Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma.
The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor, were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL). Patients with relapsed/refractory PCNSL, Karnofsky performance status ≥70, and normal end-organ function received tirabrutinib 320 and 480 mg once daily (q.d.) in phase I to evaluate dose-limiting toxicity (DLT) within 28 days using a 3 + 3 dose escalation design and with 480 mg q.d. under fasted conditions in phase II. Forty-four patients were enrolled; 20, 7, and 17 received tirabrutinib at 320, 480, and 480 mg under fasted conditions, respectively. No DLTs were observed, and the maximum tolerated dose was not reached at 480 mg. Common grade ≥3 adverse events (AEs) were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg q.d. had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). Independent review committee assessed overall response rate (ORR) at 64%: 60% with 5 complete responses (CR)/unconfirmed complete responses (CRu) at 320 mg, 100% with 4 CR/CRu at 480 mg, and 53% with 6 CR/CRu at 480 mg under fasted conditions. Median progression-free survival was 2.9 months: 2.1, 11.1, and 5.8 months at 320, 480, and 480 mg under fasted conditions, respectively. Median overall survival was not reached. ORR was similar among patients harboring CARD11, MYD88, and CD79B mutations, and corresponding wild types. These data indicate favorable efficacy of tirabrutinib in patients with relapsed/refractory PCNSL. JapicCTI-173646.


Cell-penetrating Peptide-modified Targeted Drug-loaded Phase-transformation Lipid Nanoparticles Combined with Low-intensity Focused Ultrasound for Precision Theranostics against Hepatocellular Carcinoma.
Objective: Prepare a multifunctional ultrasound molecular probe, hyaluronic acid-mediated cell-penetrating peptide-modified 10-hydroxycamptothecin-loaded phase-transformation lipid nanoparticles (HA/CPPs-10-HCPT-NPs), and to combine HA/CPPs-10-HCPT-NPs with low-intensity focused ultrasound (LIFU) for precision theranostics against hepatocellular carcinoma (HCC). Methods: HA/CPPs-10-HCPT-NPs were prepared using thin-film dispersion, ultrasound emulsification, and electrostatic effects. HA/CPPs-10-HCPT-NPs were characterized for particle size, zeta potential, encapsulation efficiency and drug-loading efficiency. In vitro, HA/CPPs-10-HCPT-NPs were tested for acoustic droplet vaporization (ADV) at different time points/acoustic intensities; the ability of HA/CPPs-10-HCPT-NPs to target SMMC-7721 cells was detected by confocal laser scanning microscopy (CLSM); the penetrating ability of CG-TAT-GC-modified NPs was verified by CLSM in a 3D multicellular tumor spheroid (MCTS) model; the effect of HA/CPPs-10-HCPT-NPs combined with LIFU on killing SMMC-7721 cells was measured by CCK-8 and flow cytometry. In vivo, the tumor-target efficiency of HA/CPPs-10-HCPT-NPs was evaluated by a small-animal fluorescence imaging system and CLSM; the enhanced ultrasound imaging efficiency of HA/CPPs-10-HCPT-NPs combined with LIFU was measured by an ultrasound imaging analyzer; the therapeutic effect of HA/CPPs-10-HCPT-NPs combined with LIFU was evaluated by tumor volume, tumor inhibition rate, and staining (hematoxylin and eosin (H & E), proliferating cell nuclear antigen (PCNA) and TUNEL). Results: Mean particle size and mean zeta potential of HA/CPPs-10-HCPT-NPs were 284.2±13.3 nm and - 16.55±1.50 mV, respectively. HA/CPPs-10-HCPT-NPs could bind to SMMC-7721 cells more readily than CPPs-10-HCPT-NPs. Penetration depth into 3D MCTS of HA/CPPs-10-HCPT-NPs was 2.76-fold larger than that of NPs without CG-TAT-GC. HA/CPPs-10-HCPT-NPs could enhance ultrasound imaging by undergoing ADV triggered by LIFU. HA/CPPs-10-HCPT-NPs+LIFU group demonstrated significantly higher efficiency of anti-proliferation and apoptosis percentage than all other groups. In mouse liver tumor xenografts, HA/CPPs-10-HCPT-NPs could target tumor sites and enhance ultrasound imaging under LIFU. HA/CPPs-10-HCPT-NPs+LIFU group had a significantly smaller tumor volume, lower proliferative index (PI), and higher tumor inhibition and apoptotic index (AI) than all other groups. Conclusions: Combined application of HA/CPPs-10-HCPT-NPs and LIFU should be a valuable and promising strategy for precise HCC theranostics.


Failure of angiotensin II inhibitor to modify hyperacute rejection.
The effect of angiotensin II inhibitor (sar1,gly8 angiotensin II) upon the pig-to-dog (10 pigs to 20 dogs) modified renal xenograft model has been studied. The angiotensin II inhibitor does not prevent hyperacute rejection (HAR). This implies that the vasocaonstriction which occurs during the HAR is not related to high levels of angiotensin II.


Effects of group therapy on female adolescent survivors of sexual abuse: a pilot study.
Treatment interventions for female sexual abuse survivors was explored through a pilot study examining the relationship between group treatment and adolescent self-image. Self-image was defined as body image, self-reliance, self-control, and impulse-control. An experimental pre-post design was utilized. Participants were 13 female adolescent high school drop-outs with a history of sexual abuse who participated in the National Guard Youth Challenge Program at Camp Shelby in Mississippi. Participants completed the Offer Self- Image Questionnaire for Adolescents. The hypothesis that group therapy was an effective intervention for sexual abuse survivors was not supported; however, this is likely due to the small sample size. Because this was a pilot study, mean trends were observed to see directional changes that may assist future researchers. Observation of mean trends revealed that participants who received group therapy increased in levels of impulse control while the group that did not receive group therapy remained the same. Mean trends also revealed that the experimental group had a decrease in self-reliance whereas the control group maintained their levels of self-reliance.


Improved PCR Amplification of Broad Spectrum GC DNA Templates.
Many applications in molecular biology can benefit from improved PCR amplification of DNA segments containing a wide range of GC content. Conventional PCR amplification of DNA sequences with regions of GC less than 30%, or higher than 70%, is complex due to secondary structures that block the DNA polymerase as well as mispriming and mis-annealing of the DNA. This complexity will often generate incomplete or nonspecific products that hamper downstream applications. In this study, we address multiplexed PCR amplification of DNA segments containing a wide range of GC content. In order to mitigate amplification complications due to high or low GC regions, we tested a combination of different PCR cycling conditions and chemical additives. To assess the fate of specific oligonucleotide (oligo) species with varying GC content in a multiplexed PCR, we developed a novel method of sequence analysis. Here we show that subcycling during the amplification process significantly improved amplification of short template pools (~200 bp), particularly when the template contained a low percent of GC. Furthermore, the combination of subcycling and 7-deaza-dGTP achieved efficient amplification of short templates ranging from 10-90% GC composition. Moreover, we found that 7-deaza-dGTP improved the amplification of longer products (~1000 bp). These methods provide an updated approach for PCR amplification of DNA segments containing a broad range of GC content.


The clinical breast exam: a skill that should not be abandoned.
The clinical breast exam (CBE) is an important tool in the care of women. However, the utility of the screening CBE has been called into question. This article discusses the importance of the CBE as a physical diagnosis tool. Recommendations regarding screening with CBE are reviewed, and evidence surrounding breast cancer screening using CBE is briefly summarized. Clinicians should strive to provide high quality CBEs as part of the general clinical exam for women, particularly those who present with breast complaints, and for patients who choose to have CBE screening. In conclusion, there is a role for the CBE in the care of women, and clinicians should be proficient at performing these exams. Simulation teaching technologies are now available at Department of Veteran Affairs (VA) facilities to enable clinicians to improve their CBE skills.


Suboptimal integration of reward magnitude and prior reward likelihood in categorical decisions by monkeys.
Sensory decisions may be influenced by non-sensory information regarding reward magnitude or reward likelihood. Given identical sensory information, it is more optimal to choose an option if it is a priori more likely to be correct and hence rewarded (prior reward likelihood bias), or if it yields a larger reward, given that it is the correct choice (reward magnitude bias). Here, we investigated the ability of macaque monkeys to integrate reward magnitude and prior reward likelihood information into a categorical decision about stimuli with high signal strength but variable decision uncertainty. In the asymmetric reward magnitude condition, monkeys over-adjusted their decision criterion such that they chose the highly rewarded alternative far more often than was optimal; in contrast, monkeys did not adjust their decision criterion in response to asymmetric reward likelihood. This finding shows that in this setting, monkeys did not adjust their decision criterion based on the product of reward likelihood and reward magnitude as has been reported to be the case in value-based decisions that do not involve decision uncertainty due to stimulus categorization.


Probing the transverse coherence of an undulator x-ray beam using brownian particles.
We present a novel method to map the two-dimensional transverse coherence of an x-ray beam using the dynamical near-field speckles formed by scattering from colloidal particles. Owing to the statistical nature of the method, the coherence properties of synchrotron radiation from an undulator source is obtained with high accuracy. The two-dimensional complex coherence function is determined at the sample position and the imaging optical scheme further allowed us to evaluate the coherence factor at the undulator output despite the aberrations introduced by the focusing optics.


Should Marijuana Be Legalized: A Scoping Review of Associations of Marijuana and Depression.
People with addiction to marijuana and those who have ever consumed marijuana at any time during their life suffer from depression at some point in their life. Depression has been associated with substance use as both a trigger and repercussion. A total of 3663 articles were analyzed, and 26 articles were collectively selected for this study. Consuming marijuana was linked to the development of depression in the majority of individuals. Marijuana consumption and its repercussions have both been connected to negative effects on the body, such as respiratory disorders and even psychological disorders, including stress and depressive disorders. Studies potentially point to a complicated causal relationship between marijuana consumption and depressive disorder, stating that early depressive symptoms enable marijuana usage, which then reduces depression. A research article clearly states that consuming marijuana can be helpful in elevating mood and anxiolytic initially, but it is subsequently followed by a rise in depressive symptoms, which manifest as mental distress and frustration. Discussions with patients about the extent of their marijuana consumption, techniques for reducing the use, and the impact of marijuana on depression may be beneficial in medical facilities where depressive disorder is treated. This research paper highlights the importance of understanding depression and the use of marijuana for temporary relief from depressive symptoms and its long-term consequences on mental health.


Intraoperative positive end-expiratory pressure evaluation using the intratidal compliance-volume profile.
Lung-protective mechanical ventilation during general surgery including the application of PEEP can reduce postoperative pulmonary complications. In a prospective clinical observation study, we evaluated volume-dependent respiratory system compliance in adult patients undergoing ear-nose-throat surgery with ventilation settings chosen empirically by the attending anaesthetist. In 40 patients, we measured the respiratory variables during intraoperative mechanical ventilation. All measurements were subdivided into 5 min intervals. Dynamic compliance (CRS) and the intratidal volume-dependent CRS curve was calculated for each interval and classified into one of the six specific compliance profiles indicating intratidal recruitment/derecruitment, overdistension or all. We retrospectively compared the occurrences of the respective compliance profiles at PEEP levels of 5 cm H2O and at higher levels. The attending anaesthetists set the PEEP level initially to 5 cm H2O in 29 patients (83%), to 7 cm H2O in 5 patients (14%), and to 8 cm H2O in 2 patients (6%). Across all measurements the mean CRS was 61 (11) ml cm H2O(-1) (40-86 ml cm H2O(-1)) and decreased continuously during the procedure. At PEEP of 5 cm H2O the compliance profile indicating strong intratidal recruitment/derecruitment occurred more often (18.6%) compared with higher PEEP levels (5.5%, P<0.01). Overdistension was practically never observed. In most patients, a PEEP of 5 cm H2O during intraoperative mechanical ventilation is too low to prevent intratidal recruitment/derecruitment. The analysis of the intratidal compliance profile provides the rationale to individually titrate a PEEP level that stabilizes the alveolar recruitment status of the lung during intraoperative mechanical ventilation. DRKS00004286.


Idiopathic restrictive cardiomyopathy with diffuse perimyocytic fibrosis--a rare observation.
Idiopathic restrictive cardiomyopathy (RCM) is rare. Even today little is understood of its etiology or underlying mechanisms, and definitive diagnostic criteria are lacking. In this report, we describe a case of idiopathic RCM in a young Japanese woman who died while awaiting cardiac transplantation during the 5-year course of the disease. Rare pathologic findings of diffuse perimyocytic fibrosis were revealed at autopsy.


The effect of adenotomy, allergy and smoking on microbial colonization of upper aerodigestive tract in children.
To evaluate microbial colonization of upper aerodigestive tract in children and to investigate the influence of adenoid hypertrophy, allergy and exposition to cigarette smoke on presence of pathogens. In 43 children with adenoid hypertrophy and 17 healthy children bacterial culture was performed by a swab from middle nasal meatus, nasopharynx and tonsils. The effect of adenotomy, presence of allergy and exposure to passive smoking on bacterial colonization were investigated. Identification of potentially pathogenic bacteria in upper aerodigestive tract was significantly higher in children with adenoid hypertrophy compare to control group. Adenotomy was associated with significantly decreased colonization by potential pathogens. Allergy was diagnosed in 33 % children with adenoid hypertrophy. Presence of allergy and exposure to tobacco smoke were associated with significantly more often colonization by potentially pathogenic bacteria in the upper aerodigestive tract. Increased colonization of upper aerodigestive tract by potential pathogens and their significant decrease after adenotomy indicate the role of pathogenic bacteria in the etiopathogenesis of adenoid hypertrophy. Allergy and tobacco smoke exposure are related to increased colonization by potentially pathogenic bacteria in the upper aerodigestive tract.


[Neoplastic secondary glaucomas].
With few exceptions all intraocular tumours can principally induce elevation of intraocular pressure (IOP). The frequency of IOP-elevation is mainly dependent on the biologic behaviour of the neoplasm (benign / malignant), its dimensions, localization, and its ability to provoke secondary changes like retinal detachment, hemorrhages, inflammation, and necroses. There are many and diverse pathomechanisms which may cause a "neoplastic glaucoma". The leading mechanisms are direct invasion of the chamber angle by tumour cells, rubeosis iridis, and forward displacement of the iris-lens-diaphragm with (lens induced) pupillary block. As intraocular tumours may have pressure-lowering effects too, eyes bearing a tumour may also be hypotonic or normotonic inspite of a "glaucomatous chamber angle morphology". The therapy of the tumour-induced glaucomas is hardly validated and generally follows the treatment of the other secondary glaucomas. However, filtration procedures are contraindicated when a malignant tumour is diagnosed or suspected. Because of the progress of tumour therapy with salvation of eyes which had to be enucleated in former times and prolongation of survival in some tumour entities (like Non Hodgkin's lymphoma and metastases) the significance of tumour-induced glaucomas will probably further increase in the future.


Hemispheric Asymmetry of Development Due to Drug Exposure.
A previous survey of the literature of fMRI brain activation for two risk factors, impulsivity and craving, for addiction were lateralized to the right and left hemispheres respectively. Most articles reported these findings without consideration of how lateral asymmetries might be relevant to understanding the underlying factors leading to addiction. The current survey is intended to extend these observations by demonstrating hemispheric asymmetry of development due to pre-natal or adolescent/adult exposure to drugs of abuse. Articles that reported either pre-natal or adolescent/adult exposure to drugs of abuse were collected and the hemisphere of the affected structures was tabulated to determine if, and which, drugs affected more structures in one hemisphere or the other or both together. Some drugs, notably cocaine and alcohol, differentially affected left or right hemisphere structures which significantly differed depending on whether individuals were exposed prenatally or as an adolescent/adult. Cocaine tended to affect more left hemisphere structures when exposed prenatally and significantly affected more in the right when exposed as adults. Alcohol had the reverse pattern. The difference in patterns of effect between pre-natal or adult exposure was significant for both. The results in this survey demonstrate that some drugs of abuse appear to have a right/left differential effect on structures of the brain. Further investigation into the reasons for this asymmetry may provide new insights into underlying factors of drug-seeking and addiction.


Cloning and characterization of F3PYC gene encoding pyruvate carboxylase in Aspergillus flavus strain (F3).
Pyruvate carboxylase is a major enzyme for biosynthesis of organic acids like; citric acid, fumeric acid, and L-malic acid. These organic acids play very important role for biological remediation of heavy metals. In this study, gene walking method was used to clone and characterize pyruvate carboxylase gene (F3PYC) from heavy metal resistant indigenous fungal isolate Aspergillus flavus (F3). 3579 bp of an open reading frame which encodes 1193 amino acid protein (isoelectric point: 6.10) with a calculated molecular weight of 131.2008 kDa was characterized. Deduced protein showed 90-95% similarity to those deduced from PYC gene from different fungal strains including; Aspergillus parasiticus, Neosartorya fischeri, Aspergillus fumigatus, Aspergillus clavatus, and Aspergillus niger. Protein generated from the PYC gene was a homotetramer (α4) and having four potential N-linked glycosylation sites and had no signal peptide. Amongst most possible N-glycosylation sites were -N-S-S-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, N-G-S-S- at 517 amino acid, and N-T-S-R- at 1111 amino acid, with several functions have been proposed for the carbohydrate moiety such as thermal stability, pH, and temperature optima for activity and stabilization of the three-dimensional structure. Hence, cloning of F3PYC gene from A. flavus has important biotechnological applications.


Extracapsular radiation dose distribution after permanent prostate brachytherapy.
The physical extent of the radiation therapy dose delivered to the periprostatic region was evaluated in 26 consecutive patients with low-risk prostate cancer (prostate-specific antigen <or=10, Gleason score <or=6, and clinical T1c/T2a) who underwent prostate brachytherapy using either 103Pd or 125I without supplemental external beam radiation therapy between October and December 1999. All patients underwent a transrectal ultrasound volumetric study of the prostate gland followed by the generation of a preplan based on a consistent, modified uniform seed-loading philosophy. The planning treatment volume (PTV) consisted of the prostate gland with approximately 5-mm anterior and lateral margins. The radiation dose was prescribed to the PTV with margin. Day 0 computed tomography-based dosimetric evaluation revealed an overall mean 100% isodose margin of 6.5 mm +/- 1.8 mm. For 125I and 103Pd, the 100% isodose margins were 6.8 mm +/- 1.6 mm and 6.3 mm +/- 1.9 mm, respectively. At the 90% and 75% isodose lines, the isodose margins differed by no more than 1 mm for the 2 isotopes. With the exception of the area near the bladder neck and the posterior border of the prostate, the 100% isodose margin was >or=5.0 mm for all slices evaluated. The utilization of preplanning periprostatic margins is strongly correlated with the administration of prescription radiation doses to the periprostatic region. The extent of the postimplant periprostatic margin (6.5 +/- 1.8 mm) satisfies the preplanning margin criterion of >5 mm.


Continuous quantum hypothesis testing.
I propose a general quantum hypothesis testing theory that enables one to test hypotheses about any aspect of a physical system, including its dynamics, based on a series of observations. For example, the hypotheses can be about the presence of a weak classical signal continuously coupled to a quantum sensor, or about competing quantum or classical models of the dynamics of a system. This generalization makes the theory useful for quantum detection and experimental tests of quantum mechanics in general. In the case of continuous measurements, the theory is significantly simplified to produce compact formulas for the likelihood ratio, the central quantity in statistical hypothesis testing. The likelihood ratio can then be computed efficiently in many cases of interest. Two potential applications of the theory, namely, quantum detection of a classical stochastic waveform and test of harmonic-oscillator energy quantization, are discussed.


Simultaneous measurement of DNA content and cell-surface immunofluorescence of human bone marrow cells using a single laser flow cytometer.
This paper describes the measurement of S phase DNA content in human bone marrow subpopulations using a single laser method for bivariate analysis of DNA content and cell-surface immunofluorescence (s-IF). Low density (less than 1.077 g/ml) bone marrow cells were labeled with a panel of unconjugated monoclonal antibodies (MoAb) for the lymphoid (CD2 + CD19), T-lymphoid (CD2), B-lymphoid (CD19), erythroid (anti-glycophorin-A), myelomonocytic (CD13, CD33; single and as cocktail) and monocytic (CD14) lineages. A fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse label was used as second step. Unfixed, MoAb-labeled cells were incubated for 24 h with a hypotonic propidium iodide solution for DNA staining. Cells were analysed on a single-laser flow cytometer, operating at 488 nm. The effect of the combined staining protocol upon both s-IF and DNA stainability was evaluated. Only a slight decrease (mean: 29.0%) in s-IF intensity was observed after DNA staining. The percentages of immunofluorescent cells in the bone marrow samples of 10 normal individuals before and after DNA staining were essentially unchanged for all the MoAbs used. The DNA histograms of the immunophenotypically defined subpopulations were of excellent quality with a mean coefficient or variation of 1.8%. This procedure allows the assessment of very low levels of S-phase DNA content, as measured in normal low density blood cells of 8 healthy volunteers (mean 0.07%).(ABSTRACT TRUNCATED AT 250 WORDS)


A quantitative measurement of peritoneal drainage in malignant ascites.
With a two-compartment model, a method is described for quantitative determination of peritoneal drainage rates in malignant ascites. Data on twenty-four patients are presented and comparison is made with the qualitative assessment of the integrity of diaphragmatic and mediastinal lymphatics on the basis of lymphoscintigrams. It is concluded that flow rates less than 50 ml/hour are usually associated with abnormalities of the diaphragmatic and mediastinal lymphatics, indicating that tumor permeation of these structures is a significant contributing factor to persistent, intractable ascites in patients with malignant diseases.


The Role of Revefenacin in Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by progressive and persistent airflow limitation that is not fully reversible. Revefenacin is an investigational long-acting muscarinic antagonist (LAMA), in late-stage development as a nebulized inhalation solution, which has been designed to produce long-acting bronchodilation, consistent with once-daily dosing, and with a high degree of lung-selectivity. It is more selective for muscarinic type 3 (M3) than muscarinic type 2 (M2) or muscarinic type 1 (M1) receptors. Its dissociation half-life for M3 is 82 minutes and 6.9 minutes for M1, respectively. The bronchoprotective effect is seen as early as five-minute post-dose and is sustained for up to 24 hours. The estimated 24-hour potency (expressed as the concentration of dosing solution) is 45.0 mg/ml. Once-daily dose of revefenacin provided long-term improvement in trough forced expiratory volume in one second (FEV1). It improved day 28 trough FEV1 over placebo significantly (p < 0.001). M3: M2 receptor half-life is 12 compared to the other antagonists that have M3: M2 receptor half-life around 6.0. A 24-hour serial spirometry, on day 84, showed that revefenacin 88 or 175 µg was associated with significant (p <0.01) improvements in trough FEV1 at all time points compared with placebo. Revefenacin is generally well-tolerated and unlike the other anti-muscarinics, it has no systemic anti-cholinergic adverse effects.


The murine epsilon receptor modulating protein: a novel serine protease which modulates CD23 binding of IgE.
In our recent previous studies, we have identified and purified a murine 17-kDa protein which diminishes the avidity of binding between IgE and CD23 (low-affinity Fc receptor for IgE) without decreasing the quantitative expression of the CD23. The protein was thus designated epsilon receptor modulating protein (epsilon RMP). In this study, we have further characterized this protein and have found that (i) epsilon RMP is inactivated by phenylmethylsulfonyl fluoride and decomposes N,alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester, as well as N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide; (ii) epsilon RMP does not work directly on B cells but requires CD4+ T cells to decrease functional expression of CD23 on B cells; and (iii) the partial internal amino acid sequence of epsilon RMP, obtained by using in situ cyanogen bromide cleavage on polyvinylidene difluoride membrane is unique. These data thus clearly demonstrate that epsilon RMP is a novel serine protease controlling the functional expression of CD23 through the participation of CD4+ T cells. Mechanisms of the involvement of CD4+ T cells are discussed.


Evaluation of growth production factors as predictors of the incidence and severity of white striping and woody breast in broiler chickens.
White striping (WS) and woody breast (WB) have been previously associated with older and heavier birds. However, there is limited information supporting the association between these 2 muscle conditions and growth parameters. The objectives of this study were 1) to investigate the relationship between WS and WB using different growth production factors and 2) to propose a predictive model that uses growth production factors to investigate the incidence and severity of WS and WB. A combined database of 4,332 broilers pooled from 7 research experiments conducted from 2016 to 2017 at Texas A&M University was used in this study. Parameters such as sex, age (4 wk, 6 wk, and 8 wk), strain (standard A vs. high-breast-yield [B and C]), live weight categories (500 g increments), and breast weight categories (250 g increments) were included in the model. Results showed that WS was 12% more likely to be present in non-WB fillets. The association between WS and WB suggests a moderate relationship between the ranks of both outcome variables (ρ = 0.57, P < 0.0001). Variables such as age, live weight, and sex were not as important as breast weight and strain in the severity prediction of WS and WB. Butterfly fillets above 750 g and with high-breast-yielding strains were more likely associated with higher severity of WS and WB scores. No post hoc variable selection was performed. Both models show good discrimination. The WS model produced an uncorrected area under the curve (AUC) of 0.739, with a bootstrap corrected estimate of 0.736. The WB model produced an uncorrected AUC of 0.753 and a bootstrap corrected estimate of 0.752. Therefore, the growth production factors analyzed in this study indicated that there is a moderate relationship between WS and WB myopathies and were jointly predictive of the severity of WS and WB. Potentially other factors not included in this study may play a major role in the relationship of these 2 myopathies. More research should be done to investigate this possibility.


Internuclear (31)P-(51)V distance measurements in polyoxoanionic solids using rotational echo adiabatic passage double resonance NMR spectroscopy.
We report the first results establishing rotational echo adiabatic passage double resonance (REAPDOR) experiments for distance measurements between a spin-1/2 (31P) and spin-7/2 (51V) pair in a series of vanadium-substituted polyoxoanionic solids from the Keggin and Wells-Dawson families. We have quantitatively measured 31P-51V distances in monovanadium substituted K4PVW11O40, 1-K7P2VW17O62, and 4-K7P2VW17O62. Numerical simulations of the experimental data yield very good agreement with the averaged P-W/P-V distances determined from the X-ray diffraction measurements in the same or related compounds. REAPDOR is therefore a very sensitive P-V distance probe anticipated to be especially useful in the absence of long-range order. Our results suggest that REAPDOR spectroscopy could be broadly applicable for interatomic distance measurements in other spin-7/2-spin-1/2 nuclear pairs.


Superoxide dismutases are involved in Candida albicans biofilm persistence against miconazole.
We investigated the cellular mechanisms responsible for the occurrence of miconazole-tolerant persisters in Candida albicans biofilms. Miconazole induced about 30% killing of sessile C. albicans cells at 75 μM. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2%. Since miconazole induces reactive oxygen species (ROS) in sessile C. albicans cells, we focused on a role for superoxide dismutases (Sods) in persistence and found the expression of Sod-encoding genes in sessile C. albicans cells induced by miconazole compared to the expression levels in untreated sessile C. albicans cells. Moreover, addition of the superoxide dismutase inhibitor N,N'-diethyldithiocarbamate (DDC) to C. albicans biofilms resulted in an 18-fold reduction of the miconazole-tolerant persister fraction and in increased endogenous ROS levels in these cells. Treatment of biofilms of C. albicans clinical isolates with DDC resulted in an 18-fold to more than 200-fold reduction of their miconazole-tolerant persister fraction. To further confirm the important role for Sods in C. albicans biofilm persistence, we used a Δsod4 Δsod5 mutant lacking Sods 4 and 5. Biofilms of the Δsod4 Δsod5 mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels compared to biofilms of the isogenic wild type (WT). In conclusion, the occurrence of miconazole-tolerant persisters in C. albicans biofilms is linked to the ROS-detoxifying activity of Sods. Moreover, Sod inhibitors can be used to potentiate the activity of miconazole against C. albicans biofilms.


New BVA Working Groups get under way.
BVA's new working groups are looking at a range of issues, including surveillance, farm assurance and antimicrobial resistance. The role of the new groups - which were developed following a review by the BVA Policy Committee - will be to have a proactive approach to policymaking.


Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy.
Continuous renal replacement therapy (CRRT) is now commonly used as a means of support for critically ill patients with renal failure. No recent comprehensive guidelines exist that provide antibiotic dosing recommendations for adult patients receiving CRRT. Doses used in intermittent hemodialysis cannot be directly applied to these patients, and antibiotic pharmacokinetics are different than those in patients with normal renal function. We reviewed the literature for studies involving the following antibiotics frequently used to treat critically ill adult patients receiving CRRT: vancomycin, linezolid, daptomycin, meropenem, imipenem-cilastatin, nafcillin, ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanic acid, cefazolin, cefotaxime, ceftriaxone, ceftazidime, cefepime, aztreonam, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, colistin, amikacin, gentamicin, tobramycin, fluconazole, itraconazole, voriconazole, amphotericin B (deoxycholate and lipid formulations), and acyclovir. We used these data, as well as clinical experience, to make recommendations for antibiotic dosing in critically ill patients receiving CRRT.


Haemostatic Indices as Markers for Monitoring Pulmonary Tuberculosis Treatment.
Tuberculosis (TB) is an infectious disease inducing a state of chronic inflammation which could affect thehaemostatic mechanism as part of host defences against infection. Proper diagnosis and monitoring of tuberculosis patientsundergoing therapy is still a challenge especially in a poor resource country such as Nigeria. This study aims to assess somehaemostatic indices of tuberculosis patients and their possible use as markers in monitoring response to anti-tuberculosistreatment. One hundred and twenty TB patients aged 15-60 years and 120 apparently healthy (control) subjects age andgender-matched were studied. Demographic/bio data was compiled by interview and from patients' case notes. Diagnosis ofTB was by sputum smear microscopy, radiography and clinical assessment. Platelet count (PLT), platelet factor 4 (PF4),prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT) and fibrinogen (FIB)were determined using standard techniques. The platelet factor 4, prothrombin time, activated partial thromboplastin timeand fibrinogen levels of TB patients were significantly higher while the thrombin clotting time was significantly lower(P<0.05) when compared with healthy subjects. While PF4, TCT and FIB improved significantly (P<0.05) as antituberculosis therapy progressed, PLT, PT and APTT remained the same. It is concluded that abnormal activation ofhaemostasis occurs in TB condition thus pre-disposing TB patients to bleeding complications. Furthermore, platelet factor4, thrombin clotting time and fibrinogen improved as therapy progressed and therefore may be used as markers for monitoringresponse to anti-tuberculosis therapy.


[Recombinant human thyrotropin in the follow-up of patients with differentiated thyroid carcinoma].
To determine the value of the use of radio-iodine scanning diagnostic and radio-iodine therapy during the follow-up of advanced differentiated thyroid cancer without stopping thyroid hormone suppression therapy. We performed 7 radio-iodine scans and 4 radioiodine therapies in 5 men and 1 woman, aged 39 to 79 years. Five patients had papillary thyroid cancer and one follicular thyroid cancer. Human recombinant thyrotropin was given intramuscularly at a dose of 0.9 mg/ml once a day for two days. Twenty-four hours after the second dose, serum thyrotropin, thyroglobulin (Tg) and thyroglobulin autoantibodies were measured and each patient was given 2 mCi of 131I in postsurgery scans and 5 mCi of 131I in patients previously treated with 131I. Whole-body scans were obtained within 54 hours of injection and in the cases of diagnostic uncertainty a second scan was performed 72 hours after the injection. Four scans were positive and two were negative. One positive scan patient was not treated due to a serious clinical condition. An effective increase of serum TSH was observed in all 6 patients. Four patients had an effective increase of serum Tg; the other 2 cases had a decrease of serum Tg: One case was undifferentiated and in the other case the mass was smaller after surgery. rhTSH is an effective means of stimulating TSH levels and allowing scan and/or radioiodine treatment. rhTSH has no significant adverse effects. The use of rhTSH avoids all the disadvantages of hypothyroidism and maintains quality of life.


Effects of neutral salts on RNA chain elongation and pausing by Escherichia coli RNA polymerase.
We examined the effects of neutral salts and the non-ionic solute 2-methyl,-2,4-pentanediol (MPD) on transcript elongation by Escherichia coli RNA polymerase and on pausing induced by the multipartite his leader pause signal. All solutes tested slowed the overall rate of elongation, with anions showing the dominant effects in the order: (most inhibitory) HPO4(2-) > OAc- > SO4(2-) > ClO4- > I- approximately NO3- > Br approximately Cl- approximately MPD (least inhibitory). Although the protein structure-stabilizing anions HPO4(2-), OAc-, and SO4(2-) also increased the pause half-life at the his leader pause site, the remaining solutes accelerated escape from pause site in the order: (greatest acceleration) NO3- > ClO4- > I- > Br- > Cl- > MPD (least acceleration). Cl(-)-induced acceleration of escape from the pause site also occurred on mutant templates altered for the 3'-proximal region, RNA 3' end, or downstream DNA. The effect was eliminated, however, by base substitutions that destabilize the pause RNA hairpin or that extend it toward the 3' end. This "perfect hairpin" itself reduced the pause half-life by a factor of 3. We suggest that the pause RNA hairpin stabilizes a paused conformation of the transcription complex through an interaction with an easily disordered region of RNA polymerase. Extending the stem of the pause hairpin may disrupt the interaction by altering the position of the hairpin in the transcription complex. Anions may either compete for the interaction directly or disorder the site of hairpin interaction by chaotropic effects. We suggest that the negative effect of structure-stabilizing anions like OAc- and SO4(2-) may reflect passage of RNA polymerase through significantly different conformations during rapid elongation, some of which may expose hydrophobic surface.


Influence of charge density on bilayer bending rigidity in lipid vesicles: a combined dynamic light scattering and neutron spin-echo study.
We report a combined dynamic light scattering and neutron spin-echo study on vesicles composed of the uncharged stabilizing lipid 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Mechanical properties of a model membrane and thus the corresponding bilayer undulation dynamics can be specifically tuned by changing its composition through lipid headgroup or acyl chain properties. We compare the undulation dynamics in lipid vesicles composed of DMPC/DOTAP to vesicles composed of a mixture of the uncharged helper lipid DMPC with the also uncharged reference lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We have performed dynamic light scattering on the lipid mixtures to investigate changes in lipid vesicle size and the corresponding center-of-mass diffusion. We study lipid translational diffusion in the membrane plane and local bilayer undulations using neutron spin-echo spectroscopy, on two distinct time scales, namely around 25 ns and around 150 ns. Finally, we calculate the respective bilayer bending rigidities κ for both types of lipid vesicles. We find that on the local length scale inserting lipid headgroup charge into the membrane influences the bilayer undulation dynamics and bilayer bending rigidity κ less than inserting lipid acyl chain unsaturation: We observe a bilayer softening with increasing inhomogenity of the lipid mixture, which could be caused by a hydrophobic mismatch between the acyl chains of the respective lipid components, causing a lateral phase segregation (domain formation) in the membrane plane.


[Metabolic frailty in malnourished heart failure patients].
Muscular wasting (MW) and cardiac cachexia (CC) are often present in patients with chronic heart failure (HF). To identify whether MW and CC are due to malnutrition or impairment of protein metabolism in HF patients. In 78 clinically stable HF patients (NYHA class II-III), aged from 32 to 89 years, we measured anthropometrical parameters and nutritional habits. In the identified 35 malnourished patients, we also measured: insulin resistance, gluconeogenetic amino acids blood concentration and nitrogen balance. Seventy-five patients had eating-related symptoms. However we found significant nutritional impairment in 35 patients only. In addition, these 35 patients had: 1) significant increase of blood Alanine independently from both presence of insulin resistance or food intake reduction and 2) positive nitrogen balance. Food intake is not impaired in CHF patients. In spite of normal food intake, 35 of 78 patients had nutritional impairment with reduced anthropometric parameters and increased blood Alanine. These findings show alteration of proteins metabolism with proteolysis. We believe that specific physical training with nutritional supplement can be an additional therapy able to prevent protein disarrangement in CHF patients.


Cancer Care in the Incarcerated Population: Barriers to Quality Care and Opportunities for Improvement.
Cancer is the leading cause of mortality in incarcerated individuals older than 45 years and the fourth leading cause of mortality overall. Health care professionals face increasing challenges to provide high-quality care under the confines of prison regulations and procedures. Adjusted for age, race, sex, and year of diagnosis, the standardized incidence ratio for all cancers is more than 2-fold higher in incarcerated vs general populations. Among deaths occurring in state and federal prison systems, cancer is the overall leading cause of mortality with lung cancer being the leading cause of cancer-related mortality followed by liver, colon, and pancreatic cancers, respectively. Access to high-quality oncological services remains variable; however, cost of care represents about a fifth of overall annual prison expenditures. Given the enormous patient burden, coupled with the rushed discretionary screenings performed by jail and prison nursing staff, early cancer symptoms are often missed altogether or misdiagnosed as a chronic illness or as acute infections. As such, many incarcerated individuals present with more advanced cancer stage. Incarcerated individuals have limited, if any, access to the internet, social media, and other sources of information, which severely limits their ability to research treatment options. Within the prison setting, access to professionals with special skills in assisting with social and spiritual concerns is also generally limited, and less than 4% of prisons have hospice programs. There are no uniform quality-of-care monitoring standards for correctional systems and facilities, nor are there mechanisms for reporting comparable performance data to enforce quality control within correctional health care systems. There is a growing trend in cancer incidence among incarcerated patients, which is multifactorial including barriers in access to care, increased burden of chronic medical conditions, and decreased screening tests. Efforts are needed to ensure quality health care outcomes for incarcerated patients with cancer.


Association of gender and specialty interest with video-gaming, three-dimensional spatial analysis, and entry-level laparoscopic skills in third-year veterinary students.
OBJECTIVE To determine whether gender or interest in pursuing specialty certification in internal medicine or surgery was associated with video-gaming, 3-D spatial analysis, or entry-level laparoscopic skills in third-year veterinary students. DESIGN Cross-sectional study. SAMPLE A convenience sample of 68 (42 female and 26 male) third-year veterinary students. PROCEDURES Participants completed a survey asking about their interest in pursuing specialty certification in internal medicine or surgery. Subsequently, participants' entry-level laparoscopic skills were assessed with 3 procedures performed in box trainers, their video-gaming skills were tested with 3 video games, and their 3-D spatial analysis skills were evaluated with the Purdue University Visualization of Rotations Spatial Test. Scores were assigned for laparoscopic, video-gaming, and 3-D spatial analysis skills. RESULTS Significantly more female than male students were interested in pursuing specialty certification in internal medicine (23/42 vs 7/26), and significantly more male than female students were interested in pursuing specialty certification in surgery (19/26 vs 19/42). Males had significantly higher video-gaming skills scores than did females, but spatial analysis and laparoscopic skills scores did not differ between males and females. Students interested in pursuing specialty certification in surgery had higher video-gaming and spatial analysis skills scores than did students interested in pursuing specialty certification in internal medicine, but laparoscopic skills scores did not differ between these 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE For this group of students, neither gender nor interest in specialty certification in internal medicine versus surgery was associated with entry-level laparoscopy skills.


The making of a modern female body: beauty, health and fitness in interwar Britain.
In interwar Britain female athleticism, keep-fit classes and physical culture were celebrated as emblems of modernity, and women who cultivated their bodies in the pursuit of beauty, health and fitness represented civic virtue. This article argues that a modern, actively managed female body was part of women's liberation during this period. A modern female body required sex reform and birth control. Fitness culture was circumscribed by traditional notions of femininity. Women's competitive sport remained controversial and slimming in pursuit of fashion was widely condemned. Women from across the social spectrum embraced sport and joined fitness organizations. The rise of a modern female body contributed towards greater equality between the sexes. However, the gender order did not change fundamentally and the ideal woman of the interwar years was represented as a modern, emancipated race mother.


Enhancement of depletion forces by electrostatic depletant repulsion.
A large variety of engaging phenomena stems from the occurrence of short-ranged attractive depletion forces. Yet, so far, most experimental studies have been interpreted on the basis of the simple Asakura-Oosawa model, where the depletion agent can be regarded as ideal. Here, conversely, we focus on a system where strong electrostatic coupling is present in the suspension. Specifically, from measurements of equilibrium sedimentation profiles, we obtain an equation of states for a colloidal system where depletion forces are tuned by the addition of a surfactant. At fixed colloid volume fraction, colloidal aggregation takes place when the surfactant concentration reaches a critical value which rises for increasing ionic strength. Screening repulsive electrostatic interactions inhibits the depletion mechanism and weakens the effective colloid-colloid attraction. The metastable coexistence curve displays the universal scaling behavior predicted for short-ranged potentials. The experimental data are compared with the theoretical predictions of a simple model which includes only electrostatic interactions. The effective depletion force on the colloids is evaluated by using the hypernetted-chain equation of liquid state theory at different salt concentrations. This model provides a convincing interpretation of the observed enhancement of the depletion mechanism by Coulomb repulsion.


Application of transrectal sonography in the diagnosis and treatment of female stress urinary incontinence.
One hundred and two women with genuine stress urinary incontinence (SUI) were examined by transrectal sonography and urodynamics. The patients were classified into five types according to their intrinsic and extrinsic continence mechanism defects. Twenty-five patients had a hypermobile bladder neck and urethra (type 1); 31 patients had an incompetent bladder neck and a hypermobile urethra (type 2); 31 patients showed an incompetent urethral sphincter in addition to urethral hypermobility (type 3); 12 patients had a cystocele accompanying incompetent urethral sphincter and hypermobile urethra (type 4); the remaining 3 showed an incompetent urethral sphincter without hypermobility of the urethra (type 5). Whereas the distance from the lower margin of symphysis pubis to the bladder neck (pubovesical ligament; PVL) showed a significant increase in straining state of types 3 and 4, this was not the case in types 1, 2 and 5. There is a significant increase in the posteroinferior rotational of PVL angle on straining compared with resting in types 1, 2, 3, and 4, but not in type 5. The angle on straining also showed an increased tendency from type 1 to 4. The functional degree of SUI showed a significant increase from type 1 to 5. With this classification, the functional class of SUI is thus well correlated with the anatomical defects. The PVL length and the angle of external rotation of this axis are significantly implicated in the severity of SUI.


Relationships between body- and udder-related type traits with somatic cell counts and potential use for an early selection method for water buffaloes (Bubalus bubalis).
Water buffalo milk is a reliable source of high-quality nutrients; however, the susceptibility of mastitis in buffaloes must be taken into consideration. An animal with somatic cell count (SCC) of greater than 250,000 cells/mL is reported to be likely to have mastitis which has serious adverse effects on animal health, reproduction, milk yield, and milk quality. Type traits (TTs) of water buffalo can affect SCC in animal milk to some extent, but few reports on the correlation between SCC and TTs are available. In this study, a total of 1908 records collected from 678 water buffaloes were investigated. The general linear model was used to identify factors associated with phenotypic variation of the somatic cell score (SCS) trait, including parity, lactation length, calving year, and calving season as fixed effects. Using PROC CORR analysis method, taking calving year and lactation length as covariates, the correlation co-efficient between TT and SCS was obtained. Our results showed that correlation co-efficients between the 45 TTs with SCS ranged from 0.003 to 0.443 (degree of correlation). The correlation between udder traits and SCS was greater than that between body structure traits and SCS. Among udder traits, distance between teats (including front and rear teat distance [r = 0.308], front teat distance [r = 0.211], and teat crossing distance [r = 0.412]) and teat circumference (r = 0.443) had the highest correlation with SCS, followed by the leg traits including rear leg height (r = -0.354) and hock bend angle (r = -0.170). Animal with high rear legs (>48 cm) and short teat crossing distance (<17 cm), and narrow teat circumference (<11 cm) exhibited low SCS. Using four nonlinear models (Von Bertalanffy, Brody, Logistic, and Gompertz), the optimal growth curves of the TTs highly correlated with the SCS (rear leg height and teat crossing distance) were fitted, and the correction co-efficients of these two TTs rear leg height and teat crossing distance of animal from young age (2 mo old) to first lactation (35 mo old) were attained for establishment of early selection method for water buffaloes with low SCS. This study provides theoretical support for early selection of low-SCS water buffaloes and lays a foundation for improving milk quality and promoting healthy development of water buffalo's dairy industry.


Comprehensive characterization of the photodissociation pathways of protonated tryptophan.
The photofragmentation of protonated tryptophan has been investigated in a unique experimental setup, in which ion and neutral issued from the photofragmentation are detected in coincidence, in time and in position. From these data are extracted the kinetic energy, the number of neutral fragments associated with an ion, their masses, and the order of the fragmentation steps. Moreover, the fragmentation time scale ranging from tens of nanoseconds to milliseconds is obtained. From all these data, a comprehensive fragmentation mechanism is proposed.


DTB Select: 6 | June 2016.
EMA reviews risk of pneumonia with inhaled corticosteroids for COPD ● Updated USA guidance on opioids for chronic pain ● Tackling high-risk prescribing ● Influencing antibiotic prescribing in primary care ● Commuting, BMI and obesity ● Cardiovascular effects of antidepressants ● PPI use and dementia ● Older people and risk of drug interactions.


Harnessing autoimmunity (vitiligo) to treat melanoma: a myth or reality?
Melanoma is a highly malignant tumor derived from skin melanocytes (pigment-producing cells), which is associated with a significant rate of systemic metastases and death. Various therapeutic approaches for melanoma have been attempted in recent years, including the use of chemotherapy, immunotherapy, and ablative surgical and radiation treatments. However, in many cases these treatments fail as the tumor becomes resistant to the treatment and rapidly spreads and causes death. Reports in the medical literature have documented the unique immunogenic nature of melanoma where antigens, antibodies, and immune complexes seem to play a major role in the course of the disease. Anti-melanoma antibodies can cross-react with antigens on normal melanocytes, therefore causing the appearance of an associated hypopigmentation that resembles vitiligo. Vitiligo is a dermatological disorder characterized by local, dispersed, or diffuse white patches on the skin as a result of the destruction of melanocytes. This disease is believed to be an autoimmune disorder since autoantibodies against membrane components of melanocytes are found in the sera of patients with vitiligo. Melanoma triggers an anti-tumor response in many patients. Unfortunately, such anti-tumor response is insufficient to elicit tumor regression and the tumor continues to proliferate. Since the prognosis of melanoma in patients and animals with vitiligo is more favorable than in the general population, it was hypothesized that sera from patients with vitiligo may react against melanoma cells. Such studies have demonstrated that exposure of tumor cells to the sera resulted in inhibition of proliferation of the melanoma cells in vitro and in regression of melanoma metastases in mice presumably on account of the presence of the high titer of anti-melanoma antibodies in the sera used in these studies. In this review we discuss the known data and hypothetical assumptions related to the use of vitiligo-associated antibodies against melanoma, as well as characterize the immune mechanisms involved in this process.


[Study on apoptosis in myelodysplastic syndromes by DNA in situ end labelling combined with APAAP].
To investigate the total in situ apoptotic cell number and the apoptotic situation in erythroid cell and megakaryocytes in patients with myelodysplastic syndromes (MDS). Apoptosis cell number and the apoptotic situation of erythroid cell and megakaryocytes were analysed on cold embedded bone marrow sections from 25 MDS patients by DNA in situ end labelling (ISEL)/alkaline phosphatase anti-alkaline phosphatase (APAAP) double stained techniques. Fourteen cases of iron deficiency anemia (IDA) were taken as control. Mean apoptotic cell numbers in MDS and control group were (39.44 +/- 29.34)/mm(2) and (13.43 +/- 8.39)/mm(2) respectively (P < 0.01). RA/RAS subtypes had a higher apoptosis ratio (47.56 +/- 32.86/mm(2)) than that in RAEB/RAEB-t subtypes (21.87 +/- 13.65/mm(2)) (P < 0.05). Double staining showed similar apoptosis percentage in erythroid cell and megakaryocytes in MDS patients comparing with that of controls (P > 0.05). Some apoptotic cells showing erythroid or megakaryocytic morphologic characteristics expressed no cluster differentiation antigen. Overapoptosis existed in MDS, RA/RAS group had a higher apoptosis ratio than RAEB/RAEB-t group. No obvious increased apoptosis in erythroid cell and megakaryocytes was observed in MDS perhaps due to the loss of surface antigens in later stages of apoptotic cells.


Simulating interfacial anisotropy in thin-film growth using an extended Cahn-Hilliard model.
We present an extended Cahn-Hilliard model for simulating interfacial anisotropy in thin-film dynamics by incorporating high-order terms in the energy from an expansion of the energy about an equilibrium state, following earlier work by Abinandanan and Haider [Philos. Mag. Sect. A 81, 2457 (2001)]. For example, to simulate SiGe/Si thin films, where diamond cubic symmetry is needed, fourth order derivatives are included in the energy. This results in a sixth order evolution equation for the order parameter. For less symmetric crystals, one needs to add terms of higher order than fourth order. One advantage of this approach is its intrinsic regularized behavior. In particular, even for strongly anisotropic surface energy, sharp corners will not form and the extended anisotropic Cahn-Hilliard equations are well-posed. For this system we develop an energy-stable numerical scheme in which the energy decreases for any time step. We present two-dimensional (2D) and three-dimensional (3D) numerical results using an adaptive, nonlinear multigrid finite-difference method. We find excellent agreement between the computed equilibrium shapes using the new model and results from an analysis associated with a Wulff construction for energy minimization. The model predictions also compare well with experimental results for silicon voids. In the context of thin films, we observe the formation of interconnected ridges, wires, and fortresses similar to those observed in SiGe/Si thin films.


[Candida arthritis: report of two cases].
Candida arthritis is extremely rare. However, there has been a steady increase in the incidence of candida arthritis during the last decade because of increasing candida infections in immunocompromised hosts, drug addicts, premature babies, and those who have received prosthetic joint operations or intraarticular injections of steroids. We report herein two cases of candida arthritis: a 27-year-old man with aplastic anemia and transfusional hemosiderosis, and a 60-year-old man with osteoarthritis who received repeated intra-articular injections of steroids. Definite diagnoses were made after repeated smear examinations of synovial fluids. In the first case, candida arthritis occurred about 2 weeks after an antecedent candidemia. Although the arthritis relapsed once due to inadequate antifungal treatment, it was finally successfully treated with systemic amphotericin B, oral ketoconazole and surgical drainage of the synovial fluid. In the second case, it took several months to make the diagnosis. The patient was also treated with amphotericin B, ketoconazole, and surgery with a satisfactory outcome. We conclude that since candida arthritis is a slow, less destructive joint infection, it can almost always be resolved. Also, late orthopedic complications can be avoided by early diagnosis and prompt treatment, including aggressive antifungal therapy, adequate drainage and necessary surgical intervention.


[Myocardial infarction revealing an antiphospholipid syndrome in a 27-year-old woman].
We report the case of a 27 year old woman, with no vascular risk factors other than moderate smoking, admitted for a first acute anterior myocardial infarction. Emergency coronarography detected an isolated thrombosis, localised at the level of the middle section of the anterior inter-ventricular artery in an otherwise normal coronary network. Angioplasty of the artery with direct stenting was performed successfully and the follow up was uncomplicated. The diagnosis of primary antiphospholipid syndrome was made on the association of a raised level of anti-cardiolipin antibodies and the absence of elements in favour of an associated connective tissue disorder.


Ceftaroline modulates the innate immune and host defense responses of immunocompetent cells exposed to cigarette smoke.
Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system's response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release were evaluated by ELISA. The constitutive expression of TLR2 and TLR4 and LPS binding were higher in differentiated compared to undifferentiated THP-1 cells. In undifferentiated THP-1 cells, CSE increased TLR2 and TLR4 protein levels, LPS binding and TNF-α release and reduced HBD2 release and ceftaroline counteracted all these effects. In differentiated THP-1, CSE did not significantly affect TLR2 and TLR4 expression and LPS binding but reduced HBD2 release and increased TNF-α release. Ceftaroline counteracted the effects of CSE on HBD2 release in differentiated THP-1. Ceftaroline counteracts the effect of CSE in immune cells by increasing the effectiveness of the innate immune system. This effect may also assist in reducing pathogen activity and recurrent exacerbations in COPD patients.


Barometric pressure and the incidence of pulmonary embolism.
Reports in the literature suggest that weather changes may play a role in venous thrombotic disease. An increase in patients with pulmonary embolism (PE) during the spring season led us to investigate the relationship between atmospheric pressure (AP) and the incidence of PE, as diagnosed in most of the patients by helical CT angiography, and in the minority of patients by conventional pulmonary angiography and lung scanning. We retrospectively investigated the charts of 91 consecutive patients with a diagnosis of PE who were evaluated by the Department of Pulmonary Medicine between August 2000 and September 2004. We documented AP changes as recorded by the Erzurum Provincial Department of Meteorology. Of the 91 patients, the diagnosis of PE was made by helical CT angiography in 84 patients, isotope lung scan in 5 patients, and conventional pulmonary angiography in 2 patients. More patients presented in the spring months (March, n = 15; April, n = 10; and May, n = 12) than during other seasons (p < 0.001). The frequency of PE was inversely related to general average AP (r = - 0.70; p < 0.01). When the average seasonal AP was correlated with the incidence of PE, however, the relationship was found to not be statistically significant (r = - 0.66; p = 0.34). There was no correlation between the severity of PE or mortality and AP. The incidence of PE was significantly higher in the spring months, when AP was low. A regional study to capture all PE patients will need to be done to confirm our findings. Other meteorologic factors should be investigated regarding their effect on thromboembolic disease.


Predictive modeling using a somatic mutational profile in ovarian high grade serous carcinoma.
Recent high-throughput sequencing technology has identified numerous somatic mutations across the whole exome in a variety of cancers. In this study, we generate a predictive model employing the whole exome somatic mutational profile of ovarian high-grade serous carcinomas (Ov-HGSCs) obtained from The Cancer Genome Atlas data portal. A total of 311 patients were included for modeling overall survival (OS) and 259 patients were included for modeling progression free survival (PFS) in an analysis of 509 genes. The model was validated with complete leave-one-out cross-validation involving re-selecting genes for each iteration of the cross-validation procedure. Cross-validated Kaplan-Meier curves were generated. Cross-validated time dependent receiver operating characteristic (ROC) curves were computed and the area under the curve (AUC) values were calculated from the ROC curves to estimate the predictive accuracy of the survival risk models. There was a significant difference in OS between the high-risk group (median, 28.1 months) and the low-risk group (median, 61.5 months) (permutated p-value <0.001). For PFS, there was also a significant difference in PFS between the high-risk group (10.9 months) and the low-risk group (22.3 months) (permutated p-value <0.001). Cross-validated AUC values were 0.807 for the OS and 0.747 for the PFS based on a defined landmark time t = 36 months. In comparisons between a predictive model containing only gene variables and a combined model containing both gene variables and clinical covariates, the predictive model containing gene variables without clinical covariates were effective and high AUC values for both OS and PFS were observed. We designed a predictive model using a somatic mutation profile obtained from high-throughput genomic sequencing data in Ov-HGSC samples that may represent a new strategy for applying high-throughput sequencing data to clinical practice.


The MHC class II transcriptional activator (CIITA) inhibits HTLV-2 viral replication by blocking the function of the viral transactivator Tax-2.
The human T-cell leukemia virus type 2 (HTLV-2), an oncogenic retrovirus closely related to HTLV-1, produces a lifelong infection whose possible association to certain human diseases is still debated. Although some viral products can influence the expression and action of cellular genes, very little is known about the molecular mechanisms involved. Here we show that the AIR-1-encoded human major histocompatibility complex (MHC) class II transactivator (CIITA) strongly inhibits viral replication, but not virus entry, in human B- and T-cell susceptible targets. This effect results from CIITA inhibiting the Tax-mediated transactivation of the HTLV-2 long-term repeat. Further molecular analysis shows that the N-terminal region of CIITA encompassing the first 321 amino acids is responsible for the inhibitory effect on viral replication. This region is crucial for the transactivation of human MHC class II genes and includes the activation domain as well as domains interacting with coactivators that also are used by the viral transactivator Tax to modulate cellular functions. These results represent the first evidence that a cellular transcriptional activator, controlling the coordinate expression of the entire family of MHC class II antigen-presenting molecules, inhibits HTLV-2 viral replication by a distinct mechanism. In this new role CIITA may represent a new tool for therapeutic strategies aimed at counteracting HTLV-2 replication and spreading.


Effects of sorghum distillers dried grains with solubles on the carcass characteristics and muscle quality of China Micro Duck drakes aged from 4 to 8 weeks.
A study was conducted to determine the effects of feeding sorghum distiller's dried grains with solubles (SDDGS) on carcasses characteristics (live weight, whole net carcass rate, breast muscle percentage, thigh muscle percentage), muscle quality (meat color, shear stress, cooking loss rate, cooked meat percentage), and meat composition of China Micro Duck (CMD) drakes aged from 4 to 8 wk. A total of 240 CMD drakes (aged 4 wk and initial weight was 496.7 g) were randomly allotted to one of 4 dietary treatments in randomized complete block design. The 4 treatments were S0(the control group, S5, S10, S15, indicating the dietary content of SDDGS (zero, 5,10 and 15%, respectively). Each treatment with 60 drakes was equally divided into 6 repeated test groups, each group with 10 drakes. The results showed that S5, S10, and S15 could decrease the thigh muscle percentage linearly (P < 0.01); however, there was no significant (p > 0.05) effect on other carcass characteristic and muscle quality indexes of live body weight (BW), whole net carcass yield (WNCY), breast muscle percentage (BMP), breast muscle color (BMC), thigh muscle color (TMC), breast shear strength (BSS), cooking loss (CL), or cooked meat percentage (CMP). For meat composition, the increasing level of SDDGS caused a linear and quadratic decrease (P < 0.01) of crude protein and a linear and quadratic (P < 0.01) increase of crude fat of thigh and breast muscle, while breast muscle ash was not significantly affected (P > 0.05). Overall, this study revealed that in the 3 kinds of diets with SDDGS, S5 had the least negative impact on carcass characteristics, muscle quality, and meat composition.


Involvement of gshAB in the interspecies competition within oral biofilm.
Although Streptococcus sanguinis has been reported to produce H2O2 to gain a competitive edge over Streptococcus mutans, the molecular mechanisms evolved by S. mutans to counter this "peer stress" are still to be identified. The current study was designed to investigate the ecological role of glutathione synthetase (gshAB) in the interspecies interaction between S. mutans and S. sanguinis. A gshAB in-frame deletion strain of S. mutans was constructed, and its phenotypic traits were characterized. The spatio-temporal interaction of the gshAB mutant with S. sanguinis was further investigated in a dual-species biofilm model by fluorescence in situ hybridization. We found that, although less tolerant for H2O2, the gshAB mutant produced more extracellular polysaccharides by up-regulating gtfs expression, so as to cluster as condensed microcolonies. In addition, the mutant was more susceptible to the conditioned medium of S. sanguinis, and its competitiveness was significantly compromised. Taken together, we believe that gshAB is essential for the competitiveness and prevalence of S. mutans through detoxifying the H2O2 produced by S. sanguinis. Given the ecological importance of bacterial equilibrium within the oral biofilm, gshAB may represent a promising target to modulate the S. mutans/S. sanguinis ratio under cariogenic conditions, thus contributing to the management of dental caries.


Assessing diversity of diurnal lepidoptera in habitat fragments: testing the efficiency of strip transects.
Species richness is the most widely used measure of biodiversity, but the relationship between the observed and true numbers of species present in a study site is not always investigated. A field study at 27 habitat remnants was used to measure the effectiveness of a survey regimen for assessing species richness of butterflies and day-active moths in southwest Western Australia. Observed species richness was compared with known species richness and to statistical estimates of true species richness, and the bootstrap was found to be the best predictor of true richness. A regimen of 10-m-wide walk transects sampled on six occasions at 2-wk intervals during the austral spring (mid-September to mid-December) gave an almost complete inventory of resident species for each site (approximately 87% of the fauna detected), consistent with two previous studies that have assessed sample completeness in temperate areas. The abundance of diurnal lepidoptera showed large temporal variation over the flight season and varied to a lesser extent with time of day and temperature, but not with cloud cover or wind speed. Transect route and sampling frequency were the most important considerations in devising a survey regimen: transects placed off tracks detected both more species and more individuals per unit length. The fraction of the site area sampled was relatively unimportant, and even low sampling fractions of 1-2% may be adequate if the number and frequency of surveys is sufficient. The design of future surveys would be facilitated if sampling fraction was routinely reported and examined in relation to sample completeness.


Molecular characteristics of Kraft-AQ pulping lignin fractionated by sequential organic solvent extraction.
Kraft-AQ pulping lignin was sequentially fractionated by organic solvent extractions and the molecular properties of each fraction were characterized by chemical degradation, GPC, UV, FT-IR, (13)C-NMR and thermal analysis. The average molecular weight and polydispersity of each lignin fraction increased with its hydrogen-bonding capacity (Hildebrand solubility parameter). In addition, the ratio of the non-condensed guaiacyl/syringyl units and the content of β-O-4 linkages increased with the increment of the lignin fractions extracted successively with hexane, diethylether, methylene chloride, methanol, and dioxane. Furthermore, the presence of the condensation reaction products was contributed to the higher thermal stability of the larger molecules.


Characteristics And Outcomes Of Anaplastic Large Cell Lymphoma Patients-A Single Centre Experience.
Anaplastic large cell lymphoma (ALCL) is the second most common T cell lymphoma and 2% of all non-hodgkin lymphoma (NHL). It is an aggressive lymphoma with three subtypes, primary cutaneous ALCL, primary systemic ALK +ve ALCL and primary systemic ALK-ve ALCL depending upon rearrangement of Anaplastic Lymphoma Kinase (ALK) gene into ALK +ve and ALK -ve ALCL. Purpose of study is to determine the outcome of patients with ALCL treated at our institute. In this retrospective analysis, 49 patients with ALCL from 2000 to 2012 were included. Their base line IPI score, stage at presentation, bone marrow involvement, type of chemotherapy, ALK status, extra nodal sites and outcome were recorded. Median age was 34 years (range 20-72 years), with males' predominance, i.e., 75.5%. At presentation, 7 (14.3%), 12 (24.5%), 14 (28.6%) and 16 (32.7%) were in stage I-IV, respectively. According to IPI risk categorization, there were 27 (55.1%) in low risk, 12 (24.5%) in low intermediate risk, 8 (16.3%) in high intermediate risk and 2 (4%) in high risk. Seventeen patients (34.7%) were ALK +ve while 21 patients (43%) were ALK +ve and 11 patients (22.4%) had unknown status. Kaplan Meir overall survival (OS) at 5 years was 49.9%. Five-year OS in ALK +ve tumour was 67.4% compared to 39.7% in ALK -ve, p=0.05. Based on our study results, ALCL is common in males with a trend towards better outcome in Alk+ disease. The majority of patients are in advanced stage of disease at the time of presentation.


Spermidine cures yeast of prions.
Prions are self-perpetuating amyloid protein aggregates which underlie various neurodegenerative diseases in mammals. The molecular basis underlying their conversion from a normally soluble protein into the prion form remains largely unknown. Studies aimed at uncovering these mechanism(s) are therefore essential if we are to develop effective therapeutic strategies to counteract these disease-causing entities. Autophagy is a cellular degradation system which has predominantly been considered as a non-selective bulk degradation process which recycles macromolecules in response to starvation conditions. We now know that autophagy also serves as a protein quality control mechanism which selectively degrades protein aggregates and damaged organelles. These are commonly accumulated in various neurodegenerative disorders including prion diseases. In our recent study [Speldewinde et al. Mol. Biol. Cell. (2015)] we used the well-established yeast [PSI+]/Sup35 and [PIN¬+ ]/Rnq1 prion models to show that autophagy prevents sporadic prion formation. Importantly, we found that spermidine, a polyamine that has been used to increase autophagic flux, acts as a protective agent which prevents spontaneous prion formation.


Studying the Dynamics of Chromatin-Binding Proteins in Mammalian Cells Using Single-Molecule Localisation Microscopy.
Single-molecule localisation microscopy (SMLM) allows the super-resolved imaging of proteins within mammalian nuclei at spatial resolutions comparable to that of a nucleosome itself (~20 nm). The technique is therefore well suited to the study of chromatin structure. Fixed-cell SMLM has already allowed temporal 'snapshots' of how proteins are arranged on chromatin within mammalian nuclei. In this chapter, we focus on how recent developments, for example in selective plane illumination and protein labelling, have led to a range of live-cell SMLM studies. We describe how to carry out single-particle tracking (SPT) of single proteins and, by analysing their diffusion parameters, how to determine whether proteins interact with chromatin, diffuse freely or do both. We can study the numbers of proteins that interact with chromatin and also determine their residence time on chromatin. We can determine whether these proteins form functional clusters within the nucleus as well as whether they form specific nuclear structures.


Patients' attitudes to wearing of gloves by dentists in Nigeria.
To evaluate patient's attitudes to the use of gloves by dentists. This consisted of a four-item questionnaire administered to 445 consecutive patients attending our dental clinic. . Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife, Nigeria. Four hundred and forty five patients above the age of fifteen years attending the dental clinic for the first time. Majority of the patients were in the 20-30 year age group and over 93% had formal education. Most of the respondents (88.8%) stated that glove wearing was essential and over 63% considered that glove wearing protected both the operator and the patient. Whilst about one-third of respondents would attend for treatment when gloves were not worn, 81.3% felt that gloves should be changed after each patient. There were statistically significant differences (p<0.05) in responses in relation to age-groups and educational attainment, however no sex differences (p>0.05) were reported. This survey showed a high level of awareness by patients on the use of gloves by dentists. It also found that age-groups and levels of educational attainment influenced patients attitude to glove use.


Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection.
This study aimed to evaluate the diagnostic utilities of monocyte HLA-DR as an infection marker in the identification of early-onset clinical infection and pneumonia in newborn infants. Term newborns in whom infection was suspected when they were <72 h of age were eligible for enrollment in the study. C-reactive protein (CRP), monocyte HLA-DR and neutrophil CD64 expressions were quantitatively measured at the time of sepsis evaluation (0 h) and 24 h afterwards by flow cytometry and standard laboratory method. A total of 288 infants with suspected sepsis were investigated, and 93 were found to be clinically infected. There were no significant differences in monocyte HLA-DR expression between the infected, non-infected and control groups at 0 h (median (interquartile range): 13,986 (10,994-18,544), 14,234 (12,045-17,474) and 18,441 (14,250-21,537) antibody phycoerythrin (PE) molecules bound/cell), and between infected and non-infected infants at 24 h (median (interquartile range): 17,772 (12,933-25,167) and 19,406 (14,885-24,225) antibody PE molecules bound/cell). The areas under the receiver operating characteristics (ROC) curves for HLA-DR, CD64 and CRP were 0.52-0.54, 0.88-0.94 and 0.75-0.77, respectively. We were unable to determine an optimal cutoff value for HLA-DR, as the diagnostic utilities of any cutoff point on the ROC curves were unable to satisfy the criteria (i.e. sensitivity and specificity >or=80%) for consideration as an useful diagnostic marker of infection. Our findings did not support the use of monocyte HLA-DR alone or in combination with other infection markers in the diagnosis of early-onset clinical infection and pneumonia in term newborns.


Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy.
Molecules that induce ribosomal read-through of nonsense mutations in mRNA and allow production of a full-length functional protein hold great therapeutic potential for the treatment of many genetic disorders. Two such read-through compounds, RTC13 and RTC14, were recently identified by a luciferase-independent high-throughput screening assay and were shown to have potential therapeutic functions in the treatment of nonsense mutations in the ATM and the dystrophin genes. We have now tested the ability of RTC13 and RTC14 to restore dystrophin expression into skeletal muscles of the mdx mouse model for Duchenne muscular dystrophy (DMD). Direct intramuscular injection of compound RTC14 did not result in significant read-through activity in vivo and demonstrated the levels of dystrophin protein similar to those detected using gentamicin. In contrast, significant higher amounts of dystrophin were detected after intramuscular injection of RTC13. When administered systemically, RTC13 was shown to partially restore dystrophin protein in different muscle groups, including diaphragm and heart, and improved muscle function. An increase in muscle strength was detected in all treated animals and was accompanied by a significant decrease in creatine kinase levels. These studies establish the therapeutic potential of RTC13 in vivo and advance this newly identified compound into preclinical application for DMD.


Carbonic Anhydrases and Metabolism.
Although the role of carbonic anhydrases (CAs, EC 126.96.36.199) in metabolism is well-established, pharmacological applications of this phenomenon started to be considered only recently. In organisms all over the phylogenetic tree, the seven CA genetic families known to date are involved in biosynthetic processes and pH modulation, which may influence metabolism in multiple ways, with both processes being amenable to pharmacologic intervention. CA inhibitors possess antiobesity action directly by inhibiting lipogenesis, whereas the hypoxic tumor metabolism is highly controlled by the transmembrane isoforms CA IX and XII, which contribute to the acidic extracellular environment of tumors and supply bicarbonate for their high proliferation rates. Many of the articles from this special issue deal with the role of cancer CAs in tumor metabolism and how these phenomena can be used for designing innovative antitumor therapies/imaging agents. The metabolic roles of CAs in bacteria and algae are also discussed.


Inducible general knockout of Runx3 profoundly reduces pulmonary cytotoxic CD8+ T cells with minimal effect on outcomes in mice following influenza infection.
Respiratory viruses pose a continuing and substantive threat to human health globally. Host innate and adaptive immune responses are the critical antiviral defense mechanisms to control viral replication and spread. The present study is designed to determine the role of transcription factor Runx3 in the host immune response to influenza A virus (IAV) infection. As Runx3 is required for embryonic development, we generated an inducible Runx3 global knockout (KO) mouse model and found that Runx3 KO in adult C57BL/6 mice minimally affected thymic function under normal conditions and survival was at least 250 days post Runx3 deletion. We applied the mouse model to IAV infection and found that Runx3 KO resulted in a huge reduction (>85%) in numbers of total and antigen-specific pulmonary CD8+ cytotoxic T cells during IAV infection, while it had a minor effect on pulmonary generation of CD4+ T cells. To our surprise, this general KO of Runx3 did not significantly alter viral clearance and animal survival following IAV infection. Interestingly, we found that Runx3 KO significantly increased the numbers of pulmonary innate immune cells such as macrophages and neutrophils and the production of pro-inflammatory cytokines during IAV infection. We further found that Runx3 was strongly detected in CCR2+ immune cells in IAV-infected mouse lungs and was induced in activated macrophages and dendritic cells (DCs). As pulmonary CD8+ cytotoxic T cells play a central role in the clearance of IAV, our findings suggest that Runx3 KO may enhance host innate immunity to compensate for the loss of pulmonary CD8+ cytotoxic T cells during IAV infection.


Contribution to the Chromatic Characterization of Unifloral Honeys from Galicia (NW Spain).
Honey color and other physicochemical characteristics depend mainly on the botanical and geographical origin. The study of these properties could make easier a correct classification of unifloral honey. This work determined the palynological characteristics and some physicochemical properties such as pH, electrical conductivity, and color (Pfund scale and the CIELa*b* coordinates), as well as the total content of the bioactive compounds phenols and flavonoids of ninety-three honey samples. Samples were classified as chestnut, blackberry, heather, eucalyptus, and honeydew honey. The study showed a close relationship between the physicochemical variables and the botanical origin. The five types of honey presented different physicochemical properties among them. A principal component analysis showed that Hue, lightness, b*, and Chroma variables were important for the honey types classification, followed by Erica pollen, pH, Cytisus, and Castanea variables. A forward stepwise regression analysis was performed introducing as dependent variables the color (mm Pfund) and the Chroma and the Hue variables. The regression models obtained explained 86%, 74%, and 86% of the variance of the data, respectively. The combination of the chromatic and physicochemical and pollen variables through the use of multivariable methods was optimal to characterize and group the honey samples studied.


Reducing STAT Portable Chest Radiograph Turnaround Times: A Pilot Study.
Our health system orders a high number of STAT priority portable chest radiographs (62%) compared to Routine (35%) and Today (3%). Retrospective chart review of 1000 chest radiographs ordered with the STAT priority revealed that 38% of studies did not indicate clinical urgency. Given the high number or STAT priority portable chest radiographs ordered, prioritizing acquisition and interpretation of true STATs has become challenging for technologists and radiologists, leading to process inefficiencies, long turnaround times (TATs), communication failures, and patient-safety errors. A multidisciplinary team analyzed the current pathway for exam order to finalized report, identified failure modes of imaging order to completion process, and developed guidelines for what constitutes a true STAT examination. A new "urgent" order category meeting the definition of true STAT was designed, tested, and implemented over a 9-month period in participating intensive care units RESULTS: Since study implementation, 108 "urgent" examinations were ordered. Median TAT for a STAT examination from order entry to image acquisition dropped from 70 minutes preimplementation to 16 minutes for "urgent" examinations. Median TAT for exam completion to radiologist image interpretation dropped from 520 minutes preimplementation to 14 minutes for "urgent" examinations. Since implementation, "urgent" examinations were found to be more concordant (70%) with the status of a critically ill patient than STAT examinations (62%). The complexity of large multispecialty medical centers and lack of direct interaction of the radiologist with clinicians has led to underappreciation of the needs of ordering providers by radiology, and elucidated system limitations of radiology by ordering providers. By involving a team of frontline clinicians, our team standardized the process of identifying, ordering, procuring, interpreting, and communicating results of true STAT examinations. The process created by our team now serves as a template for implementation in other locations and service lines of our hospital.


Genetically determined antigens of squirrel monkey (Saimiri sciureus) IgG.
Alloantigens of squirrel monkey (Saimiri sciureus) IgG were studied using alloantisera prepared by cross-immunizations among four subspecies. The results demonstrated the occurrence of IgG antigenic polymorphism. Three distinct Fd fragment allotypes were detected. Greater alloantigenic complexity occurred among Colombian and Peruvian squirrel monkeys, which occupy the more central regions of the geographic range; Bolivian and Guyanan monkeys, which occupy the extremes of the range, expressed less alloantigenic complexity.


Calcium pyruvate in the attenuation of the water deficit on the agro-industrial quality of ratoon sugarcane.
Sugarcane is one of the largest agricultural commodities when considering the export volume and the number of jobs generated. Sugarcane production in the Brazilian Northeast region is generally low due to several factors, including the irregular rainfall distribution, which highlights the importance of studies aimed at mitigating the deleterious effects of water stress. In this scenario, this study aimed to evaluate calcium pyruvate as a water deficit attenuator on the agro-industrial quality of sugarcane in the second cycle of cultivation. The experiment was conducted out under greenhouse conditions of the Federal University of Campina Grande, where five sugarcane commercial genotypes tested (G1- RB863129, G2- RB92579, G3- RB962962, G4- RB021754, and G5- RB041443) and three irrigation management strategies (E1- full irrigation, E2- water deficit with application of 30 mM of calcium pyruvate, and E3- water deficit without calcium pyruvate application), distributed in randomized blocks in 5 × 3 factorial arrangement with three replications. The RB021754 genotype under water deficit and without foliar application of calcium pyruvate increased the fiber content (13.2%) and the sugarcane moist cake weight (143.5 g). The effects of water deficit in sugarcane genotypes are attenuated by the exogenous application of 30 mM of calcium pyruvate, with benefits on the polarized sucrose content, apparent sucrose content of the juice, soluble solids content, purity, corrected cane POL, total recoverable sugars, and stem mass in relation to plants under water deficit without calcium pyruvate application.


Serum levels of endocan correlate with the presence and severity of pre-eclampsia.
Endocan, a cysteine-rich dermatan sulfate proteoglycan expressed by endothelial cells, is seemed to be a new biomarker for endothelial dysfunction. Pre-eclampsia (PE) is characterized by the new onset of hypertension, proteinuria after 20 weeks of gestation, placental vascular remodeling, systemic vascular inflammation and endothelial dysfunction. The aim of this study was to investigate the relationship of PE and its severity with serum endocan levels. A cross-sectional study was performed. Serum was collected from women with PE and normotensive controls. Serum endocan and tumor necrosis factor alpha (TNF-α) concentrations were measured by a specific enzyme linked immunosorbent assay. Patients with PE had significantly higher median (interquartile range) endocan and mean TNF-α concentrations than controls [20.04 (12.26) ng/mL vs 15.55 (6.19) ng/mL, p < 0.001 for endocan; 26.49 ± 12.14 pg/mL vs 14.62 ± 5.61 pg/mL, p < 0.001 for TNF-α; respectively]. Serum endocan concentrations were positively correlated with systolic blood pressure (r = 0.618, p < 0.001), diastolic blood pressure (r = 0.608, p < 0.001), the amount of 24-h proteinuria (r = 0.786, p < 0.001) and TNF-α (r = 0.474, p < 0.001) in women with PE. In subgroup analysis, patients with severe PE had significantly higher endocan concentrations than those with mild PE. Receiver operating characteristic analysis of endocan was used to identify the patients with PE and also discriminating between mild and severe PE. Serum endocan concentrations were significantly elevated in women with PE versus normotensive controls, and concentrations seem to be associated with the severity of the disease.


Air-trapping zone surrounding sclerosing hemangioma of the lung.
We present two cases of sclerosing hemangioma of the lung with a peculiar radiologic finding: an air-trapping zone surrounding the tumor. On microscopic examinations, the tumor was of the hemangiomatous subtype, and the radiolucent zone corresponded to enlarged alveoli with septal destruction. A possible mechanism in the production of an air-trapping zone around a sclerosing hemangioma is bleeding from the highly vascular tumor followed by expectoration in communication with an airway. We reviewed the literature on the air meniscus sign in sclerosing hemangioma and concluded that although it is not a common finding, it could be of help in the confident diagnosis of sclerosing hemangioma and in differentiating it from other benign tumors of the lung.


Protein stability imposes limits on organism complexity and speed of molecular evolution.
Classical population genetics a priori assigns fitness to alleles without considering molecular or functional properties of proteins that these alleles encode. Here we study population dynamics in a model where fitness can be inferred from physical properties of proteins under a physiological assumption that loss of stability of any protein encoded by an essential gene confers a lethal phenotype. Accumulation of mutations in organisms containing Gamma genes can then be represented as diffusion within the Gamma-dimensional hypercube with adsorbing boundaries determined, in each dimension, by loss of a protein's stability and, at higher stability, by lack of protein sequences. Solving the diffusion equation whose parameters are derived from the data on point mutations in proteins, we determine a universal distribution of protein stabilities, in agreement with existing data. The theory provides a fundamental relation between mutation rate, maximal genome size, and thermodynamic response of proteins to point mutations. It establishes a universal speed limit on rate of molecular evolution by predicting that populations go extinct (via lethal mutagenesis) when mutation rate exceeds approximately six mutations per essential part of genome per replication for mesophilic organisms and one to two mutations per genome per replication for thermophilic ones. Several RNA viruses function close to the evolutionary speed limit, whereas error correction mechanisms used by DNA viruses and nonmutant strains of bacteria featuring various genome lengths and mutation rates have brought these organisms universally approximately 1,000-fold below the natural speed limit.


A clinical update on the significance of the gut microbiota in systemic autoimmunity.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease where a loss of tolerance to nuclear antigens leads to inflammation in multiple organ systems. The cause of SLE remains ill defined, although it is known that a complex interplay between genes and environment is necessary for disease development. In recent years, case studies have reported that the incidence of SLE in the USA, for example, has increased by approximately 3 fold. Although the reason for this is likely to be multifactorial, it has been hypothesized that the increasing incidence of autoimmune disease is due to considerable shifts in the bacterial communities resident the gut, collectively known as the gut microbiota, following a change in diet and the widespread introduction of antibiotics. Furthermore, a growing body of evidence suggests that the gut microbiota plays a role in the development of a range of autoimmune diseases including inflammatory bowel disease, multiple sclerosis, type one diabetes and rheumatoid arthritis. In this review, we summarize how advances in DNA-based sequencing technologies have been critical in providing baseline information concerning the gut microbiota in health and how variation amongst individuals in controlled by multiples factors including age, genetics, environment and the diet. We also discuss the importance of the gut microbiota in the development of a healthy immune system and how changes in particular bacterial phyla have been associated with immune abnormalities in animal models of autoimmune disease. Finally, in order to place the data in a clinical context, we highlight recent findings showing that abnormalities in the gut microbiota can be detected in patients with SLE, which provides the rationale for greater investigation into whether microbiota-targeted therapies could be used for the treatment/prevention of disease.


Geobacillus icigianus sp. nov., a thermophilic bacterium isolated from a hot spring.
A Gram-reaction-positive, motile, thermophilic spore-forming strain, G1w1(T), was isolated from a hot spring of the Valley of Geysers, Kamchatka (Russia). Based on data from the present polyphasic taxonomic study, including phylogenetic analysis of 16S rRNA and spo0A gene sequences, the strain is considered to represent a novel species of the genus Geobacillus, for which the name Geobacillus icigianus sp. nov. is proposed. The type strain is G1w1(T) ( = VKM B-2853(T) = DSM 28325(T)).