A peek into the future of radiology using big data applications.
Big data is extremely large amount of data which is available in the radiology department. Big data is identified by four Vs - Volume, Velocity, Variety, and Veracity. By applying different algorithmic tools and converting raw data to transformed data in such large datasets, there is a possibility of understanding and using radiology data for gaining new knowledge and insights. Big data analytics consists of 6Cs - Connection, Cloud, Cyber, Content, Community, and Customization. The global technological prowess and per-capita capacity to save digital information has roughly doubled every 40 months since the 1980's. By using big data, the planning and implementation of radiological procedures in radiology departments can be given a great boost. Potential applications of big data in the future are scheduling of scans, creating patient-specific personalized scanning protocols, radiologist decision support, emergency reporting, virtual quality assurance for the radiologist, etc. Targeted use of big data applications can be done for images by supporting the analytic process. Screening software tools designed on big data can be used to highlight a region of interest, such as subtle changes in parenchymal density, solitary pulmonary nodule, or focal hepatic lesions, by plotting its multidimensional anatomy. Following this, we can run more complex applications such as three-dimensional multi planar reconstructions (MPR), volumetric rendering (VR), and curved planar reconstruction, which consume higher system resources on targeted data subsets rather than querying the complete cross-sectional imaging dataset. This pre-emptive selection of dataset can substantially reduce the system requirements such as system memory, server load and provide prompt results. However, a word of caution, "big data should not become "dump data" due to inadequate and poor analysis and non-structured improperly stored data. In the near future, big data can ring in the era of personalized and individualized healthcare.


Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis.
Multiple sclerosis (MS) is a multifocal inflammatory central nervous system disorder. There are now many highly effective disease-modifying therapies (DMTs) available as treatment options, which have a significant impact on disease activity and long-term disability. The aim of this article is to provide a concise overview of the diagnosis, DMTs and prognosis of MS. The diagnosis of MS is made on clinicoradiological grounds to prove dissemination of disease in both time and space in the nervous system. While the expanding options of DMTs have had a significant impact on disability, they make medication selection for individual patients more complicated. Patients with MS often have a model of care shared between the neurologist and the general practitioner. This review article summarises the key aspects of the diagnosis, DMTs and prognosis of MS relevant to the general practitioner.


Heterometallic polyhydride complexes containing yttrium hydrides with different Cp ligands: synthesis, structure, and hydrogen-uptake/release properties.
A new family of Y(4)/M(2) and Y(5)/M heterobimetallic rare-earth-metal/d-block-transition-metal-polyhydride complexes has been synthesized. The reactions of the tetranuclear yttrium-octahydride complex [{Cp''Y(μ-H)(2)}(4)(thf)(4)] (Cp'' = C(5)Me(4)H, 1-C(5)Me(4)H) with one equivalent of Group-6-metal-pentahydride complexes [Cp*M(PMe(3))H(5)] (M = Mo, W; Cp* = C(5)Me(5)) afforded pentanuclear heterobimetallic Y(4)/M-polyhydride complexes [{(Cp''Y)(4)(μ-H)(7)}(μ-H)(4)MCp*(PMe(3))] (M = Mo (2 a), W (2 b)). UV irradiation of compounds 2 a,b in THF gave PMe(3)-free complexes [{(Cp''Y)(4)(μ-H)(6)(thf)(2)}(μ-H)(5)MCp*] (M = Mo (3 a), W (3 b)). Compounds 3 a,b reacted with one equivalent of [Cp*M(PMe(3))H(5)] to afford hexanuclear Y(4)/M(2) complexes [{Cp*M(μ-H)(5)}{(Cp''Y)(4)(μ-H)(5)}{(μ-H)(4)MCp*(PMe(3))}] (M = Mo (4 a), W (4 b)). UV irradiation of compounds 4 a,b provided the PMe(3)-free complexes [(Cp''Y)(4)(μ-H)(4){(μ-H)(5)MCp*}(2)] (M = Mo (5 a), W (5 b)). C(5)Me(4)Et-ligated analogue [(Cp''Y)(4)(μ-H)(4){(μ-H)(5)Mo(C(5)Me(4)Et)}(2)] (5 a') was obtained from the reaction of 1-C(5)Me(4)H with [(C(5)Me(4)Et)Mo(PMe(3))H(5)]. On the other hand, the reaction of pentanuclear yttrium-decahydride complex [{(C(5)Me(4)R)Y(μ-H)(2)}(5)(thf)(2)] (1-C(5)Me(5): R = Me; 1-C(5)Me(4)Et: R = Et) with [Cp*M(PMe(3))H(5)] gave the hexanuclear heterobimetallic Y(5)/M-polyhydride complexes [({(C(5)Me(4)R)Y}(5)(μ-H)(8))(μ-H)(5)MCp*] (6 a: M = Mo, R = Me; 6 a': M = Mo, R = Et; 6 b: M = W, R = Me). Compound 5 a released two molecules of H(2) under vacuum to give [(Cp''Y)(4)(μ-H)(2){(μ-H)(4)MoCp*}(2)] (7). In contrast, compound 6 a lost one molecule of H(2) under vacuum to yield [{(Cp*Y)(5)(μ-H)(7)}(μ-H)(4)MoCp*] (8). Both compounds 7 and 8 readily reacted with H(2) to regenerate compounds 5 a and 6 a, respectively. The structures of compounds 4 a, 5 a', 6 a', 7, and 8 were determined by single-crystal X-ray diffraction.


Malignant urinary tract tumor in childhood.
Fifty-one patients under the age of 18 with histologic-proven malignant urinary tract tumors were encountered at the Department of Pediatrics of National Taiwan University Hospital from 1979 to 1989. There were 47 tumors arising from the kidney, 2 from the bladder, and 2 from the urethra. For upper urinary tract tumors, abdominal mass (92%) and abdominal distension (86%) were the most common symptoms and signs. For lower urinary tract tumors, painless hematuria, bladder distension and urinary difficulty were most frequently encountered. Associated anomalies were found in one-fifth of our patients, including kyphosis, undescended testes, hypospadias, inguinal hernia, intersex and congenital heart disease. Diagnosis was aided by plain X ray, abdominal ultrasonography, intravenous pyelography, computed tomography, or angiography in upper urinary tract tumors, and cystoscopy, cystography and computed tomography in lower urinary tract tumors. Multimodal treatment including total excision, multiagent chemotherapy, and radiotherapy were performed. Postoperative complications included infection (22%), ascites (19%), ileus, pleural effusion, scoliosis, neuropathies, and growth retardation. The local recurrence rate was 32%, and the metastatic rate was 34%. The overall mortality rate was 53% for an average follow-up period of 38 months. The causes of death included sepsis, respiratory failure and hepatic failure. The two-year survival rate was 47.6%. The important prognostic factors included histology, staging and vascular invasion, in addition to combined chemotherapy and radiotherapy.


Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management.
Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women's Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.


Hypercoagulable states: a review.
Vascular surgeons are often asked to evaluate patients with recurrent thromboses or thromboses in unusual locations either arterial or venous. There may be obvious inciting factors, but in many of these patients the possibility of a previously undiagnosed hypercoagulable state must be considered. Hypercoagulable states can be acquired (smoking, medication, change in physiologic status as occurs with pregnancy) or congenital. Congenital hypercoagulable disorders are more prevalent in families or patients with a history of thromboembolic events early in life or multiple miscarriages and include conditions such as protein C or S deficiencies, factor V Leiden mutation, and prothrombin gene variant. This article reviews the hypercoagulable states that are encountered in clinical practice as well as guidelines for testing and goals of therapy.


Permeability and adsorption capacity of dialysis membranes to lipid A.
Hemodialysis membranes were tested in vitro for possible penetration by low molecular weight endotoxins containing lipid A. Using lipid A from Escherichia coli as a model substance for this kind of pyrogen, different dialyzers (F4, E3. Acepal 1300, Altraflux, F 40, Polyflux 110, Filtral 12, F 60) were challenged by tangential filtration in aqueous medium. All membranes exhibited impermability to lipid A (as well as to LPS from Pseudomonas aeruginosa), which was proved by additional experiments using culture filtrates of Pseudomonas aeruginosa in bicarbonate dialysis fluid, as well as by employing miniaturized dialyzers with synthetic lipid A as a contaminant. Furthermore, the highest adsorption capacities were found for polysulfone and polyamide membranes.


Gender difference in cardiopulmonary reflex inhibition of sympathetic nerve activity.
We tested the hypothesis that reflex responses to mechanical [increase in left atrial pressure (LAP) 0-25 mmHg] and chemical stimulation [left atrial injection of phenylbiguanide (PBG), 0.5-10 mg/kg] of cardiopulmonary receptors are greater in female (n = 9; 335 +/- 9 g) than in male (n = 10; 558 +/- 23 g) age-matched rats. Anesthetized (500 mg/kg urethan and 80 mg/kg alpha-chloralose), tracheotomized, and artificially ventilated (100% oxygen), sinoaortic-denervated animals were instrumented with left atrial, femoral venous, and arterial catheters and a Tygon occluder around the ascending aorta. Reflex inhibition of lumbar sympathetic nerve activity (LSNA) vs. LAP and dose PBG was higher in female rats. A two-way analysis of variance revealed a significant gender effect, males vs. females (P = 0.023), and a significant gender x dose interaction (P < 0.001) for LSNA vs. LAP. There was also a significant gender x dose interaction (P < 0.001) for LSNA vs. PBG. However, there was no influence of gender on the reflex inhibition of mean arterial pressure (P = 0.751) or heart rate (P = 0.561). These responses were associated with a higher left ventricular weight-to-body weight ratio in females (2.14 +/- 0.06 vs. 1.95 +/- 0.07 g/kg, P = 0.039).


Giant Thermoelectric Seebeck Coefficients in Tellurium Quantum Wires Formed Vertically in an Aluminum Oxide Layer by Electrical Breakdown.
High efficiency thermoelectric (TE) materials still require high thermopower for energy harvesting applications. A simple elemental metallic semiconductor, tellurium (Te), has been considered critical to realize highly efficient TE conversion due to having a large effective band valley degeneracy. This paper demonstrates a novel approach to directly probe the out-of-plane Seebeck coefficient for one-dimensional Te quantum wires (QWs) formed locally in the aluminum oxide layer by well-controlled electrical breakdown at 300 K. Surprisingly, the out-of-plane Seebeck coefficient for these Te QWs ≈ 0.8 mV/K at 300 K. This thermopower enhancement for Te QWs is due to Te intrinsic nested band structure and enhanced energy filtering at Te/AO interfaces. Theoretical calculations support the enhanced high Seebeck coefficient for elemental Te QWs in the oxide layer. The local-probed observation and detecting methodology used here offers a novel route to designing enhanced thermoelectric materials and devices in the future.


Characterization of ventricular repolarization in male and female guinea pigs.
Since both components of the delayed rectifier K(+) currents (I(Kr) and I(Ks)) are present in guinea pig and human ventricle, the guinea pig appears as an interesting model to examine the contribution of these currents in sex-related difference of cardiac repolarization. Accordingly, we compared ventricular repolarization in adult male and female guinea pigs using electrophysiological protocols together with Western blots analysis and perfused heart preparation. Our results indicate that there was no sex-related difference in the expression levels of the different K(+) channels studied (ERG, KvLQT1, minK and Kir2.1), nor in the density of the K(+) currents (I(Kr), I(Ks) and I(K1)) encoded by these channels. Action potential durations and QTc intervals were also similar between males and females. In addition, we compared QTc intervals using Langendorff-perfused whole hearts in the presence of I(Kr) and/or I(Ks) blockers. The I(Kr) blocker (5 microM E-4031) prolonged QTc intervals to a similar extent in male (24+/-2%) and female (29+/-3%, p=0.1) hearts. Similarly, the degree of QTc prolongation induced by 0.1 microM HMR1556 (I(Ks) blocker) was similar in both sexes (males: 15+/-2% and females 18+/-2%; p=0.2). In addition to their QT prolonging effects, the I(Kr) and I(Ks) blockers significantly reduced heart rate in both male and female guinea pigs. These studies clearly demonstrate that adult guinea pigs do not display sex differences in ventricular repolarization.


Male cancer mortality by occupation: 1973-86.
To identify male occupational groups with increased risk of death from cancer in 1973-86. Age and social class standardised mortality ratios were calculated for males 15-64 years for all cancers combined and for site specific cancers by occupational group. In general, higher socio-economic groups had a lower all cancer mortality and lower socio-economic groups a higher mortality. After standardisation for age and social class, mortality ratios were increased for lung cancer in bricklayers and carpenters (SMR = 125; 95% CI: 110-141), machine tool operators (SMR = 218; 95% CI: 131-342), and welders (SMR = 140; 95% CI: 120-161), with the first group also having an increased risk for pleural mesothelioma (SMR = 222; 95% CI: 70-522). Malignant melanoma risk was increased in clerical workers (SMR = 147; 95% CI: 106-199) and not in outdoor occupations. Colon cancer mortality risk was increased in managers (SMR = 125; 95% CI: 104-148), and woodworkers (SMR = 147; 95% CI: 115-186). Stomach cancer mortality risk was raised for machine tool operators (SMR = 357; 95% CI: 128-782). Painters had an increased ratio for multiple myeloma (SMR = 352; 95% CI: 140-729) and machine tool operators an increase for leukaemia (SMR = 172; 95% CI: 45-446). The use of routinely collected data to examine cancer mortality by occupation is a useful method to identify groups with increased risks and provide information for hypothesis generation. Further research may be warranted to investigate lung and digestive cancers in woodworkers and machine tool operators, and cancer of the haemopoietic and lymphatic systems in painters and machine tool operators.


Cross-cultural adaptation to Spanish of the Perceived Sensivity to Medicines scale.
Patients' views regarding the actions and side effects of medicines can be measured with the Perceived Sensitivity to Medicines (PSM) scale. The aim of this study was to translate and adapt the PSM scale for use in the Spanish population. The translation and cultural adaptation of the PSM scale and a pretest of the Spanish version were carried out with 50 patients receiving outpatient care in various specialties. There were no difficulties in the stages of the translation and adaptation process. In the cognitive interview, participants found the five items easy to understand (mean score of 3.86±0.24 out of 4). Given its brevity, the Spanish version of the PSM scale represents an easily applicable tool for both research and clinical purposes.


Surface Adsorption in Ternary Surfactant Mixtures above the Critical Micelle Concentration: Effects of Asymmetry on the Composition Dependence of the Excess Free Energy.
The composition of the adsorbed layer of a ternary surfactant mixture at the air-water interface has been studied by neutron reflectivity. The adsorption of the ternary mixture of octaethylene monododecyl ether (C12E8) sodium dodecyl 6-benzene sulfonate (LAS), and sodium dioxyethylene glycol monododecyl sulfate (SLES), as well as each of the binary mixtures, at solution concentrations greater than the mixed critical micelle concentration is highly nonideal. In the ternary mixture, the surface adsorption is dominated by C12E8 and LAS, and there is little SLES at the interface. The departure from ideality in the binary mixtures can be quantitatively described by applying the pseudophase approximation with quadratic and cubic terms in the excess free energy of mixing (GE) both at the surface and in the micelles. The same parameters that describe the binary interactions give a quantitative fit to the adsorbed fractions in the ternary mixture over a wide range of composition. A similar analysis is effective for the mixture containing sodium dodecyl sulfate instead of SLES. Of the set of six GE required to fit the ternary data, one is ideal (SLES-LAS) and three, LAS-C12E8 (micelle) and C12E8-SLES (micelle and surface), have minima occurring at a composition (mole fraction) of the anionic species of 1/3.


Anterior condylar confluence dural arteriovenous fistula: a rare cause of hoarseness.
Hoarseness secondary to an anterior condylar confluence (ACC) dural arteriovenous fistula (DAVF) has not been previously described. We present a 58-year-old patient with a 3-week history of progressive unilateral left-sided headaches and hoarseness. Nasolaryngoscopy and CT neck showed the presence of unilateral vocal cord palsy with no identifiable cause along the expected course of the recurrent laryngeal nerve. MRI revealed an incidental finding of abnormal serpiginous vessels in the left hypoglossal canal which led to a diagnostic cerebral angiogram, confirming the presence of an ACC DAVF. The patient underwent transvenous coil embolisation with subsequent resolution of arteriovenous shunting and symptoms. Follow-up MRI at 6 months showed no recurrence and there was complete resolution of clinical symptoms.


Monitoring nonadiabatic avoided crossing dynamics in molecules by ultrafast X-ray diffraction.
We examine time-resolved X-ray diffraction from molecules in the gas phase which undergo nonadiabatic avoided-crossing dynamics involving strongly coupled electrons and nuclei. Several contributions to the signal are identified, representing (in decreasing strength) elastic scattering, contributions of the electronic coherences created by nonadiabatic couplings in the avoided crossing regime, and inelastic scattering. The former probes the charge density and delivers direct information on the evolving molecular geometry. The latter two contributions are weaker and carry spatial information through the transition charge densities (off-diagonal elements of the charge-density operator). Simulations are presented for the nonadiabatic harpooning process in the excited state of sodium fluoride.


Spectral analysis of organic LED emitters' orientation in thin layers by resonant emission on dielectric stacks.
Purposely tailored thin film stacks sustaining surface waves have been utilized to create a unique link between emission angle and wavelength of fluorescent dye molecules. The knowledge of the thin film stack's properties allows us to derive the intrinsically emitted luminescence spectrum as well as to gain information about the orientation of fluorophores from angularly resolved experiments. This corresponds to replacing all the equipment necessary for polarized spectroscopy with a single smart thin film stack, potentially enabling single shot analyses in the future. The experimental results agree well with those from other established techniques, when analyzing the Rubrene derivative in a 2,4,6-tris(biphenyl-3-yl)-1,3,5-triazine (T2T) host used for the fabrication of optimized organic light-emitting diodes. The findings illustrate how resonant layered stacks can be applied to integrated spectroscopic analyses.


Modeling aeolian transport of soil-bound plutonium: considering infrequent but normal environmental disturbances is critical in estimating future dose.
Dose assessments typically consider environmental systems as static through time, but environmental disturbances such as drought and fire are normal, albeit infrequent, events that can impact dose-influential attributes of many environmental systems. These phenomena occur over time frames of decades or longer, and are likely to be exacerbated under projected warmer, drier climate. As with other types of dose assessment, the impacts of environmental disturbances are often overlooked when evaluating dose from aeolian transport of radionuclides and other contaminants. Especially lacking are predictions that account for potential changing vegetation cover effects on radionuclide transport over the long time frames required by regulations. A recently developed dynamic wind-transport model that included vegetation succession and environmental disturbance provides more realistic long-term predictability. This study utilized the model to estimate emission rates for aeolian transport, and compare atmospheric dispersion and deposition rates of airborne plutonium-contaminated soil into neighboring areas with and without environmental disturbances. Specifically, the objective of this study was to utilize the model results as input for a widely used dose assessment model (CAP-88). Our case study focused on low levels of residual plutonium found in soils from past operations at Los Alamos National Laboratory (LANL), in Los Alamos, NM, located in the semiarid southwestern USA. Calculations were conducted for different disturbance scenarios based on conditions associated with current climate, and a potential future drier and warmer climate. Known soil and sediment concentrations of plutonium were used to model dispersal and deposition of windblown residual plutonium, as a function of distance and direction. Environmental disturbances that affected vegetation cover included ground fire, crown fire, and drought, with reoccurrence rates for current climate based on site historical patterns. Using site-specific meteorology, accumulation rates of plutonium in soil were modeled in a variety of directions and distances from LANL sources. Model results suggest that without disturbances, areas downwind to the contaminated watershed would accumulate LANL-derived plutonium at a relatively slow rate (<0.01 Bq m(-2) yr(-1)). However, model results under more realistic assumptions that include environmental disturbances show accumulation rates more than an order-of-magnitude faster. More generally, this assessment highlights the broader need in radioecology and environmental health physics to consider infrequent but normal environmental disturbances in longer-term dose assessments.


Conformer-specific and two-fold adiabatic photoisomerization of ZZ-1,4-di-(2-quinolylethenyl)benzene.
Irradiation of the ZZ stereoisomer of 1,4-di-(2'-quinolylethenyl)-benzene was found to cause direct adiabatic (one photon-two bond) isomerization to a product having the same lifetime as the EE isomer but a rather different spectrum with respect to that obtained by direct excitation of the EE one. To clarify this unexpected behaviour, the conformational equilibria of the EE stereoisomer have been studied in non-polar solvent by fluorimetry. The most abundant conformers, formed by the hindered rotation of the condensed-ring groups around the quasi-single bond with the ethenic carbons, have been characterized by the selective effect of the excitation energy on the fluorescence spectrum. The combined application of the principal component analysis allowed the separation of the spectral properties of three conformers to be achieved. Information on their structures was obtained by theoretical calculations. The results of the present conformational study clearly indicated that the fluorescence spectrum of the photoproduct of ZZ belongs to a specific component of the conformer mixture of the EE isomer.


Analysis of serum and whole blood values in relation to helminth and ectoparasite infections of feral pigs in Texas.
In the summers of 1996 and 1997, 60 wild pigs (Sus scrofa) were necropsied from three sites in south Texas (USA) to test the hypothesis that serum and whole blood parameters vary significantly (P < or = 0.05) with the prevalence and intensity of parasites infecting wild pigs. We found ten parasite species: five nematodes (Metastrongylus salmi, Metastrongylus pudentotectus, Stephanurus dentatus, Oesophagostomum dentatum, and Physocephalus sexalatus); four ixodid ticks (Amblyomma cajennense, Amblyomma maculatum, Amblyomma americanum, and Dermacentor variabilis); and one trematode (Fascioloides magna). Among juvenile pigs, the intensity of the four species of ticks, collectively, was negatively correlated (P < or = 0.05) with whole blood principal component number one (PC-1); this factor was positively associated with lymphocytes and eosinophils. Lungworm intensity (Metastrongylus spp.) among adult pigs was negatively correlated (P < or = 0.05) with whole blood PC-2; this factor was negatively associated with segmented neutrophils and monocytes. There were no significant correlations found between parasite prevalences and either serum or whole blood principal component factors. The correlations observed between parasite intensities and serum and whole blood parameters generally were weak. Thus, we found no strong evidence that serum and whole blood parameters provided good predictive information on parasite infections in wild pigs for most practical management decisions.


The ligninolytic peroxidases in the genus Pleurotus: divergence in activities, expression, and potential applications.
Mushrooms of the genus Pleurotus are comprised of cultivated edible ligninolytic fungi with medicinal properties and a wide array of biotechnological and environmental applications. Like other white-rot fungi (WRF), they are able to grow on a variety of lignocellulosic biomass substrates and degrade both natural and anthropogenic aromatic compounds. This is due to the presence of the non-specific oxidative enzymatic systems, which are mainly consisted of lacasses, versatile peroxidases (VPs), and short manganese peroxidases (short-MnPs). Additional, less studied, peroxidase are dye-decolorizing peroxidases (DyPs) and heme-thiolate peroxidases (HTPs). During the past two decades, substantial information has accumulated concerning the biochemistry, structure and function of the Pleurotus ligninolytic peroxidases, which are considered to play a key role in many biodegradation processes. The production of these enzymes is dependent on growth media composition, pH, and temperature as well as the growth phase of the fungus. Mn(2+) concentration differentially affects the expression of the different genes. It also severs as a preferred substrate for these preoxidases. Recently, sequencing of the Pleurotus ostreatus genome was completed, and a comprehensive picture of the ligninolytic peroxidase gene family, consisting of three VPs and six short-MnPs, has been established. Similar enzymes were also discovered and studied in other Pleurotus species. In addition, progress has been made in the development of molecular tools for targeted gene replacement, RNAi-based gene silencing and overexpression of genes of interest. These advances increase the fundamental understanding of the ligninolytic system and provide the opportunity for harnessing the unique attributes of these WRF for applied purposes.


Sequential Dy(OTf)3 -Catalyzed Solvent-Free Per-O-Acetylation and Regioselective Anomeric De-O-Acetylation of Carbohydrates.
Dysprosium(III) trifluoromethanesulfonate-catalyzed per-O-acetylation and regioselective anomeric de-O-acetylation of carbohydrates can be tuned by adjusting the reaction medium. In this study, the per-O-acetylation of unprotected sugars by using a near-stoichiometric amount of acetic anhydride under solvent-free conditions resulted in the exclusive formation of acetylated saccharides as anomeric mixtures, whereas anomeric de-O-acetylation in methanol resulted in a moderate-to-excellent yield. Reactions with various unprotected monosaccharides or disaccharides followed by a semi-one-pot sequential conversion into the corresponding acetylated glycosyl hemiacetal also resulted in high yields. Furthermore, the obtained hemiacetals could be successfully transformed into trichloroimidates after Dy(OTf)3 -catalyzed glycosylation.


The relationship between preoperative factors and the presence of intramedullary increased signal intensity on T2-weighted magnetic resonance imaging in patients with cervical spondylotic myelopathy.
To investigate preoperative factors affecting the presence of intramedullary increased signal intensity (ISI) on T2-weighted magnetic resonance imaging (MRI) in patients with cervical spondylotic myelopathy (CSM) and the impact of ISI on clinical manifestations. Eighty-nine patients with CSM were retrospectively reviewed from January 2013 to December 2016 in our hospital. Based on the presence or absence of ISI on axial and sagittal T2-weighted MRI, patients were divided into ISI group (48 cases) and non-ISI group (41 cases). Factors such as age, sex, body mass index (BMI), duration of symptoms, clinical symptoms and signs, number and distribution of spinal cord compression levels, preoperative Japanese Orthopedic Association (JOA) score, preoperative C2-C7 lordotic angle, preoperative C2-C7 range of motion (ROM), maximal canal compromise (MCC) and maximal spinal cord compression (MSCC) were initially compared using univariate analysis. Factors with significant result in univariate analysis were included in multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were applied to evaluate the reliability of multivariate logistic regression model. Univariate analysis showed that the number of spinal cord compression levels, preoperative JOA score, MCC and MSCC might be related to the presence of ISI (P < 0.05). Furthermore, multivariate logistic regression analysis revealed that the number of spinal cord compression levels (OR = 0.203, P < 0.05), preoperative JOA score (OR = 4.274, P < 0.05) and MSCC (OR = 0.250, P < 0.05) were independent preoperative risk factors associated with the presence of ISI, yielding an AUC of 0.9558. Patients with ISI showed a trend of increasing clinical symptoms and signs, and also exhibited statistically significantly increased frequencies of clumsy hands, lower limb spasticity, impairment of gait, broad-based, unstable gait, weakness and motor deficits (P < 0.05). Multilevel spinal cord compression, lower preoperative JOA score and greater MSCC are independent preoperative risk factors related to the presence of ISI on T2-weighted MRI in patients with CSM. Patients with ISI tend to have more clinical symptoms and signs, especially in lower limb manifestations and motor deficits.


Sex hormones reduce NNK detoxification through inhibition of short-chain dehydrogenases/reductases and aldo-keto reductases in vitro.
Carbonyl reduction is an important metabolic pathway for endogenous and xenobiotic substances. The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine ketone) is classified as carcinogenic to humans (IARC, Group 1) and considered to play the most important role in tobacco-related lung carcinogenesis. Detoxification of NNK through carbonyl reduction is catalyzed by members of the AKR- and the SDR-superfamilies which include AKR1B10, AKR1C1, AKR1C2, AKR1C4, 11β-HSD1 and CBR1. Because some reductases are also involved in steroid metabolism, five different hormones were tested for their inhibitory effect on NNK carbonyl reduction. Two of those hormones were estrogens (estradiol and ethinylestradiol), another two hormones belong to the gestagen group (progesterone and drospirenone) and the last tested hormone was an androgen (testosterone). Furthermore, one of the estrogens (ethinylestradiol) and one of the gestagens (drospirenone) are synthetic hormones, used as hormonal contraceptives. Five of six NNK reducing enzymes (AKR1B10, AKR1C1, AKR1C2, AKR1C4 and 11β-HSD1) were significantly inhibited by the tested sex hormones. Only NNK reduction catalyzed by CBR1 was not significantly impaired. In the case of the other five reductases, gestagens had remarkably stronger inhibitory effects at a concentration of 25 μM (progesterone: 66-88% inhibition; drospirenone: 26-87% inhibition) in comparison to estrogens (estradiol: 17-51% inhibition; ethinylestradiol: 14-79% inhibition) and androgens (14-78% inhibition). Moreover, in most cases the synthetic hormones showed a greater ability to inhibit NNK reduction than the physiologic derivatives. These results demonstrate that male and female sex hormones have different inhibitory potentials, thus indicating that there is a varying detoxification capacity of NNK in men and women which could result in a different risk for developing lung cancer.


Alginate lyase promotes diffusion of aminoglycosides through the extracellular polysaccharide of mucoid Pseudomonas aeruginosa.
We demonstrated that a 2% suspension of Pseudomonas aeruginosa alginate completely blocked the diffusion of gentamicin and tobramycin, but not that of carbenicillin, illustrating how alginate production can help protect P. aeruginosa growing within alginate microcolonies in patients with cystic fibrosis (CF) from the effects of aminoglycosides. This aminoglycoside diffusion barrier was degraded with a semipurified preparation of P. aeruginosa alginate lyase, suggesting that this enzyme deserves consideration as an adjunctive agent for CF patients colonized by mucoid strains of P. aeruginosa.


Cultivation of microalgal Chlorella for biomass and lipid production using wastewater as nutrient resource.
Using wastewater for microalgal cultures is beneficial for minimizing the use of freshwater, reducing the cost of nutrient addition, removing nitrogen and phosphorus from wastewater and producing microalgal biomass as bioresources for biofuel or high-value by-products. There are three main sources of wastewater, municipal (domestic), agricultural and industrial wastewater, which contain a variety of ingredients. Some components in the wastewater, such as nitrogen and phosphorus, are useful ingredients for microalgal cultures. In this review, the effects on the biomass and lipid production of microalgal Chlorella cultures using different kinds of wastewater were summarized. The use of the nutrients resource in wastewater for microalgal cultures was also reviewed. The effect of ammonium in wastewater on microalgal Chlorella growth was intensively discussed. In the end, limitations of wastewater-based of microalgal culture were commented in this review article.


Human uroplakin lb gene structure and promoter analysis.
The uroplakin Ib (UPIb) gene is predominantly expressed in urothelium and is overexpressed in 50% of transitional cell carcinoma (TCC). Molecular cloning of the genomic 5' region and comparison to a chromosome 3q genomic contig determined that the gene spans 31 kb and has eight exons including a noncoding exon 1. Multiple transcription start sites were identified in exon 1 by 5'RACE and ribonuclease protection assay (RPA). In vitro reporter gene analysis was performed with 2.3 kb of genomic DNA sequence flanking the 5' end of UPIb. A 235-bp 5' fragment that included UPIb exon 1 generated strong transcriptional activity in normal and malignant human urothelial cell lines. Established malignant cell lines had greater transcriptional activity from the UPIb promoter than normal human cells. The identification of a functional human UPIb gene promoter may find application in targeting gene therapy strategies for bladder cancer.


Induction of early pregnancy factor activity in vitro by platelet-activating factor in mice.
The rosette inhibition test was used to determine early pregnancy factor activity in culture media from oestrous mouse ovaries and oviducts stimulated in vitro for early pregnancy factor production under different experimental conditions. Embryo conditioned media, platelet-activating factor and cortical granule release media could all stimulate the production of early pregnancy factor by oestrous mouse ovaries and oviducts. This stimulation was completely blocked by the presence of BN 52021, a platelet-activating factor receptor antagonist. This study indicates that platelet-activating factor is the 'ovum factor' released by the zygote on fertilization to initiate the synthesis of early pregnancy factor.


Umbilical temperature correlation with core and skin temperatures at rest, in the heat and during physical activity.
to determine the correlation of umbilical temperatures (Tumb) with simultaneously recorded chest wall temperature (Tchest) and rectal temperature (Trectal) in adults during rest, heat exposure and exercise. A total of 28 healthy men, wearing different types of clothing (athletic garb, a spandex full body heating garment, firefighter bunker gear) had average and peak umbilical, chest wall and rectal temperature measurements taken during sedentary temperature stabilisation stages, heat exposure periods and active exercise phases. Curvilinear relationships were noted between Tchest and Tumb compared with Trectal and their association became noticeably positive and linear at approximately 35.5 °C. Polynomial regression analysis of Trectal with linear and quadratic forms of Tchest and Tumb indicated an overall R2 of 0.657 and 0.767, respectively. Bivariate analysis of a restricted data set (where Tchest and Tumb ≥35.5°), indicated that Tumb was significantly associated with Trectal (raverage = 0.710, p <0.001; rpeak = 0.841, p <0.001) and Tchest was also significantly associated with Trectal, but less so (raverage = 0.570, p <0.001; rpeak = 0.699, p <0.001). the umbilicus offers a non-invasive, peripheral site for measurement of temperature that more closely correlated with body core temperature than Tchest when core temperature was ≥35.5 °C.


Exploring couple attributes and attitudes and marital violence in Vietnam.
Using a couple-centered approach, this study focuses on the relative attributes and attitudes of spouses as predictors of marital violence. Analysis of data from Vietnam showed that 37% of married women have ever been hit by their husbands. Regression results found that husbands with lower resources or status than their wives were more likely to have abused. Results also found that the association between husbands' gender attitudes and marital violence depends on the level of equity of wives'attitudes. The decline in violence among couples in which husbands expressed gender equitable attitudes was greater when wives also expressed equitable attitudes.


Inhibitors of Mycobacterium marinum virulence identified in a Dictyostelium discoideum host model.
Tuberculosis remains one of the major threats to public health worldwide. Given the prevalence of multi drug resistance (MDR) in Mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. Inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. In this study, we used a Dictyostelium discoideum host model to assess virulence of Mycobacterium marinum and to identify compounds inhibiting mycobacterial virulence. Among 9995 chemical compounds, we selected 12 inhibitors of mycobacterial virulence that do not inhibit mycobacterial growth in synthetic medium. Further analyses revealed that 8 of them perturbed functions requiring an intact mycobacterial cell wall such as sliding motility, bacterial aggregation or cell wall permeability. Chemical analogs of two compounds were analyzed. Chemical modifications altered concomitantly their effect on sliding motility and on mycobacterial virulence, suggesting that the alteration of the mycobacterial cell wall caused the loss of virulence. We characterized further one of the selected compounds and found that it inhibited the ability of mycobacteria to replicate in infected cells. Together these results identify new antimycobacterial compounds that represent new tools to unravel the molecular mechanisms controlling mycobacterial pathogenicity. The isolation of compounds with anti-virulence activity is the first step towards developing new antibacterial treatments.


The anticonvulsant, local anesthetic and hemodynamic properties of some chiral aminobutanol derivatives of xanthone.
In the present study, several pharmacological tests in animals were carried out to assess potential anticonvulsant, local anesthetic and hemodynamic activity of novel 2- and 4-substituted aminobutanol chiral derivatives of xanthone (hydrochlorides of: (R,S)-2-[(7-chloro)-2-xanthonemethyl)]-N-methylaminobutan-1-ol (MH-2(R,S)), (R,S)-2-(4-xanthonemethyl)-aminobutan-1-ol (MH-20(R,S)) and (R,S)-2-[(6-methoxy)-2-xanthonemethyl]-aminobutan-1-ol (MH-26(R,S)) and their pure enantiomers R and S). The obtained results provided evidence that the most interesting anticonvulsant (in maximal electroshock-test) activity was shown by compound MH-2(R), which in dose 100 mg/kg p.o., protected the mice against tonic cramp of extensors similarly as phenytoin. Moreover, this compound, in concentrations from 0.25 to 1%, also possessed high local anesthetic activity (in infiltration anesthesia), comparable to the reference compound, mepivacaine. All examined compounds suppressed the spontaneous locomotor activity in mice, especially compound MH-2(R,S) and MH-20(R,S), and their enantiomers. The impairment of motor coordination (in chimney test) for applied doses was not observed. Furthermore, compound MH-20(S) at dose corresponding to 1/10 LD50 displayed an interesting hemodynamic activity and significantly decreased systolic and diastolic blood pressure in rats. All examined compounds showed chronotropic negative effect in anesthetized rats ECG record. The most reducing heart frequency was observed for enantiomers S of aminobutanol derivatives of xanthone, especially MH-2(S). The LD50 values of the investigated compounds were comparable with LD50 value of the reference compound in local anesthesia tests--mepivacaine. These studies demonstrated different strength of enantiomers and racemic mixture in carried out tests, where the R enantiomers presented rather central and local anesthetic properties, whereas S enatiomers influenced the hemodynamic activity.


Sciatic Nerve to Pudendal Nerve Transfer: Anatomical Feasibility for a New Proposed Technique.
Aim Restoration of bladder and bowel continence after pudendal nerve anastomosis has been shown successfully in animal models and may be applicable in humans. Aim of this cadaveric study was to assess feasibility of pudendal nerve neurotization using motor fascicles from sciatic nerve. Methods Pudendal and sciatic nerves were exposed via gluteal approach in 5 human cadavers (10 sites). Size of pudendal and sciatic nerves and the distance between two nerves was measured. Results There were four male and one female cadavers. Mean age was 62 (range, 50-70) years. Mean pudendal nerve diameter was 2.94 mm (right side) and 2.82 mm (left side). Mean sciatic nerve diameter was 11.2 mm (right side) and 14.2 mm (left side). The distance between two nerves was 23.4 mm on both sides. Conclusion Transfer of the motor fascicles from sciatic nerve to pudendal nerve to restore the bladder and bowel continence is feasible.


Electromyographic (EMG) study of cold shivering in the chronic spinal dog.
Cold shivering in six chronic spinal dogs (T9-10), which became capable of weight-bearing standing and/or walking with their hindlimbs, was studied by electromyography (EMG). In the forequarters, EMG activities in the form of grouping discharges (GD) accompanied by visible tremor (VT) were induced at an ambient temperature of 15 degrees C in all the dogs. In the hindquarters, GD with VT were induced at 3 degrees C in one dog. Although GD with VT were not induced in in the remaining dogs, GD without VT were produced by additional cutaneous stimuli to the hindquarters at 3 degrees C. These stimuli never produced GD in the hindquarters at room temperature. Though the mean frequency of GD in the hindquarters was lower than that in the forequarters, the range of the frequency in the hindquarters was much the same as that in the forequarters. During the experiment, the drop in rectal temperature was less than 0.6 degrees C in all of the dogs. These findings suggest that the chronically isolated spinal cord is responsible for cold shivering, while its excitability to cold exposure is less than that of the spinal cord governed by the supraspinal center.


Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy.
Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place. We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis. Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability. Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.


The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice.
Endoplasmic reticulum (ER) stress has been associated with development of inflammatory bowel disease. We examined the effects of ER stress-induced chaperone response and the orally active chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (PBA), which facilitate protein folding and reduce ER stress, in mice with colitis. We used dextran sulfate sodium (DSS) to induce colitis in mice that do not express the transcription factor ATF6α or the protein chaperone P58(IPK). We examined the effects of TUDCA and PBA in cultured intestinal epithelial cells (IECs); in wild-type, P58(IPK-/-), and Atf6α(-/-) mice with colitis; and in Il10(-/-) mice. P58(IPK-/-) and Atf6α(-/-) mice developed more severe colitis following administration of DSS than wild-type mice. IECs from P58(IPK-/-) mice had excessive ER stress, and apoptotic signaling was activated in IECs from Atf6α(-/-) mice. Inflammatory stimuli induced ER stress signals in cultured IECs, which were reduced by incubation with TUDCA or PBA. Oral administration of either PBA or TUDCA reduced features of DSS-induced acute and chronic colitis in wild-type mice, the colitis that develops in Il10(-/-) mice, and DSS-induced colitis in P58(IPK-/-) and Atf6α(-/-) mice. Reduced signs of colonic inflammation in these mice were associated with significantly decreased ER stress in colonic epithelial cells. The unfolded protein response induces expression of genes that encode chaperones involved in ER protein folding; these factors prevent induction of colitis in mice. Chemical chaperones such as TUDCA and PBA alleviate different forms of colitis in mice and might be developed for treatment of inflammatory bowel diseases.


Crystallization and preliminary X-ray crystallographic analysis of Ca2+-free primary Ca2+-sensor of Na+/Ca2+ exchanger.
The plasma-membrane Na(+)/Ca(2+) exchanger (NCX) regulates intracellular Ca(2+) levels in cardiac myocytes. Two Ca(2+)-binding domains (CBD1 and CBD2) exist in the large cytosolic loop of NCX. The binding of Ca(2+) to CBD1 results in conformational changes that stimulate exchange to exclude Ca(2+) ions, whereas CBD2 maintains the structure, suggesting that CBD1 is the primary Ca(2+)-sensor. In order to clarify the structural scaffold for the Ca(2+)-induced conformational transition of CBD1 at the atomic level, X-ray structural analysis of its Ca(2+)-free form was attempted; the structure of the Ca(2+)-bound form is already available. Recombinant CBD1 (NCX1 372-508) with a molecular weight of 16 kDa was crystallized by the sitting-drop vapour-diffusion method at 293 K. The crystals belonged to the hexagonal space group P6(2)22 or P6(4)22, with unit-cell parameters a = b = 56.99, c = 153.86 A, beta = 120 degrees , and contained one molecule per asymmetric unit (V(M) = 2.25 A(3) Da(-1)) with a solvent content of about 55% (V(S) = 45.57%). Diffraction data were collected within the resolution range 27.72-3.00 A using an R-AXIS detector and gave a data set with an overall R(merge) of 10.8% and a completeness of 92.8%.


Prevalence of Enthesopathies in Adults With X-linked Hypophosphatemia: Analysis of Risk Factors.
Enthesopathies are the determinant of a poor quality of life in adults with X-linked hypophosphatemia (XLH). To describe the prevalence of patients with enthesopathies and to identify the risk factors of having enthesopathies. Retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism between June 2011 and December 2020. Adult XLH patients with full body X-rays performed using the EOS® low-dose radiation system and clinical data collected from medical records. The main outcome measures were demographics, PHEX mutation, conventional treatment, and dental disease with the presence of enthesopathies. Of the 114 patients included (68% women, mean age 42.2 ± 14.3 years), PHEX mutation was found in 105 patients (94.6%), 86 (77.5%) had been treated during childhood. Enthesopathies (spine and/or pelvis) were present in 67% of the patients (n = 76). Patients with enthesopathies were significantly older (P = .001) and more frequently reported dental disease collected from medical records (P = .03). There was no correlation between the PHEX mutations and the presence of enthesopathies. Sixty-two patients had a radiographic dental examination in a reference center. Severe dental disease (number of missing teeth, number of teeth endodontically treated, alveolar bone loss, and proportion of patients with 5 abscesses or more) was significantly higher in patients with enthesopathies. Adult XLH patients have a high prevalence of enthesopathies in symptomatic adults patients with XLH seen in a reference center. Age and severe dental disease were significantly associated with the presence of enthesopathies.


Photoinduced Bimolecular Electron Transfer in Ionic Liquids: Cationic Electron Donors.
Recently, we have reported a systematic study of photoinduced electron-transfer reactions in ionic liquid solvents using neutral and anionic electron donors and a series of cyano-substituted anthracene acceptors [ Wu , B. ; Maroncelli , M. ; Castner , E. W. Jr Photoinduced Bimolecular Electron Transfer in Ionic Liquids . J. Am. Chem. Soc. 139 , 2017 , 14568 ]. Herein, we report complementary results for a cationic class of 1-alkyl-4-dimethylaminopyridinium electron donors. Reductive quenching of cyano-substituted anthracene fluorophores by these cationic quenchers is studied in solutions of acetonitrile and the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Varying the length of the alkyl chain permits tuning of the quencher diffusivities in solution. The observed quenching kinetics are interpreted using a diffusion-reaction analysis. Together with results from the prior study, these results show that the intrinsic electron-transfer rate constant does not depend on the quencher charge in this family of reactions.


Globoid cell leukodystrophy in a Beagle.
Globoid cell leukodystrophy was diagnosed in a purebred Beagle bitch. Clinical signs and histopathologic and ultrastructural features were consistent with those reported in globoid cell leukodystrophy in man, cat, and other breeds of dogs. The occurrence of the disorder in 2 clinically affected females from a related litter and a familial history of inbreeding support the existence of a familial pattern.


Aurintricarboxylic acid promotes the conversion of naive CD4+CD25- T cells into Foxp3-expressing regulatory T cells.
Naive peripheral CD4(+)CD25(-) T cells can be converted into Foxp3-expressing regulatory T cells under appropriate stimulation conditions. Considering that continuous exposure to antigens is one of the prerequisites for the differentiation and maintenance of Treg cells, we investigated whether preventing activation-induced cell death while providing continuous TCR stimulation could promote the expression of Foxp3 in murine naive CD4(+) T cells. Among the several anti-apoptotic agents tested, aurintricarboxylic acid (ATA) was found to induce the in vitro conversion of naive CD4(+) T cells into Foxp3(+) Treg cells with suppressive activity. Neutralizing studies with an antibody against transforming growth factor (TGF)-β revealed that ATA requires the presence of TGF-β to induce Foxp3 expression in naive CD4(+)CD25(-) T cells. Although ATA itself did not activate the Smad signaling pathway, it down-regulated the extracellular signal-regulated kinase and mammalian target of rapamycin signaling cascade in activated T cells. Lastly, combined exposure to ATA and TGF-β had a synergistic effect on the rate of induction and maintenance of Foxp3 expression. These results indicate that ATA could be exploited to efficiently prepare inducible regulatory T cells in vitro and may aid in more precisely identifying the specific signaling pathways that drive Foxp3 expression in T cells.


RECIPROCAL ACTIVITIES OF THE VENTROMEDIAL AND LATERAL HYPOTHALAMIC AREAS OF CATS.
Statistical treatment of recordings of spontaneous unit discharges from the ventromedial nucleus and the lateral area of the hypothalamus (the activities in one area being recorded while the other was stimulated) revealed significant reciprocal relations. The concept that glucose-sensitive neurons are present in the ventromedial nucleus was supported by the effects on the spontaneous unit discharges of injecting glucose and other-solutions intravenously.


Preliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea.
Magnaporthe grisea are pathogenic, directly penetrating fungi which cause rice blast disease. Isolated, non-pathogenic mutant strains which are defective in the biosynthesis of dihydroxynapthalene-derived melanin fail to infect host plants and have been shown to lack certain key enzymes in melanin biosynthesis. One such enzyme is scytalone dehydratase that converts scytalone to 1,3,8-trihydroxy-naphthalene. Crystallization trials of scytalone dehydratase were undertaken with the expectation that structural information on this enzyme would facilitate design of high affinity inhibitors which might find use in the control of rice blast disease. We now report that recombinant scytalone dehydratase, complexed with a tight binding inhibitor, has been crystallized with PEG 4000 as a precipitant. The crystals are trigonal and belong to the space group P321 with the cell dimension: a = b = 75.5 A, c = 73.8 A. The observed diffraction extends to 2.5 A. Analysis of the packing in the cell suggests that scytalone dehydratase forms a symmetric trimer. These results are consistent with sedimentation equilibrium experiments indicating that the solution aggregation state of scytalone dehydratase was trimeric over a 24,000-fold concentration range.


Incidence and Risk Factors of Postoperative Adjacent Segment Degeneration Following Anterior Decompression and Instrumented Fusion for Degenerative Disorders of the Cervical Spine.
To explore incidence and risk factors of postoperative adjacent segment degeneration (ASD) following anterior decompression and instrumented fusion for degenerative disorders of the cervical spine. Medical records from January 2005 to September 2011 of 283 patients were retrospectively reviewed. Patients were divided into 2 groups based on occurrence of ASD at follow-up: ASD group and no ASD group. To investigate risk for occurrence of ASD, 3 sets of factors were analyzed statistically: patient characteristics, surgical variables, and radiographic parameters. Postoperative ASD developed in 68 of 283 patients. There was no statistically significant difference between the 2 groups in patient characteristics or the surgical variables of surgical strategy, surgical time, and blood loss. The number of patients receiving 2-level spinal fusion was higher in the ASD group. Upper instrumented vertebra at C5 was more common in the ASD group. There was no difference between groups in all but 1 of the radiographic parameters; the plate-to-disc distance was much smaller in the ASD group. Logistic regression analysis revealed that upper instrumented vertebra at C5, plate-to-disc distance <3.0 mm, and 2-level anterior cervical fusion were independently associated with ASD. Patients with degenerative disorders of the cervical spine who receive 2-level cervical fusion and with upper instrumented vertebra at C5 are at high potential risk of ASD.


The effect on consent rates for deceased organ donation in Wales after the introduction of an opt-out system.
Organ transplantation saves and transforms lives. Failure to secure consent for organ retrieval is widely regarded as the single most important obstacle to transplantation. A soft opt-out system of consent for deceased organ donation was introduced into Wales in December 2015, whilst England maintained the existing opt-in system. Cumulative data on consent rates in Wales were compared with those in England, using a two-sided sequential procedure that was powered to detect an absolute difference in consent rates between England and Wales of 10%. Supplementary risk-adjusted logistic regression analysis examined whether any difference in consent rates between the two nations could be attributed to variations in factors known to influence UK consent rates. Between 1 January 2016 and 31 December 2018, 8192 families of eligible donors in England and 474 in Wales were approached regarding organ donation, with overall consent rates of 65% and 68%, respectively. There was a steady upward trend in the proportion of families consenting to donation after brain death in Wales as compared with England and after 33 months, this reached statistical significance. No evidence of any change in the donation after circulatory death consent rate was observed. Risk-adjusted logistic regression analysis revealed that by the end of the study period the probability of consent to organ donation in Wales was higher than in England (OR [95%CI] 2.1 [1.26-3.41]). The introduction of a soft opt-out system of consent in Wales significantly increased organ donation consent though the impact was not immediate.


Comparative effects of single-dose ceftriaxone versus three oral antibiotic regimens on stool colonization by resistant bacilli in children.
The use of short-term intramuscular ceftriaxone for pediatric ambulatory conditions raises concerns regarding the promotion of resistance among colonizing enteric bacteria. This study was designed to assess the prevalence of stool colonization with resistant Gram-negative bacilli after single-dose ceftriaxone treatment compared with other regimens for acute otitis media. Children age 3 months to 7 years and diagnosed with acute otitis media were randomized to receive treatment with single-dose ceftriaxone or with oral cefprozil, amoxicillin or azithromycin. Stool samples were obtained at enrollment and then 3-5 days, 10-14 days, and 28-30 days after therapy was initiated and screened for the presence of facultative Gram-negative bacilli resistant to ceftriaxone, cefprozil, amoxicillin, piperacillin, piperacillin-tazobactam and tobramycin. Mean prevalence of colonization by resistant organisms for each treatment group was compared at each time point. One thousand nine subjects were enrolled. The prevalence of colonization by a Gram-negative bacillus resistant to at least 1 of the screening antibiotics decreased after receipt of ceftriaxone but returned close to values measured at study entry by 30 days. A qualitatively similar pattern was noted for the 3 other regimens, but a quantitatively greater decrease in the prevalence of colonization by a resistant bacterium was noted at the 3- to 5-day and 10- to 14-day visits among azithromycin recipients (P < 0.001). Colonization by a Gram-negative bacillus resistant specifically to ceftriaxone was unusual at each study visit, regardless of treatment assignment. A single intramuscular dose of ceftriaxone had a similar effect on the prevalence of antibiotic-resistant Gram-negative facultative bacilli in the stool of healthy children when compared with commonly used oral agents.


Combined Traction Force-Atomic Force Microscopy Measurements of Neuronal Cells.
In the course of the development of the nervous system, neuronal cells extend (grow) axons, which navigate over distances of the order of many cell diameters to reach target dendrites from other neurons and establish neuronal circuits. Some of the central challenges in biophysics today are to develop a quantitative model of axonal growth, which includes the interactions between the neurons and their growth environment, and to describe the complex architecture of neuronal networks in terms of a small number of physical variables. To address these challenges, researchers need new experimental techniques for measuring biomechanical interactions with very high force and spatiotemporal resolutions. Here we report a unique experimental approach that integrates three different high-resolution techniques on the same platform-traction force microscopy (TFM), atomic force microscopy (AFM) and fluorescence microscopy (FM)-to measure biomechanical properties of cortical neurons. To our knowledge, this is the first literature report of combined TFM/AFM/FM measurements performed for any type of cell. Using this combination of powerful experimental techniques, we perform high-resolution measurements of the elastic modulus for cortical neurons and relate these values with traction forces exerted by the cells on the growth substrate (poly acrylamide hydrogels, or PAA, coated with poly D-lysine). We obtain values for the traction stresses exerted by the cortical neurons in the range 30-70 Pa, and traction forces in the range 5-11 nN. Our results demonstrate that neuronal cells stiffen when axons exert forces on the PAA substrate, and that neuronal growth is governed by a contact guidance mechanism, in which axons are guided by external mechanical cues. This work provides new insights for bioengineering novel biomimetic platforms that closely model neuronal growth in vivo, and it has significant impact for creating neuroprosthetic interfaces and devices for neuronal growth and regeneration.


[Discussion on methods for searching traditional Chinese medical literature in English in PubMed-MEDLINE database].
The methods for searching traditional Chinese medical literature in English with subject headings in PubMed-MEDLINE database were discussed from the practical view, and seven useful searching methods with free words according to practical experiences were put forward in order to assist the domestic TCM researchers to utilize PubMed-MEDLINE database in searching overseas TCM literature in English.


MC2R/MRAP2 activation could affect bovine ovarian steroidogenesis potential after ACTH treatment.
Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, reducing fertility by interfering with the mechanisms that regulate the timing of events within the follicular phase of the estrous cycle. In the HPA axis, melanocortin 2 receptor (MC2R) mediates responses to adrenocorticotropic hormone (ACTH) in concert with melanocortin receptor accessory protein 2 (MRAP2). The aims of the present study were: (1) to evaluate the effects of ACTH administered in cows in the preovulatory period on the expression of the MC2R/MRAP2 complex in the dominant follicle; and (2) to analyze the involvement of Extracellular signal Regulated Kinase 1 (ERK1) signaling in the activation of MC2R and the expression of key enzymes involved in the biosynthesis of glucocorticoids (GCs) in the dominant follicle. To this end, 100 IU ACTH was administered to Holstein cows from a local dairy farm during pro-estrus every 12 h for four days until ovariectomy, which was performed before ovulation. Protein immunostaining of MC2R was higher in the dominant follicles of ACTH-treated cows (p < 0.05). Also, Western blot analysis showed higher activation of the ERK1 signaling pathway in ACTH-treated cows (p < 0.05). Finally, immunohistochemistry performed in the dominant follicles of ACTH-treated cows detected higher expression of CYP17A1 and CYP21A2 (p < 0.05). These results suggest that the bovine ovary is able to respond locally to ACTH as a consequence of stress altering the expression of relevant steroidogenic enzymes. The results also confirm that the complete GC biosynthesis pathway is present in bovine dominant follicle and therefore GCs could be produced locally.


"Bringing home more than a paycheck:" an exploratory analysis of Black lesbians' experiences of stress and coping in the workplace.
Although the workplace stress that Black women and lesbian, gay, bisexual and transgender (LGBT) people experience due to prejudice and discrimination has been well-documented in the social science literature, much of this literature focuses on Black women or LGBTs as if these groups were distinct and mutually exclusive. Consequently, there is a void of theory and research on the workplace stress that Black lesbians experience. This qualitative study involved exploratory analyses of workplace stress due to race, sex/gender, and sexual orientation, and coping strategies among a predominantly middle-class, highly educated sample of 19 Black lesbians between the ages of 26 and 68. Four workplace stressors emerged, those relevant to: heterosexism/ sexual identity; racism/race; sexism/sex/gender; and intersections of race, sex/gender, and sexual orientation. Three primary coping strategies emerged: being out and managing being out, covering their sexual orientation, and confronting or educating coworkers about prejudice and discrimination.


Immunohistochemical staining of human breast cancer with a new tumour marker MCA: relation to axillary lymph node involvement, metastasis, and survival.
The immunohistochemical reactivity of a new tumour marker MCA (mucinous carcinoma associated antigen) was determined in human breast cancer. The material consisted of paraffin-embedded biopsies from the breast tumours in 95 patients. The age of the patients at the time of diagnosis was 58.1 +/- 13.1 years. The maximal follow-up time was 13.3 years and the mean follow-up time 12.4 years (range 11.5-13.3 years). MCA positivity was not related to histological type or size of the tumour. It was, however, related to axillary node involvement (p = 0.05) and metastasis (p = 0.06) during the follow-up time. The prediction of metastasis (p = 0.05) and node involvement (p = 0.048) was better in postmenopausal women. Crude survival or breast cancer survival could not be predicted with statistical significance on the basis of MCA staining. The disease-free survival had an almost statistically significant correlation with MCA positivity (p = 0.09). Our results suggest that the new tumour marker antigen MCA reacts with breast cancer cells in paraffin sections. It might be used in identification of cancer cells in tissue sections. MCA can also be used as a weak indicator of aggressiveness of the tumour.


Echocardiography-Derived Left Ventricular Outflow Tract Gradient and Left Ventricular Posterior Wall Thickening Are Associated with Outcomes for Anatomic Repair in Congenitally Corrected Transposition of the Great Arteries.
Congenitally corrected transposition of the great arteries is a rare form of congenital heart disease. Management is controversial; options include observation, physiologic repair, and anatomic repair. Assessment of morphologic left ventricle preparedness is key in timing anatomic repair. This study's purpose was to review the modalities used to assess the morphologic left ventricle preoperatively and to determine if any echocardiographic variables are associated with outcomes. A retrospective review of patients with congenitally corrected transposition of the great arteries eligible for anatomic repair at Lucile Packard Children's Hospital from 2000 to 2016 was conducted. Inclusion criteria were (1) presurgical echocardiography, magnetic resonance imaging, and cardiac catheterization and (2) clinical follow-up information. Echocardiographic measurements included left ventricular (LV) single-plane Simpson's ejection fraction, LV eccentricity index, LV posterior wall thickening, pulmonary artery band (PAB)/LV outflow tract (LVOT) pressure gradient, and LV and right ventricular strain. Magnetic resonance imaging measurements included LV mass, ejection fraction, eccentricity index, and LV thickening. LV pressure, PAB/LVOT gradient, right ventricular pressure, pulmonary vascular resistance, and Qp/Qs constituted catheterization data. Outcomes included achieving anatomic repair within 1 year of assessment in patients with LVOT obstruction or within 1 year of pulmonary artery banding and freedom from death, transplantation, or heart failure at last follow-up. Forty-one patients met the inclusion criteria. PAB/LVOT gradients of 85.2 ± 23.4 versus 64.0 ± 32.1 mm Hg (P = .0282) by echocardiography and 60.1 ± 19.4 versus 35.9 ± 18.9 mm Hg (P = .0030) by catheterization were associated with achieving anatomic repair and freedom from death, transplantation, and heart failure. Echocardiographic LV posterior wall thickening of 35.4 ± 19.8% versus 20.6 ± 15.0% (P = .0017) and MRI LV septal wall thickening of 37.1 ± 18.8% versus 19.3 ± 18.8% (P = .0306) were associated with achieving anatomic repair. Inter- and intraobserver variability for echocardiographic measurements was very good. PAB/LVOT gradient and LV posterior wall thickening are highly reproducible echocardiographic measurements that reflect morphologic LV performance and can be used in assessing patients with congenitally corrected transposition of the great arteries undergoing anatomic repair.


Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis.
Objective The purpose of this study was to assess the risk of ischaemic heart disease (IHD) and stroke (non-fatal and fatal) among adult ever-users of smokeless tobacco (ST). Design The study design involved a systematic review and meta-analysis of observational studies. Methods Data sources for the review included key electronic databases and reference lists. Studies were included based on design (cohort or case-control), exposure (exclusive use of ST or adjusted for smoking), and outcome (non-fatal and fatal IHD and stroke). Data extraction included reported measures of association (risk ratios (RRs) or odds ratios (ORs)) between ever-use of ST (current or past) and cardiovascular disease (CVD) outcomes among non-smokers, and other study characteristics. The Newcastle-Ottawa scale was used to assess study quality. Summary measures were estimated using random effects models. Results Twenty studies were included in the meta-analyses. Overall, significantly increased risk of IHD deaths (1.15, 95% confidence interval (CI: 1.01-1.30) and stroke deaths (1.39, 95% CI: 1.29-1.49) was found among ever-users of ST. We did not find an overall significant increased risk for IHD (1.14, 95% CI: 0.92-1.42) or stroke (1.01, 95% CI: 0.90-1.13). But geographical variations were marked for IHD, with significant positive association in Asian studies (1.40, 95% CI: 1.01-1.95), and the INTERHEART study, where ST data was mainly reported from Asia (2.23, 95% CI: 1.41-3.53). European studies did not show an increased risk for non-fatal CVD. Conclusion An association was found between ever use of ST and risk of fatal IHD and stroke, consistent with previous reviews. ST consumption also appears to significantly increase risk of non-fatal IHD among users in Asia, but not in Europe.


[Preliminary study of exon sequence in pneumoconiosis using high-throughput and intervention of EGFR-TKIs on silicosis rats].
Objective: To observe the effect of epidermal growth factor receptor tyrosinase inhibitor (EGFR-TKIs) on silica (SiO(2))-induced pulmonary fibrosis in rats, and to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in pulmonary fibrosis. Methods: A rat model of SiO(2) silicosis was established (high, medium and low dose intervention groups, and the model group was infused with silica suspension). The control group was intratracheally injected with the same amount of sterile saline. The rats were intragastrically administered with different concentrations of EGFR-TKIs (13.5 mg/day, 6.75 mg/day, 3.375 mg/day). The model group and the control group were given the same amount of normal saline. Six rats in each group were euthanized on the 3rd, 7th, and 14th days after modeling. HE staining was used to observe the pathological of lung tissue. Masson staining to observe pulmonary fibrosis. Immunohistochemistry (IHC) expression of p-EGFR. Determination of hydroxyproline content by alkaline hydrolysis of the sample, Western Blot was used to detect the contents of TGF-α, Ras, p-Erkl/2, PI-3KCG and Aktl protein in lung tissue. Results: The degree of fibrosis and hydroxyproline content in HE staining and Masson staining decreased with the increase of intervention dose, which was statistically significant (7 d, 14 d). Compared with the model group, the relative expressions of TGF-α, p-Erkl/2 and Aktl protein in lung tissue of each intervention group were statistically significant (P<0.05). The down-regulation of Ras and PI-3KCG protein in the high- and medium-dose intervention group was statistically significant (P<0.05), and there was no significant difference in the low-dose intervention group.Compared with the intervention group, the down-regulation of TGF-α, Ras, and p-Erkl/2 protein in the lung tissue was statistically different in the low-dose group (P<0.05). There was no significant difference between the dose and the medium dose intervention group (P>0.05). PI-3KCG was significantly different only in the high-dose intervention group and the low-dose intervention group on the 7th and 14th day (P<0.05), and there was no difference between the other groups (P>0.05). There was a statistically significant difference in Akt1 between the dose intervention groups (P<0.05). Conclusion: EGFR-TKIs inhibits EGFR-related intracellular tyrosine kinase activity and intracellular phosphorylation, and inhibits the downstream signal transduction pathways of EGFR/PI-3K/AKt and Ras/ERK/MAPK target protein Ras, p-Erkl/2, PI3K, Akt1, thereby alleviating changes in pulmonary fibrosis, this process is dose-dependent, and the high-dose and medium-dose intervention groups have a significant effect.


Effect of Emergency Department and ICU Occupancy on Admission Decisions and Outcomes for Critically Ill Patients.
ICU admission delays can negatively affect patient outcomes, but emergency department volume and boarding times may also affect these decisions and associated patient outcomes. We sought to investigate the effect of emergency department and ICU capacity strain on ICU admission decisions and to examine the effect of emergency department boarding time of critically ill patients on in-hospital mortality. A retrospective cohort study. Single academic tertiary care hospital. Adult critically ill emergency department patients for whom a consult for medical ICU admission was requested, over a 21-month period. None. Patient data, including severity of illness (Mortality Probability Model III on Admission), outcomes of mortality and persistent organ dysfunction, and hourly census reports for the emergency department, for all ICUs and all adult wards were compiled. A total of 854 emergency department requests for ICU admission were logged, with 455 (53.3%) as "accept" and 399 (46.7%) as "deny" cases, with median emergency department boarding times 4.2 hours (interquartile range, 2.8-6.3 hr) and 11.7 hours (3.2-20.3 hr) and similar rates of persistent organ dysfunction and/or death 41.5% and 44.6%, respectively. Those accepted were younger (mean ± SD, 61 ± 17 vs 65 ± 18 yr) and more severely ill (median Mortality Probability Model III on Admission score, 15.3% [7.0-29.5%] vs 13.4% [6.3-25.2%]) than those denied admission. In the multivariable model, a full medical ICU was the only hospital-level factor significantly associated with a lower probability of ICU acceptance (odds ratio, 0.55 [95% CI, 0.37-0.81]). Using propensity score analysis to account for imbalances in baseline characteristics between those accepted or denied for ICU admission, longer emergency department boarding time after consult was associated with higher odds of mortality and persistent organ dysfunction (odds ratio, 1.77 [1.07-2.95]/log10 hour increase). ICU admission decisions for critically ill emergency department patients are affected by medical ICU bed availability, though higher emergency department volume and other ICU occupancy did not play a role. Prolonged emergency department boarding times were associated with worse patient outcomes, suggesting a need for improved throughput and targeted care for patients awaiting ICU admission.


IgE antibodies for penicillins and cephalosporins in rats. II. Antigenic specificity of rat anti-penicillin-OvA IgE sera.
Sprague Dawley (SD) rats were immunized with various penicillin-ovalbumin (OvA) in combination with aluminum hydroxide (alum) and thimerosal-killed Bordetella pertussis for the purpose of obtaining rat anti-penicillin IgE sera. In the rat 60-hour passive cutaneous anaphylaxis (PCA) reaction and the hapten inhibition test, a weak cross reaction between penicillin G (PCG) and ampicillin (ABPC) was observed, but not cross reaction was observed between sulbenicillin (SBPC) and other penicillins. Rat anti-6-formamidopenicillanic acid (FPC) IgE serum reacted with PCG-bovine gamma globulin (BGG), ABPC-BGG and SBPC-BGG, but FPC-BGG did not react with rat anti-PCG, anti-ABPC and anti-SBPR IgE sera and the PCA reaction between anti-FPC IgE sera and FPC-BGG was inhibited by FPC, PCG, ABPC and SBPC. These results indicate that the antigenic active sites of PCG, ABPC and SBPC are limited to the acyl side chain moiety of penicillins, while the antigenic active site of FPC is confined to the penicilloyl moiety of the penicillin.


Job strain-associated inflammatory burden and long-term risk of coronary events: findings from the MONICA/KORA Augsburg case-cohort study.
We examined the association between job strain and coronary heart disease (CHD) and investigated the role of markers of inflammation and endothelial dysfunction as possible mediators of job strain-associated CHD risk. The sample (n = 1027) included employed participants (35-64 years old, 68% male) from the population-based MONICA/KORA (Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg) studies. At baseline Karasek's Job Strain Index was assessed during standardized personal interviews, and nine biological markers were measured (1984-1995). Participants were followed (average, 12 years) to assess incident events (sudden cardiac death or fatal and nonfatal myocardial infarction). In this case-cohort design, the final sample contained 114 cases and 913 noncases. Baseline distributions of cardiometabolic risk factors were significantly different between cases and noncases, with no detectable job strain-specific differences. However, cases with high job strain had higher monocyte chemoattractant protein-1, interleukin (IL)-8, and IL-18 compared with noncases with high job strain. High-sensitivity C-reactive protein, IL-6, and soluble intercellular adhesion molecule-1 were increased in cases versus noncases, regardless of work stress. Job strain was associated with incident coronary events in Cox proportional hazards models adjusted for age, sex, and survey (hazard ratio = 2.57, 95% confidence interval = 1.09-6.07) and after adjustment for CHD risk factors (2.35, 1.003-5.49). Adjustment for monocyte chemoattractant protein-1 or IL-8 increased this risk estimate by 14.5% or 9.4%, respectively, whereas adjustment for C-reactive protein and soluble intercellular adhesion molecule-1 led to decreased hazard ratios (-9.9% and -5.5%, respectively). Job strain increased CHD risk in healthy workers; the associated inflammatory burden may contribute to stress-related coronary pathogenesis.


Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria mellonella.
Innate-immunity-related genes in humans are activated during urinary tract infections (UTIs) caused by pathogenic strains of Escherichia coli but are suppressed by commensals. Epigenetic mechanisms play a pivotal role in the regulation of gene expression in response to environmental stimuli. To determine whether epigenetic mechanisms can explain the different behaviors of pathogenic and commensal bacteria, we infected larvae of the greater wax moth, Galleria mellonella, a widely used model insect host, with a uropathogenic E. coli (UPEC) strain that causes symptomatic UTIs in humans or a commensal-like strain that causes asymptomatic bacteriuria (ABU). Infection with the UPEC strain (CFT073) was more lethal to larvae than infection with the attenuated ABU strain (83972) due to the recognition of each strain by different Toll-like receptors, ultimately leading to differential DNA/RNA methylation and histone acetylation. We used next-generation sequencing and reverse transcription (RT)-PCR to correlate epigenetic changes with the induction of innate-immunity-related genes. Transcriptomic analysis of G. mellonella larvae infected with E. coli strains CFT073 and 83972 revealed strain-specific variations in the class and expression levels of genes encoding antimicrobial peptides, cytokines, and enzymes controlling DNA methylation and histone acetylation. Our results provide evidence for the differential epigenetic regulation of transcriptional reprogramming by UPEC and ABU strains of E. coli in G. mellonella larvae, which may be relevant to understanding the different behaviors of these bacterial strains in the human urinary tract.


Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids.
To preserve genome integrity when faced with DNA lesions, cells activate and coordinate a multitude of DNA repair pathways to ensure timely error correction or tolerance, collectively called the DNA damage response (DDR). These interconnecting damage response pathways are molecular signal relays, with protein kinases (PKs) at the pinnacle. Focused efforts in model eukaryotes have revealed intricate aspects of DNA repair PK function, including how they direct DDR pathways and how repair reactions connect to wider cellular processes, including DNA replication and transcription. The Kinetoplastidae, including many parasites like Trypanosoma spp. and Leishmania spp. (causative agents of debilitating, neglected tropical infections), exhibit peculiarities in several core biological processes, including the predominance of multigenic transcription and the streamlining or repurposing of DNA repair pathways, such as the loss of non-homologous end joining and novel operation of nucleotide excision repair (NER). Very recent studies have implicated ATR and ATM kinases in the DDR of kinetoplastid parasites, whereas DNA-dependent protein kinase (DNA-PKcs) displays uncertain conservation, questioning what functions it fulfills. The wide range of genetic manipulation approaches in these organisms presents an opportunity to investigate DNA repair kinase roles in kinetoplastids and to ask if further kinases are involved. Furthermore, the availability of kinase inhibitory compounds, targeting numerous eukaryotic PKs, could allow us to test the suitability of DNA repair PKs as novel chemotherapeutic targets. Here, we will review recent advances in the study of trypanosomatid DNA repair kinases.


Low miR-187 expression promotes resistance to chemoradiation therapy in vitro and correlates with treatment failure in patients with esophageal adenocarcinoma.
Esophageal adenocarcinoma (EAC) has a poor prognosis and is increasing in incidence in many western populations. Neoadjuvant chemoradiation therapy (CRT) followed by surgery is increasingly the standard of care for locally advanced EAC; however, resistance to treatment is a significant clinical problem. The identification of both novel biomarkers predicting response to treatment and novel therapeutic targets to enhance the efficacy of CRT are key to improving survival rates in EAC. In this study we performed global microRNA (miRNA) profiling of pre-treatment EAC biopsies and identified 67 miRNA significantly altered in patients who are resistant to CRT. One of these miRNA, miR-187, was significantly decreased in pre-treatment EAC tumors from patients having a poor response to neoadjuvant CRT, highlighting downregulation of miR-187 as a potential mechanism of treatment resistance in EAC. In vitro, miR-187 was demonstrated to play a functional role in modulating sensitivity to X-ray radiation and cisplatin in EAC and its dysregulation was demonstrated to be due to chromosomal alterations. In vitro, miR-187 altered expression of a diverse array of pathways, including the immune regulator complement component 3 (C3), serum levels of which we have previously demonstrated to predict patient response to CRT. In vivo, expression of C3 was significantly increased in tumors from patients having a poor response to CRT. This study highlights for the first time a role for miR-187 as a novel biomarker of response to CRT and a potential therapeutic target for enhancing the efficacy of CRT in EAC.


Air pollution, physical activity, and markers of acute airway oxidative stress and inflammation in adolescents.
The airway inflammatory response is likely the mechanism for adverse health effects related to exposure to air pollution. Increased ventilation rates during physical activity in the presence of air pollution increases the inhaled dose of pollutants. However, physical activity may moderate the relationship between air pollution and the inflammatory response. The present study aimed to characterize, among healthy adolescents, the relationship between dose of inhaled air pollution, physical activity, and markers of lung function, oxidative stress, and airway inflammation. With a non-probability sample of adolescents, this observational study estimated the association between air pollution dose and outcome measures by use of general linear mixed models with an unstructured covariance structure and a random intercept for subjects to account for repeated measures within subjects. A one interquartile range (IQR) (i.e., 345.64 μg) increase in ozone (O3) inhaled dose was associated with a 29.16% average decrease in the percentage of total oxidized compounds (%Oxidized). A one IQR (i.e., 2.368E+10 particle) increase in total particle number count in the inhaled dose (PNT) was associated with an average decrease in forced expiratory flow (FEF25-75) of 0.168 L/second. Increasing activity levels attenuated the relationship between PNT inhaled dose and exhaled nitric oxide (eNO). The relationship between O3 inhaled dose and percent oxidized exhaled breath condensate cystine (%CYSS) was attenuated by activity level, with increasing activity levels corresponding to smaller changes from baseline for a constant O3 inhaled dose. The moderating effects of activity level suggest that peaks of high concentration doses of air pollution may overwhelm the endogenous redox balance of cells, resulting in increased airway inflammation. Further research that examines the relationships between dose peaks over time and inflammation could help to determine whether a high concentration dose over a short period of time has a different effect than a lower concentration dose over a longer period of time.


Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins.
Formation of atypical L-isoaspartyl residues in proteins and peptides is a common, spontaneous and nonenzymatic modification of aspartyl and asparaginyl sites. The enzyme protein-L-isoaspartyl methyltransferase (PIMT) catalyzes the transfer of the methyl group of S-adenosyl-L-methionine (SAM) to these L-isoaspartyl sites, thereby allowing reisomerization and restoration of the original alpha peptide linkage. Because SAM is in part a product of folate metabolism, the present study was undertaken to determine the effects of folate deficiency on the presence of L-isoaspartyl residues in hepatic proteins. Young (weanling) and older (12 mo) Sprague-Dawley rats were fed a folate-sufficient (2 mg folate/kg diet) or folate-deficient (0 mg folate/kg diet) diet for 20 wk. Liver proteins were analyzed for L-isoaspartyl residues. This analysis was based on the PIMT-dependent incorporation of [(3)H]-methyl groups from [(3)H]-SAM and the subsequent (nonenzymatic) sublimation of these methyl groups into a nonaqueous scintillant. The amount of L-isoaspartyl residues in hepatic proteins was higher in younger folate-deficient than in folate-sufficient rats (deficient: 187 +/- 71, sufficient: 64 +/- 43 pmol/mg protein, P < 0.025). This difference, however, was not seen among the older groups of rats who instead exhibited a much larger accumulation of L-isoaspartyl residues in their hepatic proteins (deficient: 528 +/- 151, sufficient: 470 +/- 204 pmol/mg protein, P = 0.568). The importance of these observations is discussed.


Precise and non-invasive circulating tumor cell isolation based on optical force using homologous erythrocyte binding.
Precise isolation of circulating tumor cells (CTCs) is proved to be significant for early cancer diagnosis and downstream analysis. Most of the existing strategies yield low purity or cause unexpected damage to cells because of foreign material introduction. To avoid foreign material caused damage and achieve high efficiency simultaneously, this work presents an innovative strategy using tumor cell targeting molecules to bind homologous red blood cells (RBCs) with tumor cells, which results in obvious optical constant differences (both size and mean refractive index) between CC-RBCs (RBC conjugated CTCs) and other blood cells. Then the modified CTCs can be precisely separated under laser illumination in an optofluidic system. Experiments show that CTCs are efficiently modified with erythrocytes and finally isolated from blood at high purity (more than 92%) and a high recovery rate (over 90%). In the whole process, CTCs are proved to keep membrane and function integrity. The combination of homologous RBC binding and an optofluidic system will provide a convenient tool for cancer early diagnosis and treatment monitoring, which exhibits good performance in CTC non-invasive and precise isolation, thus showing great potential.


The efficacy and safety of intralesional injection of collagenase Clostridium histolyticum for Peyronie's disease: A meta-analysis of published prospective studies.
Background: Peyronie's disease (PD) is a progressive fibrotic disorder of the penis that is adverse to men's health. Currently, effective and reliable non-surgical options for PD are limited. Since the Food and Drug Administration (FDA) approved it in 2013, intralesional injection of collagenase Clostridium histolyticum (CCH) became the only licensed treatment for PD. This meta-analysis aims to evaluate the clinical efficacy and safety of CCH in treating PD, predominantly based on post-FDA studies. Methods: The primary outcome was clinical efficacy evaluated by the percentages of improvement in penile curvature (PC) and Peyronie's disease symptom bother score (PD bother score). The secondary outcome was the safety assessed by treatment-related adverse events (TRAEs). Heterogeneity was assessed by Cochran's Q and I 2 tests. Sensitivity and subgroup analyses were performed to explore the source of heterogeneity. Funnel plots and Egger's test were used to evaluate the publication bias. Results: A total of 11 studies with 1,480 intentions to treat (ITT) population were included. The pooled effect of the improvement of PC was 35% (95% CI: 0.33-0.38), and the pooled improvement of the PD bother score was 41% (95% CI: 0.37-0.45). No heterogeneity was found at the pooled improvement of PC (p = 0.845, I 2 = 0.00%). Meanwhile, some heterogeneity existed in the pooled improvement of the PD bother score (p = 0.069, I 2 = 43.4%). The pooled effect of TRAEs was 93% (95% CI 0.88-0.97) with significant heterogeneity (p < 0.000, I 2 = 92.3%). Conclusion: The intralesional injection of CCH could significantly improve the penile deformity of PD patients. Meanwhile, CCH appears to ameliorate the PD bother score to some extent and has acceptable clinical safety. Future studies are required to clarify the long-term outcomes of CCH injection in the treatment of PD.


Cas9-mediated excision of Nematostella brachyury disrupts endoderm development, pharynx formation and oral-aboral patterning.
The mesoderm is a key novelty in animal evolution, although we understand little of how the mesoderm arose. brachyury, the founding member of the T-box gene family, is a key gene in chordate mesoderm development. However, the brachyury gene was present in the common ancestor of fungi and animals long before mesoderm appeared. To explore ancestral roles of brachyury prior to the evolution of definitive mesoderm, we excised the gene using CRISPR/Cas9 in the diploblastic cnidarian Nematostella vectensisNvbrachyury is normally expressed in precursors of the pharynx, which separates endoderm from ectoderm. In knockout embryos, the pharynx does not form, embryos fail to elongate, and endoderm organization, ectodermal cell polarity and patterning along the oral-aboral axis are disrupted. Expression of many genes both inside and outside the Nvbrachyury expression domain is affected, including downregulation of Wnt genes at the oral pole. Our results point to an ancient role for brachyury in morphogenesis, cell polarity and the patterning of both ectodermal and endodermal derivatives along the primary body axis.


[Past and present of plasmatrix].
The plasmatrix has good biological activity, it derives from patients' themselves tissues and has no adverse reactions, thus it has been widely used in tissue regeneration. With the development of biomedicine and material science, plasmatrix have gone through different stages of development, their preparation methods, product characteristics and biology have all changed. This article summarizes past research and systematically introduces the development process, theoretical basis and product characteristics of plasmatrix, so as to provide guidance for their application in the process of tissue regeneration.