Sleep disorder status of nurses in general hospitals and its influencing factors.
This study aimed to evaluate the current sleep disorder status of nurses in general hospitals and analyze its influencing factors. A total of 2,033 nurses who have worked for 6 months in 3 general hospitals, namely, The First Affiliated Hospital of Harbin Medical University, The Second Affiliated Hospital of Harbin Medical University, and The Third Affiliated Hospital of Harbin Medical University, were selected by random sampling from April 2015 to November 2015 and investigated. The Effort-Reward Imbalance Questionnaire (ERI) and Job Content Questionnaire (JCQ) were applied to evaluate occupational stress. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep disorder status of the research subjects. Logistic regression analysis was adopted to determine the influencing factors of nurses' sleep disorders. The average PSQI score of 2,003 research subjects is 7.26±3.56, including 860 subjects with PSQI ≥8, accounting for 42.9%. The female research subjects in the department of gynecology and obstetrics, emergency department, and ICU show high risks of sleep disorders (i.e., many years of working; job title: registered nurse; many times of night shift per month; no frequent exercise; many efforts and few rewards; high decision-making autonomy). Educational background and marital status did not exhibit statistical relevance with sleep disorders. The sleep disorder status of nurses in general hospitals is closely related to occupational stress. As such, nurse managers should focus more attention to the influencing factors of nurses' sleep disorders and relieve their occupational stress to reduce the occurrence rate of sleep disorders.


Influence of silver nanoparticle solution on the mechanical properties of resin cements and intrarradicular dentin.
This study evaluated the influence of silver nanoparticle on mechanical properties of the components of underlying dentin and resin cement in different regions of intraradicular dentin. Ninety extracted single-rooted human teeth were used in this study. After endodontic preparation, the teeth were divided into five groups, according to the irrigating agents: distilled water, 5.25% sodium hypochlorite, 25% polyacrylic acid, 2% chlorhexidine and 23 ppm silver nanoparticles dispersion. Then, the groups were divided in 3 subgroups (n = 6) according to the technique adopted for adhesive cementation: SUA group: Scotchbond Universal Adhesive + RelyX ARC; U200 group: RelyX U200; and MCE group: MaxCem Elite. The mechanical properties of hardness and elastic modulus were measured in resin cement and underlying dentin in ultra-micro hardness tester in different thirds of radicular dentin surface. Data were subjected to ANOVA and Fisher's test (p = 0.05). In the underlying dentin, in general, there was no statistically significant difference in different thirds of intraradicular dentin according to the different solutions used. In the resin cements, higher hardness values were found, in general, for the cervical third. When silver nanoparticle solution was used, higher mechanical properties were generally obtained for resin cement for the SBU and U200 groups, with little or no changes in mechanical properties for the dentin. Silver nanoparticle application is a viable option for irrigation the intraradicular dentin previously through the cementation process of glass fiber posts. The mechanical properties are influenced by irrigant solutions used and the depth intraradical analyzed area.


Ossicular chain lesions in cholesteatoma.
The aim of the study was to describe ossicle resorption in chronic otitis with cholesteatoma and correlate it with clinical parameters such as age, contralateral ear condition, tympanic membrane aspect, cholesteatoma pathogenesis and extension, associated lesions and hearing threshold. Preoperative clinical data were collected for 140 patients with chronic otitis with cholesteatoma, whose ossicles were evaluated during surgery. 82% of patients showed ossicle resorption, with incus damage in 78% of cases. Multiple involvement was found in 45% of cases and the incus-stapes association was the most frequent. In 13 patients (11%) with ossicle damage, the ossicular chain was in continuity with a hearing threshold similar to patients without ossicular resorption. Ossicles were always damaged in congenital cholesteatoma and in case of associated lesions. Cholesteatoma extension was related to the incidence of ossicle resorption (p < 0.0001). Air and bone conduction worsened as the number of involved ossicles increased, while the air-bone gap remained stable. In conclusion, the origin and location of cholesteatoma are related to the site of ossicular damage, which is subsequent to the contact between bone and cholesteatoma. Pure-tone audiometry and air-bone gap do not reflect actual ossicular chain status. None of the other preoperative clinical parameters considered were reliable predictors of the condition of the ossicular chain.


Figures of merit for the determination of the polymorphic purity of carbamazepine by infrared spectroscopy and multivariate calibration.
Polymorphism is an important property in the quality control of pharmaceutical products. In this regard, partial least squares regression and the net analytical signal were used to build and validate a multivariate calibration model using diffuse reflectance infrared spectroscopy in the region of 900-1100 cm(-1) for the determination of the polymorphic purity of carbamazepine. Physical mixtures of the polymorphs were made by weight, from 80 to 100% (w/w) form III mixed with form I. Figures of merit, such as sensitivity, analytical sensitivity, selectivity, confidence limits, precision (mean, repeatability, intermediate), accuracy, and signal-to-noise ratio were calculated. Feasible results were obtained with maximum absolute error of 2% and an average error of 0.53%, indicating that the proposed methodology can be used by the pharmaceutical industry as an alternative to the X-ray diffraction (United States Pharmacopoeiamethod).


Construction of an allogenic chimeric mouse model for the study of the behaviors of donor stem cells in vivo.
It is essential to establish an animal model for the elucidation of the biological behaviors of stem cells in vivo. We constructed a chimeric animal model by in utero transplantation for investigation of stem cell transplantation. This chimerism was achieved by injecting the stem cells derived from the bone marrow of green fluorescence protein (GFP)-transgenic mice into fetal mice at 13.5 days of gestation. Several methods such as polymerase chain reaction (PCR), real-time PCR, fluorescence-assisted cell sorting (FACS) and fluorescence in situ hybridization (FISH) were used for the observation of donor cells. Under a fluorescence microscope, we observed the GFP cells of donor-origin in a recipient. PCR, FACS analysis and FISH indicated chimerism at various intervals. Real-time PCR indicated that some donor cells existed in chimera for more than 6 months. Allogenic stem cells may exist in recipients for a long time and this allogenic animal model provides a useful tool for studying the behavior of hematopoietic stem cells and also offers an effective model system for the study of stem cells.


Aspiration cytology of elastofibroma dorsi: case report with ultrastructural and immunohistochemical findings.
Elastofibroma is a well-recognized tumor-like process which typically occurs in the soft tissue of the shoulder. Although fine-needle aspiration (FNA) represents a quick and simple method for definitive diagnosis, the possibility of a false-negative diagnosis is high due to the hypocellularity of the smears. However, a high index of suspicion based on the clinical presentation of a firm mass in a typical location in an elderly person, usually female, aids in the diagnosis. We describe the FNA findings of elastofibroma dorsi in an 89-yr-old woman which, although hypocellular, contained diagnostic aggregates of petaloid globules within a collagenous matrix. The cytologic material showed a green-yellow autofluorescence of the altered elastic fibers with ultraviolet light. Transmission electron microscopy revealed an elongated beaded appearance with small electron densities and obliteration of the central elastin core. The presence of a hypocellular aspirate with autofluorescent elastic fibers should suggest the possibility of elastofibroma dorsi.


Evaluating distant metastases in breast cancer: from biology to outcomes.
There is an urgent need to understand distant metastases in breast cancer as they are the most lethal form of recurrence and a major cause of mortality in patients. Some predictors for distant metastases, including nodal status, tumor grade, and hormonal status, are useful in identifying patients at increased risk for distant metastases. Adjuvant endocrine therapy has been the treatment of choice for postmenopausal women with hormone-sensitive breast cancer, and some therapies have shown significant reductions in the risk of distant metastases. Skeletal metastases in breast cancer are treated with bisphosphonates with a certain level of success. With more new agents undergoing clinical trials, a thorough review of the specific and long-term safety of these agents is essential, as is a better understanding of the deterioration in the quality of life and cost concerns of patients who develop distant metastases. Gene-expression profiling is a new entrant in the field of distant metastases diagnosis, which is largely successful in defining gene signatures that predict the development of distant metastases. This review will discuss the biology and the impact of distant metastases on outcomes for patients with breast cancer; it also encompasses the current status, emerging focus, and future perspectives in treatment of skeletal metastases in patients with breast cancer.


Accelerating Realtime TDDFT with Block-Orthogonalized Manby-Miller Embedding Theory.
Realtime time-dependent density-functional theory (RT-TDDFT) is one of the most practical techniques available to simulate electronic dynamics of molecules and materials. Promising applications of RT-TDDFT to study nonlinear spectra and energy transport demand simulations of large solvated systems over long time scales, which are computationally quite costly. In this paper, we apply an embedding technique developed for ground-state SCF methods by Manby and Miller to accelerate realtime TDDFT. We assess the accuracy and speed of these approximations by studying the absorption spectra of solvated and covalently split chromophores. Our embedding approach is also compared with less accurate, less costly QM/MM charge embeddings. We find that by mixing levels of detail the embedded mean-field theory scheme is a simple, accurate, and effective way to accelerate RT-TDDFT simulations.


Coherence resonance and polymodality in inhibitory coupled excitable oscillators.
We have analyzed the firing activity of two and three excitable FitzHugh-Nagumo oscillators, coupled via slow variable diffusion and under the action of an external noise. We find a different form of coherence resonance in this system, which is, in contrast to previous studies, intrinsically based on the antiphase behavior of coupled elements. Additionally, we show that an exchange, performed by this form of coupling, is remarkably rhythmogenic and results in polymodal interspike distributions without any external periodic stimuli. The dependence of these distributions on the noise amplitude and the coupling strength is studied.


Gastroesophageal reflux and respiratory phenomena in infants: status of the intraluminal impedance technique.
The coincidence of recurrent respiratory symptoms and gastroesophageal reflux (GER) is a well-known phenomenon in infants. Twenty-four-hour pH metry is the presumed gold standard of diagnostic tools for this symptom complex, but with this method, only acid (pH <4) and alkaline (pH >7) GER can be detected. Gastroesophageal reflux with an esophageal pH in the physiological range (pH 5-6.8) may represent many cases of clinically relevant GER unrecognized by pH metry. In this study the intraluminal multiple electrical impedance (IMP) procedure for complete registration of GER was compared with pH metry for its diagnostic value in the presence of respiratory symptoms. Twenty-two infants with recurrent regurgitation or pulmonary problems were investigated simultaneously with IMP, pH metry, and polygraphy during two feeding periods. Heart rate, oxygen saturation, sleep states, and oronasal flow were recorded, among other parameters. Three hundred sixty-four occurrences of GER were detected by IMP; only 11.4% had a pH less than 4 and were therefore recognized by pH metry. Three hundred twelve (84.8%) occurrences were associated with breathing abnormalities, and 11.9% of these were detected by pH metry. Nineteen instances were accompanied by a decrease of oxygen saturation of more than 10% of the initial value. Only three (15.8%) of these had a pH less than 4. The remaining 16 reflux episodes were recognized by IMP only. After software-aided preselection, 165 instances of apnea were visually validated, 49 of which were accompanied by GER. Thirty-eight (77.6%) of these were exclusively recorded by IMP. The use of pH metry alone cannot detect most GER incidents accompanied by respiratory symptoms and therefore does not appear to be suitable for this approach. The pH-independent IMP technique promises to be a reliable tool for presumably GER-associated respiratory symptoms.


The relationship of underage drinking laws to reductions in drinking drivers in fatal crashes in the United States.
This study reports on an effort to evaluate and interrelate the existence and strength of two core laws and 14 expanded laws designed to (a) control the sales of alcohol, (b) prevent possession and consumption of alcohol, and (c) prevent alcohol impaired driving by youth aged 20 and younger. Our first analysis determined if the enactment of the possession and purchase laws (the two core minimum legal drinking age laws) was associated with a reduction in the ratio of drinking to nondrinking drivers aged 20 and younger who were involved in fatal crashes controlling for as many variables as possible. The ANOVA results suggest that in the presence of numerous covariates, the possession and purchase laws account for an 11.2% (p=0.041) reduction in the ratio measure. Our second analysis determined whether the existence and strength of any of the 16 underage drinking laws was associated with a reduction in the percentage of drivers aged 20 and younger involved in fatal crashes who were drinking. In the regression analyses, making it illegal to use a false identification to purchase alcohol was significant. From state to state, a unit difference (increase) in the strength of the False ID Use law was associated with a 7.3% smaller outcome measure (p=0.034).


A variant of the Escherichia coli anaerobic transcription factor FNR exhibiting diminished promoter activation function enhances ionizing radiation resistance.
We have previously generated four replicate populations of ionizing radiation (IR)-resistant Escherichia coli though directed evolution. Sequencing of isolates from these populations revealed that mutations affecting DNA repair (through DNA double-strand break repair and replication restart), ROS amelioration, and cell wall metabolism were prominent. Three mutations involved in DNA repair explained the IR resistance phenotype in one population, and similar DNA repair mutations were prominent in two others. The remaining population, IR-3-20, had no mutations in the key DNA repair proteins, suggesting that it had taken a different evolutionary path to IR resistance. Here, we present evidence that a variant of the anaerobic metabolism transcription factor FNR, unique to and isolated from population IR-3-20, plays a role in IR resistance. The F186I allele of FNR exhibits a diminished ability to activate transcription from FNR-activatable promoters, and furthermore reduces levels of intracellular ROS. The FNR F186I variant is apparently capable of enhancing resistance to IR under chronic irradiation conditions, but does not increase cell survival when exposed to acute irradiation. Our results underline the importance of dose rate on cell survival of IR exposure.


Silencing of carboxypeptidase E inhibits cell proliferation, tumorigenicity, and metastasis of osteosarcoma cells.
Carboxypeptidase E (CPE), a prohormone processing enzyme, has been implicated in the progression of multiple malignancies. However, the biological role and molecular mechanisms of CPE in osteosarcoma remain elusive. In this study, we assessed the effects of CPE on cell proliferation, tumorigenicity, migration, and invasion in osteosarcoma. Our results showed that silencing of CPE significantly inhibited cell proliferation, caused cell cycle arrest at G0/G1 phase, decreased the expression levels of cell cycle protein, cyclin D1, and inhibited tumorigenicity in vivo. Additionally, CPE downregulation repressed the migratory and invasive capacities of osteosarcoma cells in vitro. Furthermore, overexpression of CPE-ΔN (a splice variant of CPE) enhanced the cell growth, migration, and invasion of osteosarcoma cells. It is possible that both CPE forms are involved in the tumorigenesis and development of osteosarcoma, and therefore CPE may provide a promising biological target for osteosarcoma therapy.


Patellofemoral Stabilization: Postoperative Redislocation and Risk Factors Following Surgery.
Patellofemoral instability is a common knee problem that is difficult to manage owing to its multifactorial etiology as well as the fact that predisposing pathoanatomic features vary from individual to individual. There is limited knowledge regarding the demographic and pathoanatomic risk factors or the relationship between these risk factors and the redislocation rate after surgical stabilization for this challenging condition. To analyze the postoperative redislocation rates and the prevalence of demographic and pathoanatomic risk factors for patients undergoing a patellofemoral stabilization. Case series; Level of evidence, 4. Patients with symptomatic recurrent patellofemoral instability underwent a soft tissue patellofemoral stabilization procedure. A total of 342 patellofemoral stabilization procedures (reconstruction, n = 256; imbrication, n = 86) were assessed at a mean follow-up of 24.3 months. Concomitant procedures were performed in accordance with the à la carte concept of addressing significant anatomic or biomechanical characteristics. Two surgical cohorts were analyzed separately for reconstruction or imbrication to address laxity of the medial patellofemoral ligament (MPFL). Failure of the patellofemoral stabilization procedure was defined as postoperative redislocation of the patella. Prevalence of demographic and pathoanatomic risk factors was determined for all patients. Disease-specific patient-reported outcomes were assessed with the Banff Patella Instability Instrument (BPII). A redislocation rate of 5.1% was identified for MPFL reconstruction and 20.9% for MPFL imbrication. For both MPFL procedures, age at time of surgery was significantly younger for the failed group as compared with the intact group. Postoperative BPII scores were significantly lower for patients who subsequently experienced a surgical failure as compared with intact surgery for both MPFL reconstruction (P = .048) and MPFL imbrication (P = .003). Patellofemoral stabilization with an à la carte approach to surgical selection demonstrated a low postoperative redislocation rate and good clinical results. Younger age at time of surgery was associated with surgical failure. This information may be used to guide surgical decision making and patient education.


Electromechanical response of articular cartilage in indentation--considerations on the determination of cartilage properties during arthroscopy.
A finite element formulation of streaming potentials in articular cartilage was incorporated into a fibril-reinforced model using the commercial software ABAQUS. This model was subsequently used to simulate interactions between an arthroscopic probe and articular cartilage in a knee joint. Fibril reinforcement was found to account for large fluid pressure at considerable strain rates, as has been observed in un-confined compression. Furthermore, specific electromechanical responses were associated with specific changes in tissue properties that occur with cartilage degeneration. For example, the strong strain-rate dependence of the load response was only observed when the collagen network was intact. Therefore, it is possible to use data measured during arthroscopy to evaluate the degree of cartilage degeneration and the source causing changed properties. However, practical problems, such as the difficulty of controlling the speed of the hand-held probe, may greatly reduce the reliability of such evaluations. The fibril-reinforced electromechanical model revealed that high-speed transient responses were associated with the collagen network, and equilibrium response was primarily determined by proteoglycan matrix. The results presented here may be useful in the application of arthroscopic tools for evaluating cartilage degeneration, for the proper interpretation of data, and for the optimization of data collection during arthroscopy.


Kinetic Spinodal Instabilities in the Mott Transition in V_{2}O_{3}: Evidence from Hysteresis Scaling and Dissipative Phase Ordering.
We present the first systematic observation of scaling of thermal hysteresis with the temperature scanning rate around an abrupt thermodynamic transition in correlated electron systems. We show that the depth of supercooling and superheating in vanadium sesquioxide (V_{2}O_{3}) shifts with the temperature quench rates. The dynamic scaling exponent is close to the mean field prediction of 2/3. These observations, combined with the purely dissipative continuous ordering seen in "quench-and-hold" experiments, indicate departures from classical nucleation theory toward a barrier-free phase ordering associated with critical dynamics. Observation of critical-like features and scaling in a thermally induced abrupt phase transition suggests that the presence of a spinodal-like instability is not just an artifact of the mean field theories but can also exist in the transformation kinetics of real systems, surviving fluctuations.


Fundamentals of calcium channel blockers.
The important role calcium ions play in cellular function and specifically in muscular contraction has been well established. The details of the calcium migration into the cell and its specific mechanism of action however have only recently been elucidated. Still, our current understanding of these issues represents only a tip of the iceberg. The introduction of the calcium channel blockers have heralded to some extent a new revolution in the management of many cellular disfunctions (disease states) which are, in part, related to and are dependent on the migration of calcium ions across the cell membrane. In this article, an overview of the current understanding of the role of calcium ions in cellular function with special attention to the cardiovascular system is presented. In addition, the mechanism of action of the calcium channel blockers is discussed. Finally, the usefulness of these agents in clinical medicine is mentioned, and a review of several major studies demonstrating beneficial effects of calcium channel blockers in various disorders is presented.


Sex difference in norepinephrine surge in response to psychological stress through nitric oxide in rats.
Psychological stress elevates blood pressure through sympathetic nerve activation. This pressor response is supposedly associated with cardiovascular events. We investigated a sex difference in the pressor response and norepinephrine surge to cage-switch stress in rats. Wistar male and female rats were catheterized for blood pressure monitoring and blood sampling. Six days post-surgery, the rats were exposed to the cage-switch stress and blood samples were collected at rest and 30 min after the start of the stress. The stress-induced pressor response was greater in the male than in the female rats. The stress significantly increased the norepinephrine level in the male, but not in the female rats. Pre-treatment with N(G)-nitro-l-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, attenuated the norepinephrine response significantly in the male rats. There was no sex difference in the endothelial NO synthase expression in the gastrocnemius muscle. However the phosphorylation at serine 1177, a marker for eNOS activation, was higher in the male than in the female rats. These results suggest that NO is involved in the norepinephrine surge to psychological stress in the male rats, but not in the female rats. This is the first report on a sex difference in the norepinephrine surge in response to psychological stress through NO, in association with pressor response.


The prognostic risk stratification model for metastatic small-cell lung cancer: An analysis of the SEER database.
Distant metastases of small-cell lung cancer (DM-SCLC) is an important factor in the selection of treatment strategies. In this study, we established a nomogram to predict DM-SCLC and determine the benefit of radiotherapy (RT) for DM-SCLC. We analyzed DM-SCLC prognosis based on surveillance, epidemiology, and end result database (SEER) data. A comprehensive and practical nomogram that predicts the overall survival (OS) of DM-SCLC was constructed and the results were compared with the 7th edition of the American Joint Committee on Cancer (AJCC) TNM stage system. A concordance index (C-index) and receiver operating characteristic plot were generated to evaluate the nomogram discrimination. The calibration was evaluated with a calibration plot, and its effectiveness was evaluated by a decision curve analysis (DCA). A score was assigned to each variable, and a total score was established for the risk stratification model. A total of 13,403 DM-SCLC patients were included. Eight characteristic variables were identified as independent prognostic variables. The C-index of the validation and training cohorts was 0.716 and 0.734, respectively. The area under the receiver operating characteristic curve (AUC) values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, 3-year survival rates showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, 3-year DCA compared with the AJCC stage system. A predictive nomogram and risk stratification model have been constructed to evaluate the prognosis of DM-SCLC effectively and accurately. This nomogram may provide a reference for prognosis stratification and treatment decisions.


Physiologically Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long-Acting Nanoformulations for HIV.
Antiretrovirals are currently used for the treatment and prevention of HIV infection. However, poor adherence and low tolerability of some existing oral formulations can hinder their efficacy. Long-acting (LA) injectable nanoformulations could help address these complications by simplifying antiretroviral administration. The aim of this study is to inform the optimisation of intramuscular LA formulations for eight antiretrovirals through physiologically based pharmacokinetic (PBPK) modelling. A whole-body PBPK model was constructed using mathematical descriptions of molecular, physiological and anatomical processes defining pharmacokinetics. These models were validated against available clinical data and subsequently used to predict the pharmacokinetics of injectable LA formulations The predictions suggest that monthly intramuscular injections are possible for dolutegravir, efavirenz, emtricitabine, raltegravir, rilpivirine and tenofovir provided that technological challenges to control their release rate can be addressed. These data may help inform the target product profiles for LA antiretroviral reformulation strategies.


Associations between practice patterns and dental education in special care dentistry.
The goal of this study is to determine whether alumni who completed training in the Center for Patients with Special Needs (CPSN) feel more prepared and treat more patients with special healthcare needs (SHCN) than alumni who completed training prior to the establishment of the Center (pre-CPSN). Alumni graduating in 2000-2017 from the University of Pittsburgh School of Dental Medicine (Pitt Dental Medicine) completed a survey addressing how well their dental school training prepared them to treat patients with SHCN and their current practice patterns as dental professionals. Alumni completed self-reported questionnaires online or on paper by mail. The authors obtained a 16% response rate (N = 209; nPre-CPSN = 75; nCPSN = 134). Compared with the pre-CPSN alumni, CPSN alumni reported feeling more prepared in all 12 skills surveyed (t = 4.86, P < 0.05). There was a 0.85-point difference between groups, on average, across the 12 skills. However, CPSN alumni were no more likely to treat individuals with SHCN than the pre-CPSN alumni. Information obtained from this survey supports the hypothesis that experience is associated with perceptions of preparedness and raises new questions about factors associated with deciding whether to treat or refer. This information may inform schools of the amount of training necessary to reach preparedness goals.


Application of random sample consensus method for parameter estimation of reflectometry density profile in toroidal plasma.
Microwave reflectometry diagnostics have been widely used to measure density profiles in fusion plasma. However, the high sensitivity of the diagnostics to plasma turbulence often results in large radial deviations in the edge density profile and causes difficulty in profile evaluation. To improve the performance of profile evaluation, a modified RANdom SAmple Consensus (RANSAC) method has been applied to fit the density profiles measured by reflectometry on the experimental advanced superconducting tokamak. Compared with the traditional least-squares method, the modified RANSAC method is much more efficient and robust in fitting the experimental profiles. Furthermore, a combination of RANSAC and a genetic algorithm (GA-RANSAC) is used to further optimize the profile evaluation procedure. The results show that this GA-RANSAC method yields better performance and stabler convergence than the modified RANSAC alone.


Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity.
A key issue in cancer biology is whether oncogenic transformation of different cell types of origin within an adult tissue gives rise to distinct tumour subtypes that differ in their prognosis and/or treatment response. We now show that initiation of prostate tumours in basal or luminal epithelial cells in mouse models results in tumours with distinct molecular signatures that are predictive of human patient outcomes. Furthermore, our analysis of untransformed basal cells reveals an unexpected assay dependence of their stem cell properties in sphere formation and transplantation assays versus genetic lineage tracing during prostate regeneration and adult tissue homeostasis. Although oncogenic transformation of basal cells gives rise to tumours with luminal phenotypes, cross-species bioinformatic analyses indicate that tumours of luminal origin are more aggressive than tumours of basal origin, and identify a molecular signature associated with patient outcome. Our results reveal the inherent plasticity of basal cells, and support a model in which different cells of origin generate distinct molecular subtypes of prostate cancer.


A systematic approach identifies p53-DREAM pathway target genes associated with blood or brain abnormalities.
p53 (encoded by Trp53) is a tumor suppressor, but mouse models have revealed that increased p53 activity may cause bone marrow failure, likely through dimerization partner, RB-like, E2F4/E2F5 and MuvB (DREAM) complex-mediated gene repression. Here, we designed a systematic approach to identify p53-DREAM pathway targets, the repression of which might contribute to abnormal hematopoiesis. We used Gene Ontology analysis to study transcriptomic changes associated with bone marrow cell differentiation, then chromatin immunoprecipitation-sequencing (ChIP-seq) data to identify DREAM-bound promoters. We next created positional frequency matrices to identify evolutionary conserved sequence elements potentially bound by DREAM. The same approach was developed to find p53-DREAM targets associated with brain abnormalities, also observed in mice with increased p53 activity. Putative DREAM-binding sites were found for 151 candidate target genes, of which 106 are mutated in a blood or brain genetic disorder. Twenty-one DREAM-binding sites were tested and found to impact gene expression in luciferase assays, to notably regulate genes mutated in dyskeratosis congenita (Rtel1), Fanconi anemia (Fanca), Diamond-Blackfan anemia (Tsr2), primary microcephaly [Casc5 (or Knl1), Ncaph and Wdr62] and pontocerebellar hypoplasia (Toe1). These results provide clues on the role of the p53-DREAM pathway in regulating hematopoiesis and brain development, with implications for tumorigenesis.


Comment on "Comment on 'Constant temperature molecular dynamics simulations by means of a stochastic collision model. II. The harmonic oscillator' [J. Chem. Phys. 104, 3732 (1996)]" [J. Chem. Phys. 106, 1646 (1997)].
An argument brought forward by Sholl and Fichthorn against the stochastic collision-based constant temperature algorithm for molecular dynamics simulations developed by Kast et al. is refuted. It is demonstrated that the large temperature fluctuations noted by Sholl and Fichthorn are due to improperly chosen initial conditions within their formulation of the algorithm. With the original form or by suitable initialization of their variant no deficient behavior is observed.


Ultraviolet-ultraviolet hole burning spectroscopy in a quadrupole ion trap: dibenzo[18]crown-6 complexes with alkali metal cations.
Conformation selective: A new technique of ultraviolet-ultraviolet hole burning spectroscopy that can be applied to ions stored in a quadrupole ion trap (QIT) is developed and used to obtain the conformation-selective electronic spectra of dibenzo[18]crown-6 complexes with alkali metal cations (M(+), see picture; F(+) = fragment).


Dapagliflozin in the treatment of heart failure with preserved ejection fraction.
We present obese patient with numerous comorbidities in this case report, who's treatment of heart failure with preserved ejection fraction (HF PEF) has been managed in our office for several years. The treatment was limited by the patient's comorbidities (renal failure, obesity, atrial fibrillation, anemia) and by the patient's preferences. The patient's trust and cooperation is essential, as this case report confirms. The patient paid for empagliflozin which he did not tolerate. The patient however was willing to try dapagliflozin at his own expense. Dapaglifllozin was well tolerated by the patient and improved his quality of life significantly. Intolerance of one drug does not necessarily mean intolerance of the whole class. Another member of the same drug class could be beneficial as shown by this case report.


WHEN DID EVE LIVE? AN EVOLUTIONARY DETECTIVE STORY.
Various estimates of the time at which the human mitochondrial Eve lived have ranged from as little as 60,000 yr to more than 500,000 yr ago. Because of this immense range, it is impossible to distinguish between single-origin and multiple-origins hypotheses for the evolution of our species. In an attempt to reduce the uncertainty, I have examined the largest available body of sequence information, comprising the mitochondrial control region, for clues to how the observed diversity arose. In this region it is possible to show, by examining the distribution of polymorphic sites, that transitions have occurred at some sites at a much higher rate than at others. Computer simulations can, when two rates for transitions are postulated, provide close approximations to the distribution of substitutions seen in the actual data. The "best fit" was obtained when the rate at ¾ of the sites was 4 times the transversion rate, and the rate at the remainder 160 times the transversion rate. The likelihood of such a high rate at some sites helps to explain why tree-building methods employing these data have provided so little phylogenetic information. Furthermore, it is possible to show that transversions do not appear to occur preferentially at these transition "hot-spot" sites and that such huge differences in substitution rates are not seen for transversions, suggesting that the rules governing the mutation and acceptance or rejection of transversions are different from those governing transitions. The great majority of transversions appear to occur at a low rate throughout the region. Thus, methods for determining the age of Eve that are based on recent divergence in human populations, or on applying a mutation probability matrix based on an assumption of uniform mutation rates, are likely to result in underestimates. The rate of accumulation of transversions is shown to be a more accurate estimator of the age of Eve. The conclusion is reached that Eve probably lived (depending on when the ancestors of humans and chimpanzees diverged) between 436,000 and 806,000 yr ago.


Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues.
Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and "liquid biopsies" for patients with CNS metastases.


ORIGIN OF PROTOTROPHIC VARIANTS IN MIXTURES OF AUXOTROPHIC MUTANTS OF SERRATIA MARCESCENS.
Dushman, Mariam B. (Massachusetts Institute of Technology, Cambridge). Origin of prototrophic variants in mixtures of auxotrophic mutants of Serratia marcescens. J. Bacteriol. 86:1173-1181. 1963.-The mechanism whereby mixed cultures of Serratia marcescens auxotrophs gave rise to prototrophs was shown not to be a genetic exchange by mating, since cell-to-cell contact was not required for the formation of new types. New types arose when the two "parental" strains were not mixed; they were kept separate by means of a Millipore membrane filter. In mixed cultures on media selective for new cell types, these new types arose as a result of reversions in one strain, the apparent recipient, during residual growth promoted by materials excreted by the other strain, the apparent donor or "feeder." Strains bearing one reverting and one nonreverting marker gave rise only to those types that could be accounted for by reversion. Ultraviolet irradiation of the feeder strain increased the frequency of formation of new types; streptomycin treatment of a streptomycin-sensitive feeder, even starting several hours after the onset of mixed cultivation, prevented the formation of apparent recombinants.


Component Restoration in the Bilateral Intermediate Cleft Tip Rhinoplasty.
The intermediate cleft tip rhinoplasty is frequently performed during childhood to address nasal tip anomalies in cleft patients before the most critical period of psychosocial development. The authors previously described the component restoration intermediate cleft tip rhinoplasty technique for the unilateral cleft nose, which was developed to systematically address the lining deficiency, cleft lower lateral cartilage malpositioning, and cleft lateral cartilage weakness using a combination of lower lateral cartilage release, lateral cartilage repositioning, and placement of an auricular composite chondrocutaneous graft. In this work, the authors evaluate the utility of this technique to the bilateral cleft nose. Preoperative and postoperative (mean ± SD, 18.6 ± 10.8 months) photographs of bilateral cleft patients treated with the component restoration intermediate cleft tip rhinoplasty (n = 7) were evaluated using photogrammetric measurements and aesthetic assessments. From preoperatively to postoperatively, the columella length-to-alar width ratio on basal photographs increased (0.19 ± 0.05 versus 0.28 ± 0.05; p = 0.001). On lateral view, the columella-labial angle decreased from preoperatively to postoperatively [138 degrees (interquartile range, 132 to 144 degrees) versus 123 degrees (interquartile range, 122 to 139 degrees); p = 0.04]. Aesthetic ratings performed by four blinded observers also improved from preoperatively to postoperatively (1.6 ± 0.8 versus 2.4 ± 0.7; p = 0.004). As a comparison, bilateral cleft nose patients who did not undergo intermediate cleft tip rhinoplasty (n = 3) of similar ages were subjected to the same photogrammetric and aesthetic analyses, which showed no differences from preoperatively to postoperatively. In combination, the current work suggests that the component restoration technique in the bilateral intermediate cleft tip rhinoplasty improves nasal tip support and aesthetic outcomes.


Competitive SWIFT cluster templates enhance detection of aging changes.
Clustering-based algorithms for automated analysis of flow cytometry datasets have achieved more efficient and objective analysis than manual processing. Clustering organizes flow cytometry data into subpopulations with substantially homogenous characteristics but does not directly address the important problem of identifying the salient differences in subpopulations between subjects and groups. Here, we address this problem by augmenting SWIFT--a mixture model based clustering algorithm reported previously. First, we show that SWIFT clustering using a "template" mixture model, in which all subpopulations are represented, identifies small differences in cell numbers per subpopulation between samples. Second, we demonstrate that resolution of inter-sample differences is increased by "competition" wherein a joint model is formed by combining the mixture model templates obtained from different groups. In the joint model, clusters from individual groups compete for the assignment of cells, sharpening differences between samples, particularly differences representing subpopulation shifts that are masked under clustering with a single template model. The benefit of competition was demonstrated first with a semisynthetic dataset obtained by deliberately shifting a known subpopulation within an actual flow cytometry sample. Single templates correctly identified changes in the number of cells in the subpopulation, but only the competition method detected small changes in median fluorescence. In further validation studies, competition identified a larger number of significantly altered subpopulations between young and elderly subjects. This enrichment was specific, because competition between templates from consensus male and female samples did not improve the detection of age-related differences. Several changes between the young and elderly identified by SWIFT template competition were consistent with known alterations in the elderly, and additional altered subpopulations were also identified. Alternative algorithms detected far fewer significantly altered clusters. Thus SWIFT template competition is a powerful approach to sharpen comparisons between selected groups in flow cytometry datasets.


Trends in coronary heart disease morbidity and mortality and acute coronary care and case fatality from 1985-1989 in southern Germany and south-western France.
Although it has been shown that coronary heart disease mortality rates are decreasing in industrialized countries, little is known about time trends in coronary heart disease incidence. Further, although a number of randomized clinical trials have shown that percutaneous transluminal coronary angioplasty and thrombolysis improve survival of acute myocardial infarction patients, it is not known if widespread use of these therapeutic procedures has contributed to a decrease in in-hospital case fatality on a population basis. The change over time of coronary heart disease attack, incidence and mortality rates was assessed in men and women (35 to 64 years) using data collected between 1985 and 1989 by the Augsburg (Germany) and Toulouse (France) MONICA Centres. Acute coronary care and 28-day case fatality for hospitalized 24-h survivors were also assessed. Men and women from Augsburg had higher age-standarized attack, incidence and mortality rates than their Toulouse counterparts. In both centres, attack, incidence and mortality rates declined in men, but increased in women. Patients in Toulouse received more percutaneous transluminal coronary angioplasty and thrombolysis and had lower 28-day case fatality than patients in Augsburg. The therapeutic procedures, percutaneous transluminal coronary angioplasty and thrombolysis increased in both centres; however, only in Toulouse was this increase associated with a decrease (non significant) in 28-day hospital case fatality. The increase in morbidity and mortality rates of coronary heart disease in women stresses the need for preventive measures in this group. The absence of a favourable effect of acute coronary care on 28-day fatality for hospitalized 24-h survivors in the Augsburg centre will be further investigated.


[Analysis of curative effect of surgical therapy for male prolactinoma].
To summarize the treatment outcome of surgery for male prolactinoma. One hundred and eighty-four cases of male prolactinoma who underwent surgery were analyzed retrospectively.The average age of patients was 36.3 years, and the mean course was 41.9 months.The main clinical manifestation included sexual dysfunction (47.4%), headache (55.9%) and visual disturbance (46.7%). The serum prolactin levels ranged from 6.83 to 9 325.32 nmol/L.The size of tumors varied from 6 mm to 70 mm.Suprasellar adenoma with visual deficits accounted for 40.7%. 98.9% patients underwent pituitary adenoma resection via single nasal transsphenoidal approach. Postoperative pathological Ki-67 index of most patients (45.1%) were less than 1%.After surgical therapy, 163 patients (88.6%) got relief of symptoms, 57 patients (31.0%) achieved initial remission, and 26 patients (45.6%) unfortunately recurred. The possibility of gross resection decreased as tumor size increased (P<0.05). Preoperative PRL had no significant relation with both tumor size and extent of resection (P>0.05). The favorable prognosis predictive factors included microadenoma, intrasellar adenoma and Ki-67 index≤3 (P<0.01). Male prolactinomas is an invasive tumor with higher serum prolactin level.Tumor size could predict degree of gross resection while predictors for recurrence include tumor size, growth pattern and Ki-67 index.


p53 expression in Barrett's oesophagus, dysplasia, and adenocarcinoma using antibody DO-7.
Barrett's oesophagus has a well-recognized association with oesophageal adenocarcinoma, with phenotypic progression through dysplasia to malignancy. The nuclear phosphoprotein p53 is a putative tumour suppressor with mutations resulting in both loss of negative growth regulatory function and possible gain of oncogene function. Many mutant forms have a prolonged half-life and are demonstrable with immunohistochemical techniques. We examined 62 endoscopic oesophageal biopsies and 36 oesophageal resections for p53 overexpression using the monoclonal antibody DO-7 on paraffin-embedded tissue. The series included 40 cases of Barrett's metaplasia, 13 cases of dysplasia, and 81 cases of adenocarcinoma. None of the cases of metaplasia was p53-positive, compared with 4/13 cases of dysplasia and 52/81 cases of adenocarcinoma. There was no association between the degree of dysplasia and p53 expression, although a trend emerged of increasing p53 expression with higher tumour grade. We conclude that p53 overexpression is frequent in oesophageal adenocarcinoma and may be related to tumour grade. p53 overexpression is not restricted to neoplastic lesions and mutation of this tumour suppressor may occur early in the malignant progression of Barrett's oesophagus.


Multiple targets for flecainide action: implications for cardiac arrhythmogenesis.
Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca2+ -mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro-arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization. These were studied in murine genetic models with modified Nav channel or intracellular ryanodine receptor (RyR2)-Ca2+ channel function. Flecainide accesses its transmembrane Nav 1.5 channel binding site during activated, open, states producing a use-dependent antagonism. Closing either activation or inactivation gates traps flecainide within the pore. An early peak INa related to activation of Nav channels followed by rapid de-activation, drives action potential (AP) upstrokes and their propagation. This is diminished in pro-arrhythmic conditions reflecting loss of function of Nav 1.5 channels, such as BrS, accordingly exacerbated by flecainide challenge. Contrastingly, pro-arrhythmic effects attributed to prolonged AP recovery by abnormal late INaL following gain-of-function modifications of Nav 1.5 channels in LQTS3 are reduced by flecainide. Anti-arrhythmic effects of flecainide that reduce triggering in CPVT models mediated by sarcoplasmic reticular Ca2+ release could arise from its primary actions on Nav channels indirectly decreasing [Ca2+ ]i through a reduced [Na+ ]i and/or direct open-state RyR2-Ca2+ channel antagonism. The consequent [Ca2+ ]i alterations could also modify AP propagation velocity and therefore arrhythmic substrate through its actions on Nav 1.5 channel function. This is consistent with the paradoxical differences between flecainide actions upon Na+ currents, AP conduction and arrhythmogenesis under circumstances of normal and increased RyR2 function. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.


Extent and high frequency of a short conversion between the human A gamma and G gamma fetal globin genes.
Southern blotting and DNA sequencing after polymerase chain reaction (PCR) amplification provide evidence for the frequent occurrence (in 7 out of 24 chromosomes) of a short conversion G gamma----A gamma in the 3' end of the human fetal A gamma globin gene. This short conversion is characterized by the presence, 3 nucleotides downstream from the termination codon of the A gamma gene, of the TCAC sequence that is normally present at the equivalent position at the 3' end of the G gamma gene; it is therefore identical to a conversion already described. Interestingly, we have found that this conversion is associated with the presence of the HindIII polymorphic restriction site in the A gamma IVS2, occupying an equivalent position in both the G gamma and A gamma genes. Our observations strengthen the hypothesis that the presence of the HindIII polymorphic restriction site in A gamma IVS2 and the presence of the sequence TCAC at the 3' end of the A gamma gene might be the result of a single conversion event.


Marine Prasinoviruses and Their Tiny Plankton Hosts: A Review.
Viruses play a crucial role in the marine environment, promoting nutrient recycling and biogeochemical cycling and driving evolutionary processes. Tiny marine phytoplankton called prasinophytes are ubiquitous and significant contributors to global primary production and biomass. A number of viruses (known as prasinoviruses) that infect these important primary producers have been isolated and characterised over the past decade. Here we review the current body of knowledge about prasinoviruses and their interactions with their algal hosts. Several genes, including those encoding for glycosyltransferases, methyltransferases and amino acid synthesis enzymes, which have never been identified in viruses of eukaryotes previously, have been detected in prasinovirus genomes. The host organisms are also intriguing; most recently, an immunity chromosome used by a prasinophyte in response to viral infection was discovered. In light of such recent, novel discoveries, we discuss why the cellular simplicity of prasinophytes makes for appealing model host organism-virus systems to facilitate focused and detailed investigations into the dynamics of marine viruses and their intimate associations with host species. We encourage the adoption of the prasinophyte Ostreococcus and its associated viruses as a model host-virus system for examination of cellular and molecular processes in the marine environment.


Carotid Intima-Media Thickness in Patients With a History of Kawasaki Disease.
Kawasaki disease (KD) is an acute pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Concerns have been raised regarding the possibility of a predisposition of KD to premature cardiovascular disease (CVD) risk later in life. Our aim was to assess carotid intima-media thickness (cIMT), as a surrogate marker of CVD risk, in patients with a history of KD compared with unaffected controls. B-mode ultrasound cIMT measurements were performed in 168 patients with a history of KD, and 82 controls; 7 patients were excluded because of incomplete cIMT assessments. Mean cIMT (±SD) was increased in patients with KD compared with controls (0.378±0.030 mm vs. 0.360±0.027 mm, respectively; P adjusted <0.0001). If the cIMTs of CAA-negative patients and controls were plotted against age, increased cIMT was only apparent at young age. In patients with CAA, increased cIMT was observed over the entire age range. Our findings show that arterial wall thickening is more apparent in patients with a history of KD as compared with controls. In CAA-negative patients, cIMT is indistinguishable from controls at older age, whereas an increased cIMT is observed at any age in patients with CAA, suggesting a more general and severe effect of KD on the arterial wall.


Effect of premilking stimulation and milking frequency on milking-induced prolactin release in lactating dairy cows.
Four experiments were conducted to investigate the factors controlling prolactin (PRL) release at milking. Each experiment used 9 dairy cows in mid-lactation in a 3 × 3 Latin square design. Experiment 1 evaluated the effect of premilking stimulation. The milking unit was attached after 0, 20, or 120 s of manual stimulation. Blood samples were collected from 20 min before to 60 min after milking-unit attachment. The peak value and total PRL release (area under the curve) were not affected by the treatments, but the 120-s stimulation hastened PRL release. Stimulation (20 or 120 s) increased the β-endorphin peak value (P = 0.02), but the magnitudes of PRL and β-endorphin releases were not correlated. Experiment 2 evaluated the effect of milking frequency. Cows were milked twice, at 7 AM and 7 PM; 3 times, at 7 AM, 1 PM, and 7 PM; or 7 times, at 7 AM, 9 AM, 11 AM, 1 PM, 3 PM, 5 PM, and 7 PM. The amount of PRL released at the 7 PM milking decreased as the number of milkings increased (P < 0.01), and peak values were smaller with 7 milkings than with 2 and 3 milkings (P < 0.05). Beta-endorphin release was not affected by milking frequency and not correlated with the magnitude of PRL release. Experiment 3 evaluated the effect of manual stimulation between milkings on milking-induced PRL release. Cows received no stimulation; 5 stimulations (5 min each), at 9 AM, 11 AM, 1 PM, 3 PM, and 5 PM; or 1 stimulation at 5 PM. Manual stimulation reduced (P < 0.5) the amount of PRL released and the maximum PRL concentration at the 7 PM milking, but no difference were found between 1 and 5 stimulations. Manual stimulation did not affect the amount of cortisol released but did impair milk ejection. Experiment 4 evaluated the effect of milking frequency on the PRL release induced by manual stimulation. Cows were milked at 7 AM only; at 7 AM, 9 AM, 11 AM, 1 PM, 3 PM, and 5 PM; or at 7 AM and 5 PM. All cows then received manual stimulation at 7 PM. Milking every 2 h or once 2 h before manual stimulation reduced the amount of PRL released and the maximum PRL concentration but did not affect cortisol release. In conclusion, the length of premilking stimulation has no significant effect on milking-induced PRL release, but increasing milking frequency reduces the amount of PRL released at milking. This effect is due not to the number of milkings or the amount of milk harvested during the milking but to the interval since the preceding milking.


α-Catenin levels determine direction of YAP/TAZ response to autophagy perturbation.
The factors regulating cellular identity are critical for understanding the transition from health to disease and responses to therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptional regulators of the Hippo pathway via unrelated mechanisms. Here, we confirm that autophagy perturbation in different cell types can cause opposite responses in growth-promoting oncogenic YAP/TAZ transcriptional signalling. These apparently contradictory responses can be resolved by a feedback loop where autophagy negatively regulates the levels of α-catenins, LC3-interacting proteins that inhibit YAP/TAZ, which, in turn, positively regulate autophagy. High basal levels of α-catenins enable autophagy induction to positively regulate YAP/TAZ, while low α-catenins cause YAP/TAZ activation upon autophagy inhibition. These data reveal how feedback loops enable post-transcriptional determination of cell identity and how levels of a single intermediary protein can dictate the direction of response to external or internal perturbations.


Effects of work burden, job strain and support on depressive symptoms and burnout among Japanese physicians.
Days off, on call, night duty, working hours and job stress can affect physicians' mental health, and support from supervisors and co-workers may have a buffering effect. This study elucidates whether job strain and job factors affect physicians' mental health, and whether support from supervisors and co-workers has a protective effect on their mental health. The subjects included 494 physicians. The Brief Job Stress Questionnaire (BJSQ) was used to evaluate job demand, job control and support. High job strain was defined as a combination of high job demand and low job control. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The Maslach Burnout Inventory-General Survey was used to evaluate burnout. Possible confounder adjusted logistic regression analyses were performed to obtain odds ratios for depressive symptoms and burnout. As per the analysis, high job strain had significantly higher odds ratios, and support from co-workers had significant protective odds ratios for depressive symptoms. High job strain and having only 2-4 days off per month (compared to > 8 days off per month) had significantly higher odds ratios, and support from co-workers had significant protective odds ratios for burnout. High job strain was related to depressive symptoms and burnout, and support from co-workers had a buffering effect on depressive symptoms and burnout. An inadequate number of days off was related to burnout. Assessment of job strain may be a good tool to measure physicians' mental health, and a sufficient number of days off may be needed to prevent burnout.


What is the social impact of ADHD in girls? A multi-method assessment.
This study explores the social impact of ADHD, with and without opposition-defiant behaviour (ADHD+ODD (n= 22) and ADHD-only (n= 18)), in 9- to 12- year old girls compared to girls without ADHD (n= 40). Girls played a computer game involving simulated players, and mothers and teachers completed rating scales. In general, mothers and teachers saw girls with ADHD+ODD as more overtly and relationally aggressive and less prosocial than girls with ADHD-only, who were seen as more overtly and relationally aggressive and less prosocial than control girls. On the computer game, girls with ADHD+ODD were more overtly aggressive, more directly relationally aggressive, and showed less skilled behaviour than the other groups. Girls with ADHD-only showed less covert, indirect relational aggression and more socially awkward interactions than girls in the control group on the computer game. In all, the results indicate that girls with ADHD, with and without ODD behaviour, engage in socially detrimental behaviours.


Identification of the severe acute respiratory syndrome coronavirus by simultaneous multigene DNA sequencing.
The recent severe acute respiratory syndrome (SARS) outbreak resulted in calls for an accurate diagnostic test that can be used not only for routine testing but also for generating nucleotide sequences to monitor the epidemic. Although the identity of the SARS coronavirus (SARS-CoV) genome was confirmed by DNA sequencing, it is impractical to sequence the entire 29-kb SARS-CoV genome on a routine basis. Therefore, alternative assay methods such as the enzyme-linked immunosorbent assay and PCR have been pursued for routine testing, primarily to resolve probable cases. We report here a modification of standard DNA sequencing technology for accurate identification of SARS-CoV in routine testing. Instead of requiring the sequencing of the whole SARS-CoV genome, our modification enables the simultaneous sequencing of three regions of the SARS-CoV genome, the spike protein-encoding gene (35 nucleotides), gene M (43 nucleotides), and gene N (45 nucleotides), in a single electropherogram. Comparing these nucleotide sequences to DNA databank entries (National Institutes of Health) conclusively identified them as SARS-CoV sequences.


Normal peak expiratory flow in healthy adult male and female subjects.
Peak expiratory flows (PEF) were measured in 830 and 270 healthy male and female subjects respectively using Autospiro model AS-500 (Minato, Japan) fitted with a heated pneumotachograph. All measurements were made in the standing position. Male subjects gave significantly larger PEF values than female subjects (P < 0.001), and PEF decreased with age at a rate of about 6.45% year. In the female subjects, PEF increased with age to reach a peak at about 32 years decreasing thereafter. The equations representing peak expiratory flow for this population are: PEF = 0.042H - 0.051A + 3.5 (l.s-1) for the male subjects and PEF = 0.014H + 4.445 (l.s-1) for female subjects, where H and A represent height (cm) and age (years) respectively. Regression equations for predicting PEF constructed in this study gave smaller PEF values than values from prediction equation derived from a Caucasian population. It is therefore, highly desirable that equations suitable for predicting PEF in our region be established and more research in this area is required to cover some of the minority tribes in our region.


Influence of counter-rotating von Kármán flow on cylindrical Rayleigh-Bénard convection.
The axisymmetric flow in an aspect-ratio-one cylinder whose upper and lower bounding disks are maintained at different temperatures and rotate at equal and opposite velocities is investigated. In this combined Rayleigh-Bénard/von Kármán problem, the imposed temperature gradient is measured by the Rayleigh number Ra and the angular velocity by the Reynolds number Re. Although fluid motion is present as soon as Re not equal 0 , a symmetry-breaking transition analogous to the onset of convection takes place at a finite Rayleigh number higher than that for Re=0 . For Re<95 , the transition is a pitchfork bifurcation to a pair of steady states, while for Re>95 , it is a Hopf bifurcation to a limit cycle. The steady states and limit cycle are connected via a pair of saddle-node infinite-period bifurcations except very near the Takens-Bogdanov codimension-two point, where the scenario includes global bifurcations. Detailed phase portraits and bifurcation diagrams are presented, as well as the evolution of the leading part of the spectrum, over the parameter ranges 0<or=Re<or=120 and 0<or=Ra<or=30 000 .


Does elongation training effectively improve motor function?-a single-case design verification study.
[Purpose] The aim of this study was to investigate whether elongation training (ELT) was effective in improving motor function in a single case. [Participant and Methods] A 90-year-old male with Parkinson's syndrome participated in this study. This study used the A-B-A type of single case design. In the 'A' period, normal lower limb exercises (extension and abduction of the hip joint) were performed. The same exercise from the 'A' period was performed using an elongation band in the 'B' period for ELT. The implementation period included 2 weeks of the 'A' period, 2 weeks of the 'B' period, and then 2 weeks of the 'A' period again. Motor function was evaluated using the one-leg standing time on each side, and the Timed Up and Go Test (TUG). [Results] In the 'A' period, there was no change in the one-leg standing time on each side and the TUG. However, in the 'B' period, the one-leg standing time on each side increased, and the TUG values decreased. When returning to the 'A' period, the one-leg standing time on each side decreased, and the TUG increased. [Conclusion] It can be suggested that ELT safely improves motor function at home, even in older people.


Diabetes and atherothrombotic disease: linked through inflammation?
Inflammation has been accepted as a key pathobiological mechanism in the development of cardiovascular disease, and acceptance is likely on its way for diabetes as well. Inflammation provides a linking mechanism between these two disorders, allowing them to influence each other in a wide variety of ways. Interventions aimed broadly at inflammation are likely to influence both diseases, and pathway-specific interventions may prove useful as well. The role of genetic variation remains poorly understood.


Keeping viruses in Chk: DNA damage signaling puts the brakes on transformation.
Oncogenic viruses infect many cells but rarely lead to tumorigenesis. In this issue of Cell Host & Microbe, Nikitin et al. describe how a protective DNA damage response acts to suppress transformation in the majority of cells latently infected with Epstein-Barr virus (EBV).


Intraoperative Renal Replacement Therapy in Orthotopic Liver Transplantation.
Acute kidney injury in patients admitted to the hospital for liver transplantation is common, with up to 80% of pretransplant patients having some form of acute kidney injury. Many of these patients start on dialysis prior to their transplant and have it continued intraoperatively during their surgery. This review discusses the limited existing literature and expert opinion around the indications and outcomes around intraoperative dialysis (intraoperative renal replacement therapy) during liver transplantation. More specifically, we discuss which patients may benefit from intraoperative renal replacement therapy and the impact of hyponatremia and hyperammonemia on the dialysis prescription. Additionally, we discuss the complex interplay between anesthesia and intraoperative renal replacement therapy and how the need for clearance and ultrafiltration changes throughout the different phases of the transplant (preanhepatic, anhepatic, and postanhepatic). Lastly, this review will cover the limited data around patient outcomes following intraoperative renal replacement therapy during liver transplantation as well as the best evidence for when to stop dialysis.


Photoisomerisation of azobenzene crystals in aqueous dispersions examined by higher order derivative spectra.
Photo-induced UV-Vis spectral changes of azobenzene (Az) in solution and aqueous crystalline dispersions were analysed by means predominantly of fourth order derivatives. Weak bands due to vibration level transitions (VLT) of E-isomers in solution were well-resolved in derivatives to estimate conversion of photoisomerisation by tracing extrema of a VLT sub-peak. The photo-induced derivative-spectral changes of Az crystals dispersed in aqueous PVA solutions generated many common crossing points to indicate that Az dissolves partially in a PVA solution to lead to photoisomerisation in a homogeneous phase and the reversible alteration of particle size. The solid-state photoisomerisation of Az was investigated by the preparation of PVA-free aqueous dispersions of powdery nanohybrids comprised of Az and silica nanoparticles. The fourth order derivatives of spectral changes revealed that the photochemical process involves three kinds of species including non-aggregated and aggregated E-isomers as well as Z-isomers.


Exudation in Patients With Neovascular Age-Related Macular Degeneration Treated With the Port Delivery System or Monthly Injections.
To evaluate for the presence, severity, and type of exudation at each study visit for a subgroup of patients with neovascular age-related macular degeneration from the Archway and Portal trials. Retrospective analysis of prospectively obtained data. Spectral-domain optical coherence tomography scans from each study visit of 44 patients from the Port Delivery System (PDS) arm and 32 patients from the monthly injection arm of Archway were evaluated, and composites of horizontal scans through the fovea were created. Each composite was graded for the presence, type, and severity of exudation and impact on best-corrected visual acuity. After PDS implantation, 20 of 44 eyes (45%) never showed any exudation in the fovea, 2 (5%) never showed exudation in the fovea but had several missed visits, whereas 15 (34%), 3 (7%), and 4 (9%) showed mild, moderate, or severe exudation at 1 or more study visits, respectively. When exudation was present, it was most commonly subretinal fluid (50%). Of 32 patients randomized to monthly injections, 15 (47%) had no exudation in the fovea during monthly injections or after PDS implantation. Fluctuation of exudation in the fovea over time was seen in some patients after PDS implantation or during monthly injections with little or no identifiable impact on best-corrected visual acuity. In the 7 eyes with moderate or severe exudation in the fovea after PDS implantation, final vision was good in 5 (20/25 in 3, 20/40 in 1, and 20/50 in 1) and 2 had reduced vision from submacular hemorrhage. The PDS provides excellent control of exudation in the fovea in patients with neovascular age-related macular degeneration, and when exudation occurs, it often resolves without a negative impact on vision.


[Tobacco use disorder prevalence among hospital workers].
In Spain, as in other countries, numerous studies on tobaccoism have been carried out. The purpose of this survey was to evaluate the prevalence of tobaccoism in a representative sample of hospital employees and its association with age, sex, profession level and attitudes. Following a pilot study, a survey was carried out amongst a representative and random sample (n = 360) of hospital personnel, who were asked about their attitudes towards smoking, classified according to age, sex and professional level. The total percentage of smokers was 36.4%, but no significant statistical differences were found between sex or age group. The professional levels with the highest percentage of smokers are ATS/DUE and clerks. 42.8% of non-smokers declared having smoked in the past. ATS/DUE, clerks and doctors showed the highest percentage. 40.5% of smokers declare that they were willing to give up smoking, whereas people over 50 were the most reluctant. The majority of cigarette smokers admitted that they smoke in the hospital. Most of them are intermediate smokers (10-20 cigarettes per day) and have been so for many years. The majority of former smokers gave up smoking in recent years. These results prove that a large number of hospital employees are smokers. However, many are willing to give up the habit. We should therefore encourage these people to give up smoking and help them by different means such as: anti-smoking advice, medical advice and health education. We propose to declare hospitals as "Non-Smoking Area" as of the year 2000 which includes employees, patients and visitors, according to the WHO "Health for All." program.


Common brain activations for painful and non-painful aversive stimuli.
Identification of potentially harmful stimuli is necessary for the well-being and self-preservation of all organisms. However, the neural substrates involved in the processing of aversive stimuli are not well understood. For instance, painful and non-painful aversive stimuli are largely thought to activate different neural networks. However, it is presently unclear whether there is a common aversion-related network of brain regions responsible for the basic processing of aversive stimuli. To help clarify this issue, this report used a cross-species translational approach in humans (i.e. meta-analysis) and rodents (i.e. systematic review of functional neuroanatomy). Animal and human data combined to show a core aversion-related network, consisting of similar cortical (i.e. MCC, PCC, AI, DMPFC, RTG, SMA, VLOFC; see results section or abbreviation section for full names) and subcortical (i.e. Amyg, BNST, DS, Hab, Hipp/Parahipp, Hyp, NAc, NTS, PAG, PBN, raphe, septal nuclei, Thal, LC, midbrain) regions. In addition, a number of regions appeared to be more involved in pain-related (e.g. sensory cortex) or non-pain-related (e.g. amygdala) aversive processing. This investigation suggests that aversive processing, at the most basic level, relies on similar neural substrates, and that differential responses may be due, in part, to the recruitment of additional structures as well as the spatio-temporal dynamic activity of the network. This network perspective may provide a clearer understanding of why components of this circuit appear dysfunctional in some psychiatric and pain-related disorders.


Increase in thyroglobulin antibody and thyroid peroxidase antibody levels, but not preterm birth-rate, in pregnant Danish women upon iodine fortification.
The presence of thyroid antibodies in pregnancy has been associated with preterm birth. In the non-pregnant population, the implementation of the Danish iodine fortification program has increased the prevalence of thyroid antibodies. This study investigated the prevalence of thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) in pregnant Danish women before, during and after implementation of the iodine fortification program and association with preterm birth. Comparative cohort study of 1368 pregnancies from three cohorts gathered before (1996-1998), during (2000-2003) and after (2008-2009) the iodine fortification program. In cohort 1 (n = 297), TPOAbs were measured (DYNOtest (BRAHMS)). In cohorts 2 (n = 148) and 3 (n = 923), both TPOAbs and TgAbs were measured (Kryptor immunofluorescent assay (BRAHMS)). The prevalence and effect of antibody positivity were explored using three cut-offs: TPOAbs and/or TgAbs >100 kU/L, TPOAbs and/or TgAbs >60 kU/L and TPOAbs >30 and/or TgAbs >20 kU/L. National preterm birth data were extracted from the National Birth Registry. In the three cohorts, TPOAb levels >60 kU/L were found in 5.4, 8.1 and 12.0% (χ2(2, n = 1367) = 11.7, P = 0.003) respectively, and TPOAbs and/or TgAbs >60 kU/L in 8.1 and 16.2% in cohorts 2 and 3 respectively (χ2(2, n = 1070) = 6.5, P = 0.01). TgAb levels (>20 kU/L) had increased plenty-fold from cohort 2 to 3 (χ2(1, n = 1071) = 136.5, P < 0.001). Preterm birth occurred in 4.1% of all pregnancies with no effect from antibody positivity (TPOAbs and/or TgAbs >60 kU/L, χ2(1, n = 1039) = 0.0, P = 0.98, aOR = 1.1, 95% CI (0.4-2.7)). The national preterm birth-rate showed no increase over the same period. Thyroid antibody positivity in Danish pregnant women has more than doubled upon the implementation of the iodine fortification program without an increase in preterm birth-rate.


Visible Light-Induced Antibacterial Activity of Pigments Extracted from Dregs of Green and Black Teas.
Chlorophyll and its derivatives are potential natural sensitizers frequently applied in antimicrobial photodynamic therapy. Chlorophyll derivatives are formed naturally during tea processing, but they do not contribute to the color of tea infusions and thus are presumably left in the tea dregs. The present study aimed to investigate (i) the chlorophyll remnants in the pigments recovered from dregs of green and black teas and (ii) the antibacterial activity of pigments extracted from the tea dregs upon illumination using a light-emitting diode (LED) as the light source. Pigment analysis using high-performance liquid chromatography (HPLC) revealed the presence of main degradation products of chlorophylls, such as pheophytin and its epimers, pyropheophytin, and pheophorbides. In vitro assays demonstrated significant reductions in the number of viable bacteria in the presence of the pigments after 30 min of incubation with LED light irradiation. The descending order of bacterial susceptibility was Listeria monocytogenes > Staphylococcus aureus > Escherichia coli > Salmonella typhi. At an equivalent irradiation intensity, the blue and red LEDs could stimulate a comparable inactivation effect through photodynamic reactions. These findings demonstrated the valorization potential of tea dregs as a source of chlorophyll derivatives with visible light-induced antibacterial activity.


Tocilizumab Labeling with 99mTechnetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma.
Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. To radiolabel Tocilizumab with 99mTechnetium as a potential imaging agents for MM. IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with 99mTc. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice. LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of 99mTc- HYNIC-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours. Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease.


Expression of cytoskeletal and molt-related genes is temporally scheduled in the hypodermis of the crayfish Procambarus clarkii during premolt.
The rigid crustacean exoskeleton, the cuticle, is composed of the polysaccharide chitin, structural proteins and mineral deposits. It is periodically replaced to enable growth and its construction is an energy-demanding process. Ecdysis, the shedding event of the old cuticle, is preceded by a preparatory phase, termed premolt, in which the present cuticle is partially degraded and a new one is formed underneath it. Procambarus clarkii (Girard 1852), an astacid crustacean, was used here to comprehensively examine the changing patterns of gene expression in the hypodermis underlying the cuticle of the carapace at seven time points along ~14 premolt days. Next generation sequencing was used to construct a multi-tissue P. clarkii transcript sequence assembly for general use in a variety of transcriptomic studies. A reference transcriptome was created here in order to perform digital transcript expression analysis, determining the gene expression profiles in each of the examined premolt stages. The analysis revealed a cascade of sequential expression events of molt-related genes involved in chitin degradation, synthesis and modification, as well as synthesis of collagen and four groups of cuticular structural genes. The new description of major transcriptional events during premolt and the determination of their timing provide temporal markers for future studies of molt progress and regulation. The peaks of the expression of the molt-related genes were preceded by expression peaks of cytoskeletal genes that are hypothesized to be essential for premolt progress through regulating protein synthesis and/or transport, probably by remodeling the cytoskeletal structure.


Risk Factors for Low Back Disorders in Saskatchewan Farmers: Field-based Exposure Assessment to Build a Foundation for Epidemiological Studies.
Studies of many geographical settings and agricultural commodities show that low back disorders are an important public health issue among farmers, who represent a special rural population. However, few studies have examined the impact of low back disorders on farmers' work or the strategies that they adopt to avoid associated pain and disability. This study protocol will investigate 3 issues related to low back disorders in Saskatchewan farmers: (1) the vibration, heavy lifting, and awkward postures farmers encounter during their work that might contribute to low back disorders; (2) the impact low back disorders have on farmers in terms of their ability to work; and (3) the types of preventative measures and solutions that farmers implement to reduce the occurrence of low back pain. To answer these questions, researchers will travel to 30 farms to make measurements of vibration, lifting, and posture during the farmers' regular work tasks. Farmers will be interviewed about any pain and/or disability using standardized interview questions. Farmers will also be asked about safety measures they have implemented at their farm, such as modified tools or equipment, to reduce the occurrence of low back disorders or pain. Data collection is currently underway for this study, with the intention to complete all data collection and analysis by the end of 2018. Occupational determinants of health such as vibration, heavy lifting, and awkward postures are important in the development and progression of low back disorders, and the results of this study will allow for cost-effective epidemiological studies of these determinants in the future. In identifying prevention strategies, this study will also facilitate future research evaluating the effectiveness of safety measures.


Stachybotrysins A-G, Phenylspirodrimane Derivatives from the Fungus Stachybotrys chartarum.
Seven new phenylspirodrimane derivatives named stachybotrysins A-G (2-8), together with five known compounds (1, 9-12), were isolated from Stachybotrys chartarum CGMCC 3.5365. Stachybotrysin D (5) is the first reported example of a naturally occurring alcoholic O-sulfation of a phenylspirodrimane, and stachybotrysins F and G (7 and 8) are the first examples possessing an isobenzotetrahydrofuran ring with an acetonyl moiety attached. The structures of these compounds were elucidated on the basis of extensive spectroscopic data analysis and by comparison with reported data. The absolute configurations of 1-8 were determined by X-ray single-crystal diffraction, electronic circular dichroism (ECD), and calculated ECD. Compounds 1 and 8 displayed anti-HIV activity with IC50 values of 15.6 and 18.1 μM, respectively, and 2, 7, 9, and 11 showed inhibitory effect on influenza A virus with IC50 values ranging from 12.4 to 18.9 μM.


Transposable element annotation in non-model species: The benefits of species-specific repeat libraries using semi-automated EDTA and DeepTE de novo pipelines.
Transposable elements (TEs) are significant genomic components which can be detected either through sequence homology against existing databases or de novo, with the latter potentially reducing the risk of underestimating TE abundance. Here, we describe the semi-automated generation of a de novo TE library using the newly developed EDTA pipeline and DeepTE classifier in a non-model teleost (Corydoras fulleri). Using both genomic and transcriptomic data, we assess this de novo pipeline's performance across four TE based metrics: (i) abundance, (ii) composition, (iii) fragmentation, and (iv) age distributions. We then compare the results to those found when using a curated teleost library (Danio rerio). We identify quantitative differences in these metrics and highlight how TE library choice can have major impacts on TE-based estimates in non-model species.


Membrane-bound TNF induces protective immune responses to M. bovis BCG infection: regulation of memTNF and TNF receptors comparing two memTNF molecules.
Several activities of the transmembrane form of TNF (memTNF) in immune responses to intracellular bacterial infection have been shown to be different from those exerted by soluble TNF. Evidence is based largely on studies in transgenic mice expressing memTNF, but precise cellular mechanisms are not well defined and the importance of TNF receptor regulation is unknown. In addition, memTNF activities are defined for a particular modification of the extracellular domain of TNF but a direct comparison of different mutant memTNF molecules has not been done in vivo. To understand the activities of memTNF we compared two commonly used mouse strains lacking soluble TNF but possessing functional and normally regulated membrane-bound TNF knockin (memTNF KI) for their capacity to generate cell-mediated immune responses and resistance to M. bovis BCG infection, and to regulate TNF receptors. M. bovis BCG infection resulted in similar bacterial loads in one strain of memTNF KI (memTNF(Δ1-9,K11E)) and in wild-type mice, in contrast, the other strain of memTNF KI mice (memTNF(Δ1-12)) showed higher sensitivity to infection with high mortality (75%), greater bacterial load and massive lung pathology. The pattern of cytokines/chemokines, inflammatory cells, pulmonary NF-κB phosphorylation, antigen-dependent IFN-γ response, and splenic iNOS was impaired in M. bovis BCG-infected memTNF(Δ1-12) KI mice. Macrophages expressing TNFR2 were reduced but soluble TNFRs were higher in memTNF(Δ1-12) KI mice during the infection. In vitro, M. bovis BCG-induced NF-κB activation and cytokines were also decreased in memTNF(Δ1-12) KI bone marrow-derived macrophages. Our data show that two memTNF molecules exerted very different activities upon M. bovis BCG infection resulting in protection or not to bacterial infection. These results suggest a regulatory mechanism of memTNF and TNF receptors being critical in the outcome of the infection and highlight the role of cell-bound and soluble TNFR2 in memTNF-mediated anti-microbial mechanisms.


Arthroscopic revision of osteochondral autograft in distal tibia: A case report demonstrating precision of intraoperative 3D fluoroscopy.
Graft failures of the tibial plafond are very rare. This article presents the technique of precise antegrade osteochondral auto-grafting under three-dimensional (3D) fluoroscopy. A 20-year-old athletic patient with a recurrent osteochondral lesion of the tibial plafond on a first osteochondral autograft after two years of follow-up was admitted. The revision osteochondral autograft was performed under real-time perioperative arthroscopic and 3D fluoroscopic control for greater precision. Surgery was followed by six weeks of non-weight-bearing in a walking boot. At one-year follow-up, the patient was effusion and pain free and returned to his previous activity level completely. Revision osteochondral autografting under arthroscopic and 3D fluoroscopic control seems to be an effective therapeutic option.


Evidence for autoimmunity to heart-specific antigens in patients with Emery-Dreifuss muscular dystrophy.
Dilated cardiomyopathy is one of the leading abnormalities in Emery-Dreifuss Muscular Dystrophy (EDMD). The pathogenesis of heart involvement in EDMD is, however, unknown. Autoimmune mechanisms have also to be taken into account. The aim of this study was to search for the presence of anti-heart antibodies in EDMD patients. The anti-heart auto-antibodies were detected in serum of 14 EDMD patients (the X-linked and the AD-Autosomal Dominant form). The control groups comprised 10 patients with Dilated Cardiomyopathy (DCM) and 10 healthy subjects. To screen serum for anti-heart antibodies against ventricular muscle proteins, they were separated by polyacrylamide gel electrophoresis, followed by Western blotting. In EDMD and DCM, IgG anti-heart antibodies against heart ventricular proteins were detected. In both diseases, 85 kD protein appeared to be the most immunogenic. Anti-troponin I (24 kD), anti-tropomyosin (35 kD) and anti-actin (43 kD) reactivity was less intense. There were significant differences in the reactivity of auto-antibodies between both EDMD forms, and also between EDMD and the DCM patients. No clear-cut correlation between the reactivity and frequency of the antibodies and clinical parameters of the EDMD patients was detected. The anti-heart proteins are reliable markers of immune involvement in dilated cardiomyopathy in the course of EDMD. Short- and long-term follow-up may define the role of anti-heart antibodies in predicting the susceptibility at risk of dilated cardiomyopathy in EDMD patients.


Neuroprotective Effects of Selected Microbial-Derived Phenolic Metabolites and Aroma Compounds from Wine in Human SH-SY5Y Neuroblastoma Cells and Their Putative Mechanisms of Action.
Moderate wine consumption has shown the potential to delay the onset of neurodegenerative diseases. This study investigates the molecular mechanisms underlying the protective effects of wine-derived phenolic and aroma compounds in a neuroinflammation model based on SIN-1 stress-induced injury in SH-SY5Y neuroblastoma cells. Cell pretreatment with microbial metabolites found in blood after wine consumption, 3,4-dihydroxyphenylacetic (3,4-DHPA), 3-hydroxyphenylacetic acids and salicylic β-d-O-glucuronide, at physiologically concentrations (0.1-10 μM) resulted in increased cell viability versus SIN-1 control group (p < 0.05). Results also showed significant decreases in mitogen-activated protein kinase (MAPK) p38 and ERK1/2 activation as well as in downstream pro-apoptotic caspase-3 activity by some of the studied compounds. Moreover, pretreatment with p38, MEK, and ERK1/2-specific inhibitors, which have a phenolic-like structure, also resulted in an increase on cell survival and a reduction on caspase-3 activity levels. Overall, these results contribute with new evidences related to the neuroprotective actions of wine, pointing out that wine-derived human metabolites and aroma compounds may be effective at protecting neuroblastoma cells from nitrosative stress injury by inhibiting neuronal MAPK p38 and ERK1/2, as well as downstream caspase 3 activity.


Characterization of a 23 kDa sperm-binding polypeptide of the golden hamster epididymis.
A 23 kDa polypeptide has been identified on the flagellum of sperm obtained from the cauda epididymis of the golden hamster. A monospecific antiserum to the 23 kDa hamster polypeptide was prepared and used to study its distribution on sperm, in the epididymis, and in epididymal fluid. In the cauda, the polypeptide is found on the midpiece and endpiece of the sperm tail, in detergent extracts of sperm, and in epididymal luminal fluid-enriched fractions. It is not present on sperm or in luminal fluid-enriched fractions from the caput epididymis. Immunocytochemical staining of epididymal tissue has demonstrated the 23 kDa polypeptide in the Golgi region of the principal cells of the proximal cauda and on sperm in the tubules of this segment and in tubules distal to it. Antiserum to the 23 kDa golden hamster polypeptide cross-reacts with sperm from rats and Chinese hamsters, but not with sperm from rabbits, cattle, mice, and guinea pigs. The antigen is localized to the tail of sperm obtained from the cauda of the rat and from the distal caput of the Chinese hamster. Immunoblots of detergent extracts of sperm and luminal fluid-enriched fractions from these two species reveal a 26 dKa polypeptide that is immunologically related to the golden hamster polypeptide.


[Histochemical changes in Clonorchis sinensis after pyquiton treatment].
Some histochemical changes in adult C. sinensis collected from rats infected artificially and treated with pyquiton were observed. 1 h after administration the glycogen content showed a slight decrease which became prominent 24h later and almost disappeared at 48h post-medication. There was an increase in protein content in the parenchymal tissues of worms 1h after treatment, especially in the reproductive organ 24h after treatment. RNA content was decreased 1h post administration and continued decreasing gradually so that very little could be seen 48h later. An increase in the activities of SDH, MDH and Ca-ATPase was seen at the beginning and became marked 24h after medication, while that for G-6-PDH was detected 48h after drug administration. No obvious changes in DNA, lipid, AKP, ACP and phenolase were detected within 1-48h after treatment.


Emergent single-balloon enteroscopy for overt bleeding of small intestinal vascular malformation.
A 28-year-old man presented with anemia symptoms and intermittent tarry stool passage for three days. No stigmata of hemorrhage were identified using esophagogastroduodenoscopy, ileocolonoscopy, and contrast-enhanced computed tomography. He then developed massive tarry stool passage with profound hypovolemic shock and hypoxic respiratory failure. Emergent angiography revealed active bleeder, probably from the jejunal branches of the superior mesenteric artery, but embolization was not performed due to possible subsequent extensive bowel ischemia. His airway was secured via endotracheal intubation with ventilator support, and emergent antegrade single-balloon enteroscopy was performed at 8 h after clinical overt bleeding occurrence; the procedure revealed a 2-cm pulsating subepithelial tumor with a protruding blood plug at the distal jejunum. Laparoscopic segmental resection of the jejunum with end-to-end anastomosis was performed after emergent endoscopic tattooing localization. Pathological examination revealed a vascular malformation in the submucosa with an organizing thrombus. He was uneventfully discharged 5 d later. This case report highlights the benefit of early deep enteroscopy for the treatment of small intestinal bleeding.


Slowing in reading and picture naming: the effects of aging and developmental dyslexia.
We examined the slowing in vocal reaction times shown by dyslexic (compared to control) children with that of older (compared to younger) adults using an approach focusing on the detection of global, non-task-specific components. To address this aim, data were analyzed with reference to the difference engine (DEM) and rate and amount (RAM) models. In Experiment 1, typically developing children, children with dyslexia (both attending sixth grade), younger adults and older adults read words and non-words and named pictures. In Experiment 2, word and picture conditions were presented to dyslexic and control children attending eighth grade. In both experiments, dyslexic children were delayed in reading conditions, while they were unimpaired in naming pictures (a finding which indicates spared access to the phonological lexicon). The reading difficulty was well accounted for by a single multiplicative factor while only the residual effect of length (but not frequency and lexicality) was present after controlling for over-additivity using a linear mixed effects model with random slopes on critical variables. Older adults were slower than younger adults across reading and naming conditions. This deficit was well described by a single multiplicative factor. Thus, while slowing of information processing is limited to orthographic stimuli in dyslexic children, it cuts across verbal tasks in older adults. Overall, speed differences in groups such as dyslexic children and older adults can be effectively described with reference to deficits in domains encompassing a variety of experimental conditions rather than deficits in single specific task/conditions. The DEM and RAM prove effective in teasing out global vs. specific components of performance.