program evaluation. These studies examined the following types of interventions: school (9), preschool (1), and community based educational programs (5); fire response training programs for children (7), blind adolescents (2), and mentally retarded adults (5) and children (1); office based counseling (4); home inspection programs (3); smoke detector giveaway campaigns (5); and smoke detector legislation (1). This review of house fire prevention interventions underscores the importance of program evaluation. There is a need for more rigorous evaluation of educational programs, particularly those targeted at schools. An evidence based, coordinated approach to house fire injury prevention is critical, given current financial constraints and the potential for program overload for communities and schools.


Evolutionary and plastic responses of freshwater invertebrates to climate change: realized patterns and future potential.
We integrated the evidence for evolutionary and plastic trait changes in situ in response to climate change in freshwater invertebrates (aquatic insects and zooplankton). The synthesis on the trait changes in response to the expected reductions in hydroperiod and increases in salinity indicated little evidence for adaptive, plastic, and genetic trait changes and for local adaptation. With respect to responses to temperature, there are many studies on temporal trait changes in phenology and body size in the wild that are believed to be driven by temperature increases, but there is a general lack of rigorous demonstration whether these trait changes are genetically based, adaptive, and causally driven by climate change. Current proof for genetic trait changes under climate change in freshwater invertebrates stems from a limited set of common garden experiments replicated in time. Experimental thermal evolution experiments and common garden warming experiments associated with space-for-time substitutions along latitudinal gradients indicate that besides genetic changes, also phenotypic plasticity and evolution of plasticity are likely to contribute to the observed phenotypic changes under climate change in aquatic invertebrates. Apart from plastic and genetic thermal adjustments, also genetic photoperiod adjustments are widespread and may even dominate the observed phenological shifts.


Growth mode and strain effect on relaxor ferroelectric domains in epitaxial 0.67Pb(Mg1/3Nb2/3)O3-0.33PbTiO3/SrRuO3 heterostructures.
Controlling the growth of complex relaxor ferroelectric thin films and understanding the relationship between biaxial strain-structural domain characteristics are desirable for designing materials with a high electromechanical response. For this purpose, epitaxial thin films free of extended defects and secondary phases are urgently needed. Here, we used optimized growth parameters and target compositions to obtain epitaxial (40-45 nm) 0.67Pb(Mg1/3Nb2/3)O3-0.33PbTiO3/(20 nm) SrRuO3 (PMN-33PT/SRO) heterostructures using pulsed-laser deposition (PLD) on singly terminated SrTiO3 (STO) and ReScO3 (RSO) substrates with Re = Dy, Tb, Gd, Sm, and Nd. In situ reflection high-energy electron diffraction (RHEED) and high-resolution X-ray diffraction (HR-XRD) analysis confirmed high-quality and single-phase thin films with smooth 2D surfaces. High-resolution scanning transmission electron microscopy (HR-STEM) revealed sharp interfaces and homogeneous strain further confirming the epitaxial cube-on-cube growth mode of the PMN-33PT/SRO heterostructures. The combined XRD reciprocal space maps (RSMs) and piezoresponse force microscopy (PFM) analysis revealed that the domain structure of the PMN-33PT heterostructures is sensitive to the applied compressive strain. From the RSM patterns, an evolution from a butterfly-shaped diffraction pattern for mildly strained PMN-33PT layers, which is evidence of stabilization of relaxor domains, to disc-shaped diffraction patterns for high compressive strains with a highly distorted tetragonal structure, is observed. The PFM amplitude and phase of the PMN-33PT thin films confirmed the relaxor-like for a strain state below ∼1.13%, while for higher compressive strain (∼1.9%) the irregularly shaped and poled ferroelectric domains were observed. Interestingly, the PFM phase hysteresis loops of the PMN-33PT heterostructures grown on the SSO substrates (strain state of ∼0.8%) exhibited an enhanced coercive field which is about two times larger than that of the thin films grown on GSO and NSO substrates. The obtained results show that epitaxial strain engineering could serve as an effective approach for tailoring and enhancing the functional properties in relaxor ferroelectrics.


Testing for colon neoplasia susceptibility variants at the human COX2 locus.
Siblings and other first-degree relatives of patients with "sporadic" (i.e., apparently nonfamilial) colorectal cancer or precursor adenomatous colon polyps have an increased risk of developing colon neoplasia. This observation suggests the presence of inherited genetic determinants for sporadic colon neoplasia. Mice homozygous for a null cyclooxygenase 2 (COX2) (also called PTGS2) allele have a dramatically reduced susceptibility to the development of intestinal adenomas. In humans, use of pharmacologic inhibitors of COX2 enzyme activity are associated with reduced risk of colon neoplasia. This study examined whether the human COX2 locus may be linked to colon neoplasia in humans. We used the affected sibling-pair method to test for linkage of the human COX2 locus to colon neoplasia. We examined 74 concordantly affected sibling pairs from 46 sibships with colon neoplasia. One hundred five siblings from these sibships were diagnosed with either colorectal cancer or colon adenomatous polyps before age 65 years. No linkage between COX2 and colon neoplasia was found by use of a multipoint model-free linkage analysis (estimate of allele sharing was 0.44; standard error = +/-0.04; 95% confidence interval = 0.36 to 0.52). Moreover, even allowing for heterogeneity, the potential that a COX2 colon neoplasia susceptibility variant was present within a substantial subset of these sibships was strongly excluded under either a recessive or a dominant inheritance model (95% confidence to exclude a model in which 2.7% or more of the sibling pairs harbor a dominant susceptibility allele). This study of concordantly affected sibling pairs thus demonstrates that variations in the COX2 gene are unlikely to be a source of individual susceptibility to colon neoplasia in humans.


Tumor of the hypopharynx: free jejunal transfer with conservation of the larynx: a case report.
Resection of the hypopharynx or cervical esophagus for malignancy is always quite mutilating if reconstruction cannot be achieved with a one-stage procedure. Several techniques have been described, but they are often associated with laryngectomy. In the case reported, a free split jejunal segment transfer allowed reconstruction of the hypopharynx without laryngectomy, as the malignancy did not involve the larynx.


Design aspects of focal beams from high-intensity arrays.
As the applications of ultrasonic thermal therapies expand, the design of the high-intensity array must address both the energy delivery of the main beam and the character and relevance of off-target beam energy. We simulate the acoustic field performance of a selected set of circular arrays organized by array format, including flat versus curved arrays, periodic versus random arrays, and center void diameter variations. Performance metrics are based on the -3-dB focal main lobe (FML) positioning range, axial grating lobe (AGL) temperatures, and side lobe levels. Using finite-element analysis, we evaluate the relative heating of the FML and the AGLs. All arrays have a maximum diameter of 100λ, with element count ranging from 64 to 1024 and continuous wave frequency of 1.5 MHz. First, we show that a 50% spherical annulus produces focus beam side lobes which decay as a function of lateral distance at nearly 87% of the exponential rate of a full aperture. Second, for the arrays studied, the efficiency of power delivery over the -3-dB focus positioning range for spherical arrays is at least 2-fold greater than for flat arrays; the 256-element case shows a 5-fold advantage for the spherical array. Third, AGL heating can be significant as the focal target is moved to its distal half-intensity depth from the natural focus. Increasing the element count of a randomized array to 256 elements decreases the AGL-to-FML heating ratio to 0.12 at the distal half-intensity depth. Further increases in element count yield modest improvements. A 49% improvement in the AGL-to-peak heating ratio is predicted by using the Sumanaweera spiral element pattern with randomization.


Improving Leung's bidirectional learning rule for associative memories.
Leung (1994) introduced a perceptron-like learning rule to enhance the recall performance of bidirectional associative memories (BAMs). He proved that his so-called bidirectional learning scheme always yields a solution within a finite number of learning iterations in case that a solution exists. Unfortunately, in the setting of Leung a solution only exists in case that the training set is strongly linear separable by hyperplanes through the origin. We extend Leung's approach by considering conditionally strong linear separable sets allowing separating hyperplanes not containing the origin. Moreover, we deal with BAMs, which are generalized by defining so-called dilation and translation parameters enlarging their capacity, while leaving their complexity almost unaffected. The whole approach leads to a generalized bidirectional learning rule which generates BAMs with dilation and translation that perform perfectly on the training set in a case that the latter satisfies the conditionally strong linear separability assumption. Therefore, in the sense of Leung, we conclude with an optimal learning strategy which contains Leung's initial idea as a special case.


[The role of free radical oxidation in the regulation of growth and lipid formation in eukaryotic and prokaryotic organisms].
The review considers the effect of free-radical oxidation on the growth of microorganisms, intensity of their metabolism, and composition of the membrane lipids. Using both own research evidence and this presented in the literature, the authors put forward a hypothesis about a certain correlation between physico-chemical properties of the membrane lipids and the intensity of the growth of eucaryotic and procaryotic microorganisms.


Disturbance opens recruitment sites for bacterial colonization in activated sludge.
Little is known about the role of immigration in shaping bacterial communities or the factors that may dictate success or failure of colonization by bacteria from regional species pools. To address these knowledge gaps, the influence of bacterial colonization into an ecosystem (activated sludge bioreactor) was measured through a disturbance gradient (successive decreases in the parameter solids retention time) relative to stable operational conditions. Through a DNA sequencing approach, we show that the most abundant bacteria within the immigrant community have a greater probability of colonizing the receiving ecosystem, but mostly as low abundance community members. Only during the disturbance do some of these bacterial populations significantly increase in abundance beyond background levels and in few cases become dominant community members post-disturbance. Two mechanisms facilitate the enhanced enrichment of immigrant populations during disturbance: (i) the availability of resources left unconsumed by established species and (ii) the increased availability of niche space for colonizers to establish and displace resident populations. Thus, as a disturbance decreases local diversity, recruitment sites become available to promote colonization. This work advances our understanding of microbial resource management and diversity maintenance in complex ecosystems.


Uncertain breeding: a short history of reproduction in monotremes.
Although much is known about the biology of monotremes, many important aspects of their reproduction remain unclear. Studies over the last century have provided valuable information on various aspects of monotreme reproduction including the structure and function of their reproductive system, breeding behaviour, sex determination and seasonality. All three living genera of monotremes have been successfully maintained in captivity, often for long periods, yet breeding has been rare and unpredictable. When breeding has occurred, however, significant gains in knowledge have ensued; for example a more accurate estimate of the gestation period of the platypus and the incubation period for the Tachyglossus egg. One of the great challenges for zoos has been to understand why breeding of monotremes is difficult to achieve. Analysis of breeding successes of platypuses and short-beaked echidnas provides some insights. The evidence suggests that although annual breeding seasons are regionally predictable, individual adult females breed unpredictably, with some showing breeding intervals of many years. The reason for this variation in individual breeding intervals may be resource-dependant, influenced by social factors or may even be genetically induced. Better knowledge of factors that influence breeding intervals may improve the success of monotreme captive breeding programmes. More certainty in captive breeding is also an important issue for enterprises wishing to trade in Australian wildlife since current legislation limits export of Australian fauna for display to at least second-generation captive-bred individuals. Given their unique evolutionary position, knowledge of reproduction in monotremes needs to be gained in advance of any future population declines so that appropriate strategies can be developed to ensure their survival.


An Experimental Study on the Pathogenesis of Postoperative Hypoalbuminaemia1.
This paper reports a study in the rat of the changes in the plasma albumin level following laparotomy, and their correlation with the concentrations of extravascular albumin in the area of the operation wound and in the liver. The pathogenesis of postoperative hypoalbuminaemia remains a controversial and poorly understood topic. In the present study the changes in the plasma albumin level following laparotomy have been investigated by immunological methods and correlated with the concentrations of extravascular albumin in the operation wound site and in the liver. There was a fall in the plasma albumin level, accompanied by an increase in the extravascular albumin concentration at the laparotomy wound site, with no alteration in the concentration of albumin in the liver. This work confirms that postoperative hypoalbuminaemia is due to accumulation of albumin in the wound site. Increased capillary permeability is suggested as a cause of the excessive loss of plasma albumin into the surgically injured site. The role and subsequent fate of the extravascular albumin in the wound area are also discussed.


Return to work after stroke: A Swedish nationwide registry-based study.
A substantial proportion of individuals with stroke are of working age. After stroke, it is important to return to work (RTW), both for the individual's satisfaction with life and economically for society. The current comprehensive, long-term study aimed at investigating in what time period the RTW continues after stroke and what factors could predict RTW. All individuals registered in the registry Riksstroke with stroke in Sweden at ages 18-58 years during 2011 were eligible for participation. RTW was based on sickness absence data from the Social Insurance Agency covering 1 year prestroke to 5 years post-stroke. Time to RTW was analyzed with Kaplan-Meier curves. Potential predictors of RTW were analyzed with Cox regression and logistic regression. For RTW analyses, 1695 participants were included. Almost 50% RTW within 3 months, 70% within 1 year, and 80% within 2 years post-stroke. However, the RTW continued for several years, with a total of 85% RTW. Predictors of favorable time to RTW were male sex, ischemic stroke, and long university education compared with primary school education. Predictors of unfavorable times to RTW were higher stroke severity, defined by the level of consciousness, and older ages. Participants with self-expectations of RTW 1 year post-stroke had higher odds of RTW within 5 years. The RTW continues for a longer time after stroke than previously known. Both self-expectations and demographical, socioeconomic, stroke-related factors were important predictors of RTW. This knowledge could assist healthcare professionals to individualize the rehabilitation post-stroke.


Mapping impervious surface area increase and urban pluvial flooding using Sentinel Application Platform (SNAP) and remote sensing data.
Expansion of urban impervious surface (UIA) and increased urban pluvial flooding (UPF) have an impact on urban dynamics, socioeconomic activities, and our environment. Therefore, monitoring the increase in UIS and its effect on UPF is essential. The notion of this research is based on the mapping of impervious surface area increase in three major cities of Pakistan. There were two key objectives: (i) Mapping impervious surface area growth using the global impervious surface area index (GISAI) on Google Earth Engine from 1992 to 2022 and (ii) mapping the pluvial flood extent in selected urban areas using Sentinel-1 Ground Range Detected (GRD) data. Thus, we have utilized the GISAI for mapping urban impervious surface area (UISA) using Landsat time-series data on GEE. Our research findings revealed that about 16.8%, 23.5%, and 16.4% of the impervious surface have been increased in Islamabad, Lahore, and Karachi, respectively. Also, Lahore city has the highest overall accuracy, aiming at the GISAI of 93%, followed by Karachi and Islamabad with an overall accuracy of 86% and 85%, respectively. The results indicated that urban flooding has occurred in those areas where the ISA has grown during the last three decades. It shows significant changes in the impervious surface area that cause enhanced urban pluvial flooding in major cities of Pakistan. Also, Sentinel-1 data and the SNAP tool significantly mapped flooded areas in the selected zones. So, providing cities and local governments with increased quick flood detection capabilities is essential. It can also provide feasible policy recommendations for Pakistan decision-makers in city management. Therefore, we suggest a modeling-based solution to identify high-risk locations in major cities for upcoming UPF events.


Ultrastructural interrelationship between the pineal gland and the testis in the male rat.
The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.


Light-induced symmetry breaking and related giant enhancement of nonlinear properties in CdZnTe:V crystals.
We report on enormous light-induced reversible strain effects in CdZnTe:V crystals, which lead to a remarkable enhancement of their nonlinear properties, such as electrostriction and electro-optic effects. Using both high resolution x-ray diffraction and optical interferometry we measure light-induced relative deformation of the initial crystalline lattice (changes in d-spacings) up to 0.15%. The experimental findings are attributed to light-induced breaking of the initial cubic crystalline symmetry. Our results point to a family of inorganic materials whose nonlinear properties can be remarkably enhanced by light, offering new possibilities for nonlinear frequency conversion, generation of Terahertz radiation, electro-optic modulation, and self-deflection of optical beams.


Small bite-angle P-OP ligands for asymmetric hydroformylation and hydrogenation.
A series of small bite-angle phosphine-phosphite (P-OP) ligands have been synthesized by a two-step method. The key intermediate was prepared by an unprecedented asymmetric carbonyl reduction of a phosphamide using the CBS (Corey-Bakshi-Shibata) catalyst. The topology of these ligands (a configurationally stable stereogenic carbon with two heteroatom substituents) and their small bite-angle (created by the close proximity of the two ligating groups to the metal center) together provide a rigid asymmetric environment around this center, enabling high stereoselectivity in hydroformylations and hydrogenations of standard substrates.


Clinical and Ultrasonographic Features of Papillary Thyroid Carcinoma Located in the Isthmus.
The aim of this research was to investigate the clinical and ultrasonographic features of papillary thyroid carcinoma (PTC) in the isthmus. A total of 823 patients with 823 PTCs including 133 in the isthmus and 690 in the lateral lobe were included in our study. All patients were confirmed by postoperative pathology. The clinical and ultrasonographic characteristics were retrospectively analyzed and compared. Univariate analysis and multivariate logistic regression analysis were performed. Multifactor analyses showed that PTC in the isthmus was significantly different from PTC originating from the lateral lobe in aspect ratio, microcalcification, extrathyroid extension, lymph node metastases, and lymph node density ( P < 0.05, for all). There were no significant differences in age, sex, tumor size, margin, halo, echogenicity, and homogeneity ( P > 0.05, for all). The results indicated that the sonographic appearances of PTC in the isthmus were relatively atypical; however, it had a higher incidence of extrathyroidal extension, central lymph node metastasis, and a tendency of higher lymph node density. Therefore, more careful ultrasound evaluation should be performed for these nodules.


Establishment and characterization of patient-derived xenograft and its cell line of primary leiomyosarcoma of bone.
Primary leiomyosarcoma (LMS) of bone is a rare and aggressive mesenchymal malignancy that differentiates toward smooth muscle. Complete resection is the only curable treatment, and novel therapeutic approaches for primary LMS of bone have long been desired. Patient-derived xenografts (PDXs) and cell lines are invaluable tools for preclinical studies. Here, we established PDXs from a patient with primary LMS of bone and a cell line from an established PDX. Bone primary LMS tissue was subcutaneously implanted into highly immune-deficient mice. After two passages, a piece of the tumor was subjected to tissue culturing, and a morphological evaluation and proteomic analysis were performed on the PDX and the established cell line. Moreover, the responses of the established cell line to anti-cancer drugs were examined. Microscopic observations revealed that the PDX tumors retained their original histology. The cell line was established from the third-generation PDX and named NCC-LMS1-X3-C1. The cells were maintained for over 18 mo and 40 passages. The cells exhibited a spindle shape and aggressive growth. Mass spectrometric protein identification revealed that the original tumor tissue, PDX tumor tissue, and NCC-LMS1-X3-C1 cells had similar but distinct protein expression profiles. We previously established the cell line, NCC-LMS1-C1, from the tumor tissue of same patient. We found that the response to drug treatments was different between NCC-LMS1-X3-C1 and NCC-LMS1-C1, suggesting the heterogeneous traits of tumor cells in the identical tumor tissue. This set of PDXs and stable cell line will be a useful resource for bone LMS research.


Hedgehog signaling dynamics in mouse embryos determined by a bioluminiscent reporter.
Determination of cellular signaling in live embryos is key to understand the molecular processes that drive development. Here, we show that a transgenic mouse line carrying a luciferase-based gene reporter of Gli-mediated transcriptional activation (Gli-Luc) displays sonic hedgehog (Shh) signaling in discrete developmental processes during short-term cultures of whole embryos or embryo explants. The bioluminescence in E9.5 embryos was detected in regions in which Shh activity has been demonstrated. Later, in E10.5 embryos, bioluminescence intensity markedly increased, mostly corresponding to the high Shh activity of the developing midbrain and limb. Notably, the dynamic range of the Gli-Luc reporter in the developing limb revealed the progressive emergence of bioluminescence in the zone of polarizing activity, where reporter activity locally increased and spatially spread in agreement with the signaling gradient expected for Shh. In the midbrain of E9.5 mouse embryos, bioluminescence was not detected along the ventral region as expected but, instead, Shh-dependent anterior and posterior bioluminescence foci emerged by E10.5 indicating that the Gli-Luc reporter can only respond transcriptionally to relatively high levels of GliA and/or without the interaction with other transcription factors. The present work supports the use of bioluminescence to identify and study the dynamics of centers of morphogen signaling during mouse embryogenesis.


A DArT marker genetic map of perennial ryegrass (Lolium perenne L.) integrated with detailed comparative mapping information; comparison with existing DArT marker genetic maps of Lolium perenne, L. multiflorum and Festuca pratensis.
Ryegrasses and fescues (genera, Lolium and Festuca) are species of forage and turf grasses which are used widely in agricultural and amenity situations. They are classified within the sub-family Pooideae and so are closely related to Brachypodium distachyon, wheat, barley, rye and oats. Recently, a DArT array has been developed which can be used in generating marker and mapping information for ryegrasses and fescues. This represents a potential common marker set for ryegrass and fescue researchers which can be linked through to comparative genomic information for the grasses. A F2 perennial ryegrass genetic map was developed consisting of 7 linkage groups defined by 1316 markers and deriving a total map length of 683 cM. The marker set included 866 DArT and 315 gene sequence-based markers. Comparison with previous DArT mapping studies in perennial and Italian ryegrass (L. multiflorum) identified 87 and 105 DArT markers in common, respectively, of which 94% and 87% mapped to homoeologous linkage groups. A similar comparison with meadow fescue (F. pratensis) identified only 28 DArT markers in common, of which c. 50% mapped to non-homoelogous linkage groups. In L. perenne, the genetic distance spanned by the DArT markers encompassed the majority of the regions that could be described in terms of comparative genomic relationships with rice, Brachypodium distachyon, and Sorghum bicolor. DArT markers are likely to be a useful common marker resource for ryegrasses and fescues, though the success in aligning different populations through the mapping of common markers will be influenced by degrees of population interrelatedness. The detailed mapping of DArT and gene-based markers in this study potentially allows comparative relationships to be derived in future mapping populations characterised using solely DArT markers.


[Mechanism of the radioprotective effect of catecholamine receptor agonists. Inclusion in the radioprotective effect of different subtypes of beta-adrenoreceptors].
Isoproterenol of ED50 = 0.16 mumol/kg is highly effective in protecting mice against ionizing radiation and has the high therapeutical index. There are three new indications that isoproterenol exerts its radioprotective action via beta-adrenoceptors. They are: the effect of isoproterenol is prevented by three additional beta-adrenoceptor antagonists, the isoproterenol effect is reproduced by the seven studied beta-adrenoceptor agonists of different chemical structure, and with chemical analogs which fail to stimulate beta-adrenoceptors the radioprotective effect is absent. Both beta 1 and beta 2 adrenoceptor agonists are protective agents. Mechanisms of the radioprotective action are discussed.


Assessment of the exposure to WLAN frequencies of a head model with a cochlear implant.
In the last few years, significant developments have taken place in the field of Wireless Local Area Networks (WLAN), and the popularity of portable devices supporting Wireless Fidelity (Wi-Fi) is continuously growing. At the same time, the number of Active Implanted Medical Devices (AIMD) being placed in patients is widely increasing and among them, cochlear implants (CI) are becoming a common aid. The goal of this study is to investigate the effect on the electromagnetic field distribution and the specific absorption rate (SAR) due to the presence of a CI in a head model during far-field exposure to Wi-Fi frequencies. The head model was obtained by image segmentation, the implant was modelled as a geometric structure, and the exposure sources were modelled as a uniform plane wave (power density = 10 W/m(2)) at 2.4, 5.2 and 5.8 GHz. Vertical and horizontal polarizations were simulated. Conditions with and without CI were compared. The findings of that are: (1) local differences in the field distribution close to the CI, comparing the head models with or without the CI; (2) higher field strength and point SAR value in the cochlear region very close to the CI; (3) negligible differences in the field strength and point SAR value in the cochlear region far from the CI; (4) negligible variations in the average SAR values in the cochlea and head due to the presence of the CI. The results of this study conclude that insertion of a CI brings moderate localized differences in the E, H and point SAR distribution when evaluated close to the electrode array in the cochlea, while negligible differences are found in the average SAR values both in the cochlea and head, independent of frequency and wave polarization.


[74 by-passes on leg arteries (author's transl)].
74 by-passes on leg arteries have been performed during these last ten years at St Joseph's hospital to cure: femoropopliteal atherosclerotic occlusive disease (67 cases), aneurisms (5 cases), post-traumatic arteriovenous fistula (1 case), popliteal thrombosis on exostosis (1 case). The indication for operation was, in almost every case, carried on a distal advanced ischemia, followed by an imminent limb loss. In four cases, there existed an acute sensory and motor ischemia. The accumulated potency rate was 58.5% at 1 year and decreased progressively afterwards: 38.20% at 3 years and 21.6% at 5 years. However, the choice of a surgical technics doesn't find its justification in a long-dated prognosis for this operation, the aim of which being limb-salvage. In this prospect, the results are hopeful: 77% of the limbs have effectively been preserved at the end of the follow-up period.


Multi-Omics Analysis Reveals a Correlation between the Host Phylogeny, Gut Microbiota and Metabolite Profiles in Cyprinid Fishes.
Gut microbiota play key roles in host nutrition and metabolism. However, little is known about the relationship between host genetics, gut microbiota and metabolic profiles. Here, we used high-throughput sequencing and gas chromatography/mass spectrometry approaches to characterize the microbiota composition and the metabolite profiles in the gut of five cyprinid fish species with three different feeding habits raised under identical husbandry conditions. Our results showed that host species and feeding habits significantly affect not only gut microbiota composition but also metabolite profiles (ANOSIM, p ≤ 0.05). Mantel test demonstrated that host phylogeny, gut microbiota, and metabolite profiles were significantly related to each other (p ≤ 0.05). Additionally, the carps with the same feeding habits had more similarity in gut microbiota composition and metabolite profiles. Various metabolites were correlated positively with bacterial taxa involved in food degradation. Our results shed new light on the microbiome and metabolite profiles in the gut content of cyprinid fishes, and highlighted the correlations between host genotype, fish gut microbiome and putative functions, and gut metabolite profiles.


On the character of the cyclic ionic H-bond in cryogenically cooled deprotonated cysteine.
The gas phase structure of deprotonated cysteine (Cys-H(+))(-) has recently gained attention because of its counterintuitive calculated minimum energy structure in which it appears that deprotonation occurs at the -SH moiety rather than at the nominally more acidic carboxylic acid group. Because previous experimental efforts have not yielded to a consensus regarding the structure of the anion, we report the cryogenic ion vibrational predissociation (CIVP) spectra of its cryogenically cooled H/D isotopologues in an effort to clarify the situation. The unexpected isotope dependence of key features in the spectrum and the similarity of the band pattern to that displayed by the intramolecular H-bonded linkage in a deprotonated diacid (HCO2(CH2)10CO2(-)) indicate that the dominant form of the anion occurs with a strongly shared proton between the thiolate (-S(-)) and carboxylate (-CO2(-)) groups. An interesting aspect of this (-S(-)···H(+)···(-)O2C-) linkage is that, although the global minimum places the shared proton closer to the oxygen atom, the soft potential energy curve calculated for displacement of the bridging proton would likely support sufficient zero-point motion both to blur the distinction between thiolate- and carboxylate-based structures and to account for the unusual isotope effects.


Developing ciprofloxacin dry powder for inhalation: A story of challenges and rational design in the treatment of cystic fibrosis lung infection.
Cystic fibrosis (CF) is an inherited multisystem disease affecting the lung which leads to a progressive decline in lung function as a result of malfunctioning mucociliary clearance and subsequent chronic bacterial infections. Pseudomonas aeruginosa is the predominant cause of lung infection in CF patients and is associated with significant morbidity and mortality. Thus, antibiotic therapy remains the cornerstone of the treatment of CF. Pulmonary delivery of antibiotics for lung infections significantly reduces the required dose and the associated systemic side effects while improving therapeutic outcomes. Ciprofloxacin is one of the most widely used antibiotics against P. aeruginosa and the most effective fluoroquinolone. However, in spite of the substantial amount of research aimed at developing ciprofloxacin powder for inhalation, none of these formulations has been commercialized. Here, we present an integrated view of the diverse challenges associated with delivering ciprofloxacin dry particles to the lungs of CF patients and the rationales behind recent formulations of ciprofloxacin dry powder for inhalation. This review will discuss the challenges in developing ciprofloxacin powder for inhalation along with the physiological and pathophysiological challenges such as ciprofloxacin lung permeability, overproduction of viscous mucus and bacterial biofilms. The review will also discuss the current and emerging particle engineering approaches to overcoming these challenges. By doing so, we believe the review will help the reader to understand the current limitations in developing an inhalable ciprofloxacin powder and explore new opportunities of rational design strategies.


Racial/ethnic differences in patients with anemia and folate deficiency.
To determine the presence of racial/ethnic differences in patients with anemia and serum folate deficiency. We performed a retrospective analysis of data from patient samples collected from January 2010 to October 2018. Reference laboratory ranges were determined by Mayo Clinic Reference Laboratories. Race and ethnicity were classified according to National Institutes of Health categories. The analysis comprised 197 974 samples. Hemoglobin, hematocrit, and SF results were available for 173 337, 173 056, and 129 760 samples, respectively. Of the samples, 46 505 (26.8%) showed anemia, with a higher prevalence among American Indian/Alaskan Natives (AI/AN) 42.9% and African Americans (AA) 47.2% (P < .001). SF deficiency was present in 897 (0.7%), with a higher prevalence among AI/AN (9, [1.4%]) and AA (78, [1.2%]) and a lower prevalence in non-Hispanic whites (NHW) (758, [0.7%]), Hispanics (40, [0.6%]), and Asians (8, [0.3%]). In multivariable analysis, the prevalence of anemia was higher in all non-NHW racial/ethnic groups: AA (OR, 3.67, [95%CI: 3.47-3.88, P < .001]), AI/AN (OR, 3.25, [95%CI: 2.71-3.90, P < .001]), Asians (OR, 1.62, [95%CI: 1.47-1.77, P < .001]), and Hispanics (OR, 1.41, [95%CI: 1.32-1.50, P < .001]). SF deficiency was more common in AA (OR, 1.48, [95%CI: 1.17-1.88, P.001]) and less common in Asians (OR, 0.35, [95%CI: 0.17-0.70, P = .003]), compared with NHW. We showed significant racial/ethnic differences in anemia and SF deficiency. Differences were observed especially among NHW, AA, and Asians. We believe that these differences may be explained by social determinants of health. More research is needed regarding the causes of these differences and their clinical implications at a population level.


[Use of H2-receptor blocker famotidine (quamatel) in anesthesiology for cardiopulmonary bypass surgery].
The efficiency of perioperative therapy with quamatel (histamine H2-receptor blocker) for preventing gastrointestinal complications in cardiosurgical patients was evaluated. Quamatel was used in 68 cardiosurgical patients subjected to aortocoronary bypass surgery for coronary disease. Perioperative pH profile of the gastric contents was evaluated by a Gastroscan-5 acidogastrometer (Russia). The volume of gastric juice secretion was evaluated after induction anaesthesia, at the end of operation, and 6-8 h after the intervention. Quamatel was highly effective and well tolerated by cardiosurgical patients with concomitant gastrointestinal diseases during preparation to surgery. Use of quamatel for premedication, particularly in patients with gastrointestinal diseases, stabilized pH and decreased the gastric juice hypersecretion during the entire intraoperative and early postoperative period, thus preventing gastrointestinal complications. High therapeutic efficiency of quamatel and its good tolerance recommend it for cardiosurgical patients and to surgical patients of other profiles for prevention of gastrointestinal complications.


The relationship between cephalic scales and bones in lizards: a preliminary microtomographic survey on three lacertid species.
In the last two decades, there has been a great deal of interest in the morphology and anatomy of the lizard skull in an ecological and evolutionary perspective. However, the relationship between variations in many key anatomical features remains largely unknown. Using microtomography and geometric morphometrics, we examined the relationship between bones and scales associated with the parietal foramen in the three lizards species most common in the Italian peninsula: Podarcis muralis, P. sicula, and Lacerta bilineata. The imprints of the scales are clearly recognizable on the outer bone surface, and this may suggest a structural interaction between these elements. The temporal osteoderms are visible in the larger males and in the larger females of L. bilineata, but they are absent in the smaller specimens of L. bilineata and in all Podarcis specimens. Two parallel rows of pterygoid teeth are present in all the specimens of L. bilineata and are absent in the smaller male of L. bilineata and in both Podarcis species. Cheek osteoderms occurred only in the largest specimens of our sample (i.e., large L. bilineata), being possibly related to hyperostotic processes and densitometric thresholds more than to phylogeny. Minor differences may be also associated with the form of the parietal foramen. In absolute terms the parietal foramen tends to be largest in L. bilineata but in relation to skull length the foramen tends to be larger in P. muralis. In this latter species the foramen is also more elongated. In all three species the fronto-parietal suture occupies a similar location relatively to the scale spatial organization. A shared allometric pattern shows that the main vault enlargement can be localised at the areas anterior to the fronto-parietal suture, providing further information on the possible morphogenetic dynamics associated with the interaction between scales and bones around this structure.


Predictors of mortality in inflammatory bowel disease patients treated for pneumonia.
Community-acquired pneumonia is among the most common infections affecting ulcerative colitis and Crohn's disease patients. Data regarding epidemiology and outcomes of pneumonia in inflammatory bowel disease patients is lacking. We aimed to identify predictors of adverse outcomes among inflammatory bowel disease patients treated for pneumonia. This was a retrospective cohort study that included adult patients admitted to Sheba Medical Center for pneumonia between 2012 and 2018. Data was collected from an electronic repository of all emergency department admissions and included tabular demographic and clinical variables and free-text physician records. Pneumonia cases were extracted using the International Classification of Diseases (ICD-10) coding. Of 16,732 admissions with pneumonia, 97 were inflammatory bowel disease patients (45 Crohn's disease; 52 ulcerative colitis). We found a similar rate of 30-day mortality among inflammatory bowel disease and non-inflammatory bowel disease patients (12.1% versus 11.3%, p = 0.824) and between Crohn's disease and ulcerative colitis patients (11.1% versus 11.5%, p = 0.947). There was an increased hospitalization rate among inflammatory bowel disease patients (92.8% versus 85.6%, p = 0.045), but similar hospitalization duration (4 versus 4 days, p = 0.384). Crohn's disease patients had a shorter hospitalization duration compared with ulcerative colitis patients (3 versus 5.5 days, p = 0.029). Bronchiectasis (adjusted odds ratio 60.95, 95% confidence interval 2.72-1364.39, p = 0.01) and opioids use (adjusted odds ratio 13.21, 95% confidence interval 1.29-135.18, p = 0.03) were associated with an increased 30-day mortality rate in inflammatory bowel disease patients. This is the first study to identify predictors of mortality in inflammatory bowel disease patients with pneumonia. The rate of mortality and hospitalization duration of stay were similar among inflammatory bowel disease and non-inflammatory bowel disease patients. Use of opioids and presence of bronchiectasis were associated with a higher risk of mortality in inflammatory bowel disease patients with pneumonia.


[AIDS Hotline Flanders: results in 1988].
The Stichting Aids Gezonheidszorg informs the general public about the disease via the Aids hotline. The aims are twofold: 1. We want to inform and support people; if necessary, we also refer to more adequate organisations for assistance; 2. We want to know who calls us and what are the needs so that we can help in organizing prevention campaigns. In 1988 we answered 1.987 authentic calls, about the same as in 1987. To allow more people to call, the opening hours of the hot-line will be increased from September 1989 onwards. 70% of the callers are men, 28% women. We notice two important subgroups: people who visit prostitutes and male homosexuals. Most callers are between 26 and 40 years old. Also more young people under 25 called last year. Prostitutes and I.V. drug users however rarely called. A lot of people call because they think to have run some risk. Therefore most questions deal with sexual transmission and blood tests. The number of people who had their blood tested is rather small. Most of them are homosexuals or visitors of prostitutes. This last group is most acquainted with the use of a condom, more than homosexuals and heterosexuals. Still a rather big percentage of people from all groups never use a condom. Therefore efficient campaigns are highly necessary.


Acute myocardial infarction revealing a polycythemia vera.
The occurrence of myocardial infarction in myeloproliferative disease is mostly attributed to coronary thrombosis due to hyperviscosity and thrombocytosis. We report a 55-year-old man case with polycythemia vera none diagnosed before and revealing with ST-segment elevation myocardial infarction; this is a relative rare association. The clinical status, comorbidities and patient outcome were studied. This case illustrates the importance of early diagnosis of polycythemia vera and research almost systemic thrombotic complications.


Surface and Bulk Stresses Drive Morphological Changes in Fibrous Microtissues.
Engineered fibrous tissues consisting of cells encapsulated within collagen gels are widely used three-dimensional in vitro models of morphogenesis and wound healing. Although cell-mediated matrix remodeling that occurs within these scaffolds has been extensively studied, less is known about the mesoscale physical principles governing the dynamics of tissue shape. Here, we show both experimentally and by using computer simulations how surface contraction through the development of surface stresses (analogous to surface tension in fluids) coordinates with bulk contraction to drive shape evolution in constrained three-dimensional microtissues. We used microelectromechanical systems technology to generate arrays of fibrous microtissues and robot-assisted microsurgery to perform local incisions and implantation. We introduce a technique based on phototoxic activation of a small molecule to selectively kill cells in a spatially controlled manner. The model simulations, which reproduced the experimentally observed shape changes after surgical and photochemical operations, indicate that fitting of only bulk and surface contractile moduli is sufficient for the prediction of the equilibrium shape of the microtissues. The computational and experimental methods we have developed provide a general framework to study and predict the morphogenic states of contractile fibrous tissues under external loading at multiple length scales.


An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
Purpose: This study aims to assess the performance of an analysis method to measure in vivo the movement speed of tear film particles post-blink as a measure of tear film spreading.Materials and methods: Ocular surface parameters and the recording of tear film particles' spreading post-blink were assessed in eighty-one healthy volunteers (43.7 ± 27.0 years) using Keratograph 5 M. The developed software automatically decomposed the video into frames to manually track particles' position for 1.75 seconds after a blink. The following tear film-dynamic metrics were automatically calculated: mean, median, maximum, and minimum particles' speed at different times after blinking and time for particle speed to decrease to <1.20 mm/second. Repeatability of each tear film-dynamic metric and its correlations with ocular surface signs and symptoms were analyzed. Binomial logistic regression was performed to assess the predictability of new metrics to ocular parameters.Results: Repeatability tended to be lower just after blinking (variability of 12.24%), whereas the metrics from 0.5 s onwards had acceptable repeatability (variability below 10%). Tear film-dynamic metrics correlated positively with Non-Invasive Break-Up Time (NIKBUT) while negatively with meibomian gland drop-out. Binomial logistic regression analysis revealed that tear film-dynamic metrics were able to predict NIKBUT. Nevertheless, no statistically significant association was found with gland drop-out. This means that higher particle speed is related to larger NIKBUT. The metric "time for particle speed to decrease to <1.20 mm/second" can be considered the best metric to assess the quality of the tear film, since it was more strongly correlated with NIKBUT (r = 0.42, p = .004), it was more strongly associated in the binomial logistic regression analysis with NIKBUT and showed good repeatability (variability = 5.49%).Conclusions: Tear film-dynamic metrics are emerging homeostasis parameters for assessing indirectly the tear film quality in natural conditions with acceptable repeatability.


Bitter melon (Momordica charantia L.) inhibits adipocyte hypertrophy and down regulates lipogenic gene expression in adipose tissue of diet-induced obese rats.
Bitter melon (Momordica charantia; BM) has been shown to ameliorate diet-induced obesity and insulin resistance. To examine the effect of BM supplementation on cell size and lipid metabolism in adipose tissues, three groups of rats were respectively fed a high-fat diet supplemented without (HF group) or with 5 % lyophilised BM powder (HFB group), or with 0.01 % thiazolidinedione (TZD) (HFT group). A group of rats fed a low-fat diet was also included as a normal control. Hyperinsulinaemia and glucose intolerance were observed in the HF group but not in HFT and HFB groups. Although the number of large adipocytes (>180 microm) of both the HFB and HFT groups was significantly lower than that of the HF group, the adipose tissue mass, TAG content and glycerol-3-phosphate dehydrogenase activity of the HFB group were significantly lower than those of the HFT group, implying that BM might reduce lipogenesis in adipose tissue. Experiment 2 was then conducted to examine the expression of lipogenic genes in adipose tissues of rats fed low-fat, HF or HFB diets. The HFB group showed significantly lower mRNA levels of fatty acid synthase, acetyl-CoA carboxylase-1, lipoprotein lipase and adipocyte fatty acid-binding protein than the HF group (P < 0.05). These results indicate BM can reduce insulin resistance as effective as the anti-diabetic drug TZD. Furthermore, BM can suppress the visceral fat accumulation and inhibit adipocyte hypertrophy, which may be associated with markedly down regulated expressions of lipogenic genes in the adipose.


Regulated genes in transgenic plants.
Transgenic plants are an effective system for the study of regulated gene expression. Developmental control of expression can be monitored by assaying different tissues or by assaying a plant at different developmental stages. Analysis of the petunia 5-enolpyruvylshikimate-3-phosphate synthase gene, which is highly expressed in flowers, allowed identification of an upstream region that confers tissue-specific and developmentally regulated expression. The cell specificity of expression in floral tissues has been defined by histochemical localization. This expression is contrasted to that of the 35S promoter of cauliflower mosaic virus, a nominally constitutive promoter that shows a definite specificity of expression in floral tissues. Moreover, this expression differs in transgenic hosts of different species.


Functional Passenger-Strand miRNAs in Exosomes Derived from Human Colon Cancer Cells and Their Heterogeneous Paracrine Effects.
Exosome-mediated microRNAs (miRNAs) are closely related to the occurrence, development, invasion, metastasis, therapeutic resistance, diagnosis and treatment of malignant tumors. Guide-strand miRNA and passenger-strand miRNA (miRNA*) exist in miRNA processing, but the function of passenger-strand miRNA is often overlooked. In this study, we attempted to identify functional miRNA*s in exosomes derived from human colon cancer SW620 cells. miRNA expression profiles of human normal colonic epithelial cells NCM460 and colon cancer cells SW620 were compared by high-throughput sequencing. According to the sequencing results, we defined two sets of differentially expressed miRNAs: "high in exosome and high in cell" (HEHC) and "high in exosome but low in cell" (HELC). As passenger-strand miRNAs, miR-2277-3p and miR-26b-3p, which belong to different sets, have diametrically opposite functions. MiR-2277-3p promotes proliferation, migration, and invasion of SW620 cells by targeting NUPR1L, while miR-26b-3p exerts an inhibitory effect by targeting PFDN1. Using exosomes as transport vectors, the effect of exosomes rich in miR-2277-3p on cells is consistent with the effect of liposome-transfected overexpressed miR-2277-3p, resulting in a cancer-promoting effect. However, exosomes rich in miR-26b-3p did not have a tumor suppressor effect. Further analysis revealed that exosomes rich in miR-2277-3p also had a high abundance of integrin β4. Altering the abundance of integrin β4 in exosomes changes the ability of exosomes to be taken up by cells, thereby altering the paracrine effects of exosomes. In summary, we revealed the fact that a large number of passenger-strand miRNAs exist in exosomes of colon cancer cells, these miRNAs are preliminarily categorized into two sets, and miR-2277-3p and miR-26b-3p, as representatives of each set, showed opposite functions. In addition, we revealed that integrin β4 is a marker of exosome heterogeneity in colon cancer cells, which directly correlates with the ability of exosomes to be uptaken by cells of the same kind, thus regulating the paracrine effect of exosomes.


Survival Outcomes Are Not Affected When Liver Transplant Surgery Is Done at Night, During Weekends, or Summer Months.
It has been suggested that hospitalized patients may get suboptimal care in nights or on weekends or summer holidays due to sleep deprivation, physician fatigue, or reduced medical staffing. Our objective was to determine whether there were differences in outcomes when surgery was performed in the night (10 pm-6 am), on weekends (Saturday or Sunday), or during summer months (June-August). We used United Network for Organ Sharing (UNOS) data sets of adults transplanted between February 27, 2002, and September 30, 2016. We estimated the start time of liver transplant surgery by utilizing the cross-clamp time and cold ischemia time (cross-clamp time + cold ischemia time - 2 h). The survival outcomes were estimated by Kaplan-Meier survival analysis. Patients with hepatocellular carcinoma (HCC) were analyzed separately. The independent effect of time of transplant on outcomes was analyzed after adjusting for common confounders, including Model for End-stage Liver Diseases scores and transplant center volume. During the study period, 4 434 (9.6%) were done in the night, 12 147 (26.4%) over weekends, and 11 976 (26%) during summer months. The graft and patient survival and complications were not influenced by the time of transplant for both HCC and non-HCC population. Cox regression analysis after adjusting for risk factors, including Model for End-stage Liver Diseases, donor risk index, and liver center volume, confirmed that there were no significant differences in outcomes. Our study showed that the time of transplant surgery whether done during nights, weekends, or summer months had no effect on graft or patient survival irrespective of center volume, patient, or donor risk factors.


Enhancing Buruli ulcer control in Ghana through social interventions: a case study from the Obom sub-district.
Buruli ulcer is considered a re-emerging disease in West Africa where it has suffered neglect over the years, though children below the age of 16 years are the worst affected in most endemic regions. Due to delayed health seeking, the disease leads to disabilities resulting from amputation and loss of vital organs like the eye leading to school dropout and other social and economic consequences for the affected family. Early treatment with antibiotics is effective; however, this involves daily oral and intramuscular injection at distant health facilities for 56 days making it a challenge among poor rural folks living on daily subsistence work. The mode of transmission of Buruli ulcer is not known and there is no effective preventive vaccine for Buruli ulcer. Thus the only effective control tool is early case detection and treatment to reduce morbidity and associated disabilities that occurs as a result of late treatment. It is therefore essential to implement interventions that remove impediments that limit early case detection; access to early effective treatment and this paper reports one such effort where the feasibility of social interventions to enhance Buruli ulcer control was assessed. This was a qualitative study using in-depth interviews to generate information to ascertain the benefit or otherwise of the intervention implemented. Clinical records of patients to generate data to determine the feasibility and effectiveness of social interventions in the fight against Buruli ulcer was examined. In all, 56 in-depth interviews (28 at baseline and 28 at evaluation) were conducted for this report. At full implementation, treatment default and dropout reduced significantly from 58.8% and 52.9% at baseline to 1.5% and 1.5% respectively. The number of early case detection went up significantly. Affected families were happy with social interventions such as provision of transportation and breakfast to patients on daily basis. Families were happy with the outpatient services provided under the intervention where no patient was admitted into the hospital. The study showed that with a little more investment in early case detection, diagnosis and treatment, coupled with free transportation and breakfast for patients, most of the cases could be treated effectively with the available antibiotics to avoid disability and complications from the disease.


Revival of apoptotic cells that display early-stage dynamic membrane blebbing.
The critical point at which apoptosis becomes irreversible and how cells attain an anti-apoptotic state remain unknown. Here, we report that apoptotic cells undergoing early-stage dynamic membrane blebbing revive. We examined this phenomenon in cell lines that stably express 2DED2DD, a modified FADD produced by fusing the tandem death effector domains (DEDs) and tandem death domains (DDs). Induction of apoptosis caused rapid blebbing. Eight hours later, most cells shrunk while some detached from the flask. Twenty-four hours later, when activated caspase 3 decreased, more than half the cells revived and appeared normal, probably due to the induction of unidentified anti-apoptotic proteins.


Intrathecal and intraventricular antibiotics for postoperative Gram-negative meningitis and ventriculitis.
Postoperative meningitis is a growing cause of concern, especially with the evolution of multidrug-resistant organism. The authors evaluate the use of intraventricular/intrathecal (IVT/IT) antibiotics for postoperative gram-negative meningitis in patients whom intravenous antibiotics were ineffective. Medical records were retrospectively reviewed and neurosurgery patients with gram-negative postoperative infection meningitis/ventriculitis were enrolled in the study. Their demographics, hospital course, and outcomes were recorded in a pro forma and analyzed using Statistical Package for the Social Sciences, version 19. The review identified 21 patients with postneurosurgical gram-negative meningitis/ventriculitis who were treated with IVT or IT antibiotics. The most common organism was Acinetobacter species (n = 14; 66%). Amikacin was used in 7 patients, polymyxin B in 9 patients, and colistin in 5 patients. A combination of antibiotics was used in one patient. Cerebrospinal fluid sterility was achieved in all patients with no incidence of relapse. There was a single death, though that was not related to the infectious process as the patient had a massive pulmonary embolism. The findings of this study suggest that IVT and IT antibiotic therapy is a useful option in patients who are nonresponsive to standard intravenous therapy with little or no side effects.


Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab).
NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions.


Fever, hyperdynamic shock, and multiple-system organ failure. A pseudo-sepsis syndrome associated with chronic salicylate intoxication.
To describe a sepsis-like syndrome associated with chronic salicylate intoxication. Retrospective clinical study. University-affiliated county hospital. Five patients who became accidentally intoxicated while ingesting salicylates on a long-term daily basis. All five salicylate-intoxicated patients had clinical and laboratory features that were highly suggestive of sepsis, but no bacteriologic or pathologic evidence of infection could be documented. Features included fever, leukocytosis with increased band forms, hypotension with a reduced SVR and multiple system organ failure (ARDS, encephalopathy, renal failure, and DIC). A diagnosis of salicylate intoxication was made at the time of admission to the hospital in only one case. In the other four cases, the presumptive diagnosis was sepsis; a correct diagnosis of salicylate intoxication was not established until between 16 h and 10 days after admission in these four cases. Two patients died, one patient required permanent hemodialysis, and two patients recovered fully only after prolonged and complicated hospitalizations. The pathogenesis of this syndrome is uncertain. In two cases, serum levels of TNF-alpha, IL-1 beta and IL-6 were measured by ELISA. In both cases serum IL-6 was markedly increased, and in one case serum TNF-alpha was also elevated. Occult salicylate intoxication should be considered when apparent sepsis syndrome occurs without a readily easily identifiable source of infection.


Squid Suckerin Biomimetic Peptides Form Amyloid-like Crystals with Robust Mechanical Properties.
We present the self-assembly of fibers formed from a peptide sequence (A1H1) derived from suckerin proteins of squid sucker ring teeth (SRT). SRT are protein-only biopolymers with an unconventional set of physicochemical and mechanical properties including high elastic modulus coupled with thermoplastic behavior. We have identified a conserved peptide building block from suckerins that possess the ability to assemble into materials with similar mechanical properties as the native SRT. A1H1 displays amphiphilic characteristics and self-assembles from the bottom-up into mm-scale fibers initiated by the addition of a polar aprotic solvent. A1H1 fibers are thermally resistant up to 239 °C, coupled with an elastic modulus of ∼7.7 GPa, which can be explained by the tight packing of β-sheet-enriched crystalline building blocks as identified by wide-angle X-ray scattering (WAXS), with intersheet and interstrand distances of 5.37 and 4.38 Å, respectively. A compact packing of the peptides at their Ala-rich terminals within the fibers was confirmed from molecular dynamics simulations, and we propose a hierarchical model of fiber assembly of the mature peptide fiber.