Age-Related Changes in Voice Emotion Recognition by Postlingually Deafened Listeners With Cochlear Implants.
Identification of emotional prosody in speech declines with age in normally hearing (NH) adults. Cochlear implant (CI) users have deficits in the perception of prosody, but the effects of age on vocal emotion recognition by adult postlingually deaf CI users are not known. The objective of the present study was to examine age-related changes in CI users' and NH listeners' emotion recognition. Participants included 18 CI users (29.6 to 74.5 years) and 43 NH adults (25.8 to 74.8 years). Participants listened to emotion-neutral sentences spoken by a male and female talker in five emotions (happy, sad, scared, angry, neutral). NH adults heard them in four conditions: unprocessed (full spectrum) speech, 16-channel, 8-channel, and 4-channel noise-band vocoded speech. The adult CI users only listened to unprocessed (full spectrum) speech. Sensitivity (d') to emotions and Reaction Times were obtained using a single-interval, five-alternative, forced-choice paradigm. For NH participants, results indicated age-related declines in Accuracy and d', and age-related increases in Reaction Time in all conditions. Results indicated an overall deficit, as well as age-related declines in overall d' for CI users, but Reaction Times were elevated compared with NH listeners and did not show age-related changes. Analysis of Accuracy scores (hit rates) were generally consistent with d' data. Both CI users and NH listeners showed age-related deficits in emotion identification. The CI users' overall deficit in emotion perception, and their slower response times, suggest impaired social communication which may in turn impact overall well-being, particularly so for older CI users, as lower vocal emotion recognition scores have been associated with poorer subjective quality of life in CI patients.


Visualization of human karyopherin beta-1/importin beta-1 interactions with protein partners in mitotic cells by co-immunoprecipitation and proximity ligation assays.
Karyopherin beta-1/Importin beta-1 is a conserved nuclear transport receptor, acting in protein nuclear import in interphase and as a global regulator of mitosis. These pleiotropic functions reflect its ability to interact with, and regulate, different pathways during the cell cycle, operating as a major effector of the GTPase RAN. Importin beta-1 is overexpressed in cancers characterized by high genetic instability, an observation that highlights the importance of identifying its partners in mitosis. Here we present the first comprehensive profile of importin beta-1 interactors from human mitotic cells. By combining co-immunoprecipitation and proteome-wide mass spectrometry analysis of synchronized cell extracts, we identified expected (e.g., RAN and SUMO pathway factors) and novel mitotic interactors of importin beta-1, many with RNA-binding ability, that had not been previously associated with importin beta-1. These data complement interactomic studies of interphase transport pathways. We further developed automated proximity ligation assay (PLA) protocols to validate selected interactors. We succeeded in obtaining spatial and temporal resolution of genuine importin beta-1 interactions, which were visualized and localized in situ in intact mitotic cells. Further developments of PLA protocols will be helpful to dissect importin beta-1-orchestrated pathways during mitosis.


[Role of tumor necrosis factor-α in Chlamydia Muridarum infection in the urogenital tract of mice].
To explore the role of tumor necrosis factor-α (TNF-α) in immune response to urogenital chlamydial infection and urogenital pathology in mice. Fifteen female wild-type (WT) C57BL/6J mice and 15 TNF-α receptor knockout (TNF-αR KO) mice were inoculated intravaginally with 1×104 inclusion forming units (IFUs) of live C. muridarum. At 56 days after the first inoculation, 8 mice from each group were subjected to a second inoculation at the same dose. Vaginal swabs were taken every 3 or 4 days to detect the number of inclusion bodies of chlamydia. On day 80 after the first inoculation, the mice were euthanized and peritoneal macrophages were collected and the vaginal tract and spleen were dissected. The pathologies in the fallopian tube and the uterine horn were observed and the severity of inflammatory cell infiltration and lumen dilatation were semi-quantitatively scored. The levels of interleukin-6 (IL-6), IL-8, IL-1α, IL-1β and TNF-α in the supernatant of the peritoneal macrophage were detected. Spleen cell suspension was prepared, and after stimulation with chlamydia EB in vitro, the levels of the cytokines including IL-4, IL-5, IL-17 and interferon-γ (IFN-γ) were determined in the cells. The clearance rate of Chlamydia from the urogenital tract was similar between TNF-αR KO mice and WT mice regardless of the primary or second infection. The severity of inflammation in the fallopian tube and the uterine horn did not differ significantly between the two groups, but TNF-αR KO mice had significantly milder dilation of the fallopian tubes (P < 0.05). The peritoneal macrophages from TNF-αR KO mice produced a significantly higher level of TNF-α than those from WT mice (P < 0.05); the spleen cells from the two groups both produced high levels of IFN-γ, but IL-17 production by the spleen cells was significantly lower in TNF-αR KO mice than in WT mice (P < 0.05). TNF-α is not associated with protective immune response against C. muridarum infection, and can worsen the inflammatory damages of the urogenital tract caused by C. muridarum in mice.


Ozone, but not nitrogen dioxide, fragments elastin and increases its susceptibility to proteolysis.
The effects of ozone (O3) and nitrogen dioxide (NO2) on the solubility and proteolytic susceptibility of elastin were examined to better understand how these oxidant air pollutants might damage the lung. In vitro O3 exposures at pH 7.4 resulted in the complete solubilization of elastin, but NO2 had no effect on solubility. The initial solubilization rate was 65 micrograms/mumol of O3, which increased to 150 micrograms/mumol in the midregion of a sigmoidal solubilization curve. Peptide fragments of the O3-solubilized elastin ranged in size from 5 to 20 kD. The conversion of insoluble elastin into soluble fragments by O3 was not due to the destruction of desmosine crosslinks. The effect of O3 on the proteolytic susceptibility of elastin was measured using insoluble elastin recovered from exposures that resulted in 5.3%, 12.8%, and 26.3% solubilization. Human neutrophil elastase (HNE) digested the remaining insoluble elastin samples 4.3, 6.0, and 9.8 times faster than unexposed elastin. In contrast, NO2-exposed elastin was no more susceptible to digestion by HNE. Ascorbate, EDTA, and uric acid reduced the proteolytic susceptibility of O3-exposed elastin, but mannitol afforded no protection. These findings indicate that the inhalation of O3 may contribute to lung disease by directly damaging elastin and by increasing its susceptibility to proteolysis, whereas NO2 probably damages lungs via alternative mechanisms.


Education for outreach: development of an interprofessional MSc in critical care.
This article describes the development of a new multi-professional Master's degree programme, which is aimed at supporting the education of practitioners in meeting the needs of Level 1 critically ill patients. The main drivers that influenced its development were Comprehensive Critical Care (Department of Health, 2000a) and the National Health Service Modernisation Agency for Critical Care. The programme was aimed primarily at junior doctors, senior ward nurses, senior physiotherapists and members of Outreach teams. The programme was designed to maximize work-based learning and is framed around two clinically focused units. The programme is informed by principles of quality improvement and aims to prepare practitioners to meet the needs of Level 1 patients 'at the point of need'.


Microfluidic device with reconfigurable spatial temporal gradients reveals plastic astrocyte response to stroke and reperfusion.
As a leading cause of mortality and morbidity, stroke constitutes a significant global health burden. Ischemic stroke accounts for 80% of cases and occurs due to an arterial thrombus, which impedes cerebral blood flow and rapidly leads to cell death. As the most abundant cell type within the central nervous system, astrocytes play a critical role within the injured brain. We developed a novel microphysiological platform that permits the induction of spatiotemporally controlled nutrient gradients, allowing us to study astrocytic response during and after transient nutrient deprivation. Within 24 h of inducing starvation in the platform, nutrient deprivation led to multiple changes in astrocyte response, from metabolic perturbations to gene expression changes, and cell viability. Furthermore, we observed that nutrient restoration did not reverse the functional changes in astrocyte metabolism, which mirrors reperfusion injury observed in vivo. We also identified alterations in numerous glucose metabolism-associated genes, many of which remained upregulated or downregulated even after restoration of the nutrient supply. Together, these findings suggest that astrocyte activation during and after nutrient starvation induces plastic changes that may underpin persistent stroke-induced functional impairment. Overall, our innovative device presents interesting potential to be used in the development of new therapies to improve tissue repair and even cognitive recovery after stroke.


Radioiodine in the treatment of hereditary medullary carcinoma of the thyroid.
The effect of 131I therapy as an adjunct to surgery in the management of patients with hereditary medullary carcinoma of the thyroid (MCT) was studied in 20 patients from 3 kindreds. Plasma calcitonin levels were measured before and after a dose of 131I sufficient to ablate postoperative thyroid remnants. In patients with residual biochemical MCT no significant reduction of the calcitonin levels was found after administration of radioiodine. In patients with normal postoperative calcitonin levels no (biochemical) recurrence developed 3 months to 2 yr subsequent to radioiodine therapy. It is concluded that 131I therapy as an adjunct to surgery is not indicated in the management of patients with residual hereditary MCT, although 131I may be of value in the prevention of tumor recurrence in patients with normal postoperative calcitonin values.


Bias in composite milk samples with unequal milking intervals.
Milk samples from a herd with milk intervals approximately 14-h nights and 10-h days were used to examine potential bias in measurements with composite samples. Six consecutive milkings were weighted and sampled individually. Composite samples for a day were determined mathematically from the data. Composite samples with equal amounts from a.m. and p.m. milkings gave fat percentage measurements that were .07% above the true daily measurement. Using the milking interval to determine the portion of sample from each milking reduced this bias to -.02%. Protein percentage and SCC were satisfactory with equal sampling (mean bias of .01% and 7, respectively) but were improved slightly with milking interval sampling regimen (mean bias of .00% and 1, respectively). Fat yields were determined with equal portions, milking interval portions, and two plans available from DHIA, namely, alternate component sampling and alternate a.m.-p.m. Based on mean deviation from true fat yield, alternate a.m.-p.m. was as accurate as alternate component sampling, but variations were greater with alternate a.m.-p.m.


The influence of the age and sex distributions of drivers on the reduction of impaired crashes: Ontario, 1974-1999.
Legislative changes and public media campaigns to prevent impaired driving are often cited as explanations for the reduction in the rate of impaired crashes over the past 25 years in most of the industrialized world. Other factors may have contributed to these reductions, such as changes in the age and sex distribution of the driver population. The primary purpose of this article is to assess the extent to which the reduction in impaired crashes in Ontario, Canada, may be attributable to the changing age and sex distribution of drivers. In Ontario, the rate of impaired crashes declined by 78.1% from 1974 to 1999. During this time period, the average age of drivers increased from 39.4 years in 1974 to 43.2 in 1999. Similarly, from 1974 to 1999 the percentage of all drivers that were women increased from 39.6% to 46.8%. Since statistics show the likelihood of impaired crashes is lower for both older drivers and women, the reduction of impaired crashes is partially due to these demographic changes. Using indirect standardization, the aging population accounted for an 8.6% decline in the rate of impaired crashes. The changing sex distribution of drivers accounted for a 9.4% decline in impaired crashes. Other global factors may also help to explain the reduction of impaired crashes, such as general road safety improvements and reductions in per adult consumption of alcohol.


Fibril Surface-Dependent Amyloid Precursors Revealed by Coarse-Grained Molecular Dynamics Simulation.
Amyloid peptides are known to self-assemble into larger aggregates that are linked to the pathogenesis of many neurodegenerative disorders. In contrast to primary nucleation, recent experimental and theoretical studies have shown that many toxic oligomeric species are generated through secondary processes on a pre-existing fibrillar surface. Nucleation, for example, can also occur along the surface of a pre-existing fibril-secondary nucleation-as opposed to the primary one. However, explicit pathways are still not clear. In this study, we use molecular dynamics simulation to explore the free energy landscape of a free Abeta monomer binding to an existing fibrillar surface. We specifically look into several potential Abeta structural precursors that might precede some secondary events, including elongation and secondary nucleation. We find that the overall process of surface-dependent events can be described at least by the following three stages: 1. Free diffusion 2. Downhill guiding 3. Dock and lock. And we show that the outcome of adding a new monomer onto a pre-existing fibril is pathway-dependent, which leads to different secondary processes. To understand structural details, we have identified several monomeric amyloid precursors over the fibrillar surfaces and characterize their heterogeneity using a probability contact map analysis. Using the frustration analysis (a bioinformatics tool), we show that surface heterogeneity correlates with the energy frustration of specific local residues that form binding sites on the fibrillar structure. We further investigate the helical twisting of protofilaments of different sizes and observe a length dependence on the filament twisting. This work presents a comprehensive survey over the properties of fibril growth using a combination of several openMM-based platforms, including the GPU-enabled openAWSEM package for coarse-grained modeling, MDTraj for trajectory analysis, and pyEMMA for free energy calculation. This combined approach makes long-timescale simulation for aggregation systems as well as all-in-one analysis feasible. We show that this protocol allows us to explore fibril stability, surface binding affinity/heterogeneity, as well as fibrillar twisting. All these properties are important for understanding the molecular mechanism of surface-catalyzed secondary processes of fibril growth.


Mucous cell metaplasia in rat nasal epithelium after a 20-month exposure to ozone: a morphometric study of epithelial differentiation.
The present study was designed to examine the effects of long-term ozone exposure on nasal epithelia and intraepithelial mucosubstances (IM) throughout the nasal airways of F344/N rats. Animals were exposed to 0 (controls), 0.12, 0.5, or 1.0 ppm ozone, 6 h/day, 5 days/wk, for 20 mo. Rats were killed 1 wk after the end of the exposure, and nasal tissues were processed for light and electron microscopy. Standard morphometric techniques were used to determine epithelial cell densities and the amounts of IM in the surface epithelium lining the nasal airways. No mucous cells or IM were present in the epithelia lining the nasal lateral meatus and maxillary sinus of rats exposed to 0 or 0.12 ppm ozone. In contrast, rats exposed to 0.5 or 1.0 ppm ozone had marked mucous cell metaplasia (MCM) with numerous mucous cells and conspicuous amounts of IM in the surface epithelium lining these upper airways. Ozone-induced increases in total epithelial cells (i.e., epithelial hyperplasia) were present only in rats exposed to 1.0 ppm. The results of this study indicate that rats chronically exposed to 1.0 or 0.5 ppm, but not 0.12 ppm, ozone can develop marked MCM with significant increases in IM in both proximal and distal nasal airways. The epithelial changes observed throughout the nasal passages of ozone-exposed rats may be adaptive responses in an attempt to protect the upper and lower respiratory tract from further ozone-induced injury.


Effect of Product Dimensions and Surface Browning Method on Salmonella Contamination in Frozen, Surface-Browned, Breaded Chicken Products Treated with Antimicrobials.
Not-ready-to-eat breaded chicken products formulated with antimicrobial ingredients were tested for the effect of sample dimensions, surface browning method and final internal sample temperature on inoculated Salmonella populations. Fresh chicken breast meat portions (5 × 5 × 5 cm), inoculated with Salmonella (7-strain mixture; 5 log CFU/g), were mixed with (5% v/w total moisture enhancement) (i) distilled water (control), (ii) caprylic acid (CAA; 0.0625%) and carvacrol (CAR; 0.075%), (iii) CAA (0.25%) and ε-polylysine (POL; 0.5%), (iv) CAR (0.15%) and POL (0.5%), or (v) CAA (0.0625%), CAR (0.075%) and POL (0.5%). Sodium chloride (1.2%) and sodium tripolyphosphate (0.3%) were added to all treatments. The mixtures were then ground and formed into 9 × 5 × 3 cm (150 g) or 9 × 2.5 × 2 cm (50 g) portions. The products were breaded, browned in (i) an oven (208 °C, 15 min) or (ii) deep fryer (190 °C, 15 s), packaged, and stored at -20 °C (8 d). Overall, maximum internal temperatures of 62.4 ± 4.0 °C (9 × 2.5 × 2 cm) and 46.0 ± 3.0 °C (9 × 5 × 3 cm) were reached in oven-browned samples, and 35.0 ± 1.1 °C (9 × 2.5 × 2 cm) and 31.7 ± 2.6 °C (9 × 5 × 3 cm) in fryer-browned samples. Irrespective of formulation treatment, total (after frozen storage) reductions of Salmonella were greater (P < 0.05) for 9 × 2.5 × 2 cm oven-browned samples (3.8 to at least 4.6 log CFU/g) than for 9 × 5 × 3 cm oven-browned samples (0.7 to 2.5 log CFU/g). Product dimensions did not (P ≥ 0.05) affect Salmonella reductions (0.6 to 2.8 log CFU/g) in fryer-browned samples. All antimicrobial treatments reduced Salmonella to undetectable levels (<0.3 log CFU/g) in oven-browned 9 × 2.5 × 2 cm samples. Overall, the data may be useful for the selection of antimicrobials, product dimensions, and surface browning methods for reducing Salmonella contamination.


Correction: Adaptable piezoelectric hemispherical composite strips using a scalable groove technique for a self-powered muscle monitoring system.
Correction for 'Adaptable piezoelectric hemispherical composite strips using a scalable groove technique for a self-powered muscle monitoring system' by Nagamalleswara Rao Alluri et al., Nanoscale, 2018, 10, 907-913.


A novel device for in situ study of gas adsorption under rotation.
The effect of rotation on adsorption kinetics of CO2 on activated carbon (AC) is studied using a novel rotation device. The device consists of a rotating cylindrical cell with inner dimensions of 4.5 cm radius and 1 mm height, while it operates at 5000 and 8000 rpm. Various cases of the CO2/AC system are examined under a rotation field: in particular, (a) solid at vacuum, (b) gas without solid, (c) gas/solid at a non-equilibrium state of the adsorption process, and (d) gas/solid near an equilibrium state of the adsorption process. Micro-fragmentation of solid particles is observed at 8000 rpm but not at 5000 rpm; the latter is then chosen as the preferable speed for the rest of the experiments. During rotation of the gas, a well is noticed at the pressure curve, the size of which is in accordance with theoretical predictions of the behavior of a spinning gas. Rotation at an early stage of the adsorption process can suppress the filling time of a rotating storage reservoir to half of its value. Rotation near the equilibrium point reveals an enhanced adsorption capacity of the solid. The physics behind these phenomena are discussed with the aid of N2-adsorption porosimetry and scanning electron microscopy measurements.


[Chemical biology--a new branch of science].
Chemical biology is a new branch of science characteristic with global description of biological processes occurring within the cell. It covers synthesis of new chemical compounds for systems biology studies and search for natural small molecular weight chemical compounds with high cellular regulatory potential. Chemical biology power is based on 3 pillars as chemical synthesis, computer calculations and systems biology.


Cell shape changes and the mechanism of inversion in Volvox.
Inversion is a dominant aspect of morphogenesis in Volvox. In this process, the hollow, spheroidal Volvox embryo turns inside-out through a small opening called the phialopore to bring flagella from its inner to its outer surface. Analyses of intact, sectioned, and fragmented embryos by light, scanning electron, and transmission electron microscopy, suggest that shape changes preprogrammed into the cells cause inversion. First, cells throughout the embryo change from pear to spindle shape, which causes the embryo to contract and the phialopore to open. Then cells adjacent to the phialopore become flask-shaped, with long, thin stalks at their outer ends. Simultaneously, the cytoplasmic bridges joining all adjacent cells migrate from the midpoint of the cells to the stalk tips. Together, these changes cause the lips of cells at the phialopore margin to curl outward. Now cells progressively more distal to the phialopore become flask-shaped while the more proximal cells become columnar, causing the lips to curl progressively further over the surface of the embryo until the latter has turned completely inside-out. Fine structural analysis reveals a peripheral cytoskeleton of microtubules that is apparently involved in cellular elongation. Cell clusters isolated before inversion undergo a similar program of shape changes; this suggests that the changes in cellular shape are the cause rather than an effect of the inversion process.


Waardenburg's Syndrome with Leprosy.
A rare association of Waardenburg's syndrome and tuberculoid leprosy in a 13-year-old patient is described. This is an unrecorded feature in the literature. These two disorders are quite unrelated entities and their occurrence in the same patient is a casual one. All the classical features of Waardenburg's syndrome except deafness were present and the disease manifested as an isolated case in the family. The pertinent literature is briefly reviewed.


Electrically programmable magnetoresistance in [Formula: see text]-based magnetic tunnel junctions.
We report spin-dependent transport properties and I-V hysteresis characteristics in an [Formula: see text]-based magnetic tunnel junction (MTJ). The bipolar resistive switching and the magnetoresistances measured at high resistance state (HRS) and low resistance state (LRS) yield four distinctive resistive states in a single device. The temperature dependence of resistance at LRS suggests that the resistive switching is not triggered by the metal filaments within the [Formula: see text] layer. The role played by oxygen vacancies in [Formula: see text] is the key to determine the resistive state. Our study reveals the possibility of controlling the multiple resistive states in a single [Formula: see text]-based MTJ by the interplay of both electric and magnetic fields, thus providing potential applications for future multi-bit memory devices.


Value of serum protective activity against acid precipitation of poly (U) in the differentiation between cirrhotic patients with and without hepatocellular carcinoma.
The serum protective activity against acid precipitation of poly (U) and a-fetoprotein levels were compared in 39 cirrhotic patients with hepatocellular carcinoma (HCC) and in 33 patients with chronic liver disease (CLD) alone, in order to differentiate malignant and nonmalignant chronic liver disease. All but one (97.4%) patients with HCC were found to have serum protective activity levels of greater than or equal to 21 micrograms/ml, whereas all but one (97%) patients with CLD had serum protective activity levels of less than or equal to 20 micrograms/ml. Mean serum protective activity levels were significantly higher in the HCC group than in those with CLD (p less than 0.0001). Serum a-fetoprotein concentrations of over 500 ng/ml, suggesting malignancy, were observed in 54% of patients with HCC and in 15% of patients with CLD. Application of the best discriminating values for protective activity (greater than 21 micrograms/ml) and for a-fetoprotein (greater than 500 ng/ml) to 72 patients with or without HCC revealed an efficiency of 97.2% for protective activity and only 68.1% for a-fetoprotein.


Phytoremediation of phenanthrene by transgenic plants transformed with a naphthalene dioxygenase system from Pseudomonas.
Genes from microbes for degrading polycyclic aromatic hydrocarbons (PAHs) are seldom used to improve the ability of plants to remediate the pollution because the initiation of the microbial degradation of PAHs is catalyzed by a multienzyme system. In this study, for the first time, we have successfully transferred the complex naphthalene dioxygenase system of Pseudomonas into Arabidopsis and rice, the model dicot and monocot plant. As in bacteria, all four genes of the naphthalene dioxygenase system can be simultaneously expressed and assembled to an active enzyme in transgenic plants. The naphthalene dioxygenase system can develop the capacity of plants to tolerate a high concentration of phenanthrene and metabolize phenanthrene in vivo. As a result, transgenic plants showed improved uptake of phenanthrene from the environment over wild-type plants. In addition, phenanthrene concentrations in shoots and roots of transgenic plants were generally lower than that of wild type plants. Transgenic plants with a naphthalene dioxygenase system bring the promise of an efficient and environmental-friendly technology for cleaning up PAHs contaminated soil and water.


Loss, transition and trust: perspectives of terminally ill patients and their oncologists when transferring care from the hospital into the community at the end of life.
Most people prefer to die at home. However, most continue to die in hospital. Little is known about the impact on the patient of transferring care from acute sector specialist follow-up to the community. In one cancer centre, a new service-Hospital2Home was set up to facilitate this transfer of care. This study aimed to explore patients' and oncologists' perspectives of the meanings involved in this transition. Qualitative study using semistructured one-to-one interviews with 8 terminally ill cancer patients and 13 oncologists. The interviews were audio recorded, transcribed verbatim and analysed using the framework approach. 3 main themes were identified: loss, transition and community care. The theme of loss referred to losses associated with the end of treatment and losses associated with the familiar safe relationship between the patient and oncologist. Transition refers to the change from hospital-led to community-based care. Barriers to transition included patient and family acceptance, attachment and concerns about community services. Transition was more acceptable if initiated in a gradual manner. Community care: participants found the Hospital2Home service crucial in establishing new trustworthy relationships between community providers and the patient. Transfer of care from the acute sector to the community represents a delicate crossroad where complex notions of loss should not be underestimated. A gradual transfer of care may improve this if the patient's condition allows. Therefore, introductions to the community team should be timely, and a staggered transfer should be planned. This would improve the experience of the patient, carer and oncologist.


Robot-Assisted Abdominoperineal Resection: Clinical, Pathologic, and Oncologic Outcomes.
The extralevator approach to abdominoperineal resection is associated with a decreased incidence of rectal perforation and circumferential resection margin positivity translating to lower recurrence rates. The abdominoperineal resection, as such, is an operation associated with poorer outcomes in comparison with low anterior resections, and any improvements in short-term outcomes are likely to be related to surgical technique. Robot assistance in extralevator abdominoperineal resection has shown improvement in these pathologic outcomes. Because these are surrogate markers for local recurrence and disease-free survival, long-term survival data are needed to assess the efficacy of this robot-assisted technique, exclusively in a dedicated abdominoperineal resection cohort. We assessed the perioperative, pathologic, and oncologic outcomes of the robot-assisted extralevator abdominoperineal resection for rectal cancer. This study was a review of a prospective database of patients over a 5-year period. Procedures were performed in the colorectal division of a tertiary hospital from April 2007 to July 2012. Patients with rectal cancer were operated on robotically. Indications for abdominoperineal resection were low rectal cancers invading the sphincter complex or location in the anal canal precluding anastomosis. All patients received a robot-assisted extralevator abdominoperineal resection. Operative and perioperative measures, pathologic outcomes, and disease-free survival and overall survival were documented and assessed. Twenty-two patients (15 men) with a mean age of 65.5 years and mean BMI of 28.6 kg/m underwent robotic abdominoperineal resection. Circumferential resection margin was positive in 13.6%. There was 1 tumor/rectal perforation. At a mean follow-up of 33.9 months, overall survival was 81.8% with a disease-free survival of 72.7%. Local recurrence was 4.5%. This was a single-institution study with no comparative open or laparoscopic group. Robot-assisted abdominoperineal resection is safe, feasible, and oncologically sound with short-term and long-term outcomes comparable to open and laparoscopic surgery.


Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry.
Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.


Magnetic resonance-guided, high-intensity focused ultrasound sonolysis: potential applications for stroke.
Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity. Unfortunately, a substantial number of stroke patients either are ineligible or do not significantly benefit from contemporary medical and interventional therapies. To address this void, investigators recently made technological advances to render transcranial MR-guided, high-intensity focused ultrasound (MRg-HIFU) sonolysis a potential therapeutic option for both acute ischemic stroke (AIS)-as an alternative for patients with emergent large-vessel occlusion (ELVO) who are ineligible for endovascular mechanical thrombectomy (EMT) or as salvage therapy for patients in whom EMT fails-and intracerebral hemorrhage (ICH)-as a neoadjuvant means of clot lysis prior to surgical evacuation. Herein, the authors review the technological principles behind MRg-HIFU sonolysis, its results in in vitro and in vivo stroke models, and its potential clinical applications. As a noninvasive transcranial technique that affords rapid clot lysis, MRg-HIFU thrombolysis may develop into a therapeutic option for patients with AIS or ICH. However, additional studies of transcranial MRg-HIFU are necessary to ascertain the merit of this treatment approach for thrombolysis in both AIS and ICH, as well as its technical limitations and risks.


Characterization of novel markers of senescence and their prognostic potential in cancer.
Cellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood. As a consequence, the markers currently utilized to detect senescent cells are limited and lack specificity. In order to address this issue, we screened for plasma membrane-associated proteins that are preferentially expressed in senescent cells. We identified 107 proteins that could be potential markers of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3, B2MG, LANCL1, VPS26A and PLD3). We demonstrated that a combination of these proteins can be used to specifically recognize senescent cells in culture and in tissue samples and we developed a straightforward fluorescence-activated cell sorting-based detection approach using two of them (DEP1 and B2MG). Of note, we found that expression of several of these markers correlated with increased survival in different tumours, especially in breast cancer. Thus, our results could facilitate the study of senescence, define potential new effectors and modulators of this cellular mechanism and provide potential diagnostic and prognostic tools to be used clinically.


Effective treatment of simultaneous small cell lung cancer and B-cell lymphoma.
Malignant lymphomas have been reported previously to coincide with adenocarcinomas of the stomach and, rarely, the kidney, breast, colon, liver, or lung. Here, we describe the first case to our knowledge of a malignant lymphoma and an extensive disease small cell cancer of the lung. A 60-year-old male was admitted for severe back pain and was found to have multiple enlarged lymph nodes, hepatosplenomegaly, and bilateral pleural effusions. A B-cell non-Hodgkin's lymphoma (NHL) was diagnosed from biopsies of the stomach and liver. Further staging revealed a dense infiltration of the bone marrow by both a small cell lung cancer and a malignant lymphoma. Both tumors responded well to chemotherapy. This unique case report demonstrates that the simultaneous occurrence of small cell lung cancers and malignant lymphomas is extremely rare and may effectively be treated with chemotherapy.


Duplication and deletion of CFC1 associated with heterotaxy syndrome.
Heterotaxy syndrome, which causes significant morbidity and mortality, is a class of congenital disorders, in which normal left-right asymmetry cannot be properly established. To explore the role of copy number variants (CNVs) in the occurrence of heterotaxy syndrome, we recruited 93 heterotaxy patients and studied 12 of them by the Affymetrix Genome-Wide Human SNP 6.0 Array. The results were confirmed in the remaining 81 patients and 500 healthy children by quantitative real-time polymerase chain reaction (qPCR). The analysis of the SNP6.0 array showed a duplication of chromosome 2q21.1, which was verified by qPCR. The result of qPCR in the other 81 patients showed that 8/81 patients had the CNVs of 2q21.1 and the only overlapping gene in these patients is CFC1. However, in the 500 healthy children, only one carried the duplication of CFC1 (p=3.5×10(-7)). The duplication and deletion of CFC1 may play key roles in the occurrence of heterotaxy syndrome. Moreover, the transposed great arteries, double outlet right ventricle, single atrium, and single ventricle may share a common genetic etiology with the heterotaxy syndrome.


Force balance of hydrogen bubbles growing and oscillating on a microelectrode.
Hydrogen evolution in acidic aqueous electrolytes was recently found to be characterized by a carpet of microbubbles covering the microelectrode and feeding the growth of the main bubbles by coalescence. Besides this, oscillatory behavior of the main bubbles was observed prior to departure. Extending earlier studies, this work delivers the forces acting on the main bubble more accurately by taking into account further geometric and electrochemical details measured during experiments. Combining simulation work and measurements makes it possible to confirm the role of an attractive electrical (Coulomb) force caused by the adsorption of hydrogen ions at the bubble interface and to obtain a better understanding of the bubble dynamics observed.


Diboron as a reductant for nickel-catalyzed reductive coupling: rational design and mechanistic studies.
Diboron (B2pin2) has been identified as an efficient and environmentally benign reducing reagent for reductive coupling reactions for the first time, which enables the nickel-catalyzed reductive tetramerization of alkynes to be performed with high efficiency. Mechanistic and kinetic studies indicate that the facile reductive elimination to form the B-B bond from the dinuclear Ni-Ni complexes is responsible for the high efficiency. The activation enthalpy (ΔH(‡) = 56.5 kJ mol(-1)), entropy (ΔS(‡) = -128 J mol(-1) K(-1)) and the substituent effect (ρ = 1.43) on this reaction were obtained.


Successful Management of a Chronic Refractory Leg Ulcer in an Adolescent with Sickle Cell Anemia.
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by a wide range of clinical manifestations. Chronic leg ulcers are a disabling complication with repercussions on the quality of life. We report the case of a 14-year-old girl with a diagnosis of SCD who developed a chronic leg ulcer that was successfully treated with a multi-disciplinary approach, including local and systemic therapies. The role of different treatments, in particular low molecular weight heparin, in the refractory chronic leg ulcer healing process will be discussed.


[Study of hepatitis B surface antigen by 2 different serological methods].
This investigation was carried out in order to determine the sensitivity of Discontinous-Counter-Immunoelectrophoresis (DCIE) and passive erythrocyte hemagglutination (RPHA) teste in screening the presence of HBsAg in normal population and blood donors. 1321 sera from apparently normal individuals and 156 sera from blood donors were tested. Among, normal individuals, the carriers were 22 (1.66%) with DCIE test and 122 (9.22%) with RPHA test; and among blood donors, 6 (3.84%) with DCIE test and 36 (23.0%) with RPHA test.


Origin of sensation in the esophagus.
The sensory innervation of the esophagus is important both to physicians, for whom esophageal sensation can cause clinical confusion, and to physiologists, who wish to understand the regulation of esophageal motion. Sensory mechanisms in the gut in general are not well understood. Mechanoreceptive reflexes and their pathways, both parasympathetic and sympathetic, have been studied in the esophagus, and thermoreceptive reflex pathways that are parasympathetic have recently been described. The terminal sensory innervation of the esophagus contains several structures that may be receptors to such stimuli. Esophageal striated muscle contains muscle spindles like those of somatic muscle. Within the myenteric plexus, the bodies of certain ganglion cells themselves may be mechanoreceptive. Also, complex subcapsular laminar arborizations that arise from cells of the nodose ganglion have been described in ganglia of the esophageal myenteric plexus. Similar laminar arborizations have been found on vessels of the submucosa in the midesophagus. In the esophageal mucosa, the terminal innervation ends in structures of diverse form located both superficially and deep in the squamous epithelium. Thus, a variety of specific neural structures that seem to represent the terminals of sensory nerves exist in the esophagus and may serve the mechanoreceptive and thermoreceptive reflexes that modify esophageal motility.


Safety of influenza vaccination in adults with asthma.
The results of a study to investigate whether influenza vaccination produces symptoms or exacerbations in adults with asthma are reported. Twenty-eight subjects with asthma were followed up over three-week periods, during which they received both influenza vaccinations and placebo injections. Subjective assessment of asthma symptoms and objective assessment of bronchoconstriction by means of peak expiratory flow rate measurements were carried out each day. No evidence for the asthmagenicity of influenza vaccination was found. The relevance of this finding in the assessment of patients for influenza vaccination is discussed.


Seasonal variation of serotonin uptake in normal controls and depressed patients.
Serotonin (5-HT) uptake in blood platelets from depressed patients and normal controls were studied over a 2-year period to determine if seasonal variations were present. Vmax, a measure of the number of 5-HT uptake sites in normal controls and depressed patients, was significantly higher in fall and winter than in spring and summer; Vmax in the depressed patients was lower than in normal controls throughout the year. Normal controls showed lower Vmax in April and June. A similar trend was present in the depressed patients but the lowest values were found in the month of December. The necessity of considering seasonal variations in this and other putative biological markers is emphasized.


[Dimensional structure of bacterial communities of the winter plankton Pechora sea and its formation].
For the Pechora sea, according to microbiological shootings during winter seasons 2002-2005, the analysis of conditions forming of an abundance winter bacterial communities a plankton is carried out. For the outlined varieties of waters, regularities of distribution of segregate groups bacterial communities are discussed. The natural modification of microbiologic indicators ona gradient of parametres a physical and chemical complex is shown. In subglacial conditions average number bacterioplankton 234 thousand in cell/ml, cellular volume - 0.58 μm3, at square of 550 mm2/L. A biomass store a stratum of probed harbour area Pechora sea of 0-25 m to 187 x 10(90 G.


The 1987 Borden Award lecture. Protein metabolism in premature human infants.
Our studies have focused on the regulation of whole body and skeletal muscle protein metabolism in premature infants. Net deposition of protein is the result of a positive balance between protein synthesis and breakdown. To measure protein metabolism we have employed end-product studies with [15N]glycine and 13[C]leucine. Myofibrillar protein degradation was estimated by measuring the excretion of N-t-methylhistidine in urine. Energy expenditure and substrate utilization were also measured. Premature infants have high rates of protein synthesis (12 g.kg-1.d-1), twice those measured in children and four times those found in adults. Intrauterine malnourished babies have increased rates of protein turnover. Very low birth weight infants (less than 1500 g) have higher myofibrillar protein turnover than larger babies. Intravenous feeding decreases whole body protein turnover, and we estimate visceral protein synthesis to be approximately 4 g.kg-1.d-1. Suboptimal energy intake worsens nitrogen utilization by reducing the reutilization of endogenous amino acids for protein synthesis. We have also examined the effects of varying the source of nonprotein energy (i.e., glucose only versus glucose plus lipid) at requirement levels and have shown there is no effect on protein metabolism. Recent improvements in technology have opened the way to detailed study of individual amino acid metabolism in neonates in the future.


Dimethylsphingosine and miltefosine induce apoptosis in lung adenocarcinoma A549 cells in a synergistic manner.
Lung cancer is one of the most common and lethal types of oncological diseases. Despite the advanced therapeutic approaches, the prognosis for lung cancer still remains poor. Apparently, there is an imperative need for more efficient therapeutic strategies. In this work we report that concurrent treatment of human adenocarcinoma A549 cells with specific concentrations of two antitumor agents, the sphingosine kinase 1 inhibitor N, N dimethylsphingosine (DMS) and the alkylphosphocholine miltefosine, induced synergistic cytotoxic effect, which was confirmed by calculation of the combination index. The simultaneous action of these agents, induced significant decrease of A549 cell number, as well as pronounced morphological alterations. Combined drugs caused substantial apoptotic events, and significant reduction of the pro-survival marker sphingosine- 1-phosphate (S1P), when compared to the individual treatments with each of the anticancer drugs alone. Miltefosine is known to affect the synthesis of choline-containing phospholipids, including sphingomyelin, but we report for the first time that it also reduces S1P. Here we suggest a putative mechanism underlying the effect of miltefosine on sphingosine kinase 1, involving miltefosine-induced inhibition of protein kinase C. In conclusion, our findings provide a possibility for treatment of lung cancer cells with lower concentrations of the two antitumor drugs, DMS and miltefosine, which is favorable, regarding their potential cytotoxicity to normal cells.


Andrographolide inhibits human hepatoma-derived Hep3B cell growth through the activation of c-Jun N-terminal kinase.
Andrographolide (Andro) is a potentially anti-inflammatory diterpenoid lactone isolated from the traditional herbal medicine ANDROGRAPHIS PANICULATA, which has been effectively used for the treatment of infection, inflammation, cold, fever and diarrhea in China for centuries. In the current study, we found that Andro significantly decreased the number of surviving hepatoma-derived Hep3B cells in the MTT assay and induced cell apoptosis. Further study showed that Andro induced activation of mitogen-activated protein kinases (MAPKs) including p38 kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-related kinases (ERK1/2), but had no significant effect on caspase-3, Bcl-xL and Bcl-2, which are apoptosis-related proteins. Moreover, inhibition of JNK activation partially rescued the toxic effect of Andro on Hep3B cells. Therefore, our results indicate that the JNK signaling pathway plays an important role in the toxic effect of Andro on Hep3B cells.


Cue-utilization in the imagination inflation effect paradigm in older adults with mild cognitive impairment.
We investigated the imagination inflation effect in healthy older adults and older adults with mild cognitive impairment (MCI) to determine whether an intervention can reduce susceptibility to these distortions, with implications for daily functioning. Fifty-seven older adults aged 69-90 participated. In Session 1, participants either: listened to an action statement being read, performed the action, or imagined performing the action. Actions were either functional (encountered actions of daily life; e.g., "fill the pillbox") or nonfunctional (not routinely encountered; e.g., "put the toy duck on a plate"). During Session 2, participants imagined action statements from the first session. In Session 3, participants were asked to determine whether action statements were performed during the first session. Intervention participants were instructed before the first and third sessions to attend various sensory aspects of their experience using a cue-utilization technique. Memory was worse for functional compared to nonfunctional actions. For older adults with MCI, the intervention increased correct identifications of functional actions that were performed. For healthy older adults, the intervention increased source memory of functional actions that were imagined. The intervention did not impact the accuracy of nonfunctional actions or the rates of misremembering an action as having been performed. These initial findings supported the efficacy of a cue-utilization intervention to improve memory for functional actions in an imagination inflation effect paradigm in community-dwelling older adults. The use of such strategies represents an important first step in designing interventions that are applicable to daily life. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Deficits in speech perception predict language learning impairment.
Specific language impairment (SLI) is one of the most common childhood disorders, affecting 7% of children. These children experience difficulties in understanding and producing spoken language despite normal intelligence, normal hearing, and normal opportunities to learn language. The causes of SLI are still hotly debated, ranging from nonlinguistic deficits in auditory perception to high-level deficits in grammar. Here, we show that children with SLI have poorer-than-normal consonant identification when measured in ecologically valid conditions of stationary or fluctuating masking noise. The deficits persisted even in comparison with a younger group of normally developing children who were matched for language skills. This finding points to a fundamental deficit. Information transmission of all phonetic features (voicing, place, and manner) was impaired, although the deficits were strongest for voicing (e.g., difference between/b/and/p/). Children with SLI experienced perfectly normal "release from masking" (better identification in fluctuating than in stationary noise), which indicates a central deficit in feature extraction rather than deficits in low-level, temporal, and spectral auditory capacities. We further showed that speech identification in noise predicted language impairment to a great extent within the group of children with SLI and across all participants. Previous research might have underestimated this important link, possibly because speech perception has typically been investigated in optimal listening conditions using non-speech material. The present study suggests that children with SLI learn language deviantly because they inefficiently extract and manipulate speech features, in particular, voicing. This result offers new directions for the fast diagnosis and remediation of SLI.


Scaling left ventricular mass in adolescent boys aged 11-15 years.
Normalizing left ventricular mass (LVM) for inter-individual variation in body size is a central issue in human biology. During the adolescent growth spurt, variability in body size descriptors needs to be interpreted in combination with biological maturation. To examine the contribution of biological maturation, stature, sitting height, body mass, fat-free mass (FFM) and fat mass (FM) to inter-individual variability in LVM in boys, using proportional allometric modelling. The cross-sectional sample included 110 boys of 11-15 years (12.9-1.0 years). Stature, sitting height, body mass, cardiac chamber dimensions and LVM were measured. Age at peak height velocity (APHV) was predicted and used as an indicator of biological maturation. Percentage fat was estimated from triceps and subscapular skinfolds; FM and FFM were derived. Exponents for body size descriptors were k = 2.33 for stature, k = 2.18 for sitting height, k = 0.68 for body mass, k = 0.17 for FM and k = 0.80 for FFM (adjusted R(2 )= 19-62%). The combination of body descriptors and APHV increased the explained variance in LVM (adjusted R(2)( )= 56-69%). Stature, FM and FFM are the best combination for normalizing LVM in adolescent boys; when body composition is not available, an indicator of biological maturity should be included with stature.


Lipid oxidation inactivates the anticoagulant function of protein Z-dependent protease inhibitor (ZPI).
Lipid oxidation due to oxidative stress plays an important role in the pathogenesis of inflammatory and thrombotic cardiovascular diseases. Several findings suggest that lipid peroxidation can alter the function of coagulation proteins and contribute to a hypercoagulable state, but the molecular mechanisms are unclear. Here, we report that oxidized phospholipids suppress the anticoagulant function of the serpin, protein Z-dependent protease inhibitor (ZPI), a specific inhibitor of membrane-associated factor Xa (FXa) that requires protein Z (PZ), phospholipid, and calcium as cofactors. We found that this suppression arises from a diminished ability of the oxidized membrane to function as a cofactor to promote ZPI inhibition of membrane-bound FXa, due fully or in part to the susceptibility of the bound ZPI-PZ complex to oxidative inactivation. Surprisingly, free ZPI was also susceptible to inactivation by oxidized membrane vesicles in the absence of calcium. Oxidized vesicles containing both phosphatidylserine and polyunsaturated fatty acids were required to promote inactivation of the ZPI-PZ complex or free ZPI, indicating that binding of the PZ-complexed or free ZPI to peroxide-modified phospholipid vesicles mediates the inactivation. Heparin protected the ZPI-PZ complex and free ZPI from inactivation, suggesting that blocking the heparin-binding site on ZPI interferes with ZPI binding to lipid or to PZ. This was confirmed by direct lipid-binding experiments. Native PAGE indicated that oxidization induced dissociation of the ZPI-PZ complex and increased the negative charge of ZPI. We conclude that compromised ZPI anticoagulant function could contribute to thrombus initiation and growth in oxidative stress-induced cardiovascular diseases.


Cell cycle checkpoint control: The cyclin G1/Mdm2/p53 axis emerges as a strategic target for broad-spectrum cancer gene therapy - A review of molecular mechanisms for oncologists.
Basic research in genetics, biochemistry and cell biology has identified the executive enzymes and protein kinase activities that regulate the cell division cycle of all eukaryotic organisms, thereby elucidating the importance of site-specific protein phosphorylation events that govern cell cycle progression. Research in cancer genomics and virology has provided meaningful links to mammalian checkpoint control elements with the characterization of growth-promoting proto-oncogenes encoding c-Myc, Mdm2, cyclins A, D1 and G1, and opposing tumor suppressor proteins, such as p53, pRb, p16INK4A and p21WAF1, which are commonly dysregulated in cancer. While progress has been made in identifying numerous enzymes and molecular interactions associated with cell cycle checkpoint control, the marked complexity, particularly the functional redundancy, of these cell cycle control enzymes in mammalian systems, presents a major challenge in discerning an optimal locus for therapeutic intervention in the clinical management of cancer. Recent advances in genetic engineering, functional genomics and clinical oncology converged in identifying cyclin G1 (CCNG1 gene) as a pivotal component of a commanding cyclin G1/Mdm2/p53 axis and a strategic locus for re-establishing cell cycle control by means of therapeutic gene transfer. The purpose of the present study is to provide a focused review of cycle checkpoint control as a practicum for clinical oncologists with an interest in applied molecular medicine. The aim is to present a unifying model that: i) clarifies the function of cyclin G1 in establishing proliferative competence, overriding p53 checkpoints and advancing cell cycle progression; ii) is supported by studies of inhibitory microRNAs linking CCNG1 expression to the mechanisms of carcinogenesis and viral subversion; and iii) provides a mechanistic basis for understanding the broad-spectrum anticancer activity and single-agent efficacy observed with dominant-negative cyclin G1, whose cytocidal mechanism of action triggers programmed cell death. Clinically, the utility of companion diagnostics for cyclin G1 pathways is anticipated in the staging, prognosis and treatment of cancers, including the potential for rational combinatorial therapies.


Primary hydatid cyst of the thigh: a case report of an unusual localization.
The sartorius muscle is a rare location of primary hydatid cyst. In this report, the clinical, pathologic, and radiologic features are discussed, with special emphasis on the pathologic and radiographic features. We report a case of hydatid cyst of the proximal thigh in an eight-year-old girl. Magnetic resonance (MR) images revealed muscular hydatid cyst in the sartorius muscle, with a striking appearance of daughter cysts. We did not find any visceral organ involvement. Wide excision was performed without destroying the cyst wall. Primary muscular hydatidosis should be kept in mind in the differential diagnosis of a cystic mass of a skeletal muscle.


[Clinical significance of incomplete right bundle branch block].
In authors' opinion the majority of the physicians speak about an incomplete right bundle branch block in cases of a terminal r'wave in lead V1 of the ECG, when the QRS complex is not wider than 0.12 sec. These ECG anomalies are not properly separated in the literature, either. Authors define 4 groups whose separation is possible by the analysis of leads V1 and V2. 1. Right ventricular conduction defect--the ECG width is 0.09-0.13 sec. This picture generally signs normal or only slight higher right ventricular pressure. 2. Real incomplete right bundle branch block--the terminal vector directs forward only in this group and it causes also an r' in V2 next to the high R' in lead V1. This group can be harmless, only a conduction defect, but it can mean an advanced stadium of serious right ventricular systolic or diastolic overloading, too. 3. Right ventricular diastolic overloading--the QRS width is normal. We saw this picture in slight forms of atrial septal defect. One of our conclusions was that in case of normal V1 a haemodynamic significant ASD I or ASD II can be excluded. 4. Normal variant: normal QRS width and only a very low r' in lead V1. It was seen in young patients or in patients with flat chest. Authors remark that this pattern can possibly be seen in childhood or in case of inexact ECG (V1) registration.


Inductively coupled plasma-optical emission spectrometry for on-line determination of multi trace elements in environmental samples after preconcentration by using Borassus flabellifer inflorescence loaded with 2-propylpiperidine-1-carbodithioate.
A procedure was developed for the determination of Cu, Mn, Pb, Cd, Co, Cr, and Zn in water samples by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) after preconcentration on synthesized 2-propylpiperidine-1-carbodithioate supported by Borassus flabellifer Inflorescence (BFI). The sorbed element was subsequently eluted with 0.4 M HNO3, and the acid eluates were analyzed by ICP-OES. The influence of various parameters such as pH, flow rate of sample, eluent concentration, volume of the sample, and volume of eluent were investigated. Under the optimal conditions, Cu, Mn, Pb, Cd, Co, Cr, and Zn in aqueous samples were concentrated ca. 100-fold. Recoveries were obtained by the proposed method in the range of 97.8-99.9%. This method was also applied for the analysis of spiked, natural waters and soil samples. The results provide strong evidence to support the hypothesis of an adsorption mechanism.


Bacterial Signaling Nucleotides Inhibit Yeast Cell Growth by Impacting Mitochondrial and Other Specifically Eukaryotic Functions.
We have engineered Saccharomyces cerevisiae to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP. Mutations compromising mitochondrial function and chromatin remodeling show negative epistatic interactions with all three nucleotides. In contrast, certain mutations that cause defects in chromatin modification and ribosomal protein function show positive epistasis, alleviating growth inhibition by at least two of the three nucleotides. Uniquely, cdiGMP is lethal both to cells growing by respiration on acetate and to obligately fermentative petite mutants. cdiGMP is also synthetically lethal with the ribonucleotide reductase (RNR) inhibitor hydroxyurea. Heterologous expression of the human ppGpp hydrolase Mesh1p prevented the accumulation of ppGpp in the engineered yeast and restored cell growth. Extensive in vivo interactions between bacterial signaling molecules and eukaryotic gene function occur, resulting in outcomes ranging from growth inhibition to death. cdiGMP functions through a mechanism that must be compensated by unhindered RNR activity or by functionally competent mitochondria. Mesh1p may be required for abrogating the damaging effects of ppGpp in human cells subjected to bacterial infection.IMPORTANCE During infections, pathogenic bacteria can release nucleotides into the cells of their eukaryotic hosts. These nucleotides are recognized as signals that contribute to the initiation of defensive immune responses that help the infected cells recover. Despite the importance of this process, the broader impact of bacterial nucleotides on the functioning of eukaryotic cells remains poorly defined. To address this, we genetically modified cells of the eukaryote Saccharomyces cerevisiae (baker's yeast) to produce three of these molecules (cdiAMP, cdiGMP, and ppGpp) and used the engineered strains as model systems to characterize the effects of the molecules on the cells. In addition to demonstrating that the nucleotides are each capable of adversely affecting yeast cell function and growth, we also identified the cellular functions important for mitigating the damage caused, suggesting possible modes of action. This study expands our understanding of the molecular interactions that can take place between bacterial and eukaryotic cells.


Classical, Thermostated Ring Polymer, and Quantum VSCF/VCI Calculations of IR Spectra of H7O3+ and H9O4+ (Eigen) and Comparison with Experiment.
We report vibrational IR spectra of the protonated water clusters H7O3+ and H9O4+ (Eigen) in the range from 0 to 4000 cm-1, from classical molecular dynamics (MD) and thermostated ring polymer molecular dynamics (TRPMD) calculations, using recent high-level ab initio potential and dipole moments surfaces. The MD spectra are done at 20 and 100 K, whereas the computationally intensive TRPMD spectra are done at 100 K. These spectra are compared with previous quantum vibrational self-consistent field/virtual state configuration interaction (VSCF/VCI) and quasi-classical MD calculations, using the same potential and dipole moment surfaces, and with experimental spectra for cold (∼20 K) clusters. As expected, the 20 K MD spectra have vibrational bands close to the harmonic ones, and at 100 K some downshifting of the bands is seen along with significant broadening. The TRPMD calculations, using two different thermostats (path integral Langevin equation and generalized Langevin Equation thermostat), show substantial downshifting relative to the classical spectrum at 100 K, especially for the intense proton-stretch bands. However, the downshifting is not sufficient to produce quantitative agreement with the VSCF/VCI (and experimental) band positions. An analysis of these positions is given based on a previously reported linear correlation between the hydronium O-H bond length and the harmonic frequency.


Sources of the scalp-recorded amplitude-modulation following response.
The scalp-recorded amplitude-modulation following response (AMFR) is gaining recognition as an objective audiometric tool, but little is known about the neural sources that underlie this potential. We hypothesized, based on our human studies and single-unit recordings in animals, that the scalp-recorded AMFR reflects the interaction of multiple sources. We tested this hypothesis using an animal model, the unanesthetized rabbit. We compared AMFRs recorded from the surface of the brain at different locations and before and after the administration of agents likely to enhance or suppress neural generators. We also recorded AMFRs locally at several stations along the auditory neuraxis. We conclude that the surface-recorded AMFR is indeed a composite response from multiple brain generators. Although the response at any modulation frequency can reflect the activity of more than one generator, the AMFRs to low and high modulation frequencies appear to reflect a strong contribution from cortical and subcortical sources, respectively.


A randomized clinical trial comparing pulsed ultrasound and erythromycin phonophoresis in the treatment of patients with chronic rhinosinusitis.
Therapeutic ultrasound, an important physiotherapy modality, has been used successfully in the treatment of patients with chronic rhinosinusitis (CRS). No study has compared pulsed ultrasound (PUS) with erythromycin phonophoresis (EP). The aim of this randomized, double-blind, parallel group study with concealed allocation was to compare PUS with EP. Sixty CRS patients were randomly allocated into two groups. Group 1 had PUS and Group 2 had EP. Patients were treated 3 days a week for 10 sessions over 4 weeks. The severity of nine CRS symptoms was self-rated by patients on an ordinal scale of 0-3 (absent, mild, moderate or severe) at baseline and after the 10th treatment session. Individual symptom scores were summed to obtain a "Total Symptom Score" (TSS). The outcome measure included percentage improvement in the TSS. A statistically significant improvement in TSS occurred with both PUS and EP therapy groups (p < 0.05). The percentage improvement in the EP group was statistically greater than in the PUS group (67.2 versus 49.3%) (p = 0.03). The effect sizes in both therapy groups were large; PUS: d = 1.36 and EP: d = 2.15. EP was found to be superior over PUS therapy.


Rapid Microwave-Assisted Solvothermal Synthesis of Non-Olivine Cmcm Polymorphs of LiMPO4 (M = Mn, Fe, Co, and Ni) at Low Temperature and Pressure.
Lithium transition-metal phosphates, LiMPO4 (M = Mn, Fe, Co, and Ni), have attracted significant research interest over the past two decades as an important class of lithium ion battery cathode materials. However, almost all of the investigations thus far have focused on the olivine polymorph that exists in the orthorhombic Pnma space group. In this study, a distinct orthorhombic but non-olivine polymorph of LiMPO4, described by a Cmcm space group symmetry, has been synthesized with M = Mn, Fe, Co, and Ni. Of these, LiMnPO4 in the Cmcm space group is reported for the first time. A rapid microwave-assisted solvothermal (MW-ST) heating process with tetraethylene glycol (TEG) as the solvent and transition-metal oxalates as precursors facilitates the synthesis of these materials. The peak reaction temperatures and pressures were below 300 °C and 30 bar, respectively, which are several orders of magnitude lower than those of the previously reported high-pressure (gigapascals) method. X-ray diffraction (XRD) confirms the crystal structure with the Cmcm space group, and scanning electron micrographs indicate a submicrometer thin platelet-like morphology. The synthesis process conditions have been optimized to obtain impurity-free samples with the correct stoichiometry, as characterized by XRD and inductively coupled plasma-optical emission spectroscopy (ICP-OES). Upon heat treatment to higher temperatures, an irreversible transformation of the metastable Cmcm polymorphs into olivine is observed by XRD and Fourier transform infrared spectroscopy. Although the electrochemical activity of these polymorphs as lithium ion cathodes turns out to be poor, the facile synthesis under mild conditions has permitted easy access to these materials in a nanomorphology, some of which were not even possible before.


(7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists.
S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.


Electronic energy transfer on CaO surfaces.
We excite low-coordinated surface sites of nanostructured CaO samples using tunable UV laser pulses and observe hyperthermal O-atom emission indicative of an electronic excited-state desorption mechanism. The O-atom yield increases dramatically with photon energy, between 3.75 and 5.4 eV, below the bulk absorption threshold. The peak of the kinetic energy distribution does not increase with photon energy in the range from 3.9 to 5.15 eV. These results are analyzed in the context of a laser desorption model developed previously for nanostructured MgO samples. The data are consistent with desorption induced by exciton localization at corner-hole trapped surface sites following electronic energy transfer from higher coordinated surface sites.


Parents of children with haemophilia--a transforming experience.
Owing to the improvements in the management of haemophilia, children with severe haemophilia in the United Kingdom have very different experiences of their condition compared with many adults' early experiences of haemophilia. However, haemophilia can still have physical and social effects which can impact on the quality of life, not only for a child who has the condition, but also for their parents. The purpose of this study was to undertake a qualitative exploration of the impact of haemophilia on parents. The participants included 12 parents of children with severe haemophilia who took part in interviews or focus groups. Four major themes emerged from the data which were initial experiences, managing the condition, engaging with others and developing mastery. The findings highlighted the importance of evaluating parents' experiences. Parents are deeply affected by their child's condition and their lives are transformed by the experiences of living with a child with haemophilia. Parents' responses are influenced by how well the child manages the disorder and the difficulties they experience. Further studies are required in order to develop a more complete understanding of the impact of haemophilia on parent's lives.


The effects of iron-containing superoxide dismutases on haemodynamic parameters in spontaneously hypertensive rats.
The product of FeSOD activity is hydrogen peroxide (H2O2). Furthermore, FeSOD can modify the chemical versatility of NO into its redox-active forms: nitrosonium cation (NO+) and nitroxyl anion (NO-). All of these low molecular weight species are vasoactive and, in particular, NO- induces calcitonin gene-related peptide (CGRP) synthesis (known to be the most potent relaxation-promoting peptide). In this study the effects of bolus infusions of iron-containing superoxide dismutase (FeSOD) and of superoxide dismutase containing both iron and manganese (FeMnSOD) on the arterial blood pressure (MAP), the arterial blood pressure (CO) and the total vascular resistance (TVR) in spontaneously hypertensive (SH) rats were determined. Bolus infusion of FeSOD induced a biphasic response in the MAP (an initial increase was followed by a significant decrease). At the end of the experiment the MAP returned to its basal value. FeMnSOD (the enzymatically inactive form of FeSOD) had no effect on the MAP in these experiments. Bolus infusions of FeSOD and of FeMnSOD had no effect either on the both the CO or on the TVR in SH rats. Our results indicate that arterial relaxation changes mediated by NO- may be important for regulation of blood pressure in SH rats.


The SKHR motif is required for biological function of the VirR response regulator from Clostridium perfringens.
The response regulator VirR and its cognate sensor histidine kinase, VirS, are responsible for toxin gene regulation in the human pathogen Clostridium perfringens. The C-terminal domain of VirR (VirRc) contains the functional FxRxHrS motif, which is involved in DNA binding and is conserved in many regulatory proteins. VirRc was cloned, purified, and shown by in vivo and in vitro studies to comprise an independent DNA binding domain. Random and site-directed mutagenesis was used to identify further amino acids that were required for the functional integrity of the protein. Random mutagenesis identified a unique residue, Met-172, that was required for biological function. Site-directed mutagenesis of the SKHR motif (amino acids 216 to 219) revealed that these residues were also required for biological activity. Analysis of the mutated proteins indicated that they were unable to bind to the DNA target with the same efficiency as the wild-type protein.


Universal Sign Control of Coupling in Tight-Binding Lattices.
We present a method of locally inverting the sign of the coupling term in tight-binding systems, by means of inserting a judiciously designed ancillary site and eigenmode matching of the resulting vertex triplet. Our technique can be universally applied to all lattice configurations, as long as the individual sites can be detuned. We experimentally verify this method in laser-written photonic lattices and confirm both the magnitude and the sign of the coupling by interferometric measurements. Based on these findings, we demonstrate how such universal sign-flipped coupling links can be embedded into extended lattice structures to impose a Z_{2}-gauge transformation. This opens a new avenue for investigations on topological effects arising from magnetic fields with aperiodic flux patterns or in disordered systems.


Pattern of splenectomy indications in kashan shahid-beheshti hospital: a 5-year study.
The spleen is amongst the most vulnerable organs which are easily injured in abdominal trauma. Nowadays, blunt trauma is the most prevalent indication of splenectomy. We conducted this study to determine the pattern of indications for open splenectomies carried out during the past five years in Shahid-Beheshti hospital, a central hospital in Kashan, Iran. Demographic data of all patients who had undergone an open splenectomy in Kashan Shahid-Beheshti hospital during the past five years (2007-2012), indications for this type of surgery and outcome of patients were collected and entered into the study. During the study period, the data from a total of 99 open splenectomies were entered in our study. Sixty-eight (68.7%) patients were male and 31 (31.1%) female. The mean age was 31.64 years, 75.8% of the cases had indications of trauma and 24.2% were elective. The most prevalent indication for trauma was motor-bike rider accidents and for elective ones portal hypertension. Most cases of splenectomy in our center caused by trauma, and among the different types of trauma, blunt trauma is the dominant cause. Road traffic accidents, in particular motor vehicle accidents, especially motorbike injures, are the most frequent cause of splenectomy. Due to the instability of trauma patients, a mortality rate of 8% seems to be reasonable for splenectomy. We recommend that more research be conducted in this area and more cases enrolled with a reasonable follow-up period for splenectomy complications in this study.


The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components.
We have investigated the human cytomegalovirus (HCMV) US22 gene family members UL23, UL24, UL43 and US22. Specific antibodies were generated to identify pUL23 (33 kDa), pUL24 (40 kDa) and pUL43 (48 kDa), while pUS22 was identified by monoclonal antibody HWLF1. A C-terminally truncated UL43 product (pUL43t; 21 kDa) produced by a deletion mutant was also investigated. The UL24 and UL43 genes were expressed with early-late (gamma1) and true-late (gamma2) kinetics, respectively. Immunoblot and immuno-EM studies demonstrated that pUL23, pUL24, pUL43 and pUS22 were virion tegument components. Immunofluorescence and immuno-EM studies showed that pUL23, pUL24, pUL43 and pUL43t were located in cytoplasmic protein aggregates, manifesting two forms: complex juxtanuclear structures and smaller, membrane-bound aggregates resembling dense bodies. The complex-type aggregate is a putative site of particle maturation. Because pUL43t was present in protein aggregates, but under-represented in virus particles compared to pUL43, it was concluded that N-terminal sequences target pUL43 to protein aggregates and that C-terminal sequences are important for incorporation into particles. Since three other US22 family products (pUL36, pTRS1 and pIRS1) are documented tegument components, at least seven of the twelve US22 family genes encode tegument proteins, suggesting that the products of the remaining five genes might be similarly located. These findings demonstrate a common biological feature among most, if not all, US22 family proteins and implicate the family in events occurring immediately after virus penetration.


Effect of Bright Light Exposure on Depression and Agitation in Older Adults with Dementia.
This study examined the effects of bright light exposure on three measures of depression and four measures of agitation in persons with dementia residing in long-term care. Using a randomized controlled design, participants were randomly assigned to receive either bright light (n = 30) or low intensity light (n = 30) for eight weeks. Bright light exposure was associated with significant improvement in depression and agitation, while participants receiving low intensity light displayed higher levels of depression and agitation or no significant change. Findings support the use of bright light exposure to reduce depression and agitation in this population.


Delayed contrast enhancement in MRI in takotsubo cardiomyopathy.
We present a 21-year-old female whose clinical presentation and investigations were suggestive of takotsubo cardiomyopathy. On cardiac MRI, there was delayed gadolinium enhancement in apical and mid-segments with sparing of the base. Patient is in class III symptoms with ejection fraction of 24% at 1 year follow-up. This variant form of takotsubo cardiomyopathy with delayed contrast enhancement is associated with irreversible left ventricular dysfunction and poor outcome.


New HLA-DR2-related specificities detected in South African blacks and individuals of mixed ancestry.
This study describes a new HLA-DR2-related specificity DR2LUM (CT) present in South African Blacks and individuals of mixed ancestry (Cape Coloureds). It can be distinguished from the "classic" DR2 specificities. DRw15 and DRw16, using serological and Southern blot techniques. Although no HLA-Dw specificity could be assigned to the DR2LUM(CT) cells, borderline typing reactions with Dw2 HTCs were observed. Southern blot analysis using a DRB probe and the TaqI enzyme has shown that DR2LUM(CT) shared a 1.6 kb fragment with DRw15 and a 4.7 kb fragment with DR1 and DRw10, indicating sequence homology between DR2LUM(CT) and these alleles. In addition, another unusual HLA-DR2 haplotype was found. The DR antigen was typed serologically as DRw16 but showed a combination of restriction fragments which are associated with both the DRw15 and DRw16 specificities. This study demonstrates the value of investigating non-Caucasoid populations in further characterizing the polymorphisms of the HLA class II genes.


Complete Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae Strain 1756, Isolated from a Pus Specimen.
Carbapenem-resistant Klebsiella pneumoniae strain 1756 was isolated from a pus specimen from a Taiwanese patient. Here, the complete genome sequence of strain 1756 is presented.


[Cell biological study of cultured cells derived from the fattyoffluid portions of liposuction aspirates].
To explore an approach to isolate and culture the Adipose derived stem cells (ASCs) from the fatty and the fluid portions of liposuction aspirates, and to investigate the growth kinetics, morphology, differentiation capability, cell senescence, surface marker profiles of the ASCs. The liposuction aspirates were divided into fatty portion and liquid portion. ASCs were isolated from each portion by collagenase digestion and directly centrifugate and cultured to observe the morphology and biology characters in vitro. Cell activity was studied by MTT chromatometry and analyzed statistically. Cell cycle was detected by flow cytometry. Cells were randomly selected from the 3rd, 4th, 6th, 8th generation cells to detect senescence of ASCs by acridine orange staining. The cell surface markers were detected by flow cytometry and immunohistochemistry. Adipogenic and osteogenic lineage differentiation of ASCs was assessed by Oil Red O and alizarin bordeaux staining respectively. A large amount of ASCs could be isolated and cultured both from the fatty portion and the liquid portion, including PLA cells and LAF cells which had fibroblastic characters with strong viability and proliferative activity. The statistical result indicated that the cell activity of PLA cells and LAF cells was very similar. ASCs from passage 3, 4, 6, 8 didn't show insenecence. CD29, CD44, CD34, which were the markers of mesenchymal stem cells, vWF, CD31, CD105, SMA were all expressed in ASCs. Adipogenic differentiation of ASCs was assessed by Oil Red O staining after 2 weeks. The cells contained many lipid-filled droplets. After 2 weeks' osteogenic induction, cells were positively stained by alizarin Bordeaux. The method can isolate ASCs by directly centrifugate from the fatty and the fluid portions of human liposuction aspirates. The way of culture is convenient and economical. ASCs isolated from the liquid and fatty portions of liposuction aspirates show identical in cells numbers and quality. LAF cells and PLA cells have similar characters in growth dynamics, morphology, cell senescence, surface marker profiles and differentiation ability, etc. Expression of the cell surface marker of stem cells is also observed in ASCs. ASCs can differentiate into adipose and osteogenesis directionally. The results suggest that the ASCs, which are isolated with minimum intervention, may be the ideal seed cells for adipose tissue engineering in future.


The Val762Ala polymorphism in the poly(ADP-ribose) polymerase-1 gene is not associated with susceptibility in Turkish rheumatoid arthritis patients.
The findings of the studies on poly(ADP-ribose) polymerase-1 (PARP-1) have suggested that the enzyme inactivation provides significant protection against systemic or tissue inflammation in animal models. It has also shown that the single-nucleotide polymorphism (Val762Ala) of the PARP-1 causes about 40% decrease of enzyme activity. The aim of this study was to analyze the association of the PARP-1 Val762Ala polymorphism in Turkish patients with rheumatoid arthritis. A total of 128 RA patients and 165 normal controls from the same geographic region were studied and polymerase chain reaction (PCR)-based restriction analysis was used to identify Val762Ala polymorphism of the PARP-1. Association analyses were performed using chi (2) tests. Our results indicated that the distribution of the PARP-1 genotypes and alleles did not differ significantly among subjects with or without RA (P > 0.05). The results of the study indicate that, for our Turkish sample, the V762A polymorphism of the PARP-1 may not be involved in susceptibility to RA, implying that the polymorphism may not function as a candidate gene marker for screening RA patients.


Context learning before birth: evidence from the chick embryo.
Learning contextual information to form associative memories with stimuli of interest is an important brain function in both human and non-human animals. Intuitively, one would expect that such a sophisticated cognitive skill develops postnatally, as the organism starts exploring the surrounding environment to search for significant contingencies among stimuli. Here we show, instead, that even before hatching, domestic chicks are capable of forming associative memories between discrete alerting sounds and the surrounding context, as attested by the fact that habituation of the freezing response to the sounds is affected by the context of stimulation. This finding indicates that, while in the egg, chicks recognize and learn the context in which they are stimulated. Hence, context learning in chicks is an innate brain function already active before birth, which can provide an immediate survival advantage to the newborns of this precocial avian species.


EVOLUTIONARY RESPONSE OF PREDATORS TO DANGEROUS PREY: PREADAPTATION AND THE EVOLUTION OF TETRODOTOXIN RESISTANCE IN GARTER SNAKES.
Coevolutionary interactions typically involve only a few specialized taxa. The factors that cause some taxa and not others to respond evolutionarily to selection by another species are poorly understood. Preadaptation may render some species predisposed for evolutionary response to new pressures, whereas a lack of genetic variation may limit the evolutionary potential of other taxa. We evaluate these factors in the predator-prey interaction between toxic newts (Taricha granulosa) and their resistant garter snake predators (Thamnophis sirtalis). Using a bioassay of resistance to tetrodotoxin (TTX), the primary toxin in the prey, we examined phenotypic evolution in the genus Thamnophis. Reconstruction of ancestral character states suggests that the entire genus Thamnophis, and possibly natricine snakes in general, has slightly elevated TTX resistance compared to other lineages of snakes. While this suggests that T. sirtalis is indeed predisposed to evolving TTX resistance, it also indicates that the potential exists in sympatric congeners not expressing elevated levels of TTX resistance. We also detected significant family level variation for TTX resistance in a species of Thamnophis that does not exhibit elaborated levels of the trait. This finding suggests that evolutionary response in other taxa is not limited by genetic variability. In this predator-prey system, species and population differences in resistance appear to be largely determined by variation in the selective environment rather than preadaptation or constraint.


Synthesis of long-chain chitooligosaccharides by a hypertransglycosylating processive endochitinase of Serratia proteamaculans 568.
We describe the heterologous expression and characterization of a 407-residue single-domain glycosyl hydrolase family 18 chitinase (SpChiD) from Gram-negative Serratia proteamaculans 568 that has unprecedented catalytic properties. SpChiD was optimally active at pH 6.0 and 40 °C, where it showed a K(m) of 83 mg ml(-1), a k(cat) of 3.9 × 10(2) h(-1), and a k(cat)/K(m) of 4.7 h mg(-1) ml(-1) on colloidal chitin. On chitobiose, the K(m), k(cat), and k(cat)/K(m) were 203 μM, 1.3 × 10(2) h(-1), and 0.62 h(-1) μM(-1), respectively. Hydrolytic activity on chitooligosaccharides (CHOS) and colloidal chitin indicated that SpChiD was an endo-acting processive enzyme, with the unique ability to convert released chitobiose to N-acetylglucosamine, the major end product. SpChiD showed hyper transglycosylation (TG) with trimer-hexamer CHOS substrates, generating considerable amounts of long-chain CHOS. The TG activity of SpChiD was dependent on both the length and concentration of the oligomeric substrate and also on the enzyme concentration. The length and amount of accumulated TG products increased with increases in the length of the substrate and its concentration and decreased with increases in the enzyme concentration. The SpChiD bound to insoluble and soluble chitin substrates despite the absence of accessory domains. Sequence alignments and structural modeling indicated that SpChiD would have a deep substrate-binding groove lined with aromatic residues, which is characteristic of processive enzymes. SpChiD shows a combination of properties that seems rare among family 18 chitinases and that may resemble the properties of human chitotriosidase.


A novel catheter system for percutaneous intracoronary artery cardiomyoplasty.
Current medical and invasive treatment strategies are often found to be inadequate to treat patients with acute myocardial infarction. Cell and tissue therapies are a promising treatment alternative for patients with severe ischemic heart disease. The objective of this study was to evaluate the efficacy of a new means of direct myocardial access using the percutaneous coronary intervention (PCI) technique. We used a system consisting of an injection needle catheter that implants cells and the injection guide catheter that delivers the injection needle catheter into the target lesion. We harvested skeletal myoblasts from Yorkshire swine (n = 8; 50-60 kg), expanded them in culture and labeled them with a fluorescent cell-linker kit. The myoblasts (106 cells), along with green dye, were injected into the normal heart of swine using this novel system. Histological analysis was performed on Days 0 (n = 4) and 14 (n = 4) after injection. Working along the coronary artery, the catheter was easily delivered to the left anterior descending (LAD) coronary artery with the conventional PCI technique. No events of death, cardiac tamponade or other procedural complication occurred. Electrocardiography did not detect cardiac arrhythmia during the 14 days following the injection. On gross inspection, the heart was observed through its outer surface, and the myoblasts and green dye were well localized in the LAD area. The present study demonstrates the feasibility of a new means of a direct myocardial injection system without any adverse outcomes.


[The changes of expression level of matrix metalloprotease 9 and its inhibitor (TIMP-1) in murine pulmonary fibrosis model].
To evaluate the balance between matrix metalloprotease-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1) in bleomycin-induced pulmonary fibrosis in mice. Pulmonary fibrosis model was induced by bleomycin in mice. The histological images of lungs were studied by HE staining. Alveolar macrophages(AMs) were separated by anti-CD68 mAbs using immunomagnetic beads(d</=50 nm). The purity of AMs was determined under microscope. Cell viability was evaluated by staining with Hoechst 33258 dye. The secreted MMP-9 and TIMP-1 were assayed in macrophage supernatants, using quantitative enzyme-linked immunosorbent assays (ELISA). Collagen deposition was gradually increased in the lung tissue of mice on day 1, 3, 7, 14 and 28 after bleomycin treatment. The purity of AMs could be increased from (82.5+/-2.5)% to (99.3+/-0.7)% by mini-magnetic cell sorting system (mini-MACS, P<0.05), and the rate of living cells post-MACS was (92.5+/-1.8)% (pre-MACS (92.7+/-2.0)%, P>0.05). The concentration of MMP-9 secreted by AMs was gradually decreased on day 1, 3, 7, 14 and 28, and levels of TIMP-1 gradually increased. There was an imbalance between macrophage-derived MMP-9 and TIMP-1 in bleomycin-induced pulmonary fibrosis in mice.


Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation.
The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT. A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model. Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy. The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society.


The Potential Role for Impaired Mucosal Integrity in the Generation of Esophageal Pain Using Capsaicin in Humans: An Explorative Study.
Esophageal pain is mediated by sensory nerves, most importantly by the activation of the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor. TRPV1 is activated and sensitized by a broad range of pungent compounds, as well as inflammatory mediators and tissue irritants. Luminal stressors are suggested to impair the barrier function, which results in consequent activation of these sensory nerve terminals and pain. In this study, we investigated the effect of the perfusion of capsaicin, a TRPV1 agonist, on mucosal impedance and pain in asymptomatic volunteers. Thirteen asymptomatic volunteers completed a single-blind, saline-controlled, randomized crossover study. Capsaicin or saline was perfused for 30 minutes in the distal esophagus. Visual analog scale pain intensity scores and intraluminal impedance indicating mucosal integrity were determined. Distal and proximal biopsies were obtained 10 minutes later to measure TRPV1 messenger RNA and TRPV1 immunopositivity, as well as the intercellular space area. Capsaicin perfusion resulted in significantly greater pain intensity (P = 0.047) and impaired recovery of the mucosal impedance compared with saline-treated controls (P = 0.027). Pain response was significantly associated with decreased mucosal impedance. Similar dynamics were seen in the proximal esophagus, but mucosal impedance recovered entirely to the preinfusion values there. There was a significant association between mucosal impedance and intercellular space width in the distal esophagus. TRPV1 transcription and expression were not significantly altered within this observation period. Esophageal capsaicin perfusion results in pain, which is likely to be explained by impaired mucosal impedance and defective restoration capacity in the distal esophagus.


Screening for skin-tumor promoters.
Since attention has been drawn to the role of oxygen radicals in tumor promotion, we investigated whether or not the nitroblue tetrazolium (NBT) reduction test using mouse peritoneal macrophages was useful as a rapid screening method for skin-tumor promoters. On the basis of our results, we concluded that this test system was appropriate for the screening of 12-0-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters and bore comparison with other screening methods for tumor promoters. A large number of skin-tumor promoters, such as active phorbol esters, teleocidin and aplysiatoxin, appear to act indirectly through a free radical mechanism by binding to a membrane receptor.


[Running helps--or how you escape depression without a psychiatrist and end up running a marathon!].
We describe the case of a 27-year-old woman with adjustment disorder, disturbances of other feelings such as fear, depression, worries, anxiety and anger due to various burdens such as conflict with boyfriend and unclear job situation (ICD-10 f4323); furthermore, a status after intoxication with sleeping pills (ICD-10 X61) due to a difficult family situation. Regular endurance training helped the young woman to get over her serious life crisis and start a new life without psychiatrist and psychopharmaca. Thanks to progressively increasing running training, the patient was able to run a half-marathon in her first training year and aims for marathon and Powerman-Duathlon in the future.