Development of a tool to allocate inpatient specialized pharmacy resources at a comprehensive cancer center.
Develop an objective tool to align the needs of inpatient services at a Comprehensive Cancer Center with the available resources of hematology/oncology clinical specialist pharmacists. The shift of the pharmacy profession from product-centered to patient-centered care has expanded the scope of practice of the clinical pharmacist and their ability to specialize in a therapeutic area. However, these specialized resources are limited. The pharmacy department at The James Comprehensive Cancer Center at The Ohio State University Wexner Medical Center developed a tool to objectively determine which inpatient services would receive the most benefit from having a hematology/oncology clinical specialist pharmacist on their healthcare team. A Steering Committee was created to determine the necessary metrics needed across the 29 inpatient services at The James, and data was collected from the electronic medical record. The metrics evaluated were: patient acuity, inpatient intravenous anticancer administrations, inpatient oral anticancer administrations, presence of an outpatient anticancer treatment plan for patients admitted for an inpatient stay, and the use of high-risk hematology/oncology therapies. A novel and data-driven tool was created to allocate hematology/oncology clinical specialist pharmacists across a Comprehensive Cancer Center. Annual use of this objective tool can aid institutions in appropriate distribution of limited hematology/oncology specialized pharmacy resources.


Intensive follow-up for women with breast cancer: review of clinical, economic and patient's preference domains through evidence to decision framework.
Women treated for breast cancer are followed-up for monitoring of treatment effectiveness and for detecting recurrences at an early stage. The type of follow-up received may affect women's reassurance and impact on their quality of life. Anxiety and depression among women with breast cancer has been described, but little is known about how the intensity of the follow-up can affect women's psychological status. This study was undertaken to evaluate the effects of intensive vs. less-intensive follow-up on different health outcomes, to determine what are women's preferences and values regarding the follow-up received, and also assess the costs of these different types of follow-up. A systematic review following standard Cochrane Collaboration methods was carried out to assess the efficacy of intensive follow-up versus non-intensive follow-up in breast cancer patients. Two additional reviews on women's preferences and economic evidence were also carried out. The search was performed up to January 2016 in: MEDLINE, EMBASE, PDQ, McMaster Health Systems Evidence, CENTRAL, and NHS EED (through The Cochrane Library). The quality of evidence was assessed by GRADE (for quantitative studies) and CerQUAL (for qualitative studies). Several outcomes including mortality, breast cancer recurrences, quality of life, and patient satisfaction were evaluated. Six randomised trials (corresponding to 3534 women) were included for the evaluation of health outcomes; three studies were included for women's values and preferences and four for an economic assessment. There is moderate certainty of evidence showing that intensive follow-up, including more frequent diagnostic tests or visits, does not have effects on 5- or 10-year overall mortality and recurrences in women with breast cancer, compared with less intensive follow-up. Regarding women's preferences and values, there was important variability among studies and within studies (low confidence due to risk of bias and inconsistency). Furthermore, intensive follow-up, as opposed to less intensive follow-up, is not likely to be cost-effective. Less intensive follow-up appears to be justified and can be recommended over intensive follow-up. Resources could thus be mobilised to other aspects of breast cancer care, or other areas of healthcare.


Niacin as a potential AIDS preventive factor.
A pentad of findings consistent with niacin depletion have been described in patients with AIDS. There are also clinical and laboratory data to support the potential benefit of niacin in HIV infection. In this paper, it is hypothesized that HIV infection induces niacin depletion, and that therapeutic niacin will act as an AIDS preventive factor. While viral inhibition is incontrovertibly the primary 'AIDS preventive factor', costly antiretroviral medications are simply out of reach for the majority of the world's HIV-infected people. Along with antiviral research, investigation must go forward to look at strategies to overcome the massive metabolic disruption caused by the production of approximately one billion virus particles per day. Niacin, the same B complex vitamin found in the early part of this century to be the 'pellagra preventive factor', is proposed here as a secondary 'AIDS preventive factor' in HIV-infected persons.


Thyrotropin (TSH) stimulates cell growth and DNA synthesis in monolayer cultures of human thyrocytes independent of the adenylate-cyclase system.
Monolayer cultures of human thyrocytes from normal thyroids (n = 13), thyroid adenomas (n = 8), differentiated (n = 7), poorly and undifferentiated (n = 5) thyroid cancers as well as thyroid cancer metastases (n = 2) were established to assess the significance of TSH and cAMP on cell growth and DNA synthesis. Cell growth was stimulated by 0.1 IU bTSH/ml and inhibited by 1.0 IU bTSH/ml (P less than 0.01), while dibutyryl-cAMP (dbcAMP) failed to show any effect on cell growth at the concentrations (10-5; 10-3 mol/l), tested. Neither did the adenylate-cyclase inhibitor dideoxy-adenosine (ddA) (2 X 10-5 mol/l) stimulate thyrocyte growth. DNA synthesis, however, measured indirectly by [3H]thymidine incorporation, was stimulated not only by TSH 2-12-fold, but also by ddA 1.3-7-fold (P less than 0.01), and was not affected by dbcAMP. TSH had no effect on [3H]thymidine incorporation in fibroblasts and c-cells from c-cell carcinomas. The stimulatory effect of TSH on thyrocyte growth and DNA synthesis was unpredictable in thyrocytes from cancerous tissues (n = 14) with no obvious correlation to tumour differentiation or stage. Thus, we showed that TSH is a promotor for cell growth and DNA synthesis in monolayer cultures of human thyrocytes from normal and adenomatous human thyroid tissues with no obvious correlation to the AC system. This TSH effect is unpredictable, however, in thyrocytes from human thyroid cancer.


Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes.
The second harmonic generation (SHG) active nanocrystals have been demonstrated as attractive imaging probes in nonlinear microscopy due to their coherent, non-bleaching and non-blinking signals with a broad flexibility in the choice of excitation wavelength. For the use of these nanocrystals as biomarkers, it is essential to prepare a chemical interface for specific labeling. We developed a specific labeling scheme for barium titanate (BaTiO3) nanocrystals which we use as second harmonic radiation imaging probes. The specificity was achieved by covalently coupling antibodies onto the nanocrystals. We demonstrate highly specific labeling of the nanocrystal conjugates in an antibody microarray and also the membrane proteins of live biological cells in vitro. The development of surface functionalization and bioconjugation of SHG active nanocrystals provides the opportunities of applying them to biological studies.


Improved performance of single-chamber microbial fuel cells through control of membrane deformation.
Cation (CEMs) and anion exchange membrane (AEMs) are commonly used in microbial fuel cells (MFCs) to enhance Coulombic efficiencies (CEs) by reducing the flux of oxygen through the cathode to bacteria on the anode. AEMs typically work better than CEMs, but in initial experiments we observed the opposite using a membrane electrode assembly MFC. The reason was identified to be membrane deformation, which resulted in water and gas trapped between the membrane and cathode. To correct this, stainless steel mesh was used to press the membrane flat against the cathode. With the steel mesh, AEM performance increased to 46+/-4 W/m(3) in a single cathode MFC, and 98+/-14 W/m(3) in a double-cathode MFC. These power densities were higher than those using a CEM of 32+/-2 W/m(3) (single cathode) and 63+/-6 W/m(3) (double cathode). Higher pH gradients across the membrane and salt precipitation on the cathode were responsible for the reduced performance of the CEM compared to the AEM. CEs reached over 90% for both membranes at >2A/m(2). These results demonstrate the importance of avoiding water accumulation in thin films between membranes and electrodes, and explain additional reasons for poorer performance of CEMs compared to AEMs.


Planar EPID-Based Dosimetry for SRS and SRT Patient-Specific QA.
The study's purpose was to develop and validate Electronic Portal Imaging Device (EPID)-based dosimetry for Stereotactic Radiosurgery (SRS) and Stereotactic Radiation Therapy (SRT) patient-specific Quality Assurance (QA). The co-operation between extended Source-to-Imager Distance (SID) to reduce the saturation effect and simplify the EPID-based dosimetry model was used to perform patient-specific QA in SRS and SRT plans. The four parameters were included for converting the image to dose at depth 10 cm; dose-response linearity with MU, beam profile correction, collimator scatter and water kernel. The model accuracy was validated with 10 SRS/SRT plans. The traditional diode arrays with MapCHECK were also used to perform patient-specific QA for assuring model accuracy. The 150 cm-SID was found a possibility to reduce the saturation effect. The result of model accuracy was found good agreement between our EPID-based dosimetry and TPS calculation with GPR more than 98% for gamma criteria of 3%/3 mm, more than 95% for gamma criteria of 2%/2 mm, and the results related to the measurement with MapCHECK. This study demonstrated the method to perform SRT and SRT patient-specific QA using EPID-based dosimetry in the FFF beam by co-operating between the extended SID that can reduce the saturation effect and estimate the planar dose distribution with the in-house model.


Cholesterol polyps in the distal common bile duct: a case report.
Cholesterol polyps are rare in the common bile duct and difficult to diagnose. The small polypoid lesions often go undetected when using routine imaging methods, such as ultrasonography. We treated a patient with cholesterol polyps in the common bile duct. After failing to detect choleliths using ultrasonography, magnetic resonance cholangiopancreatography revealed mild dilation of the common bile duct. Choledochoscopy was performed during laparoscopic cholecystectomy, which revealed yellowish-white polyps circumferentially distributed across the luminal surface of the distal common bile duct. Histological examination of biopsy specimens indicated cholesterol polyps with characteristic foamy cells. The patient was treated with ursodeoxycholic acid, and the number of polyps was found to have been reduced at the 6-week follow-up based on T-tube choledochoscopic examination. Recovery was unremarkable, and the ursodeoxycholic acid treatment was discontinued at the 6-month follow-up. Our findings suggest that this rare condition can be treated pharmacologically to avoid potential postsurgical complications following resection of the distal common bile duct.


Effect of chronic iron deficiency on neuropsychological domains in infants.
The aim of this study was to assess the effects of chronic iron deficiency on neuropsychological traits in infants. We established the nutritional iron status and assessed the neuropsychological characteristics of 58 Mexican 14- to 18-month-old infants. The Bayley Scales of Infant Development, preschool language scales and an environmental sound perception task designed expressly for the study, were used. The infants' mothers were asked to fill out 2 questionnaires concerning their child's sociodemographic background. Six different neuropsychological domains were analyzed. Results showed that the chronic iron deficiency group did show significantly lower scores on language, environmental sound perception, and motor measures, when compared with infants with normal nutritional iron status at 6 and 14 to 18 months. Our conclusion is that the development of language and motor skills and environmental sound perception appeared to be sensitive to the effects of chronic iron deficiency in infants.


Vaccine Knowledge, Awareness and Hesitancy: A Cross Sectional Survey among Parents Residing at Sandakan District, Sabah.
Incomplete childhood immunization against communicable diseases is a major concern and vaccine hesitancy remains a hurdle to overcome in primary vaccination programs. This study was to examine the parents' vaccine knowledge, awareness and hesitancy in relation to their children's immunization status. A cross-sectional questionnaire study design was used. The parents who brought their children for immunization visit or follow-up at four public health clinics located in Sandakan district were invited to participate in this survey. Informed consent was obtained before each participant completed a hard copy of self-administered questionnaire in either English or Malay versions. Of 405 parents responded, they generally had good knowledge and awareness of vaccines, only a small percentage (6.8%) of parents were found vaccine hesitant. There were significant differences in vaccine knowledge and awareness in those from different education levels and employment status; similarly, these two factors also significantly affected the vaccine hesitancy among the parents. The parents' knowledge score was found to be moderately associated with their awareness (r = 0.551, p < 0.01) and inversely correlated to vaccine hesitancy (r = -0.397, p < 0.01). Most of the children (n = 376, 92.8%) in the study were immunized. The children's immunization status was significantly associated with the parents' education level (p = 0.025). There was also a significant difference in the total vaccine knowledge scores between the groups of parents with different child immunization status (p = 0.05). This study revealed that parents with higher education had a better knowledge of vaccinations, were less vaccine hesitant and were more likely to ensure that their children complete the recommended course of immunization. It is crucial to ensure parents are well-informed about the safety and efficacy of vaccines so that the children are protected from communicable diseases by the child vaccination program.


Detailed Analysis of Determination of Contact Angle Using Sphere Tensiometry
The configurations of the interfacial menisci around a sphere during the pulling process were analyzed and the methods for the simultaneous determination of surface and interfacial tension and contact angle were discussed. Furthermore, a method for the determination of contact angle using sphere tensiometry, which is independent of interfacial tension, was developed and tested with experiments. Copyright 1997Academic Press


Non-factor therapies for bleeding disorders: A primer for the general haematologist.
Management of patients with severe bleeding disorders, particularly haemophilia A and B, and to a lesser extent, von Willebrand disease, has come on leaps and bounds over the past decade. Until recently, patients relied upon the administration of factor concentrates to prevent or treat bleeding episodes. Factor administration requires intravenous access and, in up to one-third of patients, leads to the development of neutralising antibodies, or inhibitors, which are associated with more frequent bleeding episodes and higher morbidity. Novel non-factor therapies may offer a solution to these unmet needs. In this review, we discuss the factor mimetics, particularly emicizumab, and the rebalancing agents, which inhibit antithrombin, tissue factor pathway inhibitor and activated protein C, and novel treatments to enhance von Willebrand factor levels. We review the available trial data, unanswered questions and challenges associated with these new treatment modalities. Finally, we provide practical management algorithms to aid the general haematologist when faced with a patient receiving emicizumab who requires surgery or may develop bleeding.


When COVID-19 will decline in India? Prediction by combination of recovery and case load rate.
The World Health Organization (WHO) declared COVID-19 as a pandemic on March 11, 2020. There is sudden need of statistical modeling due to onset of COVID-19 pandemic across the world. But health planning and policy requirements need the estimates of disease problem from clinical data. The present study aimed to predict the declination of COVID-19 using recovery rate and case load rate on basis of available data from India. The reported COVID-19 cases in the country were obtained from website (https://datahub.io/core/covid-19#resource-covid-19_zip/). The confirmed cases, recovered cases and deaths were used for estimating recovery rate, case load rate and death rate till June 04, 2020. A total of 216919 confirmed cases were reported nationwide in India on June 04, 2020. It is found that the recovery rate increased to 47.99% and case load rate decreased to 49.21%. Death rate is found to be very low 2.80%. Accordingly, coincidence of the difference of case load rate and recovery rate (delta) will reveal a declination in expected COVID-19 cases. The epidemic in the country was mainly caused by the movement of people from various foreign countries to India. Lockdown as restricting the migration of population and decision taken by the government to quarantine the population may greatly reduce the risk of continued spread of the epidemic in India. This study predicts that when the case load rate gets lesser than recovery rate, there after COVID-19 patients would be started to decline.


Poly(Ionic Liquid) Based Chemosensors for Detection of Basic Amino Acids in Aqueous Medium.
Naked-eye detection of amino acids (AA) in water is of great significance in the field of bioanalytical applications. Herein, polymerized ionic liquids (PILs) with controlled chain length structures were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization and post-quaternization approach. The AA recognition performance of PILs with different alkyl chain lengths and molecular weights was evaluated by naked-eye color change and ultraviolet-visible (UV-vis) spectral studies. These PILs were successfully used for highly sensitive and selective detection of Arg, Lys, and His in water. The recognition performance was improved effectively with increased molecular weight of PILs. The biosensitivity of the PILs in water was strongly dependent on their aggregation effect and polarization effect. Highly sensitive and selective detection of AA was successfully accomplished by introducing positively charged pyridinium moieties and controlled RAFT radical polymerization.


Rearrangement reactions catalyzed by cytochrome P450s.
Cytochrome P450s promote a variety of rearrangement reactions both as a consequence of the nature of the radical and other intermediates generated during catalysis, and of the neighboring structures in the substrate that can interact either with the initial radical intermediates or with further downstream products of the reactions. This article will review several kinds of previously published cytochrome P450-catalyzed rearrangement reactions, including changes in stereochemistry, radical clock reactions, allylic rearrangements, "NIH" and related shifts, ring contractions and expansions, and cyclizations that result from neighboring group interactions. Although most of these reactions can be carried out by many members of the cytochrome P450 superfamily, some have only been observed with select P450s, including some reactions that are catalyzed by specific endoperoxidases and cytochrome P450s found in plants.


Property structures, demography and the crisis of the agrarian economy of colonial Bombay Presidency.
Reasons for the relative failure of agricultural development in India during the colonial period are analyzed, and the effects of the scarcity of capital, the absence of suitable technology, and the growth of the population are assessed. "The article explores the manner in which peasant possession of land and other means of subsistence limited productive utilisation of capital and technology, triggered a certain demographic regime and, in turn, disrupted further developmental possibilities." The geographical focus is on the area coinciding with the modern states of Maharashtra and Gujarat.


Insights of the Crystallization Process of Molecular Sieve AlPO4-5 Prepared by Solvent-Free Synthesis.
Crystallization of AlPO4-5 with AFI structure under solvent-free conditions has been investigated. Attention was mainly focused on the characterization of the intermediate phases formed at the early stages during the crystallization. The development in the long-range ordering of the solid phases as a function of crystallization time was monitored by XRD, SEM, IR, UV-Raman, and MAS NMR techniques. Particularly, the UV-Raman spectroscopy was employed to obtain the information on the formation process of the framework. J-HMQC (27)Al/(31)P double-resonance NMR experiments were used to identify the P-O-Al bonded species in the intermediate phases. For the first time the P-O-Al bonded species in the intermediate phases can be correctly described through using this advanced NMR technique. The crystallization under solvent-free conditions appears to follow the pathway: The initial amorphous raw material is converted to an intermediate phase which has four-/six-membered ring species, then gradually transformed into crystalline AlPO4-5. This observation is not consistent with the common idea that the intermediate phase is the semicrystalline intermediates with a three-dimensional structure.


Protocol: influence of budesonide and budesonide/formoterol on asthma control in smoking asthmatic adults.
A reduced response to inhaled corticosteroids (ICS) has been reported in smoking asthmatic patients but the effects of other medications remain to be evaluated in this population. We evaluated the effects of a combined therapy of budesonide 200 microg twice daily and formoterol 6 microg twice daily compared with budesonide 200 microg twice daily alone on asthma control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ- Juniper), pulmonary function and airway inflammation, in a cross-over randomized double-blind study with treatment periods of two months separated by a one-month wash-out period. Seventeen smoking and 22 non-smoking patients not using inhaled corticosteroids with slightly uncontrolled mild asthma completed the study. ACQ and AQLQ scores were similar in both groups at baseline and improved similarly after treatments. beta2-agonist use was higher in smokers, regardless of the treatment received (p=0.03), as it was on baseline (p=0.003). Smokers treated with budesonide/formoterol showed an increase in the number of asthma episodes (intercurrent asthma symptoms, p=0.016) while non-smoking subjects had a significant decrease in these episodes (p=0.009). No difference was found between smokers and non-smokers in regard to post-treatment airway inflammatory parameters. No significant differences were found between smoking and non-smoking subjects with mild asthma in regard to clinical changes in asthma control, pulmonary function and airway inflammation following a 2-month treatment period with budesonide or the association of budesonide and formoterol for a period of 2 months. This should be further explored in larger groups of subjects.


Thermographic mapping of perforators and skin blood flow in the free transverse rectus abdominis musculocutaneous flap.
There is no ideal method for preoperative or intraoperative mapping of cutaneous perforators or for postoperative monitoring of blood flow in cutaneous flaps. To study the suitability of thermography for the mapping and monitoring of free transverse rectus abdominis musculocutaneous (TRAM) flaps for breast reconstruction, we performed thermography pre-, intra-, and postoperatively (eight patients). The temperature of the TRAM flap increased during the induction of anesthesia and was still higher than normal on the first and second postoperative days (p < 0.05). During the operation, the flap cooled, reaching its minimum temperature (3.62 +/- 0.6 degrees C below phase 2, p < 0.05) after ligation of both pedicles of the flap. When blood flow had been re-established, all parts of the flap warmed rapidly. The locations of perforators ("hot spots") could be seen before, during, and after the operation. However, induction and cutting of both pedicles made the flap isothermic, and the perforators disappeared temporarily. Thermography is a potential method of mapping cutaneous perforators pre-, intra-, and postoperatively and of monitoring the flaps at bedside. The method is easy to use and the outcome can be seen immediately. Our results also showed that the temperature (blood flow) in free TRAM flaps is higher than in the tissue in its original position.


Superparamagnetic Composites Based on Ionic Resin Beads/CaCO3 /Magnetite.
The preparation of superparamagnetic composites obtained by CaCO3 mineralization from supersaturate aqueous solutions is presented. The preparation was conducted in the presence of oleic acid stabilized magnetite nanoparticles as a water-based magnetic fluid and insoluble templates as gel-like cross-linked polymeric beads. The presence of the magnetic particles in the composites provides a facile way for external manipulation using a permanent magnet, thus allowing the separation and extraction of magnetically modified materials. Two ion exchangers based on divinylbenzene/ethyl acrylate/acrylonitrile cross-linked copolymer-a cation ion exchanger (CIE) and an amphoteric ion exchanger (AIE)-were used, as well as different addition orders of magnetite and CaCO3 crystals growth precursors. The morphology of the composites was investigated by SEM, the polymorphs content by X-ray diffraction, and the thermal stability by thermogravimetric analysis. Polymer, CaCO3 , and magnetite in the composite particles were shown to be present by energy dispersive X-ray (EDX), XPS, and TEM. The sorption capacity for CuII ions was tested, as compared to samples prepared without magnetite.


De novo design of peptide-calcite biomineralization systems.
Many organisms produce complex, hierarchically structured, inorganic materials via protein-influenced crystal growth--a process known as biomineralization. Understanding this process would shed light on hard-tissue formation and guide efforts to develop biomaterials. We created and tested a computational method to design protein-biomineralization systems. The algorithm folds a protein from a fully extended structure and simultaneously optimizes the fold, orientation, and sequence of the protein adsorbed to a crystal surface. We used the algorithm to design peptides (16 residues) to modify calcite (CaCO(3)) crystallization. We chemically synthesized six peptides that were predicted to bind different states of a calcite growth plane. All six peptides dramatically affected calcite crystal growth (as observed by scanning electron microscopy), and the effects were dependent on the targeted state of the {001} growth plane. Additionally, we synthesized and assayed scrambled variants of all six designed peptides to distinguish cases where sequence composition determines the interactions versus cases where sequence order (and presumably structure) plays a role. Scrambled variants of negatively charged peptides also had dramatic effects on calcite crystallization; in contrast, scrambled variants of positively charged peptides had a variable effect on crystallization, ranging from dramatic to mild. Special emphasis is often placed on acidic protein residues in calcified tissue mineralization; the work presented here suggests an important role for basic residues as well. In particular, this work implicates a potential role for basic residues in sequence-order specificity for peptide-mineral interactions.


Pembrolizumab-induced large duct cholangiopathy: Diagnosis and follow.up imaging.
Immune-checkpoint inhibitor mediated hepatobiliary injury is an emerging concern in cancer treatment. Most of these adverse reactions are attributed to nivolumab and are characterized by panlobular hepatitis. Large duct cholangiopathy related to these drugs is extremely rare. We present a case of adenocarcinoma of lung treated with pembrolizumab who developed biochemical and imaging features consistent with cholangiopathy characterized by common bile duct dilatation, wall enhancement, and gallbladder wall edema. On follow-up in the fourth month, the imaging features persisted despite the normalization of liver enzymes. To the best of our knowledge, this is the first description of diagnosis and follow-up imaging of pembrolizumab-related cholangiopathy in imaging literature.


Strength Training Biases Goal-Directed Aiming.
Goal-directed movements tend to resemble the characteristics of previously executed actions. Here we investigated whether a single bout of strength training, which typically involves stereotyped actions requiring strong neural drive, can bias subsequent aiming behavior toward the direction of trained forces. In experiment 1 (n = 10), we tested the direction of force exerted in an isometric aiming task before and after 40 repetitions of 2-s maximal-force ballistic contractions toward a single directional target. In experiment 2 (n = 12), each participant completed three training conditions in a counterbalanced crossover design. In two conditions, both the aiming task and the training were conducted in the same (neutral) forearm posture. In one of these conditions, the training involved weak forces to determine whether the level of neural drive during training influences the degree of bias. In the third condition, high-force training contractions were performed in a 90° pronated forearm posture, whereas the low-force aiming task was performed in a neutral forearm posture. This dissociated the extrinsic training direction from the pulling direction of the trained muscles during the aiming task. In experiment 1, we found that aiming direction was biased toward the training direction across a large area of the work space (approximately ±135°; tested for 16 targets spaced 22.5° apart), whereas in experiment 2, we found systematic bias in aiming toward the training direction defined in extrinsic space, but only immediately after high-force contractions. Our findings suggest that bias effects of training involving strong neural drive generalize broadly to untrained movement directions and are expressed according to extrinsic rather than muscle-based coordinates.


Low-temperature fate of the 0.7 structure in a point contact: a Kondo-like correlated state in an open system.
Besides the usual conductance plateaus at multiples of 2e(2)/h, quantum point contacts typically show an extra plateau at approximately 0.7(2e(2)/h), believed to arise from electron-electron interactions that prohibit the two spin channels from being simultaneously occupied. We present evidence that the disappearance of the 0.7 structure at very low temperature signals the formation of a Kondo-like correlated spin state. Evidence includes a zero-bias conductance peak that splits in a parallel field, scaling of conductance to a modified Kondo form, and consistency between peak width and the Kondo temperature.


Ultrapure dialysis fluid: improving conventional and daily dialysis.
Dialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has been considered acceptable because the dialysis membrane was believed to be a protective barrier to blood. However, improved methods for detection of cellular activation have demonstrated that bacterial products in the dialysate may stimulate monocytes to produce cytokines with most dialysis membranes. Ultrapure dialysis fluid is practically free from bacteria and endotoxin (< 0.1 CFU/mL and < 0.03 EU/mL) and can be prepared from standard-quality dialysis fluid using a single step of controlled ultrafiltration. The European guidelines for hemodialysis (HD) set the use of ultrapure dialysis fluid as the goal for all dialysis modalities. Several clinical studies report improved inflammatory status in HD patients when ultrapure dialysis fluid is used, compared with standard-quality dialysate. The benefits include less frequent occurrence of carpal tunnel syndrome, lower C-reactive protein values, reduced need for erythropoietin, better nutritional status, and even better preservation of residual renal function. For patients on daily dialysis, dialysate quality is especially important because such patients are often treated at home where quality control of incoming water may be less rigorous, and increased treatment frequency leads to exposure to larger volumes of dialysis fluid than with conventional dialysis. The use of ultrapure dialysis fluid together with low-complement-activating membranes maximizes the biocompatibility of a dialysis treatment, a goal of treatment, although there is a lack of evidence to date supporting a beneficial effect on mortality. From a physiologic point of view the reduced inflammatory stimulus that can be achieved with ultrapure dialysis fluid is highly desirable. In addition, achieving ultrapure dialysis fluid is realistic, because today it can be practically and economically prepared using modern equipment and applying appropriate microbiologic surveillance techniques.


A shared role for sonic hedgehog signalling in patterning chondrichthyan gill arch appendages and tetrapod limbs.
Chondrichthyans (sharks, skates, rays and holocephalans) possess paired appendages that project laterally from their gill arches, known as branchial rays. This led Carl Gegenbaur to propose that paired fins (and hence tetrapod limbs) originally evolved via transformation of gill arches. Tetrapod limbs are patterned by asonic hedgehog(Shh)-expressing signalling centre known as the zone of polarising activity, which establishes the anteroposterior axis of the limb bud and maintains proliferative expansion of limb endoskeletal progenitors. Here, we use loss-of-function, label-retention and fate-mapping approaches in the little skate to demonstrate that Shh secretion from a signalling centre in the developing gill arches establishes gill arch anteroposterior polarity and maintains the proliferative expansion of branchial ray endoskeletal progenitor cells. These findings highlight striking parallels in the axial patterning mechanisms employed by chondrichthyan branchial rays and paired fins/limbs, and provide mechanistic insight into the anatomical foundation of Gegenbaur's gill arch hypothesis.


Lumbar-hip flexion motion. A comparative study between asymptomatic and chronic low back pain in 18- to 36-year-old men.
The amount of lumbar and hip flexion and the relative contribution within movement during standing forward bending was recorded on a group of asymptomatic men and a group of men with a history of chronic low back pain. To compare the relative contribution of the hip and lumbar spine to forward bending in the two groups. The hips and lumbar spine both contribute to the forward bending motion, and an aberrant pattern of contribution in one or both regions could be related to the presence of chronic low back pain. Thirty-two white men aged 18-36 years (15 with chronic low back pain and 17 asymptomatic) were assessed using a three-dimensional motion analysis system that allowed uninterrupted forward bending. The men with chronic low back pain demonstrated a significant reduction in the mean total range and mean maximum lumbar flexion relative to the asymptomatic group. Mean hip flexion was not significantly different. Data analysis for 120 degrees of gross flexion revealed a subgroup of men with chronic low back pain with a significant decrease in hip flexion. When assessing the relative motion of the lumbar spine and hips in standing forward flexion, there was measurable difference between asymptomatic men and a group of chronic low back pain patients. In particular, two subgroups of individuals with chronic low back pain appeared; one moved relatively similarly to the asymptomatic group, whereas the other sub-group demonstrated reduced hip mobility. These findings indicate the importance of assessing the lumbar and hip flexion motion in chronic low back pain patients to determine if a movement abnormality is present.


The draft lottery and AIDS: evidence against increased intravenous drug use by Vietnam-era veterans.
To investigate whether intravenous drug use begun during military service might affect risk of acquired immunodeficiency syndrome (AIDS), the authors compared AIDS cases in men eligible to be drafted with those in men who were exempt in the Vietnam-era draft lottery of 1970-1972. Draft-eligible men were less likely to develop AIDS attributed to intravenous drug use than were draft-exempt men (relative risk = 0.87; 95% confidence interval 0.80-0.95; p = 0.001). Other human immunodeficiency virus exposure categories showed no difference between the two groups. These results argue against increased intravenous drug use by Vietnam-era veterans.


Evaluation of the healing time of non-operatively managed liver injuries.
Post discharge prescriptions and follow-up protocols after non-operative treatment of blunt liver injuries are still controversial. The aim of this study was to detail the evolution of the hepatic injuries considering their different patterns and severity grades, stated by the Liver Injury Scale. Analysis of a database concerning 79 consecutive patients submitted to ultrasound follow-up until complete recovery of liver injury. All patients had an uncomplicated course and the liver restoration was demonstrated between 3 and 300 days after the trauma. The median healing time of hematomas increased with the grading (p<0.001): 6 days (IQR=6.75), 45.5 days (IQR=91) and 108 days (IQR=89) for I, II and III grade lesions, respectively. Similarly behaved the lacerations and 29 days (IQR=14.25), 34 days (IQR=43.5) and 77.5 days (IQR=83.5) was the median healing time of II, III and IV grade lesions, statistical significance emerging only comparing II to IV grade lacerations (p<0.035). Considering the different lesion patterns within the same severity grade, the liver restoration was more prompt after lacerations (p<0.001). These data suggest that medical prescriptions and follow-up protocols can be tailored considering the lesion characteristics.


Structure, magnetic properties and spin density of two alternative Mn(II) coordination polymers based on 1,4-bis(2'-carboxyphenoxy)benzene.
Two novel manganese coordination polymers [Mn2(μ2-bcpb)(μ4-bcpb)(2,2'-bipy)2]n (1) and [Mn2(μ3-bcpb)2(2,2'-bipy)2(H2O)]n (2) (H2bcpb = 1,4-bis(2'-carboxylato phenoxy)-benzene; 2,2'-bipy = 2,2'-bipyridine), have been synthesized successfully from the same reactants. This unusual selectivity was corroborated by X-ray powder diffraction. Single crystal X-ray diffraction analysis of complex 1 reveals that neighboring Mn(II) ions are linked via two bcpb2- anions to form a dinuclear Mn(II) subunit [Mn2(μ1,1-COO)2]2+ with a Mn⋯Mn distance of 3.3758 (6) Å. And π⋯π interactions between aromatic rings of the bcpb2- and 2,2'-bipy ligands stabilize the two-dimensional extended coordination network with the unprecedented Schläfli symbols {4·62}2{42·62·82}. In the [Mn2(μ1,3-COO)2]2+ subunit of 2, two linking bcpb2- ligands subtend an interaction distance of 4.4048(6) Å. Intermolecular O-H⋯O hydrogen bonds involving oxygen atoms of carboxylic acid and coordinated water molecules connect adjacent 1D chain molecules into a 2D network. Experimental temperature-dependent magnetic susceptibility measurements and spin density analyses by DFT disclose that compounds 1 and 2 display different magnetic properties.


Whole-body CT in haemodynamically unstable severely injured patients--a retrospective, multicentre study.
The current common and dogmatic opinion is that whole-body computed tomography (WBCT) should not be performed in major trauma patients in shock. We aimed to assess whether WBCT during trauma-room treatment has any effect on the mortality of severely injured patients in shock. In a retrospective multicenter cohort study involving 16719 adult blunt major trauma patients we compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90-110,<90 or >110 mmHg) at hospital admission and who received WBCT during resuscitation to those who did not. Using data derived from the 2002-2009 version of TraumaRegister®, we determined the observed and predicted mortality and calculated the standardized mortality ratio (SMR) as well as logistic regressions. 9233 (55.2%) of the 16719 patients received WBCT. The mean injury severity score was 28.8±12.1. The overall mortality rate was 17.4% (SMR = 0.85, 95%CI 0.81-0.89) for patients with WBCT and 21.4% (SMR = 0.98, 95%CI 0.94-1.02) for those without WBCT (p<0.001). 4280 (25.6%) patients were in moderate shock and 1821 (10.9%) in severe shock. The mortality rate for patients in moderate shock with WBCT was 18.1% (SMR 0.85, CI95% 0.78-0.93) compared to 22.6% (SMR 1.03, CI95% 0.94-1.12) to those without WBCT (p<0.001, p = 0.002 for the SMRs). The mortality rate for patients in severe shock with WBCT was 42.1% (SMR 0.99, CI95% 0.92-1.06) compared to 54.9% (SMR 1.10, CI95% 1.02-1.16) to those without WBCT (p<0.001, p = 0.049 for the SMRs). Adjusted logistic regression analyses showed that WBCT is an independent predictor for survival that significantly increases the chance of survival in patients in moderate shock (OR = 0.73; 95%CI 0.60-0.90, p = 0.002) as well as in severe shock (OR = 0.67; 95%CI 0.52-0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock. WBCT during trauma resuscitation significantly increased the survival in haemodynamically stable as well as in haemodynamically unstable major trauma patients. Thus, the application of WBCT in haemodynamically unstable severely injured patients seems to be safe, feasible and justified if performed quickly within a well-structured environment and by a well-organized trauma team.


Role of gut microbiota in the modulation of atherosclerosis-associated immune response.
Inflammation and metabolic abnormalities are linked to each other. At present, pathogenic inflammatory response was recognized as a major player in metabolic diseases. In humans, intestinal microflora could significantly influence the development of metabolic diseases including atherosclerosis. Commensal bacteria were shown to activate inflammatory pathways through altering lipid metabolism in adipocytes, macrophages, and vascular cells, inducing insulin resistance, and producing trimethylamine-N-oxide. However, gut microbiota could also play the atheroprotective role associated with anthocyanin metabolism and administration of probiotics and their components. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis.


A descriptive study of the CE needs of nurses serving adolescents in the community.
The purpose of this descriptive study was to develop a two-pronged community education database to improve the quality of response to professionals' self-assessed educational needs. The database was designed to include both the self-assessed level of the respondents' learning needs and their perception of the importance of mastery of specific content in reaching targeted outcomes for the adolescents they serve. Sixty-one percent of the 425 surveys mailed to professionals from central and southeastern Ohio were analyzed. Responses were weighted and a scattergraph of the mean scores for each topic was plotted. Implications for nursing continuing education (CE) are discussed.


Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness.
Bidirectional cellular communication is integral to both cancer progression and embryological development. In addition, aggressive tumor cells are phenotypically plastic, sharing many properties with embryonic cells. Owing to the similarities between these two types of cells, the developing zebrafish can be used as a biosensor for tumor-derived signals. Using this system, we show that aggressive melanoma cells secrete Nodal (a potent embryonic morphogen) and consequently can induce ectopic formation of the embryonic axis. We further show that Nodal is present in human metastatic tumors, but not in normal skin, and thus may be involved in melanoma pathogenesis. Inhibition of Nodal signaling reduces melanoma cell invasiveness, colony formation and tumorigenicity. Nodal inhibition also promotes the reversion of melanoma cells toward a melanocytic phenotype. These data suggest that Nodal signaling has a key role in melanoma cell plasticity and tumorigenicity, thereby providing a previously unknown molecular target for regulating tumor progression.


The Behavioral and Emotional Profile of Pediatric Tourette Syndrome Based on CBCL in a Chinese Sample.
Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that has a unique status of a quintessentially neuropsychiatric condition at the interface of neurology (movement disorder) and psychiatry (behavioral/emotional condition). However, the behavioral and emotional profile has seemed to be neglected in the literature thus far. This study aimed to investigate the behavioral and emotional profile of TS. A total of 124 patients aged 6-16 years with TS were included in this study, including age- and sex-matched health control, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and major depressive disorder (MDD) groups. The Child Behavior Checklist (CBCL) was used to screen the behavioral and emotional profile of the TS and other compared groups. The Yale Global Tic Severity Scale (YGTSS) was used to assess TS tic severity. Analysis of variance (ANOVA) was used to investigate the difference between the TS and other compared groups. The results showed that the eight factors of the CBCL had no association with motor tics, vocal tics, or tic severity (p > 0.05). However, positive correlations were identified between functional impairments (subscales of YGTSS) and thought problems (TP) and rule-breaking behavior (RBB). Based on the eight-factor profile of the CBCL, TS showed a similar profile to MDD but different from ADHD and OCD, which showed similar profiles. Based on the assessment of the CBCL of TS, it was found that "pure" TS might show fewer behavioral and emotional problems than OCD, ADHD, and MDD. Similar behavioral and emotional profiles were identified between TS and MDD, but not OCD and ADHD. More attention needs to be paid to the thought problems and rule break problems in the CBCL in the screening stage, which might have a potential influence on the functional impairments of TS.


[Management of hyperkalemia-induced cardiac arrest in anhepatic stage of orthotopic liver transplantation without venovenous bypass: report of 3 cases].
The causes of high serum potassium-induced cardiac arrest in anhepatic stage of orthotopic liver transplantation were analyzed in 3 cases without venovenous bypass, and the effectiveness of insulin was evaluated in correcting hyperkalemia during the anhepatic stage. To improve the survival rate of patients with such cardiac arrest, early cardiopulmonary resuscitation and timely defibrillation should be performed.


Depletion of Foxp3+ regulatory T cells but not the absence of CD19+IL-10+ regulatory B cells hinders tumor growth in a para-orthotopic neuroblastoma mouse model.
Adaptive immune cells with regulatory function reportedly mediate immune escape in a variety of tumors. Little is known regarding the relevance of the most prominent regulatory cell populations, namely Foxp3+ T regulatory cells (Tregs) and CD19+IL-10+ B regulatory cells (Bregs), for neuroblastoma (NB) survival. After establishing a novel immunocompetent syngeneic NB mouse model where orthotopic tumors can be generated after intrarenal injection of NB975A cells, we studied the importance of Tregs and Bregs in Foxp3-DTR mice whose Tregs can be depleted by diphtheria toxin (DT) application as well as in CD19-specific IL-10 deficient mice that lack IL-10+ Bregs (CD19cre+/- × IL-10fl/fl mice). We observed Foxp3 Treg cells in tumors from wild type mice. On the contrary, Bregs or B cells were scarce. Specific depletion of Tregs in Foxp3-DTR mice resulted in an 85% reduction of tumor volume and weight compared to DT-treated wild type mice and untreated Foxp3-DTR mice. In contrast, NB tumor growth was not affected in CD19-specific IL-10 deficient mice. Similarly, mice lacking mature B cells (μMT mice) and CD19 deficient mice (CD19cre mice) showed no change in growth pattern of NB tumors. In Treg-depleted mice, reduced tumor growth was associated with an increased concentration of IFN-gamma, TNF-alpha, IL-4, IL-6, and IL-10 in isolated splenocytes. In summary, transient ablation of Tregs but not absence of Bregs hindered the growth of NB, strongly suggesting the therapeutic potential of targeting Tregs for this aggressive childhood tumor.


Perfluorocarbon-filled poly(lactide-co-gylcolide) nano- and microcapsules as artificial oxygen carriers for blood substitutes: a physico-chemical assessment.
The physico-chemical suitability of perfluorocarbon-filled capsules as artificial oxygen carriers for blood substitutes is assessed on the example of biodegradable poly(lactide-co-gylcolide) micro- and nanocapsules with a liquid content of perfluorodecalin. The morphology of the capsules is studied by confocal laser scanning microscopy using Nile red as a fluorescent marker. The mechanical stability and the wall flexibility of the capsules are examined by atomic force microscopy. The permeability of the capsule walls in connection with the oxygen uptake is detected by nuclear magnetic resonance. It is shown that the preparation in fact leads to nanocapsules with a mechanical stability which compares well with the one of red blood cells. The capsule walls exhibit sufficient permeability to allow for the exchange of oxygen in aqueous environment. In the fully saturated state, the amount of oxygen dissolved within the encapsulated perfluorodecalin in aqueous dispersion is as large as for bulk perfluorodecalin. Simple kinetic studies are presently restricted to the time scale of minutes, but so far indicate that the permeability of the capsule walls could be sufficient to allow for rapid gas exchange.


Developmental mechanisms of topographic map formation and alignment.
Brain connections are organized into topographic maps that are precisely aligned both within and across modalities. This alignment facilitates coherent integration of different categories of sensory inputs and allows for proper sensorimotor transformations. Topographic maps are established and aligned by multistep processes during development, including interactions of molecular guidance cues expressed in gradients; spontaneous activity-dependent axonal and dendritic remodeling; and sensory-evoked plasticity driven by experience. By focusing on the superior colliculus, a major site of topographic map alignment for different sensory modalities, this review summarizes current understanding of topographic map development in the mammalian visual system and highlights recent advances in map alignment studies. A major goal looking forward is to reveal the molecular and synaptic mechanisms underlying map alignment and to understand the physiological and behavioral consequences when these mechanisms are disrupted at various scales.


Effects of ultraviolet irradiation on the bond strength of a composite resin adhered to stainless steel crowns.
A technique whereby the practitioner could improve the esthetic appearance of anterior stainless steel crowns (SSC) could provide a cost-effective alternative to more expensive commercially available preveneered SSCs, which may not be uniformly available. The purpose of this study was to evaluate the effects of ultraviolet (UV) irradiation of the metal crown surface on the shear bond strength of composite resin adhered to stainless steel crowns. Seventy extracted anterior bovine teeth randomly divided into 2 groups (n=35/group), were restored with primary maxillary left central incisor SSCs. Surface roughening with a green stone was performed on the labial surfaces, and the crowns of the experimental group were exposed to UV irradiation for 80 minutes. All samples were treated with metal-composite adhesive, followed by composite opaquer. Standardized composite blocks were bonded on the treated surfaces, and the shear bond strength was tested at 1 mm/minute. The values were recorded in MPa and statistically analyzed. The mean value of shear bond strength was significantly higher for the experimental group (19.7 ± 4.3 MPa) than the control group (16.3 ± 4.5 MPa). Ultraviolet irradiation of primary tooth stainless steel crowns significantly increased the shear bond strength of composite resin adhered to the facial surface.


Biological and molecular effects of small molecule kinase inhibitors on low-passage human colorectal cancer cell lines.
Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.


[Gene mapping of an ultra-dwarf mutant in upland cotton].
A ultra-dwarf mutant was newly found in upland cotton (Gossypium hirsutum L.). This mutant was controlled by single recessive gene du. Seventy pairs of polymorphic primers were selected from 1350 primers, which covered all the identified chromosomes by screening in parents and near-isogenic lines. Gene du was mapped using an F2 population derived from intraspecific crosses between "Ultra-dwarf 1" and "Xinluzao 16". Thirty-six primers were distributed in eight linkage groups, and du was linked to LG01. Seven co-dominant markers linked to du were NAU2679, NAU2749, NAU905, NAU2838, NAU5373, NAU2238, and NAU4946. Based on the known genetic map of tetraploid cotton, the markers NAU4946, NAU2238, NAU905, NAU5373, and NAU2679 were located on chromosome 6, and the target gene du was located between NAU2238 and NAU4946 with the genetic distances of 3.3 cM and 1.4 cM, respectively. Hence, gene du was located on chromosome 6.


Myocardial mechanics and arrhythmia.
The initiating cause of the first ectopic beat and its precipitation of sustained lethal arrhythmia in acute myocardial ischemia is not clear. Comparable uncertainties surround sudden death in myocardial failure. Progress in control of ventricular fibrillation has been slow, perhaps because diagnosis and treatment have been based on the premise that ischemic biochemical changes solely cause the alterations in electrophysiological behavior. Alternative approaches need exploration. Evidence that mechanical changes can initiate electrophysiological changes by a process sometimes referred to as "mechanoelectric feedback" is accumulating. It operates when any primary mechanical change in ventricular muscle, e.g., contraction produces a change in its electrical properties. Mechanical changes are prevalent in ischemia and cardiac failure. If mechanoelectric feedback operates here, it is not surprising that arrhythmias in some of these pathologies parallel the degree of mechanical myocardial dysfunction rather than electrophysiological changes, independent of etiology. This mechanoelectric feedback system may exist as an intrinsic property of normal myocardium, providing a feedback control of activation processes at both the cellular and gross levels. Its disruption during pathological events produces instability in the system and thus ventricular arrhythmia. This concept provides a new potential avenue for arrhythmia therapy.


Reconstruction of the laryngeal mucosa. A three-dimensional collagen gel matrix culture.
To prepare an in vitro reconstruction of the porcine laryngeal mucosa, for use in cell biological investigations and as a model for the study of laryngeal disease. Using separately obtained epithelial cells and fibroblasts from porcine laryngeal mucosa, we reconstructed the laryngeal mucosa in a three-dimensional collagen gel matrix culture with air-liquid interface. Porcine larynges were from 6-month-old pigs obtained from a local abattoir. We successfully reconstructed the laryngeal mucosa in vitro, including epithelium and lamina propria. The epithelial cells showed five to eight cells in thickness and were well differentiated on the reconstructed lamina propria. The differentiation-specific cytokeratin was positive. To our knowledge, this is the first report of a reconstruction of the laryngeal mucosa in a three-dimensional collagen gel matrix culture. Fibroblasts and air-liquid interface treatment exert a great influence on the proliferation and differentiation of the cultured epithelial cells. This culture system will help to provide an appropriate physiologic environment to study the differentiation and disease of the larynx.


Environmental and genetic components of stomatal behavior in two genotypes of upland cotton.
Two parental lines of Upland cotton (Gossypium hirsutum L.) plus their reciprocal F(1), F(2), and backcross populations were field-tested for environmental and genetic components of leaf diffusive resistance. Leaf resistance was measured with a diffusion porometer three times each day during 6 days in August. A large, consistent environmental component was present during the morning, afternoon, and evening, but the genetic component appeared mainly during the afternoon. Leaf water potential indicated that afternoon was the period of highest water stress. Genetic analyses revealed that leaf resistance was associated with both additive and dominance genetic variances, with an estimated narrow sense heritability of 25%. High leaf resistance was completely dominant to low resistance.


Compression of freestanding gold nanostructures: from stochastic yield to predictable flow.
Characterizing the mechanical response of isolated nanostructures is vitally important to fields such as microelectromechanical systems (MEMS) where the behaviour of nanoscale contacts can in large part determine system reliability and lifetime. To address this challenge directly, single crystal gold nanodots are compressed inside a high resolution scanning electron microscope (SEM) using a nanoindenter equipped with a flat punch tip. These structures load elastically, and then yield in a stochastic manner, at loads ranging from 16 to 110 microN, which is up to five times higher than the load necessary for flow after yield. Yielding is immediately followed by displacement bursts equivalent to 1-50% of the initial height, depending on the yield point. During the largest displacement bursts, strain energy within the structure is released while new surface area is created in the form of localized slip bands, which are evident in both the SEM movies and still-images. A first order estimate of the apparent energy release rate, in terms of fracture mechanics concepts, for bursts representing 5-50% of the structure's initial height is on the order of 10-100 J m(-2), which is approximately two orders of magnitude lower than bulk values. Once this initial strain burst during yielding has occurred, the structures flow in a ductile way. The implications of this behaviour, which is analogous to a brittle to ductile transition, are discussed with respect to mechanical reliability at the micro- and nanoscales.


Effect of Aerobic Exercise on Serum Concentration of Apelin, TNFα and Insulin in Obese Women.
Apelin is novel adipokine acting on APJ receptor, regulated by insulin and tumor necrosis factor-alpha (TNF-alpha). Plasma apelin levels are increased in obese subjects. The aim of this study was to investigate whether or not the aerobic exercise modifies the elevated plasma apelin levels in obese women. Twenty obese women (BMI 32.2 ± 6.4 kg/m(2)) were selected by random sampling method among obese women. Twelve healthy women with a BMI of 31.7 ± 0.6 kg/m(2) served as control group. The aerobic exercise was performed during 8 weeks, 3 sessions per week. The intensity of the training program proceeded form 50% to 70% in 8 weeks. Results showed that plasma levels of apelin and TNFα were higher in obese individuals compared with the control group. The exercise resulted in significant decrease (P<0.05) of BMI to 29.8± 6.3 kg/m(2) , plasma insulin (8.16 ± 0.73 to 6.58 ± 0.66 µmol/l), apelin (369 ± 25 pg/ml vs 257 ± 12 pg/ml) and TNFα levels (0.66 ± 0.04 pg/ml vs 0.56 ± 0.04 pg/ml). P< 0.05 was considered statistically significant. Exercise can decrease plasma apelin, insulin and TNFα levels in obese women. Regular physical activity causes a decrease in plasma levels of apelin if body mass index and body fat mass simultaneously decreased.


Effect of malotilate on ethanol-induced gastric mucosal damage in capsaicin-pretreated rats.
We studied the role of afferent sensory neurons in malotilate-mediated gastric mucosal protection. Intact and capsaicin sensory-denervated rats were used in the experiments. Gross gastric mucosal injury was assessed and evaluated as a main criterion of the gastroprotective effect of the tested substances. Besides malotilate, methyl-prostaglandin E2 was applied alone or in combination with malotilate to compare the effects and the mechanism of action of both substances. The results revealed that both malotilate as well as methyl-prostaglandin E2 exerted a significant protective action on 96% ethanol-induced gastric mucosal damage. However, there were no significant differences between intact and capsaicin-denervated rats. Only the use of 50% ethanol as a milder mucosal irritating agent resulted in significant differences in both groups of animals. We propose that malotilate (like methyl-prostaglandin E2) has a gastroprotective effect on ethanol-induced gastric mucosal injury. This effect is partly dependent on the sensory nervous system and the combination of both above substances has an additive effect.


The impact of type II diabetes mellitus in patients with autosomal dominant polycystic kidney disease.
The epidemic of obesity and diabetes is increasing within the USA and worldwide. We have previously shown that body mass index has increased significantly in autosomal dominant polycystic kidney disease (ADPKD) subjects seen at our center in more recent years. However, the impact of Type II diabetes in ADPKD patients has not been well studied. This retrospective cohort study compared clinical characteristics in 44 pre-renal transplant patients with ADPKD and diabetes and 88 age- and sex-matched non-diabetic patients with ADPKD who were seen at the University of Colorado between 1977 and 2008. The primary outcomes in this study were renal volume determined by renal ultrasonography, renal function assessed by estimated glomerular filtration rate and time to onset of end-stage renal disease or death by Kaplan-Meier analyses. Diabetic patients had significantly larger kidney volumes than those with ADPKD alone [geometric mean (95% confidence interval (CI)]: 2456 (1510-3992) versus 1358 (1186-1556) cm3, P=0.02. Among those whose age at hypertension diagnosis was known, the diabetic ADPKD patients had earlier median (95% CI) age at onset of hypertension compared to those with ADPKD alone: 32.5 (28-40) versus 38 (35-42) years, P=0.04. Diabetic ADPKD patients tended to have an earlier median age of death than those with ADPKD alone. Patients with ADPKD and type II diabetes have larger renal volumes, earlier age at diagnosis of hypertension and may die at a younger age compared to those patients with ADPKD alone. This study emphasizes the importance of diabetes risk management in ADPKD.


Lifetime Prevalence and Correlates of Patient-Perceived Medical Errors Experienced in the U.S. Ambulatory Setting: A Population-Based Study.
Background: The rate of safety harm self-perceived medical errors and harms reported in the U.S. ambulatory system is not well characterized. Objectives: To determine the prevalence of U.S. adult ambulatory care patient self-perceived safety harms and to gauge the degree of association between harms with various patient characteristics and outcomes. Methods: A large U.S. cross-sectional online survey of 9206 ambulatory care adults was assessed for their perception of medical errors and harms during care (misdiagnosis, mistakes in care, and wrong or delayed treatment) and also included patient demographics, health status, comorbidities, insurance status, income, barriers to care (affordability, transportation, and family and social support), number of visits to primary health care services in the past 12 months, and use of urgent or emergency care in the last 12 months. Results: The overall rate of self-perceived medical errors and harms among adult patients in the ambulatory care setting was 36%. Female patients, independent of age, and those with multiple comorbidities or barriers to care, reported the highest number of medical errors. Utilization of multiple providers was associated with a greater number of reported medical errors, often resulting in changing health care providers. Patients who reported having trouble affording health care or navigating the system to receive care also reported higher levels of harm. They were cared for by multiple providers, often switch providers, and their care is associated with greater utilization of health care resources. Patients reporting the highest rates of harm had greater use of hospital and emergency room care. Conclusions: This large U.S. adult ambulatory care study provides evidence that patient self-perceived medical errors and harms reported by patients are common. Patient self-perceived medical errors and harms occur most commonly in women, with poor health, limitation of activities, and who have three or more comorbidities.


Epidemiological Study of Pesticide Poisoning in Domestic Animals and Wildlife in Portugal: 2014-2020.
Nowadays the intentional poisoning of domestic and wild animals is a crime in the European Union (EU), but as in the past the poison is still used in rural areas of a number of European countries to kill animals that were considered harmful for human activities. From January 2014 up until October 2020, the Laboratory of Pharmacology and Toxicology of the Faculty of Veterinary Medicine (LFT-FMV) has done the analytical detection of poisoning substances in 503 samples of wildlife and domestic animals and pesticides residues were found in 239 of the samples analyzed. In this retrospective study, toxicology results from domestic species (dog, cat, sheep, cows, and horses), wildlife species (red foxes, birds of prey, lynx, and wild boar), and food baits, are presented. During this period the samples analyzed at the LFT-FMV, were received from all over the country. Analytical detections were performed via solvent extraction followed by thin layer chromatography. Molluscicides (47%, n = 109) and Carbamates (24%, n = 57) were found to be the first category of pesticides involved in intoxications, in both domestic and wild animals, followed by rodenticides (13%, n = 30)-in this group second and third generation, were the most represented; Strychnine is the third (11%, n = 26) even though this pesticide has been banned in Portugal since 1988 and in the European Union since 2006 and finally Organophosphates (5%, n = 11) in the small number. This study allowed to realize that a great number of positive samples involved banned pesticides (i.e., Aldicarb and Strychnine) but, at the same time, many positives cases were due to the exposure to commercially available products (i.e., Methiocarb and Anticoagulant rodenticides). Also, it's possible to identify the areas where domestic species are the most affected (i.e., Setubal and Lisboa) and the areas where the wild animals are the mainly affected species (i.e., Faro, Castelo Branco, and Bragança).


Myrcene as a natural base chemical in sustainable chemistry: a critical review.
Currently, a shift towards chemical products derived from renewable, biological feedstocks is observed more and more. However, substantial differences with traditional feedstocks, such as their "hyperfunctionalization," ethical problems caused by competition with foods, and problems with a constant qualitative/quantitative availability of the natural products, occasionally complicate the large-scale market entry of renewable resources. In this context the vast family of terpenes is often not taken into consideration, although the terpenes have been known for hundreds of years as components of essential oils obtained from leaves, flowers, and fruits of many plants. The simple acyclic monoterpenes, particularly the industrially available myrcene, provide a classical chemistry similar to unsaturated hydrocarbons already known from oil and gas. Hence, this Review is aimed at reviving myrcene as a renewable compound suitable for sustainable chemistry in the area of fine chemicals. The versatility of the unsaturated C(10)-hydrocarbon myrcene, leading to products with several different areas of application, is pointed out.


[Myofibrosis in childhood. Differential diagnosis in chest pain].
It is emphasised in connection with the differential diagnosis of chest complaints that after excluded the serious and urgent conditions, a searching for painful muscle bundles and trigger points at the characteristic locations in the muscles can explain the origin of the complaints. By finding of myofibrosis, other expensive or invasive diagnostic tests can be omitted and the patient gets rid off his or her claims.


[Prevalence of emphysematous changes as shown by low-dose spiral CT screening images in 6144 healthy subjects].
We assessed the prevalence of emphysematous changes among healthy workers and retired persons, using subjective evaluations of low-dose spiral CT images obtained during thoracic CT screenings for lung cancer. Among 6144 male participants (50-69 years old; mean age, 57), we detected 686 cases (11.2%) with emphysematous changes. The majority (95.3%) of CT-detected emphysema cases were in current or former smokers, and 169 cases (24.6%) showed significant obstructive impairment. Of 236 cases with emphysematous changes in the internal region (more than 20 mm from the costal margin), 98(41.5%) had significant obstructive impairment. Smoking was found to be the major risk factor for CT-detected emphysema. Longitudinal observation of the emphysema cases, as well as health care support for cessation of smoking, is very important.


Acute renal failure in the PACU.
Acute renal failure (ARF) in the PACU can lead to serious morbidity or even death. The incidence of acute renal failure appears to be increasing. This review article is intended to provide the staff in the PACU with relatively easy means to recognize the development of ARF, and provide recommendations for prompt and intensive management. Existence of renal dysfunction, complex surgical procedures that require cardiopulmonary bypass, and vascular surgery involving the aorta are associated with a high incidence of ARF. In spite of the improved overall care of the patient in the PACU, the occurrence of ARF is associated with a very high likelihood of morbidity and mortality. Prompt recognition of the ARF and aggressive management in the PACU may improve the patient's chances of survival. Large-scale, prospective, randomized clinical trials in the PACU setting are needed to determine the most effective management plan. This is a U.S. government work. There are no restrictions on its use.


In vitro attenuation of Cryptobia salmositica and its use as a live vaccine against cryptobiosis in Oncorhynchus mykiss.
The present communication reports on the attenuation of a pathogenic hemoflagellate, Cryptobia salmositica Katz (Sarcomastigophora: Kinetoplastida) and its use as a live vaccine against cryptobiosis. The parasite was attenuated by continuous in vitro culture (at 10 C for 55 wk) in minimum essential medium. Attenuated (culture) forms are morphologically similar to virulent (blood) forms. They are however more slender and have a shorter anterior flagellum and a smaller nucleus and kinetoplast. The attenuated form returned to its normal size and multiplied when inoculated into naive Oncorhynchus mykiss. It produced a low parasitemia but did not cause disease (e.g., no exophthalmia or anemia) in fish. At four wk after infection, the vaccinated fish were challenged with the virulent parasite. They were protected from the disease, whereas the control (naive) fish, infected with only the virulent parasite, had the usual clinical signs (e.g., anemia, exophthalmia). No parasite was detected in any of 10 vaccinated fish at 22 wk after challenge with the virulent parasite. However, 5 of 9 fish infected with culture forms and 6 of 9 fish infected with blood forms still had detectable parasites at 26 and 22 wk after infection, respectively.


Adolescent initiation into drug-taking behavior: comparisons over a 5-year interval.
Acquisition curves for six substances were compared for adolescents in two samples separated by a 5-year interval. Individual variations in initiation ages were found for different substances, but the general pattern of exposures to drugs was essentially stable over the time interval. The findings suggest that there appears to be a range of first experience with drugs that extends from 13 to 16 years. Special emphasis was given to the implications which the findings have for education and intervention programs, and for further research.


[Carcinoid of Meckel's diverticulum].
The carcinoid of Meckel's diverticulum is a very rare lesion, and about 100 cases in the literature have been described. Most of these tumors are casually find out at autopsy or laparoscopy for other pathology. Seldom was described a sintomatology correlated to carcinoid of Meckel's diverticulum presence, except the rare case where was formed a carcinoid syndrome. Authors present a clinical case where was casually found by a carcinoid of Meckel's diverticulum during an appendicectomy. The intention is to underline the importance of research the Meckel's diverticulum every time, and in particular in case of young subjects, remove it and perform an histological valuation, to exclude the presence of a carcinoid that could give metastases to local lymph-nodes or liver.


Morphological changes in the lingual papillae and their connective tissue cores on the 7,12-dimethylbenz[alpha]anthracene (DMBA) stimulated rat experimental model.
The aim of the study was to analyze morphological changes of the epithelial surface and underlying connective tissue cores (CTCs) of the lingual mucosa in the rat using a DMBA induced pre-cancerous experimental model. Lightmicroscopically, initially DMBA treated sections exhibited infiltration of chronic inflammatory cells. At 16 weeks, aldehyde-fuchsin (AF) positive elastic fibers decreased and were scanty in the juxtaepithelium. On the other hand, rather densely packed thick bundles of AF positive fibers were observable in the deep layers of lamina propria. Carcinomas were not found at any stage, however, epithelial dysplasia was observed at 24 weeks post-treatment with DMBA. Scanning electron microscopy revealed an irregular arrangement of filiform papillae 4-12 weeks following DMBA stimulation. Patchy degenerated areas were observed especially at 16-24 weeks post-treatment and filiform papillae were totally attenuated on the central part of the degenerated areas. After removal of the epithelium, attenuated CTCs were observed from 4-8 weeks. Morphology of CTCs seemed to be gradually remodeled and severely altered in the later stage. The CTCs were however attenuated and exhibited a patchy distribution. The animal experimental model in this study revealed degenerative morphological changes of CTCs of the lingual papillae in the precancerous stage induced by DMBA.


Polyphenol-Rich Blackcurrant Juice Prevents Endothelial Dysfunction in the Mesenteric Artery of Cirrhotic Rats with Portal Hypertension: Role of Oxidative Stress and the Angiotensin System.
Chronic liver diseases with portal hypertension are characterized by a progressive vasodilatation, endothelial dysfunction, and NADPH oxidase-derived vascular oxidative stress, which have been suggested to involve the angiotensin system. This study evaluated the possibility that oral intake of polyphenol-rich blackcurrant juice (PRBJ), a rich natural source of antioxidants, prevents endothelial dysfunction in a rat model of cirrhosis induced by chronic bile duct ligation (CBDL), and, if so, determined the underlying mechanism. Male Wistar rats received either control drinking water or water containing 60 mg/kg gallic acid equivalents of PRBJ for 3 weeks before undergoing surgery with CBDL or sham surgery. After 4 weeks, vascular reactivity was assessed in mesenteric artery rings using organ chambers. Both the acetylcholine-induced nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric artery rings were significantly reduced in CBDL rats compared to sham rats. An increased level of oxidative stress and expression of NADPH oxidase subunits, COX-2, NOS, and of the vascular angiotensin system are observed in arterial sections in the CBDL group. Chronic intake of PRBJ prevented the CBDL-induced impaired EDH-mediated relaxation, oxidative stress, and expression of the different target proteins in the arterial wall. In addition, PRBJ prevented the CBDL-induced increase in the plasma level of proinflammatory cytokines (interleukin [IL]-1α, monocyte chemotactic protein 1, and tumor necrosis factor α) and the decrease of the anti-inflammatory cytokine, IL-4. Altogether, these observations indicate that regular ingestion of PRBJ prevents the CBDL-induced endothelial dysfunction in the mesenteric artery most likely by normalizing the level of vascular oxidative stress and the angiotensin system.


Polarization of cytokine profile from Th1 into Th2 along colorectal adenoma-carcinoma sequence: implications for the biotherapeutic target?
The development of colorectal carcinoma (CRC) has been hypothesized to be raised mostly from the precancerous lesion of colorectal adenoma (CRA) through a multistep process and defined as the adenoma-carcinoma sequence. In response to the tumorigenesis, host cellular immunity acts as the most important defense factor with cytokines as the main regulator molecules. Therefore, changes of cytokines of the T helper 1 (Th1)/T helper 2 (Th2) type immune responses along this sequence may therefore reflect a functional switch of host anti-tumor immunity. This minireview focused on the recent knowledge of the Th1/Th2 balance in the adenoma-carcinoma sequence and its potential clinical and therapeutical significance.


Oral mesalamine (Pentasa) as maintenance treatment in Crohn's disease: a multicenter placebo-controlled study. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID)
Mesalamine provides a new therapeutic approach in treating Crohn's disease. To assess the efficacy and safety of slow-release mesalamine (Pentasa; Ferring AS, Vanløse, Denmark) in maintaining remission in Crohn's disease, 161 patients with inactive disease were randomized to receive either Pentasa (2 g/day) or placebo in a 2-year double-blind, multicenter trial. Two strata were defined according to the duration of their remission: < 3 months (n = 64) or 3-24 months (n = 97), presumed to be high and a low relapse risk strata, respectively. The probability of relapse was higher in the short-remission placebo group than in the three other groups (P < 0.003), showing there was a significant benefit from Pentasa in the high relapse risk stratum. In this stratum, the 2-year ongoing remission rate was of 29% +/- 9% and 45% +/- 11% (mean +/- SD) in the placebo and Pentasa groups, respectively. The incidences of side effects were similar in both groups. Pentasa (2 g/day for 2 years) is a safe and effective maintenance treatment for Crohn's disease when given within 3 months of achieving remission.


Synchronization of the neurons coupled with sequential developing electrical and chemical synapses.
There is some evidence representing the sequential formation and elimination of electrical and chemical synapses in particular brain regions. Relying on this feature, this paper presents a purely mathematical modeling study on the synchronization among neurons connected by transient electrical synapses transformed to chemical synapses over time. This deletion and development of synapses are considered consecutive. The results represent that the transient synapses lead to burst synchronization of the neurons while the neurons are resting when both synapses exist constantly. The period of the transitions and also the time of presence of electrical synapses to chemical ones are effective on the synchronization. The larger synchronization error is obtained by increasing the transition period and the time of chemical synapses' existence.


[Reconstruction of facial defects with the forehead flap: five case reports].
The authors present several cases of facial defects reconstruction with the forehead flap. They consist of three cases of nasal reconstruction after trauma, one cases of rhinectomy and orbital exenteration for spinocellular cancer of the nasolabial fold, and a case of orbital reconstruction after exenteration for malignant melanoma of the lower eyelid with an island flap. In one of the cases we used a preexpanded forehead flap and in one other a prefabricated flap with a split-thickness skin graft. In four of the cases no complications were observed and the flaps healed uneventfully with with satisfactory results according to the patients. In the case with the island flap we observed a partial flap necrosis. The authors discuss the advantages, disadvantages and results obtained after the facial defect reconstruction with the forehead flap.


Artificially formed caries-like lesions around Class II glass ionomer restorations in primary molars.
The aim of this study was to investigate the microleakage around Class II glass ionomer restorations in primary molars. Two different glass ionomer cements and one amalgam control were assessed in vitro by acidified gel technique. Assessment of caries-like lesions was performed using polarized light microscopy. The traditional glass ionomer (Chemfil II) with dentin conditioner provided the highest protection against caries attack and the amalgam restorations provided the least.


Atypical herpetic endotheliitis.
Three patients ranging in age from 26 to 40 years presented with unilateral posterior stromal lesions with diffuse stromal edema. There was no history of prior surgery, trauma, infectious disease, dystrophy or exposure to noxious agents. Only one patient had signs of anterior chamber reaction and none of the patients showed any sign of epithelial involvement or of associated blood vessels or scarring. All three patients presented with features atypical of herpetic disease, such as lack of epithelial involvement and posterior stromal opacification. They also demonstrated many of the typical characteristics of herpetic disease, however, and thus were diagnosed as having herpetic endotheliitis. All three patients were treated with a regimen of antiviral agents and corticosteroids. Two patients improved, although the time frame differed in each. One patient subjectively improved, then worsened 1 month later after discontinuing treatment on her own. She was lost to subsequent follow-up. Young patients presenting with unilateral posterior stromal opacification and stromal edema in the absence of epithelial involvement are likely to have endotheliitis of herpetic origin.


Erythrocyte-heme proteins and STEMI: implications in prognosis.
The role of erythrocytes in thrombus formation has been often neglected, but some studies have highlighted their active role in thrombotic events. Free-haemoglobin (Hb) has shown to induce oxidative-stress damage. Herein we have investigated the coordinated changes in heme-related proteins in patients with acute-coronary-syndromes (ACS), their association to ongoing thrombosis and their impact on patients' prognosis. The serum proteome of STEMI-patients (N=27) within the first 6h after event-onset and 3d after were compared to controls (N=60). Changes in heme-metabolism were characterized in a second STEMI-group by a dual proteomic approach analyzing in-vivo aspirated coronary thrombi at PCI (N=24) and the associated peripheral-blood changes (N=10). A third STEMI-group (N=132) was studied to analyze the impact of the observed changes in prognosis at 6-months-follow-up. The haptoglobin/hemopexin(Hpg/Hpx)-scavenging-system revealed a time-dependent response after STEMI with an early increase in Hpg circulating levels in the acute phase (P=0.01) and a late increase in Hpx levels 3d after (P=0.045). Beta-Hb content in coronary thrombi was directly correlated with systemic beta-Hb and Hpg (R=0.804,P=0.0029; R=0.859,P=0.0007) levels. The presence of a fully-occlusive thrombus was associated to higher circulating levels of beta-Hb (P=0.03) and unbound-Hpg (P=0.03). ELISA validation demonstrated a decreased survival rate at 6-months follow-up in STEMI-patients with lower Hpg plasma levels at admission (P=0.027). Our results show active Hb-release form erythrocytes in ACS. This release is followed by a systemic early increase in Hpg levels and a late increase in Hpx levels that can co-ordinately help to prevent systemic pro-oxidative effects. The Hb-scavenging ability of haptoglobin is related to patients' prognosis.


A polymorphic multigene family encoding an immunodominant protein from Babesia microti.
Human babesiosis in the United States is caused predominantly by Babesia microti, a tick-transmitted blood parasite. Improved testing methods for the detection of infection with this parasite are needed, since asymptomatic B. microti infection represents a potential threat to the blood supply in areas where B. microti is endemic. We performed immunoscreening of an expression library of genomic DNA from a human isolate of B. microti (strain MN1). Among 17 unique immunoreactive clones, we identified 9 which represent a related family of genes with little sequence homology to other known sequences but with an architecture resembling that of several surface proteins of Plasmodium. Within this family, a tandem array of a degenerate six-amino-acid repeat (SEAGGP, SEAGWP, SGTGWP, SGTVGP) was found in various lengths between relatively well conserved segments at the N and C termini. In order to examine within-clone variation, we developed a PCR protocol for direct recovery of a specific bmn1-6 homologue directly from 30 human blood isolates, 4 corresponding hamster isolates, and 5 geographically corresponding Peromyscus leucopus (white-footed mouse) isolates. Isolates from the hamsters had the same sequences as those found in the corresponding human blood, suggesting that genetic variation of bmn1-6 does not occur during passage. However, clones from different patients were often substantially different from each other with regard to the number and location of the degenerate repeats within the bmn1-6 homologue. Moreover, we found that strains that were closely related geographically were also closely related at the sequence level; nine patients, all from Nantucket Island, Mass., harbored clones that were indistinguishable from each other but that were distinct from those found in other northeastern or upper midwestern strains. We conclude that considerable genetic and antigenic diversity exists among isolates of B. microti from the United States and that geographic clustering of subtypes may exist. The nature of the bmn1-6 gene family suggests a mechanism of antigenic variation in B. microti that may occur by recombination, differential expression, or a combination of both mechanisms.


Detection of a stable free radical in the B2 subunit of the manganese ribonucleotide reductase (Mn-RRase) of Corynebacterium ammoniagenes.
Ribonucleotide reductases catalyze the irreversible reductive formation of 2'-deoxyribonucleotides required for DNA replication and cell proliferation, and a radical mechanism was assumed to be involved in this reaction. In order to search for a radical in the aerobic manganese ribonucleotide reductase (Mn-RRase) by electron paramagnetic resonance (EPR) the native metal-containing 100 kDa B2 subunit was deliberately prepared from the wild type strain Corynebacterium ammoniagenes ATCC 6872. Enrichment by 2'5'-ADP Sepharose 4B affinity chromatography, fast protein liquid chromatography (FPLC) with SuperoseTM12 and concentration by vacuum evaporation allowed for the first time the detection of a stable free radical by EPR spectroscopy at 77 K. The EPR spectrum exhibits an easily saturable doublet of 1.8 mT splitting and a line width of 1.3 mT at g = 2.0040. The EPR signal intensity showed a clear correlation with the enzymatic activity upon long-time storage at ambient temperature (294 K) and inactivation by the specific RRase inhibitor hydroxyurea (HU). This leads to the assumption of a protein-linked radical, with functional significance, in the metal-containing 100 kDa B2 subunit of the MnRRase of Corynebacterium ammoniagenes.


Semi-automated query construction for content-based endomicroscopy video retrieval.
Content-based video retrieval has shown promising results to help physicians in their interpretation of medical videos in general and endomicroscopic ones in particular. Defining a relevant query for CBVR can however be a complex and time-consuming task for non-expert and even expert users. Indeed, uncut endomicroscopy videos may very well contain images corresponding to a variety of different tissue types. Using such uncut videos as queries may lead to drastic performance degradations for the system. In this study, we propose a semi-automated methodology that allows the physician to create meaningful and relevant queries in a simple and efficient manner. We believe that this will lead to more reproducible and more consistent results. The validation of our method is divided into two approaches. The first one is an indirect validation based on per video classification results with histopathological ground-truth. The second one is more direct and relies on perceived inter-video visual similarity ground-truth. We demonstrate that our proposed method significantly outperforms the approach with uncut videos and approaches the performance of a tedious manual query construction by an expert. Finally, we show that the similarity perceived between videos by experts is significantly correlated with the inter-video similarity distance computed by our retrieval system.


Genotype-Independent Transformation and Genome Editing of Brassica napus Using a Novel Explant Material.
Agrobacterium-mediated transformation of canola (Brassica napus) via hypocotyl segments has been a commonly used method for the past 30 years. While the hypocotyl-based method is well-established, it is not readily adapted to elite germplasm and the prolonged process is not ideal for a production transformation setting. We developed an Agrobacterium-mediated transformation method based on epicotyl and higher stem (internodal) segments that is efficient, rapid and amenable for high-throughput transformation and genome editing. The method has been successfully implemented in multiple canola genotypes. The method appears to be genotype-independent, with varying transformation efficiencies. Internodal segment transformation was used to generate transgenic events as well as CRISPR-Cas9-mediated frameshift gene knockouts.


Reasons why patients reject digital rectal examination when screening for prostate cancer.
To evaluate the reasons why patients reject digital rectal examination (DRE) when screening for prostate cancer. Four hundred and fifty men were prospectively evaluated in a prostate cancer educational program consisting of lectures, PSA testing, and DRE. Patients rejecting DRE were compared with those accepting DRE in regard to epidemic, social and cultural variables. DRE was rejected by 8.2% of patients. Refusal rate was not different when patients were stratified by age, prostate cancer family history, school level, family income, and PSA level. Patients with a prior history of DRE had a lower rejection rate than those undergoing DRE for the first time (4.4% vs. 10.4%, p = 0.038). Patients with mild or no lower urinary tract symptoms rejected DRE more frequently than those with moderate or severe symptoms (9.6% vs. 1.4%, p = 0.018). Misconceptions about prostate cancer screening were present in 84.4% of those rejecting DRE vs. 46.9% of controls (p = 0.002); 43.7% expected severe discomfort in the group that rejected DRE vs. 28. 1% in the control group (p = 0.090); fear of finding a cancer during DRE was present in 34.4% of patients that refused DRE vs. 46.9% of controls (p = 0. 121); and 53.1% of patients rejecting DRE responded it was a source of shame vs. 15.6% of patients in the control group (p = 0.019). The main reasons patients reject DRE when attending prostate cancer screening are the lack of lower urinary tract symptoms, misconceptions about prostate cancer screening and shame, especially when undergoing screening for the first time.


Relative tissue expression of homologous torsinB correlates with the neuronal specific importance of DYT1 dystonia-associated torsinA.
A three base-pair deletion in the widely expressed TOR1A gene causes the childhood onset, neurological disease of DYT1 dystonia. Mouse Tor1a gene knockout also specifically affects the developing nervous system. However, in both cases, the basis of neuronal tissue specificity is unknown. TorsinA is one of four predicted mammalian torsin ATPases associated with assorted cellular activities (AAA+) proteins, raising the possibility that expression of a functionally homologous torsin compensates for torsinA loss in non-neuronal tissues. We find that all four mammalian torsins are endoplasmic reticulum resident glycoproteins. TorsinA, torsinB and torsin2 are all present in large M(r) complexes, which suggests that each assembles into an oligomeric AAA+ enzyme. Introducing a mutation (WB(EQ)) that typically stabilizes AAA+ proteins in a substrate-bound state causes torsinA and torsinB to associate with a shared nuclear envelope (NE) binding partner and this NE localization requires the torsinA interacting protein, lamina associated polypeptide 1. Although torsin proteins are widely expressed in the adult mouse, we identified that embryonic neuronal tissues contain relatively low torsinB levels. Therefore, our results reveal that torsinB expression inversely correlates with the cell and developmental requirement for torsinA. In conclusion, multiple cell types appear to utilize torsin AAA+ proteins and differential expression of torsinB may contribute to both the neuronal specific importance of torsinA and the symptom specificity of DYT1 dystonia.


[Two-stage treatment of Barrett's esophagus].
To evaluate the results of treatment of Barrett's esophagus using laparoscopic 270° Toupet fundoplication or radiofrequency ablation (RFA) and their combination. We have analyzed data for the period 2011-2018. Antireflux surgery was performed in the first group, RFA - in the second group, both procedures were done in the third group. The majority of patients with hiatal hernia underwent cruroraphy, laparoscopic 270° Toupet fundoplication, endoscopic treatment as the second stage was performed in some of them. Patients without hiatal hernia and no signs of reflux underwent RFA without antireflux surgery. Control endoscopic examination was carried out after 3, 6 and 12 months and then annually. There were 84 patients with Barrett's esophagus. We performed 51 RFA procedures in 47 patients and fundoplication in 71 patients. Antireflux surgery as the first stage was preferred in patients with hiatal hernia (n=60), subsequent radiofrequency ablation (RFA) was performed in 28 of them. Seven patients without hiatal hernia, but with significant gastroesophageal reflux underwent antireflux surgery too. Other 12 patients without hiatal hernia underwent RFA alone. Need for delayed antireflux surgery after endoscopic treatment occurred in 23.5% of patients. Complete regression of metaplasia was noted in 95.2% after 1 procedure and in 100% after 2 procedures. Recurrent metaplasia was registered in 4.3% of patients. Progression to dysplasia was not detected. Two-stage surgical approach including antireflux surgery and radiofrequency ablation in combination with drug therapy is optimal. Endoscopic therapy is recommended for all types and length of metaplasia.