Reversible segmental cerebral arterial vasospasm and cerebral infarction: possible association with excessive use of sumatriptan and Midrin.
To describe a patient who developed reversible segmental cerebral arterial vasospasm and cerebral infarction while taking excessive amounts of sumatriptan succinate and a combination drug (Midrin) consisting of isometheptene mucate, 65 mg, dichloralphenazone, 100 mg, and acetaminophen, 325 mg. Case report. Tertiary care center. A 43-year-old man who developed a left occipital infarct after taking a total of 23 sumatriptan succinate tablets (25 mg per tablet) and 32 Midrin tablets during a 7-day period and who on digital subtraction angiography was shown to have segmental cerebral arterial narrowing in multiple vessels. An extensive evaluation for other possible risk factors for cerebral infarction was unrevealing. Discontinuation of sumatriptan and Midrin regimens and administration of nicardipine hydrochloride led to nearly total resolution of the angiographic findings, and the patient had no recurrent strokes. One should consider the diagnosis of drug-induced vasospasm in patients with cerebral infarction and a history of excessive use of sumatriptan and Midrin. The initial angiographic abnormalities may resemble those found in patients with primary angiitis of the central nervous system.


Effects of light intensity on cyclic electron flow around PSI and its relationship to non-photochemical quenching of Chl fluorescence in tobacco leaves.
We tested the hypothesis that plants grown under high light intensity (HL-plants) had a large activity of cyclic electron flow around PSI (CEF-PSI) compared with plants grown under low light (LL-plants). To evaluate the activity of CEF-PSI, the relationships between photosynthesis rate, quantum yields of both PSII and PSI, and Chl fluorescence parameters were analyzed simultaneously in intact leaves of tobacco plants which had been grown under different light intensities (150 and 1,100 micromol photons m(-2) s(-1), respectively) and with different amounts of nutrients supplied. HL-plants showed a larger value of non-photochemical quenching (NPQ) of Chl fluorescence at the limited activity of photosynthetic linear electron flow. Furthermore, HL-plants had a larger activity of CEF-PSI than LL-plants. These results suggested that HL-plants dissipated the excess photon energy through NPQ by enhancing the ability of CEF-PSI to induce acidification of the thylakoid lumen.


Concurrent Paraspinous Myopathy and Myasthenia Gravis.
Paraspinous myopathy is a rare neuromuscular disorder characterized by selective involvement of the cervical, thoracic, or lumbar muscles. Leading clinical features include a bent spine or dropped head (antecollis). In myasthenia gravis (MG), patients may have camptocormia secondary to neuromuscular junction dysfunction of the paraspinal muscles, and this condition usually responds to acetylcholinesterase inhibitors or immunosuppressive treatments. However, concomitant MG and paraspinous myopathy with histologic and electrophysiologic evidence of myopathic changes of the paraspinal muscles has only been reported twice in the literature. In this case series, 5 patients with MG with paraspinous myopathy are reported. While neck and extension truncal weakness is not uncommon in MG, most often the weakness is due to neuromuscular junction dysfunction. Coexisting paraspinous myopathy and MG is under-recognized, is often resistant to mainstay treatments, and should be considered in patients presenting with neck or trunk extensor weakness.


Enzyme responsive mesoporous silica nanoparticles for targeted tumor therapy in vitro and in vivo.
This study reports a biocompatible controlled drug release system based on mesoporous silica nanoparticles (MSNs) for tumor microenvironment responsive drug delivery. It was fabricated by grafting phenylboronic acid conjugated human serum albumin (PBA-HSA) onto the surfaces of MSNs as a sealing agent, via an intermediate linker of a functional polypeptide, which was composed of two functional units: the polycation cell penetrating peptide (CPP) polyarginine, and matrix metalloproteinase 2 (MMP-2) substrate peptide. A series of characterizations confirmed that the system had been successfully constructed. In vitro tests proved that the anticancer drug loading system could efficiently induce cell apoptosis in vitro. More importantly, the in vivo tumor experiments confirmed that the anticancer loading system could efficiently inhibit tumor growth with minimal side effects.


Alcohol use and perceived social and emotional consequences among perpetrators of general and sexual aggression.
This study examines the relation among alcohol use, alcohol-related aggression expectancies, and the perceived negative consequences of perpetrating general and sexual aggression. Participants (N = 2,941; 59% female) were incoming college freshmen who reported on the last 3 months of their senior year of high school. Hierarchical multiple regression analyses for general aggression reveal that heavy alcohol consumption at the time of the aggression and strong alcohol-related aggression expectancies were associated with more frequent social and emotional consequences. For sexual aggression, similar regression analyses found that any alcohol use at the time of the aggression, but not outcome expectancies, was associated with social and emotional consequences. Among individuals who perpetrated general and sexual aggression, consuming alcohol at the time of the aggression was positively associated with perceived negative social and emotional consequences. Results do not support the idea that alcohol is used as an excuse for aggressive behavior.


Nutrition and sarcopenia: evidence for an interaction.
Nutritional interventions that might influence sarcopenia, as indicated by literature reporting on sarcopenia per se as well as dynapenia and frailty, are reviewed in relation to potential physiological aetiological factors, i.e. inactivity, anabolic resistance, inflammation, acidosis and vitamin D deficiency. As sarcopenia occurs in physically active and presumably well-nourished populations, it is argued that a simple nutritional aetiology is unlikely and unequivocal evidence for any nutritional influence is extremely limited. Dietary protein is probably the most widely researched nutrient but only for frailty is there one study showing evidence of an aetiological influence and most intervention studies with protein or amino acids have proved ineffective with only a very few exceptions. Fish oil has been shown to attenuate anabolic resistance of muscle protein synthesis in one study. There is limited evidence for a protective influence of antioxidants and inducers of phase 2 proteins on sarcopenia, dynapenia and anabolic resistance in human and animal studies. Also fruit and vegetables may protect against acidosis-induced sarcopenia through their provision of dietary potassium. While severe vitamin D deficiency is associated with dynapenia and sarcopenia, the evidence for a beneficial influence of increasing vitamin D status above the severe deficiency level is limited and controversial, especially in men. On this basis there is insufficient evidence for any more specific nutritional advice than that contained in the general healthy lifestyle-healthy diet message: i.e. avoiding inactivity and low intakes of food energy and nutrients and maintain an active lifestyle with a diet providing a rich supply of fruit and vegetables and frequent oily fish.


The impracticality of biomedical rejuvenation therapies: translational and pharmacological barriers.
The notion that it is possible to eradicate age-related degeneration and live a life with a negligible rate of senescence solely by using a physical "repair-oriented" approach is flawed on a number of fronts. Here, I will argue that there are so many unknown variables embedded in this line of thinking that make the final result impossible to predict. Two relatively easy-to-research areas are the search for successful cross-link breakers and an effective lysosomal degradation therapy. A more complex and speculative strategy is whole-body interdiction of lengthening of telomeres (WILT). Highlighting these as examples, I argue that it is unlikely that such rejuvenation biotechnologies will be used meaningfully by the general public. The discussion assumes that although such therapies may in theory one day be developed in the laboratory, and even possibly be formulated as physical clinical therapies, these will be unusable in practical terms when applied upon humans at large. Due to inherent characteristics of our biological, evolutionary, and psychological heritage, it is implausible that curing aging will occur by using physical interventions alone.


Point-of-care urinary pneumococcal antigen test in the emergency department for community acquired pneumonia.
Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP). Early diagnosis would allow more directed therapy and confidence in appropriate treatment for a majority of patients. The BinaxNOW pneumococcal urinary antigen (PNAG) test has been evaluated at laboratory level and is easy to perform and interpret, but its use as a point-of-care test has not been evaluated. A study was undertaken to assess whether PNAG testing can be reliably performed and interpreted by staff in an adult emergency department and whether rapid results influence initial treatment decisions. Community-living adult patients presenting to the emergency department with clinical and radiological findings of pneumonia had PNAG testing performed on the same sample in both the emergency department and the microbiology laboratory in a blinded fashion. Accuracy and turnaround time were assessed. Diagnostic yield was compared with routine culture methods. Fifty-nine patients were enrolled of whom nine (15%) had positive PNAG tests. These included three culture-proven cases and six additional cases. There was 98% concordance between emergency department and laboratory results. Turnaround time was significantly shorter when tested in the emergency department (median 2 h 39 min vs 19 h 40 min). Antibiotic prescribing was not influenced by results in this small sample. PNAG diagnosis of pneumococcal pneumonia can be accurately performed as a point-of-care test by emergency department clinical staff. Without specific efforts to achieve early urine collection, the timeframe of testing will frequently fall outside the 4-hour patient stay of a UK emergency department and may be more appropriately considered as a test for the medical admissions unit in this setting. Sensitivity is at least equal to conventional culture methods and the result is available rapidly enough to potentially influence treatment decisions, a strategy that warrants further investigation.


Preschool vision screening in Cornwall: performance indicators of community orthoptists.
The performance of community orthoptists was retrospectively assessed in a primary preschool screening programme that has been established in Cornwall since 1982. The outcome of screening was compared between random samples of two birth year cohorts corresponding to the second and fourth years of existence of the screening programme (1980, n = 298 and 1982, n = 300). The mean age at screening was significantly later for the second cohort (4.3 years compared with 4.4 years) but otherwise performance indicators improved in the second cohort. Community orthoptists achieved a sensitivity of about 90% and specificity of 99% during the study. It is unlikely that the more commonly used two tier system of health visitors referring to a community orthoptist could achieve this degree of accuracy.


Tumor-targeting hydroxyapatite nanoparticles for remodeling tumor immune microenvironment (TIME) by activating mitoDNA-pyroptosis pathway in cancer.
In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive "cold" tumor types into immuno-responsive "hot" ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.


Oxidation of nitrogen-containing pollutants by novel ferrate(VI) technology: a review.
Nitrogen-containing pollutants have been found in surface waters and industrial wastewaters due to their presence in pesticides, dyes, proteins, and humic substances. Treatment of these compounds by conventional oxidants produces disinfection by-products (DBP). Ferrate(VI) (Fe(VI)O(4)(2-), Fe(VI)) is a strong oxidizing agent and produces a non-toxic by-product Fe(III), which acts as a coagulant. Ferrate(VI) is also an efficient disinfectant and can inactivate chlorine resistant microorganisms. A novel ferrate(VI) technology can thus treat a wide range of pollutants and microorganisms in water and wastewater. The aim of this paper is to review the kinetics and products of the oxidation of nitrogen-containing inorganic (ammonia, hydroxylamine, hydrazine, and azide) and organic (amines, amino acids, anilines, sulfonamides, macrolides, and dyes) compounds by ferrate(VI) in order to demonstrate the feasibility of ferrate(VI) treatment of polluted waters of various origins. Several of the compounds can degraded in seconds to minutes by ferrate(VI) with the formation of non-hazardous products. The mechanism of oxidation involves either one-electron or two-electrons processes to yield oxidation products. Future research directions critical for the implementation of the ferrate(VI)-based technology for wastewater and industrial effluents treatment are recommended.


Soviet-American Exchange.
At hearings earlier this month on high-energy physics, held before the joint Committee on Atomic Energy, Norman F. Ramsey, professor of physics at Harvard, was testifying when Representative Melvin Price (D-III.) told of a 1959 congressional tour of the Soviet high-energy laboratory at Dubna, and asked Ramsey for comment. the exchange went as follows:


Purification and characterization of the respiratory syncytial virus fusion protein.
The fusion protein of respiratory syncytial virus was purified by affinity chromatography using a monoclonal antibody. Under various conditions the protein was recovered as a 145K dimer or a 70K monomer. The 70K monomer was composed of disulphide-linked fragments of 48K and 23K. Polyclonal rabbit serum produced to the dimerized fusion protein neutralized virus but did not inhibit fusion, while rabbit serum to the 2-mercaptoethanol-treated dimerized protein neutralized virus and inhibited fusion of infected cells. Only the latter serum strongly recognized the 23K fragment when studied by Western blot analysis.


Evaluation of soybean genotypes for reaction to natural field infection by Cercospora species causing purple seed stain.
Purple seed stain (PSS) of soybean (Glycine max (L.) Merr.) is a prevalent seed disease. It results in poor seed quality and reduced seed lot market grade, and thus undermines value of soybean worldwide. The objectives of this research were to evaluate the reaction of selected soybean genotypes collected from 15 countries representing maturity groups (MGs) III, IV, and V to PSS, and to identify new sources of resistance to PSS based on three years of evaluation of natural field infection by Cercospora spp. in the Mississippi Delta of the U. S. In this study, 42 soybean genotypes were evaluated in 2010, 2011, and 2012. Seventeen lines including six MG III (PI 88490, PI 504488, PI 417361, PI 548298, PI 437482, and PI 578486), seven MG IV (PI 404173, PI 346308, PI 355070, PI 416779, PI 80479, PI 346307, and PI 264555), and four MG V (PI 417567, PI 417420, PI 381659, and PI 407749) genotypes had significantly lower percent seed infection by Cercospora spp. than the susceptible checks and other genotypes evaluated (P ≤ 0.05). These genotypes of soybean can be used in developing soybean cultivars or germplasm lines with resistance to PSS and for genetic mapping of PSS resistance genes. In addition, among these 17 lines with different levels of resistance to PSS, nine soybean genotypes (PI 417361, PI 504488, PI 88490, PI 346308, PI 416779, PI 417567, PI 381659, PI 417567, and PI 407749) were previously reported as resistant to Phomopsis seed decay. Therefore, they could be useful in breeding programs to develop soybean cultivars with improved resistance to both seed diseases.


Evaluation of three retrospective exposure assessment methods.
To evaluate three methods for assessing retrospective exposures of acrylonitrile workers. Three methods used to develop historical exposure estimates for a retrospective cohort mortality study of acrylonitrile workers were considered. The first method was deterministic, incorporating estimates of the impact of changes that took place in the workplace. The second method used the ratio of the mean of the measurements for three similar jobs to estimate a fourth similar job. The third method was based on the development of homogeneous exposure groups (HEG). Estimates of acrylonitrile exposure were developed using these three methods and compared with measurement means (observed means) across three categories of airborne exposure concentrations (<0.5, 0.5-0.99 and >or=1 p.p.m.) and three categories based on the number of measurements used to develop the estimate (<10, 10-29 and >or=30). The correlation between the estimates and the observed values was about 0.65 for all three methods. Estimates using the deterministic method tended to overestimate the observed means by 17%, but the number of estimates was not above or below the observed means more often than expected. There was no statistically significant relationship between the exposure estimates and the acrylonitrile concentration in the air or the number of measurements used to develop the estimates. The estimates averaged within 60% of the observed means when concentrations were above 0.5 p.p.m. and 25% regardless of the number of measurements on which the estimates were based. Estimates from the ratio method were randomly distributed above and below the observed means and averaged 70% above the observed means. The air concentration did not affect the performance of the method, although above 1 p.p.m. the estimates were within 40% of the observed means. The number of measurements comprising the estimates was related on a relative scale to the performance of the method. Exposure estimates using the HEG method were neither greater nor less than the observed means more often than what was expected. The method did better as concentration and the number of measurements increased. The estimates were within 60% of the means at >0.5 p.p.m. and for all measurement categories. Overall, there was no statistically significant difference between the estimates derived from the three estimation methods. All methods performed reasonably well, but the deterministic and HEG methods appeared to develop estimates closer to the observed means for concentrations >0.5 p.p.m., regardless of the number of measurements.


Dynamic scaling in thin-film growth with irreversible step-edge attachment.
We study dynamic scaling in a model with collective diffusion (CD) of isolated atoms in terraces and irreversible aggregation at step edges. Simulations are performed in two-dimensional substrates with several diffusion to deposition ratios R identical with D/F. Data collapse of scaled roughness distributions confirms that this model is in the class of the fourth-order nonlinear growth equation by Villain, Lai, and Das Sarma (VLDS) with negligible finite-size effects, while estimates of scaling exponents show some discrepancies. This result is consistent with the prediction of a recent renormalization group approach and improves previous numerical works on related models. The roughness follows dynamic scaling as W=Lalpha/R1/2f(xi/L), with correlation length xi=(Rt)1/z, where z is the dynamic exponent. We also propose a limited mobility (LM) model where the incident atom executes up to G steps before a new atom is adsorbed, and irreversibly aggregates at step edges. This model is also shown to belong to the VLDS class. The size of the plateaus in the film surface increases as G1/2 and the lateral correlation scales as G1/2t1/z. The time evolution of the roughness reproduces that of the CD model if an equivalent parameter G approximately R2/z is chosen. This suggests the possibility of using LM models with tunable diffusion length to simulate processes with simultaneous diffusion of many atoms. A scaling approach is used to justify exponent values and dynamic relations for both models, including the significant decrease of surface roughness as R or G increases.


Pose Estimation and Non-Rigid Registration for Augmented Reality During Neurosurgery.
A craniotomy is the removal of a part of the skull to allow surgeons to have access to the brain and treat tumors. When accessing the brain, a tissue deformation occurs and can negatively influence the surgical procedure outcome. In this work, we present a novel Augmented Reality neurosurgical system to superimpose pre-operative 3D meshes derived from MRI onto a view of the brain surface acquired during surgery. Our method uses cortical vessels as main features to drive a rigid then non-rigid 3D/2D registration. We first use a feature extractor network to produce probability maps that are fed to a pose estimator network to infer the 6-DoF rigid pose. Then, to account for brain deformation, we add a non-rigid refinement step formulated as a Shape-from-Template problem using physics-based constraints that helps propagate the deformation to sub-cortical level and update tumor location. We tested our method retrospectively on 6 clinical datasets and obtained low pose error, and showed using synthetic dataset that considerable brain shift compensation and low TRE can be achieved at cortical and sub-cortical levels. The results show that our solution achieved accuracy below the actual clinical errors demonstrating the feasibility of practical use of our system. This work shows that we can provide coherent Augmented Reality visualization of 3D cortical vessels observed through the craniotomy using a single camera view and that cortical vessels provide strong features for performing both rigid and non-rigid registration.


Discrete and polymeric cobalt organophosphates: isolation of a 3-D cobalt phosphate framework exhibiting selective CO2 capture.
Structurally diverse mononuclear, dinuclear, and tetranuclear cobalt organophosphates and a three-dimensional framework based on a D4R cobalt phosphate are reported. The role of auxiliary ligands in determining the nuclearity of the phosphate clusters has further been established. Reaction of cobalt acetate tetrahydrate with 2,6-di-iso-propylphenylphosphate (dippH2) in methanol or DMSO in the presence of ancillary N-donor ligands leads to the formation of mononuclear octahedral cobalt phosphate [Co(dippH)2(py)4] (1), dinuclear octahedral cobalt phosphates [Co(dipp)(NN)(MeOH)2]2·2MeOH (NN = bpy 2; phen 3), tetrahedral cobalt phosphates [Co(dipp)(L)2]2·2(MeOH) (L = imz 4; dmpz 5) and symmetric and asymmetric tetranuclear tetrahedral cobalt phosphates [Co(dipp)(2-apy)]4 (6) and [Co4(dipp)4(2-apy)3(DMSO)]·(DMSO)·(H2O) (7), in nearly quantitative yields. The use of a linear N-donor ditopic linker, 3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine (dptz), as the ancillary ligand leads to the formation of a robust three dimensional, four-fold interpenetrated network based on the D4R platform, {[Co(dipp)(dptz)0.5]4}n (8), under ambient conditions. The new compounds have been characterized by analytical, thermo-analytical and spectroscopic techniques. Further, the molecular structures of compounds 1-8 have been established using single crystal X-ray diffraction studies. Compound 1 is a mononuclear complex in which the dippH ligands occupy trans-positions around the octahedral cobalt ion. The core structure of compounds 2-5, a Co2P2O4 ring, resembles the S4R (single-4-ring) SBU of zeolites, whereas the Co4P4O12 inorganic core found in compounds 6 and 7 resembles the D4R (double-4-ring) SBU. Cobalt organophosphate framework 8 shows significant CO2 adsorption at 273 K (7.73 wt% at 1 bar and 18.21 wt% at 15.5 bar) with high selectivity to CO2 uptake over N2 and H2 at 273 K. Magnetic studies of these symmetric complexes indicate the presence of weak antiferromagnetic interactions between the metal ions via the phosphate bridging moiety.


Development of a decision aid for primary treatment of patients with advanced-stage ovarian cancer.
Despite renewed treatment options for advanced epithelial ovarian cancer, survival remains poor. The Patient Association and the Gynecological Oncology Working Party in the Netherlands have identified a need for a tool to improve shared decision-making. The aim of this study was to develop an evidence-based online decision aid for patients with advanced epithelial ovarian cancer and their medical team. First, we identified the patients' and clinicians' needs using surveys and in-depth interviews. Second, we conducted multidisciplinary face-to-face meetings with representatives from all stakeholders (clinicians and patient representatives) to determine the content of the decision aid. Third, we developed the decision aid using standardized criteria and national guidelines. Finally, we tested the usability of the tool with patients and clinicians who participated in the needs assessment. Patients and clinicians indicated the need for more sources of reliable information that include all treatment options available in the Netherlands. Although most interviewees were satisfied with the level of information available at the time of their own treatment, the majority (90%) of the patients stated that no choice of treatment was offered. We developed a consultation sheet and an online decision aid based on patient interviews and team discussions. The sheet contains a summary of all treatment options and login codes for the decision aid; it will be offered to patients at their first consultation. The decision aid can be used at home and includes information about epithelial ovarian cancer and all available treatment options and questions about quality of life and treatment preferences, delivering a personalized summary for discussion during the following consultation about the primary treatment choices. In cooperation with patients and clinicians, we developed a decision aid for advanced-stage epithelial ovarian cancer patients and their medical team to support shared decision-making, based on a confirmed need for more extensive information sources. The decision aid is currently under assessment in a multicenter implementation trial.


Salivary epithelial cells in primary culture: characterization of their growth and functional properties.
Mouse submandibular salivary gland cells were grown in primary explant culture. After an initial period of degeneration within the explant, surviving epithelial cells proliferated rapidly and duct-like structures recolonized the explant. Autoradiographic studies showed that a peak of DNA synthesis occurred after 4 days in vitro and that proliferation was enhanced by insulin and hydrocortisone. These cells retained specialized secretory function (protease activity) for at least 2 weeks in vitro. This enzyme is a differentiated product of granular tubule cells in vivo. Between 6 and 10 days, explants attached to the substrate. An outgrowth developed, consisting largely of ultrastructurally identifiable epithelial cells which formed pseudoglandular structures in the monolayer. Epithelium survived for over 6 months in primary culture but could not be serially transferred. Secondary cultures were rapidly overgrown by mesenchymal cells.


Spatial and temporal control of nuclear envelope assembly by Ran GTPase.
Using evidence derived primarily from studies using Xenopus egg extracts, a model for the role of Ran in multiple stages during NE assembly can be proposed (Figure 2). Ran is concentrated on chromatin prior to NE assembly and recruits RCC1 that generates Ran-GTP locally. Recruitment of RCC1 to chromatin may be a specialized mechanism to initiate NE assembly following fertilization of the egg, whereas in somatic cells, RCC1 may be present on chromatin throughout mitosis. Ran-GTP recruits vesicles to the surface of chromatin, and promotes vesicle fusion to form the double membrane of the NE. Ran-GTP may recruit membrane vesicles to chromatin through binding to integral membrane proteins through importin-beta. A transient complex would be formed between Ran-GTP, importin-beta and the target protein, which would be released locally to promote assembly of a precursor complex. GTP hydrolysis by Ran would release importin-beta, but may also play a role in vesicle fusion. Ran-GTP also promotes NPC assembly by releasing nucleoporins such as Nup107 from inhibitory complexes with importin-beta. In vertebrate cells undergoing mitosis, the majority of Ran molecules are excluded from the chromosomes and dispersed into the cytoplasm. Relocalization of Ran to chromatin at the end of mitosis may co-ordinate the initiation of NE assembly with disassembly of the mitotic spindle. The function of Ran in this transition is likely to be coupled to changes in the activity of cyclin-dependent protein kinases and other activities that control the progression of the cell cycle. Thus, changes in the localization of Ran and its regulators provide temporal and spatial control of NE assembly at the end of mitosis.


Anti-tumoral effects of miR-3189-3p in glioblastoma.
Glioblastoma is one of the most aggressive brain tumors. We have previously found up-regulation of growth differentiation factor 15 (GDF15) in glioblastoma cells treated with the anticancer agent fenofibrate. Sequence analysis of GDF15 revealed the presence of a microRNA, miR-3189, in the single intron. We then asked whether miR-3189 was expressed in clinical samples and whether it was functional in glioblastoma cells. We found that expression of miR-3189-3p was down-regulated in astrocytoma and glioblastoma clinical samples compared with control brain tissue. In vitro, the functionality of miR-3189-3p was tested by RNA-binding protein immunoprecipitation, and miR-3189-3p coimmunoprecipitated with Argonaute 2 together with two of its major predicted gene targets, the SF3B2 splicing factor and the guanine nucleotide exchange factor p63RhoGEF. Overexpression of miR-3189-3p resulted in a significant inhibition of cell proliferation and migration through direct targeting of SF3B2 and p63RhoGEF, respectively. Interestingly, miR-3189-3p levels were increased by treatment of glioblastoma cells with fenofibrate, a lipid-lowering drug with multiple anticancer activities. The attenuated expression of miR-3189-3p in clinical samples paralleled the elevated expression of SF3B2, which could contribute to the activation of SF3B2 growth-promoting pathways in these tumors. Finally, miR-3189-3p-mediated inhibition of tumor growth in vivo further supported the function of this microRNA as a tumor suppressor.


Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons.
In association with NMDA receptors (NMDARs), neuronal α7 nicotinic ACh receptors (nAChRs) have been implicated in neuronal plasticity as well as neurodevelopmental, neurological, and psychiatric disorders. However, the role of presynaptic NMDARs and their interaction with α7 nAChRs in these physiological and pathophysiological events remains unknown. Here we report that axonal α7 nAChRs modulate presynaptic NMDAR expression and structural plasticity of glutamatergic presynaptic boutons during early synaptic development. Chronic inactivation of α7 nAChRs markedly increased cell surface NMDAR expression as well as the number and size of glutamatergic axonal varicosities in cortical cultures. These boutons contained presynaptic NMDARs and α7 nAChRs, and recordings from outside-out pulled patches of enlarged presynaptic boutons identified functional NMDAR-mediated currents. Multiphoton imaging of presynaptic NMDAR-mediated calcium transients demonstrated significantly larger responses in these enlarged boutons, suggesting enhanced presynaptic NMDAR function that could lead to increased glutamate release. Moreover, whole-cell patch clamp showed a significant increase in synaptic charge mediated by NMDAR miniature EPSCs but no alteration in the frequency of AMPAR miniature EPSCs, suggesting the selective enhancement of postsynaptically silent synapses upon inactivation of α7 nAChRs. Taken together, these findings indicate that axonal α7 nAChRs modulate presynaptic NMDAR expression and presynaptic and postsynaptic maturation of glutamatergic synapses, and implicate presynaptic α7 nAChR/NMDAR interactions in synaptic development and plasticity.


Selectins and IL-6 during the clinical course of idiopathic thrombocytopenic purpura.
'Stress thrombocytes', i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = -0.32, p = 0.019) and IL-6 (r = -0. 41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented 'residual platelet' functions in ITP.


Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury.
Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.


Alternative gene therapy strategies for the repair of craniofacial bone defects.
Craniofacial anomalies, bone defects and cartilage lesions pose a difficult and challenging problem for both the doctor and for patients and their families. Conventional therapies focus on orthopaedic surgery, grafting with autogenous bone, allogenic bone grafts, or distraction osteogenesis. However, the efficacy of these techniques is limited by high cost, donor morbidity, scarcity of tissue resources, and alterations in volume [Marx & Morales, 1988]. On the basis of recent insights into the development, growth, and adaptation of bone, together with the significant advances in recombinant DNA technology, gene therapy is increasingly becoming recognised as an alternative technique for augmenting and promoting bone regeneration in vivo. It can be applied in craniofacial skeletal tissues by transferring genes encoding for specific growth factors such as BMPs in osteoblasts, chondrocytes or progenitor cells for the purpose of enhancing protein production [Scaduto & Lieberman, 1999]. It can be performed by either direct administration of gene delivery vectors, or by transplantation of genetically modified cells. This review will focus on recent advances in molecular mechanisms of bone formation, and development in various viral and non-viral vectors for direct in vivo therapeutic gene transfer and genetically engineered cells ex vivo therapy.


Hemimandibular hyperplasia: treatment strategies.
Hemimandibular hyperplasia is a well-defined, rare asymmetrical mandibular malformation. It is characterized by diffuse enlargement of the condyle, the condylar neck, and the ramus and body of the mandible. Because the anomaly begins before puberty, it is understandable that the maxilla follows the downward growth of the mandible. Pathogenesis is due most likely to clear hyperactivity in the condyle, which can be documented histologically with an actively proliferating cartilage. Therapy is largely based on the patient's age. The authors present their series of nine individuals with hemimandibular hyperplasia treated with various surgical methods between 1992 and 1994. A therapeutic approach called orthopedic maxillary management applied to two of the nine patients is presented. The objective is to maintain the occlusal maxillary plane in a correct position in growing patients. All clinical results, except one, were satisfying and showed good postoperative stability.


Hybrid decompression and reconstruction technique for cervical spondylotic myelopathy: case series and review of the literature.
The primary treatment of choice for patients with cervical spondylotic myelopathy (CSM) is surgical decompression. The benefit of operative intervention has been well established but, the surgeons' decision of operative approach remains nuanced based on patient-specific variables and surgeon preference. Decompression can involve a cervical corpectomy or a discectomy. A hybrid construct is when both a cervical corpectomy and a discectomy are done in the same patient. The purpose of this study was to review the evidence on the clinical and biomechanical outcomes of hybrid decompression and reconstruction techniques in patients with multilevel CSM. A retrospective study was performed on consecutive patients who received hybrid anterior decompression and reconstruction at Rush University between 2013-2018. Preoperative clinical and radiographic variables were analyzed to characterize specific factors leading to the decision of the surgical approach. In addition, we performed a systematic review and meta-analysis to assess superiority in terms of operative time, blood loss, cervical lordosis, patient-reported outcomes (PRO), fusion rates, and complications. Hybrid surgery (HS) was utilized in cases where multilevel CSM was present in conjunction with stenosis posterior to the vertebral body or acute kyphotic deformity. Our meta-analysis highlighted comparable PRO, complications, and rate of success fusion between 3-level anterior cervical discectomy and fusion (ACDF) and hybrid technique. Furthermore, hybrid fusion led to increased postoperative cervical lordosis, higher fusion rate, lower total complication rate, lower implant failure/mesh subsidence rate, and lower blood loss than 2-level corpectomy. The cervical hybrid technique that combines cervical corpectomy and discectomy represents a balanced option with the benefits of two commonly utilized cervical spine procedures in patients with multilevel CSM. The literature on hybrid technique suggests in cases where multilevel ACDF is not feasible, combining discectomy and corpectomy is superior to two-level corpectomy with lower complication rates, improved clinical outcome, spinal alignment correction, and stronger biomechanical properties.


The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways.
CHIP is a U-box-type ubiquitin ligase that induces ubiquitylation and degradation of its substrates, which include several oncogenic proteins. The relationship between CHIP and tumour progression, however, has not been elucidated. Here, we show that CHIP suppresses tumour progression in human breast cancer by inhibiting oncogenic pathways. CHIP levels were negatively correlated with the malignancy of human breast tumour tissues. In a nude mouse xenograft model, tumour growth and metastasis were significantly inhibited by CHIP expression. In contrast, knockdown of CHIP (shCHIP) in breast cancer cells resulted in rapid tumour growth and metastastic phenotypes in mice. In cell-based experiments, anchorage-independent growth and invasiveness of shCHIP cells was significantly elevated due to increased expression of Bcl2, Akt1, Smad and Twist. Proteomic analysis identified the transcriptional co-activator SRC-3 (refs 13, 14, 15, 16, 17, 18, 19) as a direct target for ubiquitylation and degradation by CHIP. Knocking down SRC-3 in shCHIP cells reduced the expression of Smad and Twist, and suppressed tumour metastasis in vivo. Conversely, SRC-3 co-expression prevented CHIP-induced suppression of metastasis formation. These observations demonstrate that CHIP inhibits anchorage-independent cell growth and metastatic potential by degrading oncogenic proteins including SRC-3.


Association of race and ethnicity with pediatric burn outcomes: A population study of the Kids' Inpatient Database.
While most studies on burn outcomes have focused on adults, it is unclear if the same socioeconomic and environmental inequalities affect paediatric patients. This study aims to investigate the impact of race and ethnicity on outcomes in paediatric burn patients. The Kids' Inpatient Database is released by Agency for Healthcare Research and Quality, and is the largest publicly available database for the United States inpatient paediatric population. All paediatric burned patients in 2016 and 2019 were identified. Race and/or ethnicity was the primary exposure variable, and the primary outcome was a composite of several in-hospital morbidities. Secondary outcomes included death, non-routine disposition, and length of stay. Fine-Gray competing risks regression and multivariable logistic regression were used to analyze length of stay and all other outcomes, respectively. Analysis also isolated subgroups related to socioeconomic status and case severity. We included12,582 pediatric burn patients in this study. No difference was found in composite morbidity between White patients and those of other race or ethnicity groups. Hispanic ethnicity was associated with longer lengths of stay and increased odds of routine (i.e. home) discharge. Black patients had increased length of stay compared to White patients only in severe burn cases. Our study implies that race- or ethnicity-associated mechanisms driving outcome disparities in adults does not necessarily apply in paediatric burn patients.


Covid-19 and small lodging establishments: A break-even calibration analysis (CBA) model.
The COVID-19 pandemic foiled the hospitality industry offering no clear insight as to what to expect regarding the emergence of possible new industry standards as likely corollaries of the pandemic. The accommodation sector is one of the most affected sectors in the hospitality industry, especially small lodging establishments incurring the most dramatic brunt of the pandemic's long-tail effects. This study employed a breakeven (BC) analysis to examine the pandemic's opportunity cost and the financial resilience efforts that SLEs should undertake to bounce back or bounce forward. The case study centers on the Superior Small Lodgings (SSL) of Florida, USA. The results suggest that the opportunity cost varies depending on the SLE profiles, and hence resilience approaches should consider heterogeneous business responses.


Effect of Myosin Isoforms on Cardiac Muscle Twitch of Mice, Rats and Humans.
To understand how pathology-induced changes in contractile protein isoforms modulate cardiac muscle function, it is necessary to quantify the temporal-mechanical properties of contractions that occur under various conditions. Pathological responses are much easier to study in animal model systems than in humans, but extrapolation between species presents numerous challenges. Employing computational approaches can help elucidate relationships that are difficult to test experimentally by translating the observations from rats and mice, as model organisms, to the human heart. Here, we use the spatially explicit MUSICO platform to model twitch contractions from rodent and human trabeculae collected in a single laboratory. This approach allowed us to identify the variations in kinetic characteristics of α- and β-myosin isoforms across species and to quantify their effect on cardiac muscle contractile responses. The simulations showed how the twitch transient varied with the ratio of the two myosin isoforms. Particularly, the rate of tension rise was proportional to the fraction of α-myosin present, while the β-isoform dominated the rate of relaxation unless α-myosin was >50%. Moreover, both the myosin isoform and the Ca2+ transient contributed to the twitch tension transient, allowing two levels of regulation of twitch contraction.


Endoscopic cauterization of fourth branchial cleft sinus tracts.
To evaluate the effectiveness of endoscopic cauterization as definitive treatment for fourth branchial cleft sinuses. Retrospective chart review with follow-up questionnaire. Tertiary care children's hospital. Ten children (age range, 10 months to 10 years) with fourth branchial cleft sinuses treated with endoscopic cauterization between 1995 and 2002. Recurrence of neck infections after endoscopic cauterization of fourth brachial cleft sinus tracts. Seven of the 10 patients treated with endoscopic cauterization of the fourth branchial cleft sinuses showed no recurrence with an average follow-up of 3 years. Three of the patients were unavailable for follow-up, but medical records of the hospital showed no additional admissions for those patients for neck masses. No morbidity of the procedure was identified. All patients were discharged the day of surgery. Endoscopic cauterization of fourth branchial cleft sinuses appears to be an effective alternative to open excision.


Mesenchymal stem cells for cartilage regeneration in dogs.
Articular cartilage damage and osteoarthritis (OA) are common orthopedic diseases in both humans and dogs. Once damaged, the articular cartilage seldom undergoes spontaneous repair because of its avascular, aneural, and alymphatic state, and the damage progresses to a chronic and painful situation. Dogs have distinctive characteristics compared to other laboratory animal species in that they share an OA pathology with humans. Dogs can also require treatment for naturally developed OA; therefore, effective treatment methods for OA are desired in veterinary medicine as well as in human medicine. Recently, interest has grown in regenerative medicine that includes the use of mesenchymal stem cells (MSCs). In cartilage repair, MSCs are a promising therapeutic tool due to their self-renewal capacity, ability to differentiate into cartilage, potential for trophic factor production, and capacity for immunomodulation. The MSCs from dogs (canine MSCs; cMSCs) share various characteristics with MSCs from other animal species, but they show some deviations, particularly in their differentiation ability and surface epitope expression. In vivo studies of cMSCs have demonstrated that intraarticular cMSC injection into cartilage lesions results in excellent hyaline cartilage regeneration. In clinical situations, cMSCs have shown great therapeutic effects, including amelioration of pain and lameness in dogs suffering from OA. However, some issues remain, such as a lack of regulations or guidelines and a need for unified methods for the use of cMSCs. This review summarizes what is known about cMSCs, including their in vitro characteristics, their therapeutic effects in cartilage lesion treatment in preclinical in vivo studies, their clinical efficacy for treatment of naturally developed OA in dogs, and the current limitations of cMSC studies.


Equine Welfare Assessment: Exploration of British Stakeholder Attitudes Using Focus-Group Discussions.
The equine industry in Great Britain has not been subject to the same pressures as the farming industry to engage with welfare assessment, but this may change as concern about equine welfare increases. Stakeholder attitudes toward welfare assessment may impact the implementation of welfare assessment practices. Focus-group discussions regarding welfare assessment were conducted with 6 equine stakeholder groups: leisure horse owners (caregivers; n = 4), grooms (n = 5), veterinary surgeons (n = 3), welfare scientists (n = 4), welfare charity workers (n = 5), and professional riders (n = 4). Three themes emerged from the discussions: (a) Participants predominantly interpreted welfare assessment as a means of identifying and correcting poor welfare in an immediate way; (b) participants believed that horse welfare varied over time; and (c) attributes of the assessor were viewed as an important consideration for equine welfare assessment. The views of equine industry members give insight into the value welfare assessments may have to the industry and how equine welfare assessment approaches can achieve credibility within the industry and increase the positive impact of welfare assessments on equine welfare.


Late venous thromboembolism prophylaxis after craniotomy in acute traumatic brain injury.
The objective of this study is to compare rates of venous thromboembolism (VTE) in patients who receive enoxaparin prophylaxis compared with no enoxaparin prophylaxis after craniotomy for traumatic brain injury (TBI). This retrospective cohort evaluated all trauma patients admitted to a Level I trauma center from January 2006 to December 2011 who received craniotomy after acute TBI. Patients were excluded if developed VTE before administration of enoxaparin or they died within the first 72 hours of hospital admission. A total of 271 patients were included (enoxaparin prophylaxis, n = 45; no enoxaparin prophylaxis, n = 225). The median time until enoxaparin initiation was 11 ± 1 days. There was no significant difference in the proportion of patients who developed a VTE when using enoxaparin prophylaxis compared with no enoxaparin prophylaxis (2 vs 4%; P = 0.65). Rates of deep vein thrombosis (2 vs 3%; P = 0.87) and pulmonary embolism (0 vs 1%; P = 0.99) were similar between treatment groups, respectively. Late enoxaparin prophylaxis did not demonstrate a protective effect for VTE. Given the overall low event rate, the administration of pharmacologic prophylaxis against VTE late in the treatment course may not be routinely warranted after craniotomy for acute TBI. Further investigation with early administration of enoxaparin is needed.


[Importance of the bicycle ergometry test indices for predicting the outcome of stenocardia].
The predictive value of initial bicycle ergometry was assessed on the basis of long-term follow-up (averaging 5.4 years) of 272 patients with stable angina pectoris. The prognosis for anginal patients was shown to be basically worse where the threshold capacity, operation volume at the final stage of exercise and the double product at the time of an anginal attack were at low levels. It was also unfavorable in cases where electrocardiograms showed combinations of horizontal ST depression and frequent extrasystoles or ambidirectional ischemic displacements in individual leads, during an anginal attack provoked by rationed exercise. These parameters are suggested as criteria for dividing anginal patients into high and relatively low risk groups with respect to the fatal outcome.


Orthogonal site-specific protein modification by engineering reversible thiol protection mechanisms.
Covalent modification is an important strategy for introducing new functions into proteins. As engineered proteins become more sophisticated, it is often desirable to introduce multiple, modifications involving several different functionalities in a site-specific manner. Such orthogonal labeling schemes require independent labeling of differentially reactive nucleophilic amino acid side chains. We have developed two protein-mediated protection schemes that permit independent labeling of multiple thiols. These schemes exploit metal coordination or disulfide bond formation to reversibly protect cysteines in a Cys(2)His(2) zinc finger domain. We constructed a variety of N- and C-terminal fusions of these domains with maltose-binding protein, which were labeled with two or three different fluorophores. Multiple modifications were made by reacting an unprotected cysteine in MBP first, deprotecting the zinc finger, and then reacting the zinc finger cysteines. The fusion proteins were orthogonally labeled with two different fluorophores, which exhibited intramolecular fluorescene resonance energy transfer (FRET). These conjugates showed up to a threefold ratiometric change in emission intensities in response to maltose binding. We also demonstrated that the metal- and redox-mediated protection methods can be combined to produce triple independent modifications, and prepared a protein labeled with three different fluorophores that exhibited a FRET relay. Finally, labeled glucose-binding protein was covalently patterned on glass slides using thiol-mediated immobilization chemistries. Together, these experiments demonstrated that reversible thiol protection schemes provide a rapid, straightforward method for producing multiple, site-specific modifications.


Troponin I elevation and cardiac events after percutaneous coronary intervention.
Serum troponins are sensitive markers of myonecrosis and ischemia and are now widely used in clinical practice. Although percutaneous coronary intervention (PCI)-related creatine kinase-myocardial band isoenzyme (CK-MB) elevation has been associated with future cardiac events, the significance of troponin elevation in this setting is unknown. We sought to determine whether serum troponin I (Tn-I) elevation after PCI is associated with future cardiac events. Methods and Results Consecutive patients undergoing elective PCI underwent systematic postprocedure measurement of Tn-I and CK-MB levels. Serum levels were correlated with demographic, angiographic, and procedural characteristics and the development of major adverse cardiac events (MACE; defined as death, MI, or need for PCI or coronary bypass graft surgery) at 30 days, 6 months, and 1 year. In 286 consecutive procedures, postintervention myonecrosis-specific Tn-I was elevated in 13.6% of patients, and CK-MB was elevated in 12.9% of patients. Multivariable predictors of Tn-I elevation were procedural side branch occlusion and thrombus formation. Peak Tn-I and CK-MB values were well correlated (r = 0.81, P <.0001). Three-fold elevation of Tn-I after successful PCI was independently predictive of MACE (P =.01). Tn-I elevation after elective PCI is relatively common and is associated with procedural complications such as incidental side branch occlusion and thrombus formation. In addition, this study demonstrates that a 3-fold elevation of Tn-I after successful elective PCI is predictive of future cardiac events, especially the need for early repeat revascularization.


Interactions of insulin, corticosterone and prolactin in promoting milk-fat synthesis by mammary explants from pregnant rabbits.
1. The rate of fatty acid synthesis by mammary explants from rabbits pregnant for 16 days or from rabbits pseudopregnant for 11 days was stimulated up to 15-fold by culturing for 2-4 days with prolactin. This treatment initiated the predominant synthesis of C(8:0) and C(10:0) fatty acids, which are characteristic of rabbit milk. 2. Inclusion of insulin in the culture medium increased the rate of synthesis of these medium-chain fatty acids. By contrast the inclusion of corticosterone led to the predominant synthesis of long-chain fatty acids. When explants were cultured for 2-4 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased up to 42-fold, but both medium- and long-chain fatty acids were synthesized. 3. These results show that the stimulus to mammary-gland lipogenesis and the initiation of synthesis of medium-chain fatty acids observed between days 16 and 23 of pregnancy in the rabbit can be simulated in vitro by prolactin alone. 4. When mammary explants from rabbits pregnant for 23 days were cultured for 2 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased fivefold, but there was a preferential synthesis of long-chain fatty acids. Culture with prolactin alone had little effect on the rate or pattern of fatty acids synthesized. 5. The results are compared with findings in vivo on the control of lipogenesis in the rabbit mammary gland, and are contrasted with the known effects of hormones in vitro on the mammary gland of the mid-pregnant mouse.


An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation.
SRm160 (the SR-related nuclear matrix protein of 160 kDa) functions as a splicing coactivator and 3'-end cleavage-stimulatory factor. It is also a component of the splicing-dependent exon-junction complex (EJC), which has been implicated in coupling of pre-mRNA splicing with mRNA turnover and mRNA export. We have investigated whether the association of SRm160 with the EJC is important for efficient 3'-end cleavage. The EJC components RNPS1, REF, UAP56, and Y14 interact with SRm160. However, when these factors were tethered to transcripts, only SRm160 and RNPS1 stimulated 3'-end cleavage. Whereas SRm160 stimulated cleavage to a similar extent in the presence or absence of an active intron, stimulation of 3'-end cleavage by tethered RNPS1 is dependent on an active intron. Assembly of an EJC adjacent to the cleavage and polyadenylation signal in vitro did not significantly affect cleavage efficiency. These results suggest that SRm160 stimulates cleavage independently of its association with EJC components and that the cleavage-stimulatory activity of RNPS1 may be an indirect consequence of its ability to stimulate splicing. Using RNA interference (RNAi) in Caenorhabditis elegans, we determined whether interactions between SRm160 and the cleavage machinery are important in a whole organism context. Simultaneous RNAi of SRm160 and the cleavage factor CstF-50 (Cleavage stimulation factor 50-kDa subunit) resulted in late embryonic developmental arrest. In contrast, RNAi of CstF-50 in combination with RNPS1 or REFs did not result in an apparent phenotype. Our combined results provide evidence for an evolutionarily conserved interaction between SRm160 and the 3'-end cleavage machinery that functions independently of EJC formation.


[Initial experience of threefocal diffractive/refractive intraocular lenses implantation].
Due to original Russian technique of frontal photopolimerization of liquid oligomers in form the use of threefocal intraocular lense (IOL) with square relief of diffractive surface has become possible. The first 36 implantations of MIOL-Record showed good clinical and functional results. This lens provides high quality of intermediate vision without decrease of distant and near visual acuity. 94% of patients completely refused spectacle correction for all distances. The vast majority of patients are satisfied with their intermediate vision, 94% of them don't use spectacles for computer work. Incidence of disphotopsias is similar to that after other MIOLs implantation.


Collagen expression in embryonic chicken chondrocytes treated with phorbol myristate acetate.
Growth of embryonic chicken sternal chondrocytes in the presence of phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, resulted in a dramatic morphological change from spherical floating cells to adherent fibroblastic cells. This morphological change was accompanied by a quantitative switch from synthesis of cartilage-specific type II procollagen to type I procollagen. Type II procollagen mRNA levels decreased 10-fold in PMA-treated cells. Activation of type I collagen genes led to the accumulation of type I procollagen mRNA levels comparable to those of type II mRNA in these cells. However, only type I procollagen mRNA was translated. In addition to gene activation, unprocessed pro alpha 1(I) transcripts present at low levels in control chondrocytes were processed to mature mRNA species. Redifferentiation of PMA-treated chondrocytes was possible if cells were removed from PMA after the morphological change and cessation of type II procollagen synthesis but before detectable amounts of type I procollagen were synthesized. Production of type I collagen thus marks a late phase of chondrocyte "dedifferentiation" from which reversion is no longer possible. Redifferentiated cell populations contained 24-fold more pro alpha 1(II) collagen mRNA than pro alpha 1(I) collagen mRNA, but the rates of procollagen synthesis were comparable. This suggests that the PMA-mediated dedifferentiation of chondrocytes as well as their redifferentiation is under both transcriptional and posttranscriptional regulation.


Activity of cytokine-induced killer cells against bone and soft tissue sarcoma.
Cytokine-induced killer (CIK) cells are T lymphocytes expanded ex vivo that are endowed with MHC-independent tumoricidal activity. We have recently demonstrated, in a preclinical setting, that CIK cells are active against autologous bone and soft tissue sarcomas. In particular, CIK cells killed a putative sarcoma stem cell population that may underlie disease relapse and chemoresistance.


Mansonian schistosomiasis in rectum--report of a case.
Schistosomiasis is a snail-transmitted trematodiasis acquired by immersion in water which contains the cercariae. In Korea, six imported cases of urinary schistosomiasis by Schistosoma haematobium and one case of imported cerebral schistosomiasis by S. mansoni were reported. Herein we report a case of S. mansoni infecting rectum of a 46 year-old Korean male, who had been to Saudi Arabia for two years. On colonoscopy for routine physical check up, a 0.4 cm polyp in the rectum was detected and biopsy was done. Microscopically, rectal mucosa showed several granulomas which were composed of macrophages, lymphocytes, neutrophils and eosinophils. The center of each granuloma showed an ovoid egg often containing miracidium. The eggs measured 130 x 60 microns in average size. They had yellowish-brown transparent shell with the characteristic lateral spine. This is the 8th imported case of schistosomiasis in Korea and the second one infected by S. mansoni.


Improved Weather and Seasonal Climate Forecasts from Multimodel Superensemble.
A method for improving weather and climate forecast skill has been developed. It is called a superensemble, and it arose from a study of the statistical properties of a low-order spectral model. Multiple regression was used to determine coefficients from multimodel forecasts and observations. The coefficients were then used in the superensemble technique. The superensemble was shown to outperform all model forecasts for multiseasonal, medium-range weather and hurricane forecasts. In addition, the superensemble was shown to have higher skill than forecasts based solely on ensemble averaging.


Hepatitis B immunoglobulin and Lamivudine improve hepatitis B-related outcomes after liver transplantation: meta-analysis.
HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting. We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model. Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03-0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02-0.33) and 0.02 (95% CI, 0.06-0.82), respectively. Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants.


Regeneration of a deactivated surface functionalised polyacrylonitrile supported Fenton catalyst for use in wastewater treatment.
Successful attempts to regenerate a used surface functionalised nanocoated polyacrylonitrile (PAN) catalyst are described here. During use in wastewater treatment, the novel Fenton catalyst (F1) is deactivated due to iron loss caused by acid hydrolysis. In this study the deactivated catalyst (D1) is subjected to reactions with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), followed by reactions with either hydroxylamine to give sample T1 or hydroxylamine and hydrazine to give sample T2. The samples were then impregnated with iron(iii) salt to give either Fe-T1 or Fe-T2. The catalysts were characterized by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), Atomic Absorption (AA) and UV/VIS spectroscopies, Scanning Electron Microscopy (SEM) with energy-dispersive X-ray (EDX) spectroscopy and Electron Spin Resonance (ESR) spectroscopy. The iron on the regenerated catalyst was found to be in complexed form but had deposited iron oxide species as well. The catalysts were tested in batch mode and compared with the fresh modified PAN catalyst in the degradation of the dye Reactive Orange 16 (RO-16) with analysis by UV/VIS spectroscopy. The reactivated catalysts prepared with EDC were found to be more active and faster (as measured at 120 min) in decolourising RO-16 than the fresh catalytic mesh but also with a higher degree of Fe leaching (0.85% loss of iron per gram of Fe-T2 catalyst over 6 cycles compared to 0.32% loss of Fe per gram of F1 catalyst over 6 cycles). This leaching was found not to contribute significantly to degradation of the dye and the preliminary results suggest that the regime can be used for catalyst regeneration encouraging industrial uptake.


Aetiology and Pathogenesis of abomasal displacement in dairy cattle.
A clinical chemical survey is given of the complex of factors which are involved during development of clinically manifest hypotony or atony of the abomasum prior to abomasal displacemnts. The importance of a change in the acid-base balance of the animals is especially stressed as a predisposing factor. The further pathogenesis of abomasal displacement is supposed to follow different ways, according to the feeding and to prevailing periods of indigestion.


Breakdown of proteins from mouse liver subcellular fractions. Effect of nutritional changes.
The rapid restoration of liver protein mass observed in protein-depleted mice when they are fed with an adequate diet is quantitatively explained by a large decrease in the average rate of breakdown of total liver proteins. This study was performed in order to know whether this inhibition of breakdown affects in the same way all the protein constituents of the tissue, or only affects a group of these proteins belonging to a particular subcellular fraction. Subcellular fractions were obtained by differential centrifugation. The relative rates of breakdown of their proteins were estimated by the conservation of radioactivity in these proteins previously labelled by the administration of NaH14CO3 to mice. The results obtained indicated: 1) a general decrease in the rate of breakdown of proteins of subcellular fractions from re-fed livers compared with livers of protein-depleted mice; 2) a decrease of breakdown of proteins from cytosol in re-fed mice which is higher as lower is the molecular weight of the proteins subunits.


Lung fibroblast repair functions in patients with chronic obstructive pulmonary disease are altered by multiple mechanisms.
Fibroblasts are believed to be the major cells responsible for the production and maintenance of extracellular matrix. Alterations in fibroblast functional capacity, therefore, could play a role in the pathogenesis of pulmonary emphysema, which is characterized by inadequate maintenance of tissue structure. To evaluate the hypothesis that deficient fibroblast repair characterizes cells obtained from individuals with chronic obstructive pulmonary disease (COPD) compared with control subjects. Fibroblasts were cultured from lung tissue obtained from individuals undergoing thoracotomy and were characterized in vitro. Fibroblasts from individuals with COPD, defined by reduced FEV(1), manifested reduced chemotaxis toward fibronectin and reduced contraction of three-dimensional collagen gels, two bioassays associated with fibroblast repair function. At least two mechanisms appear to account for these differences. Prostaglandin E (PGE), a known inhibitor of fibroblast repair functions, was produced in increased amount by fibroblasts from subjects with COPD, which also expressed increased amounts of the receptors EP2 and EP4, both of which signal through cyclic AMP. Incubation of fibroblasts with indomethacin or with the PKA inhibitor KT-5720 partially restored COPD subject fibroblast function. In addition, fibroblasts from subjects with COPD produced more transforming growth factor (TGF)-beta1, but manifested reduced response to TGF-beta1. The functional alterations in fibroblasts correlated with both lung function assessed by FEV(1) and, for the data available, with severity of emphysema assessed by Dl(CO). Fibroblasts from individuals with COPD have reduced capability to sustain tissue repair, which suggests that this may be one mechanism that contributes to the development of emphysema.


Does proximal porous coating in short-stem humeral arthroplasty reduce stress shielding?
Short-stem humeral designs in shoulder arthroplasty have been introduced recently. A retrospective cohort study was conducted to determine if newer proximal porous titanium coating in humeral short stems produced clinical and radiologic improvements. Short-stem humeral implants (Tornier Ascend, Wright Medical) were used in 46 anatomical total shoulder replacements from October 2012 to December 2015. Clinical and radiologic measures were analyzed at one- and two-year follow-up. Nineteen shoulders received earlier grit blasted stems (Ascend Monolithic), and 27 shoulders received the later stems with proximal titanium porous coating (Ascend Flex). At two-year follow-up, radiographic changes and stress shielding were similar. Medial cortical thinning were more frequently observed in Monolithic (18 of 19) compared to Flex stems (19 of 27) on the PA films, though this was not statistically significant (P = 0.061). Clinical outcome scores improved regardless of the stem type used and independent of the radiologic adaptations on plain films. One participant with the Ascend Flex developed glenoid component failure and rotator cuff tear and was subsequently revised. Clinical and radiological outcomes are similar in both short-stem designs. Proximal titanium porous coating may reduce medial calcar cortical thinning but it does not prevent it. When compared to similarly designed uncoated grit-blasted stems, proximally porous coated humeral short stems produced similar clinical and radiological results. The proximal titanium porous coating may reduce medial cortical thinning.


Nucleotide receptors involved in UTP-induced rat arterial smooth muscle cell migration.
Many factors have been shown to be involved in the development of hyperplasic lesions of vessels, but the role of extracellular nucleotides remains largely unknown. The presence of P2Y and P2X nucleotide receptors on arterial endothelial and smooth muscle cells suggests a potential role for nucleotides in the vessel pathophysiology. Although the role of P2X in physiology of vessels is well documented, that of P2Y is not completely understood. We recently demonstrated that extracellular nucleotides, and particularly UTP, induced migration of cultured arterial smooth muscle cells (ASMCs). This migration is dependent on osteopontin expression and involves the Rho and mitogen-activated protein (MAP) kinase pathways. An important question is to determine the specific role of the different P2Y receptors of rat ASMCs in the UTP-induced migration process. Therefore, we first quantified mRNA levels of P2Y(2), P2Y(4), and P2Y(6) nucleotide receptors in cultured rat ASMCs by a competitive RT-PCR approach and demonstrated that P2Y(2) is the most highly expressed among these receptors potentially involved in the UTP-mediated response. In addition to UTP, UDP also induced ASMC migration even when UTP regeneration was inhibited, suggesting the involvement of UDP receptor P2Y(6). Moreover, suramin, a specific antagonist of rat P2Y(2) receptor, acted as an inhibitor of UTP-induced migration. Taken together, these results suggest a prominent role for the UTP receptor, P2Y(2), and for the UDP receptor, P2Y(6), in UTP-induced rat ASMC migration.


New Xist-Interacting Proteins in X-Chromosome Inactivation.
To achieve dosage compensation of X-linked gene expression, female mammalian cells inactivate one X chromosome through a process called X-chromosome inactivation (XCI). A central component of this process is the X-encoded long non-coding RNA Xist. Following upregulation from one X chromosome, Xist spreads in cis, kicking off a plethora of events that ultimately results in stable X-linked gene repression, which is then faithfully transmitted to all daughter cells. In the last decades, intensive work has been undertaken to understand each of the steps in XCI, namely Xist transcription control, Xist spreading and localization, and silencing of gene expression. Recently, several groups have spearheaded the research of Xist's interactome and the factors involved in silencing. Several novel proteins have now been shown to be required for the transcriptional silencing of the X chromosome and/or Xist spreading and localization to the inactive X chromosome. Here, we review these new findings in the context of existing knowledge about Xist-interacting factors.


[Mental health in the basic attention: an epidemic study based on the risk focus].
The transformations of stamp social, political and economical happened in the last decades they rebound significantly in all the sections of the society. And if it cannot leave of considering the influences of those transformations for the mental health of the population. It is a epidemic cohort study that aimed at accomplishing the risk for mental disease in the population assisted by the Unit of Health of the Family of the habitational group, neighborhood of Mangabeira, city of João Pessoa-PB, where Self Report Questionnaire-20 was used (SRQ-20). Association of the Risk was observed for Depression and Anxiety with the feminine sex (59,40%), among the age group from 40 to 65 years (66%), in the occupation of domestic services (65,5%). We are mischievous to recognize that the mental suffering has been growing relatively in the studied sample and starting from that verification it is done necessary an immediate attention to the problems of mental health in the community's people.


PU.1 is dominant and HAF-1 supplementary for activation of the gp91(phox) promoter in human monocytic PLB-985 cells.
Gp91(phox) is a key component of the phagocyte NADPH oxidase. Mutations of its promoter found in patients with chronic granulomatous disease cause deficient binding of PU.1 and HAF-1. Because the two factors bind to the same site (Pu box) of the promoter, we attempted to clarify their relative in vivo contributions to activation of the gp91(phox) promoter in monocytically differentiated PLB-985 cells using a dual luciferase reporter assay and a gel shift competition assay. We found that the activity of a series of single-point-mutated promoters increases or decreases according to an increase or decrease, respectively, in the affinity of the promoters to PU.1 but not to HAF-1. Two of 7 mutants showing weak binding affinity to PU.1 exhibited moderate promoter activity and normal binding affinity for HAF-1. These results suggest PU.1 is the dominant activator and HAF-1 is supplementary. The increased promoter activity of single-, double-, and triple-point-mutated constructs with sequences closer to that of the Ets-binding element correlates with their binding affinity to PU.1 but not to HAF-1, supporting that PU.1 is a more efficient activator than HAF-1. In contrast to co-expressed wild-type PU.1, dominant-negative PU.1 significantly inhibited the activity of a PU.1-optimised gp91(phox) promoter construct. Therefore, we conclude that PU.1 and HAF-1 binding to the Pu box is dominant and supplementary, respectively, for activation of the gp91(phox) promoter in human monocytic cells.


Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men.
To explore effects on serum lipids, pituitary-gonadal axis, prostate and bone turnover of the administration of the mixed oestrogen agonist/antagonist raloxifene in healthy elderly men. Thirty healthy men aged 60-70 years randomly received raloxifene 120 mg/day (n=15) or placebo (n=15) for 3 months. In this double-blind, placebo-controlled study, serum gonadotrophins, sex hormones, prostate specific antigen (PSA), a marker of bone turnover, urinary hydroxyproline (OHPro) and cholesterol were measured at baseline and after 3 months. Raloxifene significantly increased serum concentrations of LH and FSH (by 29% and 21%), total testosterone (20%), free testosterone (16%) and bioavailable testosterone (not bound to sex hormone-binding globulin (SHBG; 20%). In parallel with testosterone, 17 beta-oestradiol also increased by 21%. SHBG increased by 7%. Total cholesterol (TChol) decreased significantly, from 5.7 to 5.5 mmol/l (P=0.03). Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) showed a trend to decrease. Overall, there was no change in urinary OHPro/creatinine ratio as a marker for bone resorption. However, the raloxifene-induced increases in both serum testosterone and 17 beta-oestradiol were significantly related to a lower OHPro/creatinine ratio. Total PSA increased by 17% without significant changes in free PSA or free/total PSA ratio. Participants reported no side effects and raloxifene was well tolerated. In healthy elderly man, raloxifene 120 mg/day for 3 months increased LH, FSH and sex steroid hormones. Potentially beneficial effects were the small but significant decrease in TChol and the trend towards a decrease in LDL-c. Negative effects were the trend towards a decrease in HDL-c and the significant increase in serum PSA. A decrease in markers of bone resorption during raloxifene treatment was found only in men with relatively high increases in serum testosterone and 17 beta-oestradiol. Overall, there were no clear beneficial effects of administration of raloxifene to ageing men in this preliminary investigation.


Quality of life in chronic pancreatitis: a prospective trial comparing classical whipple procedure and duodenum-preserving pancreatic head resection.
Few data are available with respect to quality of life after pancreatic head resection in patients with chronic pancreatitis. The aim of this study was to compare the classical Whipple pancreatoduodenectomy (PD) with the Beger duodenum-preserving pancreatic head resection (DPPHR), in terms of quality of life, using standardized, valid, and reliable questionnaires. Sixty-five consecutive patients were included in this study. The PD procedure was chosen when pancreatic cancer could not be ruled out (n = 30); otherwise DPPHR was performed (n = 35). Quality of life was measured prospectively three times with the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ-C30) and the Gastrointestinal Quality-of-Life Index (GIQLI). Both procedures led to a significant improvement in quality of life, especially with regard to pain status. However, at the second follow-up examination (18 to 24 months postoperatively), all functional scales and the most important symptom scales of the EORTC QLQ-C30 revealed a better quality of life in the DPPHR group compared to the PD group. After classical PD, more patients seem to develop diabetes mellitus. The EORTC QLQ-C30 was found to be a better tool for quality-of-life assessment than the GIQLI in patients with chronic pancreatitis.


The Association Between Two Different Lipid Injectable Emulsions and Parenteral Nutrition-Associated Cholestasis in Very Low Birth Weight Infants: A Retrospective Cohort Study.
Using soybean oil-based lipid emulsions (Intralipid), which contain higher amounts of omega-6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (PNAC). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW receiving SMOFlipid vs. Intralipid. The study was conducted in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥ 21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, length of stay, weight 28 days after birth, severity of PNAC and the time to reversal of PNAC. Forty-four VLBW infants (35.5%) in the SMOFlipid group vs. 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [IQR] 55.6 [36.4] vs. 118.4 [77.2] μmol/L, P < 0.001) and the time to reversal of PNAC was shorter (median [IQR] 44 [49] vs. 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition. This article is protected by copyright. All rights reserved.


Postcesarean Analgesia With Epidural Morphine After Epidural 2-Chloroprocaine: A Randomized Noninferiority Trial.
Previous studies have suggested that administration of epidural 3% 2-chloroprocaine (CP) before epidural morphine results in decreased analgesic efficacy of epidural morphine. We sought to determine whether these observations were a result of antagonism or a window period between the conclusion of surgical anesthesia for cesarean delivery and the peak onset time of epidural morphine, and whether a method to preserve the analgesic efficacy of epidural morphine exists. Term parturients scheduled for nonemergent, unscheduled cesarean delivery with preexisting labor epidural catheters were recruited for this exploratory, randomized, single-blinded, noninferiority trial. Subjects were randomized to initial dosing to a T4 dermatome surgical anesthetic level with either 3% CP or 2% lidocaine with 1:200,000 epinephrine and sodium bicarbonate (LEB). Subsequent redosing for both groups was performed with LEB at regular intervals. Epidural morphine 3 mg was administered to both groups after delivery. Assessing the difference between the 2 groups in total opioid use for the first 24 hours after epidural morphine administration was the primary objective. The noninferiority margin of 10 oral milligram morphine equivalents was prespecified based on previous noninferiority studies. Secondary end points included time from epidural morphine administration to first rescue opioid request, numerical pain scores, nausea/vomiting, and pruritus. Data were analyzed for 40 parturients, 20 in each group. The median 24-hour opioid consumption for the CP group was 0 (Q1 = 0 and Q3 = 15.6) oral milligram morphine equivalents compared to 15 (6.3-22.5) for the LEB group. The median difference was -7.5, with a 95% confidence interval -15 to 0. Noninferiority was concluded, as the confidence interval was less than the predetermined noninferiority margin of 10 oral milligram morphine equivalents. There was no treatment effect on time to first opioid request and no statistically significant differences in pain scores or nausea, vomiting, or pruritus at all time points (4, 8, 12, and 24 hours after epidural morphine administration). While designed as an exploratory study, initial epidural dosing with 3% CP and beginning subsequent redosing with LEB within 30 minutes of the initial CP bolus provided noninferior postcesarean analgesia with epidural morphine compared to initial epidural dosing and redosing with LEB. Previous observations of decreased analgesic efficacy of epidural morphine after epidural CP were likely due to a window period that may be mitigated by redosing with lidocaine; however, larger studies are necessary to confirm these findings.


Clinical Features and Surgical Strategies of Distal Radius Posttraumatic Deformity.
To investigate the clinical features and surgical strategies of distal radius posttraumatic deformity. A retrospective analysis was performed on the data of 30 patients with distal radius posttraumatic deformity treated by osteotomy and orthopedic surgery in the department of orthopedics, the First Affiliated Hospital of Nanjing Medical University, from February 2016 to November 2018. All the patients underwent preoperative anterior and lateral X-ray plain scanning of bilateral wrist joints, showing different degrees of radius shortening, inferior ulnar and radial mismatch, palmar angle, and ulnar deviation angle, among which 11 patients had an uneven joint surface. After a full evaluation, osteotomy and orthopedic surgery were performed to restore the original anatomical structure, plaster fixation was performed for two weeks after surgery, and regular outpatient follow-up was conducted. The function of the wrist was evaluated by the MMWS (wrist joint improvement) scoring scale before and after surgery, and the changes in the wrist joint-related treatment parameters were evaluated according to X-ray. All 30 patients had no neurological symptoms after surgery, and all wounds healed within the first stage. All patients were followed up for 6-12 months, with an average healing time of 3.5 months. There was no reduction loss, internal fixation loosening, or fracture in the regular postoperative review. Postoperative MMWS (wrist joint improvement) score scale data were significantly higher than those before surgery, and there were differences between groups (P < 0.05). Postoperative treatment parameters of wrist joints such as palmar inclination angle, ulnar deviation angle, radius height, and lower ulnar and radial matching were significantly improved, and there were differences between groups (P < 0.05). The patients with distal radius posttraumatic deformity have the clinical characteristics of shortening of radius, mismatch of lower ulnar and radius, an abnormal inclination of palm, and ulnar declination. For patients with distal radius posttraumatic deformity, osteotomy and orthopedic surgery can effectively improve wrist function and improve patients' quality of life, which is worthy of clinical reference.


Geranylgeranyl diphosphate depletion inhibits breast cancer cell migration.
The objective of this study was to determine whether geranylgeranyl diphosphate synthase inhibition, and therefore geranylgeranyl diphosphate depletion, interferes with breast cancer cell migration. Digeranyl bisphosphonate is a specific geranylgeranyl diphosphate synthase inhibitor. We demonstrate that digeranyl bisphosphonate depleted geranylgeranyl diphosphate and inhibited protein geranylgeranylation in MDA-MB-231 cells. Similar to GGTI-286, a GGTase I inhibitor, digeranyl bisphosphate significantly inhibited migration of MDA-MB-231 cells as measured by transwell assay. Similarly, digeranyl bisphosphonate reduced motility of MDA-MB-231 cells in a time-dependent manner as measured by large scale digital cell analysis system microscopy. Digeranyl bisphosphonate was mildly toxic and did not induce apoptosis. Treatment of MDA-MB-231 cells with digeranyl bisphosphonate decreased membrane while it increased cytosolic RhoA localization. In addition, digeranyl bisphosphonate increased RhoA GTP binding in MDA-MB-231 cells. The specificity of geranylgeranyl diphosphonate synthase inhibition by digeranyl bisphosphonate was confirmed by exogenous addition of geranylgeranyl diphosphate. Geranylgeranyl diphosphate addition prevented the effects of digeranyl bisphosphonate on migration, RhoA localization, and GTP binding to RhoA in MDA-MB-231 cells. These studies suggest that geranylgeranyl diphosphate synthase inhibitors are a novel approach to interfere with cancer cell migration.


Impending epidemic: future projection of heart failure in Japan to the year 2055.
The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients. The statistics are based on prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030. LVD is expected to precipitate a future epidemic of heart failure in Japan.


Myiasis of the tracheostomy wound: case report.
"Myiasis" is a parasitic infestation of live human or vertebrate animal tissues or cavities caused by dipterous larvae (maggots) which feed on the host's dead or living tissue, liquid body substances or ingested food. They are extremely rare in Western countries, especially in E.N.T. practice, and to the best of our knowledge, only two cases of myiasis in a tracheostomy wound have been reported in the English literature. The case is reported, probably the first, of percutaneous tracheotomy myiasis. It was caused by infestation with larvae of Lucilia Caesar. The patient had undergone Griggs percutaneous tracheostomy 3 years earlier and was in a persistent vegetative state on account of a pontomesencephalic haemorrhage but maintained spontaneous breathing. The condition was treated by applying ether to the tracheotomy wound, which caused spontaneous exit of approximately 30 larvae, easily removed with forceps. The laboratory microbiologist observed and photographed macroscopic and microscopic characters of the larvae, of primary importance for species diagnosis. Predisposing factors could be: 1. smaller dimension of percutaneous tracheostomy in comparison to surgical tracheostomy; 2. vegetative state of patient; 3. poor hygiene of outer and inner tube; 4. bad smell of wound, which attracts flies; 5. living in a rural area. Although this is not a lethal disorder, knowledge of the disease is necessary from the preventive, diagnostic and curative standpoint. It is important to proceed with identification of the larvae, distinguishing them from other types of myiasis involving different therapeutic implications. Ecology, classification, and treatment of myiasis are reviewed.


Molecular cloning and expression of the rat beta 3-adrenergic receptor.
Rat adipose tissues contain atypical beta receptors that display certain pharmacological sensitivities that are similar to those found in the recently cloned human beta 3 receptor. However, there are also certain pharmacological differences between the human atypical beta 3 receptor and atypical receptors in rodent adipose tissues, which could indicate strong species differences, the existence of multiple atypical receptor subtypes, or both. To help decide among these possibilities, a rat beta 3 receptor clone was obtained and expressed in Chinese hamster ovary cells. The predicted primary structures of the rat and human receptors are greater than 90% similar. Despite this similarity, the pharmacological properties of the rat receptor differed from those reported for the human receptor but were similar to the properties exhibited by atypical receptors in rat adipose tissue. Specifically, the rat beta 3 receptor had a high affinity for BRL 37344 and a relatively low affinity for norepinephrine and was partially activated by the beta 1 and beta 2 receptor antagonist CGP 12177. Northern blot analysis and nuclease protection assays of RNA from rat tissues indicate that the beta 3 receptor is abundantly expressed only in adipose tissues.


Application of antimonide diode lasers in photoacoustic spectroscopy.
First investigations of photoacoustic (PA) spectroscopy (PAS) of methane using an antimonide semiconductor laser are reported. The laser fabrication is made in two steps. The structure is firstly grown by molecular beam epitaxy, then a metallic distributed-feedback (DFB) grating is processed. The laser operates at 2371.6 nm in continuous wave and at room temperature. It demonstrates single-mode emission with typical tuning coefficients of 0.04 nm mA(-1) and 0.2 nm K(-1). PA detection of methane was performed by coupling this laser into a radial PA cell. A detection limit of 20 ppm has been achieved in a preliminary configuration that was not optimised for the laser characteristics.