Residual strain in the ventricle of the stage 16-24 chick embryo.
Residual stress and strain, i.e., the stress and strain remaining in a solid when all external loads are removed, may be produced in biological tissues by differential growth. During cardiac development, residual stress and strain may play a role in cardiac morphogenesis by affecting ventricular wall stress. After a transmural radial cut, a passive ventricular cross section opens into a sector, and the size of the opening angle provides a measure of the circumferential residual strain. Residual strains were characterized in this manner for the apical region of the diastolic embryonic chick heart for Hamburger-Hamilton stages 16, 18, 21, and 24 (approximately 2.5, 3.5, 4.0, and 4.5 days, respectively, of a 21-day incubation period). The average opening angle at these stages was 107 +/- 10 degrees, 79 +/- 10 degrees, 73 +/- 11 degrees, and 74 +/- 7 degrees, respectively (n > or = 5 for each stage). These measured angles were correlated with changes in ventricular morphology. Scanning electron micrographs of the apex revealed that the wall of the ventricle is smooth at stage 16. Then at stage 18, myocardial trabeculae develop, forming ridges with primarily a circumferential orientation. By stage 21, the trabeculae develop into a mesh, giving the ventricular wall a spongelike appearance, and the preferred orientation is lost by stage 24. The large decrease in opening angle between stages 16 and 18 corresponded to the onset of trabeculation, which is the greatest change in form during the studied stages. We speculate that residual strain is an important biomechanical factor during cardiac morphogenesis.


Treatment with inhaled corticosteroids improves pulmonary function in children under 2 years old with risk factors for asthma.
To report on recent studies on the effect of inhaled corticosteroids on pulmonary function in young children with asthma. Inhaled corticosteroids are considered the most effective treatment for persistent asthma in children. Appropriate control of childhood asthma may prevent more serious disease or irreversible obstruction in later years. While some authors have described an improvement with the use of inhaled corticosteroids in young children, others found no clinical or functional benefit. Various studies have shown that inhaled corticosteroids ameliorate clinical outcomes, and recently a study demonstrated improvement in pulmonary function in young children with asthma. The use of different study designs may explain the lack of consistent results and disagreement regarding the efficacy of inhaled corticosteroids in these patients. Based on the preponderance of evidence, treatment with inhaled corticosteroids in infants and young children with recurrent wheeze and risk factors of developing asthma appears to allow better control of the illness and improve the pulmonary function.


Comparative assessment of the Willems dental age estimation methods: a Chinese population-based radiographic study.
The comparison of the two Willems dental age estimation methods (gender-specific (Willems I) and non-gender-specific (Willems II)) has not been fully investigated. Here we aimed to explore the applicability of the Willems dental age estimation in an Eastern Chinese population, which may cast light on the field of dental age estimation. A total of 1211 oral panoramic radiographs (582 boys and 629 girls) of the Chinese Han population aged 11-16 years old were collected. Dental ages (DAs) were calculated using the Willems method. Statistical significance was set at a p-value < 0.05. Age differences between chronological age (CA) and dental age were analyzed by paired t-tests and mean absolute error (MAE). The differences between CA and DA determined by the Willems I method were + 0.44 and + 0.09 years for boys and girls, respectively. When using the Willems II method, these differences were + 0.57 and - 0.09. The MAEs of the Willems I method between DA and CA were 0.95 and 1.00 years in boys and girls, respectively. For Willems II, MAEs were 1.02 and 1.00 years in boys and girls. This study showed that the Willems I method was more accurate than the Willems II method in the boys' group for predicting age from a whole scale. In comparison, Willems II is more competitive in the girls' group. Neither method may be satisfactory for 11-to-16-year-old teenagers in Eastern China.


Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review.
Clofarabine, a synthesised adenosine nucleoside, has recently demonstrated single-agent activity in the acute leukaemias. Originally developed to capture the best qualities of cladribine and fludarabine, clofarabine contains halogenated carbons, rendering it resistant to inactivating enzymes and maintaining its stability in acidic environments. Like other adenosine nucleosides, clofarabine acts by inhibiting ribonucleotide reductase and DNA polymerase, thereby depleting the amount of intracellular deoxynucleoside triphosphates available for DNA replication and also resulting in premature DNA chain termination. Clofarabine has also been shown to induce apoptosis in transformed cell lines, indicating that clofarabine results in cell death in both cycling and non-cycling cells. Interest in the development of clofarabine was initially hampered by the availability of other active nucleoside analogues for the treatment of haematological malignancies. However, the results of several early-phase trials evaluating the use of clofarabine in acute leukaemias in adults and children have rekindled enthusiasm for further investigation into its use. This article describes the development, pharmacology, toxicity and clinical activity of clofarabine, as well as discuss its potential role in the treatment of acute leukaemia.


Intraoperative Magnetic Resonance Imaging Assisted Endoscopic Endonasal Resection of Clival Chordomas.
Cranial base chordomas are typically indolent and usually appear as encapsulated tumors. They slowly grow by infiltrating the bone, along with the lines of least resistance. Due to its relationship with important neurovascular structures, skull base chordoma surgery is challenging. The usefulness of intraoperative magnetic resonance imaging (IO-MRI) in achieving the goal of surgery, is evaluated in this study. Between March 2018 and March 2020, 42 patients were operated on for resection of skull base chordomas in our institution. All of them were operated on under IO-MRI. Patients were analyzed retrospectively for identifying common residue locations, complications and early post-operative outcomes. In 22 patients (52,4%) gross total resection was achieved according to the final IO-MRI. In 20 patients (47,6%) complete tumor removal was not possible because of extension to the petrous bone (8 patients), pontocerebellar angle (6 patients), prepontine cistern (4 patients), temporobasal (1 patient), cervical axis (1 patient). In 13 patients, the surgery was continued after the first IO-MRI control was performed, which showed a resectable residual tumor. 7 of these patients achieved total resection according to the second IO-MRI, in the other 6 patients all efforts were made to ensure maximal resection of the tumor as much as possible without morbidity. Repeated IO-MRI helped achieve gross total resection in 7 patients (53.8%). Our study proves that the use of IO-MRI is a safe method that provides the opportunity to show the degree of resection in skull base chordomas and to evaluate the volume and location of the residual tumor intraoperatively. Hence IO-MRI can improve the life expectancy of patients because it provides an opportunity for both gross total resection and maximal safe resection in cases where total resection is not possible.


Inherited dyslipidaemic disorders contributing to coronary heart disease.
Lipoprotein (a) [Lp (a)] is an established independent risk factor for premature myocardial infarction (MI)/coronary artery disease (CAD). The study was conducted to determine the value of Lp (a) in prediction of CAD or MI in the offspring at risk. A total of 160 subjects were investigated. Serum Lp (a) was measured by ELISA, serum total cholesterol, triglycerides (TG) and HDL-Cholesterol by enzymatic colorimetric methods using standard kits. Differences in levels of total Lp (a) and cholesterol were observed between patients and controls. Both Lp (a) (16.23 +/-1.95 mg/dL) and cholesterol (175.00 +/- 7.60 mg/dL) of group A (patients) were higher than the corresponding controls. However an opposite trend in results was noted for serum HDL-Cholesterol in patients vs. controls. Persons found to have elevated levels of Lp (a) should focus on controlling the known modifiable risk factor for heart disease, especially smoking, hypercholesterolemia, obesity, hypertension and sedentary life style.


The physiological basis of pulmonary gas exchange: implications for clinical interpretation of arterial blood gases.
The field of pulmonary gas exchange is mature, with the basic principles developed more than 60 years ago. Arterial blood gas measurements (tensions and concentrations of O₂ and CO₂) constitute a mainstay of clinical care to assess the degree of pulmonary gas exchange abnormality. However, the factors that dictate arterial blood gas values are often multifactorial and complex, with six different causes of hypoxaemia (inspiratory hypoxia, hypoventilation, ventilation/perfusion inequality, diffusion limitation, shunting and reduced mixed venous oxygenation) contributing variably to the arterial O₂ and CO₂ tension in any given patient. Blood gas values are then usually further affected by the body's abilities to compensate for gas exchange disturbances by three tactics (greater O₂ extraction, increasing ventilation and increasing cardiac output). This article explains the basic principles of gas exchange in health, mechanisms of altered gas exchange in disease, how the body compensates for abnormal gas exchange, and based on these principles, the tools available to interpret blood gas data and, quantitatively, to best understand the physiological state of each patient. This understanding is important because therapeutic intervention to improve abnormal gas exchange in any given patient needs to be based on the particular physiological mechanisms affecting gas exchange in that patient.


Is disability any business of nurse education?
Perceptions of and assumptions about disability as diagnosis-based, individualistic, and necessarily tragic, still appear in the nursing literature as well as the general media. The rejection of a medical model of disability by writers who are themselves disabled, and the construction of an alternative social model, might appear to leave nurses--as professional interventionists--without any role in the care and support of physically disabled people. Such a view, as expressed by non-nurse writers, fails to acknowledge the fundamental changes that have occurred in both nursing and nurse education. This article criticizes the presently politically correct social model of disability, and describes an alternative 'interface model', which centres on the actual daily experience of disabled people. This model suggests that there is still a positive and welcome role, as informed partner, for the nurse and his or her disabled client.


Chorea and dystonia: a remote effect of carcinoma.
A 45-year-old woman with an acquired multifocal neurologic syndrome, including chorea, dystonia, cerebellar dysfunction, multiple cranial neuropathies, and pure sensory neuropathy, was found at autopsy to have oat cell carcinoma. Neuropathologic examination revealed several features typically associated with remote effects of malignancy on the nervous system. We believe that this is the first described case of chorea as a remote effect of malignancy.


Distrust of the health care system and self-reported health in the United States.
Despite theoretical concerns that health care related distrust may lead to poor health outcomes by interfering with effective health care, little is currently known about the prevalence or outcomes of distrust of the health care system in the United States. To investigate the association between distrust of the health care system and self-reported health status among the general population in the United States. Random-digit-dialing telephone survey. Nine hundred and sixty-one adult residents of the continental U.S. Distrust of the health care system and self-reported health status. Distrust of the health care system is relatively high in the United States, with between 20% and 80% of respondents reporting distrust for each item on the Health Care System Distrust scale and a median scale score of 31 (potential range from 10 to 50). Distrust of the health care system is strongly associated with self-reported fair/poor health (odds ratio [OR] 1.40%, 95% confidence interval [CI] 1.12 to 1.75 for each standard deviation increase in distrust), even after adjusting for sociodemographic characteristics, access to health care and trust in primary physicians. In contrast, low trust in one's primary physician is much lower (only 10% to 20% of respondents reported distrust for each item) and is not associated with health status. Distrust of the health care system is relatively high in the general population in the United States and is strongly associated with worse self-reported health. Further studies are needed to assess the direction of this association and the mechanisms involved.


Endoscopic approach to the pituitary lesions: contemporary method and review of the literature.
The present status of endoscopic transsphenoidal surgery is introduced and reviewed. The difference between endoscopic and microscopic transsphenoidal surgery is explained and also the characteristics of the transnostril approach is mentioned. The advantages of endoscopic surgery are (1) good anatomical orientation with wider view, (2) tumors at the dead angle can be removed under the direct visualization, and (3) the patients can drink, eat and even brush their teeth just after surgery. Short hospital stay and even day-surgery could be possible when a patient is carefully selected. The disadvantages and the limitation of endoscopic surgery have been solved and improved with several new instruments and ideas. Moreover, we have made use of the surgical simulation with the three-dimensional (3-D) CT virtual navigation endoscopic image and the navigation system with the ENT application and the SureTrak of the Stealth Station. There is no need for head fixation with a Mayfield clamp or a C-arm intraoperative fluoroscopic image. This image guidance enabled a correct and smooth approach even in those patients with complicated and abnormal anatomical structures by prior surgery such as for sinusitis. The sellar floor can be safely and correctly opened even in patients with conchal type sphenoid sinus using a navigation system that helps to understand the locations of the cavernous sinus and the internal carotid arteries. The overall result by endoscopic transsphenoidal surgery is as good as or better than that by the traditional microscopic transsphenoidal surgery.


Learning dynamical systems in noise using convolutional neural networks.
The problem of distinguishing deterministic chaos from non-chaotic dynamics has been an area of active research in time series analysis. Since noise contamination is unavoidable, it renders deterministic chaotic dynamics corrupted by noise to appear in close resemblance to stochastic dynamics. As a result, the problem of distinguishing noise-corrupted chaotic dynamics from randomness based on observations without access to the measurements of the state variables is difficult. We propose a new angle to tackle this problem by formulating it as a multi-class classification task. The task of classification involves allocating the observations/measurements to the unknown state variables in order to find the nature of these unobserved internal state variables. We employ signal and image processing based methods to characterize the different system dynamics. A deep learning technique using a state-of-the-art image classifier known as the Convolutional Neural Network (CNN) is designed to learn the dynamics. The time series are transformed into textured images of spectrogram and unthresholded recurrence plot (UTRP) for learning stochastic and deterministic chaotic dynamical systems in noise. We have designed a CNN that learns the dynamics of systems from the joint representation of the textured patterns from these images, thereby solving the problem as a pattern recognition task. The robustness and scalability of our approach is evaluated at different noise levels. Our approach demonstrates the advantage of applying the dynamical properties of chaotic systems in the form of joint representation of UTRP images along with spectrogram to improve learning dynamical systems in colored noise.


Neutral push-pull chromophores for nonlinear optical imaging of cell membranes.
A new class of push-pull molecules was recently identified, based on pyridine dicarboxamide as an electron acceptor group and bearing a fluorenethynyl pi-conjugated bridge. The molecules present good second and third order nonlinear properties, with a static quadratic hyperpolarisability mubeta (at 1.907 microm) of 320 x 10(-48) esu (mubeta(0) = 249 x 10(-48) esu) and a maximum two-photon absorption cross-section of 1146 GM. Starting from this generic structure, we designed a series of eight amphiphilic nonlinear probes, varying the length of the lipophilic tail and the nature of the polar head, and tested their cell membrane affinity by nonlinear optical imaging. A good membrane affinity was observed with probes bearing short alkyl chains and carbohydrate moieties as the polar head, emphasizing the importance of the lipophilic-hydrophilic balance, as well as the role of the polar head. This original approach based on carbohydrate head groups is an important advancement in the design of membrane probes, since these highly versatile functional groups confer adequate hydrophilicity and yet conserve overall molecular neutrality.


Cellulose crystallites.
This article discusses advances in understanding the structural and physicochemical characteristics of suspensions of cellulose crystallites prepared by acid hydrolysis of natural cellulose fibres. Consideration of recent developments in visualization of crystallite ultrastructure may provide clues to suspension behavior. In addition, novel applications in a diverse range of fields are presented, from iridescent pigments to biomolecular NMR studies.


miR-10a contributes to retinoid acid-induced smooth muscle cell differentiation.
MicroRNAs (miRs) have been reported to play a critical role in muscle differentiation and function. The purpose of this study is to determine the role of miRs during smooth muscle cell (SMC) differentiation from embryonic stem cells (ESCs). MicroRNA profiling showed that miR-10a expression is steadily increased during in vitro differentiation of mouse ESCs into SMCs. Loss-of-function approaches using miR-10a inhibitors uncovered that miR-10a is a critical mediator for SMC lineage determination in our retinoic acid-induced ESC/SMC differentiation system. In addition, we have documented for the first time that histone deacetylase 4 is a novel target of miR-10a and mediates miR-10a function during ESC/SMC differentiation. To determine the molecular mechanism through which retinoic acid induced miR-10a expression, a consensus NF-kappaB element was identified in the miR-10a gene promoter by bioinformatics analysis, and chromatin immunoprecipitation assay confirmed that NF-kappaB could bind to this element. Finally, inhibition of NF-kappaB nuclear translocation repressed miR-10a expression and decreased SMC differentiation from ESCs. Our data demonstrate for the first time that miR-10a is a novel regulator in SMC differentiation from ESCs. These studies suggest that miR-10a may play important roles in vascular biology and have implications for the diagnosis and treatment of vascular diseases.


Role of acyl-CoA binding protein in acyl-CoA metabolism and acyl-CoA-mediated cell signaling.
Long-chain acyl-CoA esters (LCA) act both as substrates and intermediates in metabolism and as regulators of various intracellular functions. Acyl-CoA binding protein (ACBP) binds LCA with high affinity and is believed to play an important role in intracellular acyl-CoA transport and pool formation and therefore also for the function of LCA as metabolites and regulators of cellular functions . The free concentration of cytosolic LCA is efficiently buffered to low nanomole concentration by ACBP and fatty acid binding protein (FABP). An additional important factor is the activity of acyl-CoA hydrolases. The estimated cellular free LCA concentration is two to four orders of magnitude lower than the concentrations reported to be necessary to regulate most LCA-affected cellular functions. Preliminary evidence indicates that the regulatory effect of LCA might be mediated by the LCA/ACBP complex.


Regulation of Memory T Cells by Interleukin-23.
Interleukin-23 (IL-23), a member of the IL-12 family of cytokines, is a heterodimeric cytokine. It is composed of subunits p40 (shared with IL-12) and p19 (an IL-12 p35-related subunit) and is secreted by several types of immune cells, such as natural killer cells and dendritic cells. The IL-23 receptor is composed of the subunit IL-12Rβ1 and the IL-23-specific subunit IL-23R. The binding of IL-23 to its specific cell surface receptor regulates a number of functions, including proliferation and differentiation of cells and secretion of cell factors. Memory T cells are a subset of T cells that secrete numerous important cell factors, and they function in the immune response to infection and diseases like cancer, autoimmune disease and bronchial asthma. IL-23R is expressed on the surface of memory T cells, which suggests that it can specifically regulate memory T cell function. IL-23 has been widely used as a clinical indicator in immune-related diseases and shows potential for use in disease treatment. Here we review the current progress in the study of the role of IL-23 in the regulation of memory T cells.


Nanoscale film fabrication of various peptides on neural stem cell chip.
Modification of peptide on the electrode surface is very important issue for achieving valuable information from cell chip. In this study, various kinds of cysteine-containing peptide were fabricated on the electrode surface to enhance the electrochemical signals, cell spreading, and proliferation of rat neural stem cells. Different kinds of lysine-rich and RGD peptides were self-assembled on the gold nanoparticle modified ITO surfaces via strong Au-S chemical bond, followed by seeding neural stem cells (NE-4C) on its surface. As a result, K-MAP-C peptide consists of the quadruple branches of lysine chains and cysteine terminal showed outstanding characteristics respect to the improvement of redox signals, cell spreading and proliferation on electrode surface. Hence, our stem cell chip composed of lysine-rich peptide modified electrode can be usefully applied as efficient stem cell research tool.


Lash ptosis and associated factors in Asians.
Lash ptosis (LP) is one of the important factors to be considered in blepharoplasty or correction of ptosis, but LP is an often overlooked symptom. We evaluate normal variations in the degree of LP to analyze the relationship between LP and its associated factors in Asians. One-hundred and sixty patients without ptosis and 16 patients with acquired ptosis were included in this study. We measured the degree of LP, marginal reflex distance 1, levator function, and presence or absence of a double fold. A significant difference was observed in LP rating between the nonptosis and acquired ptosis groups (P = 0.00), along with a significant correlation between LP rating and marginal reflex distance 1 (r = -0.272, P < 0.01), levator function (r = -0.170, P < 0.01), and absence or presence of double fold (r = -0.233, P < 0.01). Our results may be beneficial in the design of a basic plan for Asian patients with LP at the time of upper eyelid surgery, such as blepharoplasty or correction of ptosis.


Demographic Models for Subdivided Populations: The Renewal Equation Approach
Le Bras (Theor. Popul. Biol. 2, 100-121, 1971) and Rogers (Demography 11, 473-481, 1974), in two neglected papers, have generalized to the multisite case the Euler-Lotka renewal equation and demographic characteristics such as age structure and reproductive value. The purpose of this paper is twofold: first, to restate the multisite renewal equation in the matrix context; second, to derive results on age structure, net reproduction rate, generation time, and sensitivities, as generalizations of the one site case. The potential of this approach for population biology is illustrated using a model of a black-headed gull Larus ridibundus population.


[Institutional characteristics that interfere in the leadership of nurses].
The development of this study aimed at knowing the institutional characteristics that interfere with leadership of the nurse. This is a qualitative survey of descriptive and exploratory type, held in a large hospital located in the southern Rio Grande do Sul, Brazil, during the months of February and March 2008, in which participated 11 nurses. For the collection of data, we used semistructured interview. It was opted for the analysis of content as a technique for data processing in which emerged a category concerning institutional character that consists of six subcategories: remuneration, material resources, autonomy and institutional support, rotation, devaluation of the profession, and lack of incentive to develop leaders. It was identified that the little incentive to the improvement of the nurses front to the leadership is one institutional problem that can be minimized through the permanent education and the creation and implementation of programs of development for leaders in nursing.


Ethylene Inhibitors Partly Restore Nodulation to Pea Mutant E 107 (brz).
E107 (brz) is a pleiotropic mutant of pea (Pisum sativum L. cv Sparkle) characterized by low nodulation, leaf necrosis, excessive ion accumulation, and decreased plant size. The defective nodulation of E107 was studied by light microscopy of lateral roots. The number of infections per centimeter of lateral root was only a third that of Sparkle. Moreover, most of the infections were aborted early; i.e. in only 14% of the infections did the infection thread penetrate beyond the epidermis. Nodulation of E107 was partly restored by treating the plant with the ethylene inhibitors aminoethoxyvinylglycine (AVG) or Ag(+). Treatment with Ag(+) did not increase the number of infections, but half of the infections went to completion. Ag(+) and AVG did not alter the size of the mutant, the accumulation of cations in its shoots, nor the leaf necrosis. Thus, in E107, nodule development can be uncoupled from other pleiotropic characteristics.


Molecular and phenotypic characterization of near isogenic lines at QTL for quantitative resistance to Leptosphaeria maculans in oilseed rape (Brassica napus L.).
The most common and effective way to control phoma stem canker (blackleg) caused by Leptosphaeria maculans in oilseed rape (Brassica napus) is by breeding resistant cultivars. Specific resistance genes have been identified in B. napus and related species but in some B. napus cultivars resistance is polygenic [mediated by quantitative trait loci (QTL)], postulated to be race non-specific and durable. The genetic basis of quantitative resistance in the French winter oilseed rape 'Darmor', which was derived from 'Jet Neuf', was previously examined in two genetic backgrounds. Stable QTL involved in blackleg resistance across year and genetic backgrounds were identified. In this study, near isogenic lines (NILs) were produced in the susceptible background 'Yudal' for four of these QTL using marker-assisted selection. Various strategies were used to develop new molecular markers, which were mapped in these QTL regions. These were used to characterize the length and homozygosity of the 'Darmor-bzh' introgressed segment in the NILs. Individuals from each NIL were evaluated in blackleg disease field trials and assessed for their level of stem canker in comparison to the recurrent line 'Yudal'. The effect of QTL LmA2 was clearly validated and to a lesser extent, QTL LmA9 also showed an effect on the disease level. This work provides valuable material that can be used to study the mode of action of genetic factors involved in L. maculans quantitative resistance.


System Matrix Based Reconstruction for Pulsed Sequences in Magnetic Particle Imaging.
Improving resolution and sensitivity will widen possible medical applications of magnetic particle imaging. Pulsed excitation promises such benefits, at the cost of more complex hardware solutions and restrictions on drive field amplitude and frequency. State-of-the-art systems utilize a sinusoidal excitation to drive superparamagnetic nanoparticles into the non-linear part of their magnetization curve, which creates a spectrum with a clear separation of direct feed-through and higher harmonics caused by the particles response. One challenge for rectangular excitation is the discrimination of particle and excitation signals, both broad-band. Another is the drive-field sequence itself, as particles that are not placed at the same spatial position, may react simultaneously and are not separable by their signal phase or shape. To overcome this potential loss of information in spatial encoding for high amplitudes, a superposition of shifting fields and drive-field rotations is proposed in this work. Upon close view, a system matrix approach is capable to maintain resolution, independent of the sequence, if the response to pulsed sequences still encodes information within the phase. Data from an Arbitrary Waveform Magnetic Particle Spectrometer with offsets in two spatial dimensions is measured and calibrated to guarantee device independence. Multiple sequence types and waveforms are compared, based on frequency space image reconstruction from emulated signals, that are derived from measured particle responses. A resolution of 1.0 mT (0.8 mm for a gradient of (-1.25,-1.25,2.5) Tm-1) in x- and y-direction was achieved and a superior sensitivity for pulsed sequences was detected on the basis of reference phantoms.


Kinetics of Field-Induced Surface Patterns on PMMA.
A simple model was developed to analyze the growth of a liquid pillar under the action of an electric field between two parallel electrodes. A quadratic relationship between time and the diameter of the pillar was obtained. The diameter of the pillar increases with time. Large electric field assists the growth of the liquid pillar, while a liquid with a large viscosity hinders the growth of the liquid pillar. The field-induced formation and growth of PMMA pillars on PMMA films were observed using the configuration of a parallel capacitor. Pillars of larger sizes and smaller densities were formed on thicker PMMA films than on thinner PMMA films. The root-mean-square ( https://en.wikipedia.org/wiki/Root_mean_square ) diameter of the pillars increases with the increase of the annealing time and annealing temperature. The growth behavior of the pillars can be described by an Arrhenius relation with an activation energy of 24.4 kJ/mol, suggesting that the growth of the pillars is controlled by a thermal activation process.


[Ischemic heart disease (myocardial perfusion and viability): techniques and results].
Over the last two decades, the understanding, diagnosis and treatment of patients with suspected or known coronary artery disease have made tremendous progress, in particular with the help of the development of non-invasive methodologies for assessing myocardial perfusion and viability. Clinically, nuclear medicine techniques (particularly SPECT imaging) have predominated. With the recent technical developments allowing for a combined assessment of perfusion and irreversible damage with late enhancement imaging, MRI will now play a major role in the assessment of ischemic heart disease.


Predicting prognosis according to the updated WHO classification in patients with endocervical adenocarcinoma treated with surgery and radiotherapy.
The recently updated World Health Organization classification divides endocervical adenocarcinomas (ADCs) into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) ADCs. This study aimed to investigate the differences in the clinical features and treatment outcomes between patients with HPVA and HPVI. We retrospectively reviewed the electronic medical records and pathology slides of 123 patients with endocervical ADC who underwent radical hysterectomy and adjuvant radiation therapy. Tumor characteristics, patterns of failure, and survival outcomes were compared between HPVA and HPVI ADCs. Eighty-one (65.9%) and 42 (34.1%) patients were diagnosed with HPVA and HPVI ADCs, respectively. HPVI ADC showed more frequent positive vaginal resection margin (VRM) and peritoneal seeding than HPVA ADC. After a median follow-up of 58.1 months, local recurrence and distant metastasis were more frequently observed in HPVI ADC than in HPVA ADC. Both local recurrence-free survival (77.3% vs. 91.8%) and distant metastasis-free survival (50.1% vs. 73.7%) rates of HPVI ADC were lower than those of HPVA ADC. Disease-free survival was not significantly different between HPVI and HPVA ADCs. We demonstrated that HPVI ADC exhibited higher rates of VRM involvement and peritoneal seeding than those of HPVA ADC, resulting in higher rates of local recurrence and distant metastasis. Further studies with larger populations are warranted to explore optimal treatment strategies based on the histological subtypes of endocervical ADC.


Development of a novel malingering detection method involving multiple detection strategies.
This study utilized a novel computer-administered measure designed to assess multiple malingering detection strategies, as well as measure genuine impairment in a brain-injured sample. Ninety-four neurologically normal subjects comprised control and simulator groups. Twenty individuals with moderate to severe head injuries comprised a clinical sample. The summary score from the measure yielded a sensitivity of .81 and a specificity of .89. Total completion time and learning curves were utilized as genuine impairment indicators. Sensitivity (.95) and specificity (.95) were quite high for these dimensions. Results suggest there is utility to combining detection techniques, including indicators of genuine impairment.


A case of chronic progressive myelopathy.
Acute myelitis and optic neuritis are the main clinical features of patients with neuromyelitis optica (NMO), which usually appears as a relapsing-remitting course of disease that worsens over days and improves over weeks. We present a patient with chronic progressive myelitis over a 4-month period without remission as having a limited form of NMO that improved after plasmapheresis. Plasmapheresis may benefit patients with chronic progressive myelitis, which may be a manifestation of NMO, as well as those with a relapsing-remitting course of NMO.


Possible advantage of imiquimod and diphenylcyclopropenone combined treatment versus diphenylcyclopropenone alone: An observational study of nonresponder patients with alopecia areata.
The topical contact sensitiser diphenylcyclopropenone (DCP) remains one of the most effective treatment modalities for alopecia areata (AA). However, some patients (nonresponders) do not respond to this treatment because they do not have an allergic reaction to DCP. The aim of this study was to investigate the potential role of imiquimod in inducing an allergic reaction to DCP in nonresponders. In all, 20 nonresponders were recruited from a group of DCP-treated AA patients. Of these patients, 10 were treated with DCP and topical imiquimod and 10 were treated with DCP alone. A significantly better therapeutic outcome was measured in the DCP plus imiquimod group than in the group treated with DCP alone. The potential mechanism of imiquimod may involve the role of interleukin-12, as previously suggested in an animal model. These findings suggest that imiquimod may have the potential to improve prognosis in nonresponder AA patients treated with DCP.


The potential risk of infectious disease dissemination via artificial insemination in swine.
Artificial insemination (AI) is one of the most widely used assisted reproductive technologies in swine. To maintain a healthy semen trade, it is crucial that diligence be given to managing and minimizing the chance of extended semen playing an epidemiological role in the transmission of infectious disease. In swine, pathogens of primary importance, which may be transmitted through semen include Aujeszky's disease, brucellosis, chlamydophilosis, porcine circovirus type 2, classical swine fever, Japanese encephalitis, leptospirosis, parvovirus, porcine reproductive and respiratory syndrome, rubulavirus, foot-and-mouth disease and swine vesicular disease. This paper will summarise the current state of knowledge pertaining to these pathogens in relation to swine AI.


Effect of natural organic matter on cerium dioxide nanoparticles settling in model fresh water.
The ecological risk assessment of chemicals including nanoparticles is based on the determination of adverse effects on organisms and on the environmental concentrations to which biota are exposed. The aim of this work was to better understand the behavior of nanoparticles in the environment, with the ultimate goal of predicting future exposure concentrations in water. We measured the concentrations and particle size distributions of CeO(2) nanoparticles in algae growth medium and deionized water in the presence of various concentrations and two types of natural organic matter (NOM). The presence of natural organic matter stabilizes the CeO(2) nanoparticles in suspension. In presence of NOM, up to 88% of the initially added CeO(2) nanoparticles remained suspended in deionized water and 41% in algae growth medium after 12d of settling. The adsorbed organic matter decreases the zeta potential from about -15 mV to -55 mV. This reduces aggregation by increased electrostatic repulsion. The particle diameter, pH, electric conductivity and NOM content shows significant correlation with the fraction of CeO(2) nanoparticles remaining in suspension.


Cloning and sequence of the gene encoding a cefotaxime-hydrolyzing class A beta-lactamase isolated from Escherichia coli.
Escherichia coli TUH12191, which is resistant to piperacillin, cefazolin, cefotiam, ceftizoxime, cefuzonam, and aztreonam but is susceptible to cefoxitin, latamoxef, flomoxef, and imipenem, was isolated from the urine of a patient treated with beta-lactam antibiotics. The beta-lactamase (Toho-1) purified from the bacteria had a pI of 7.8, had a molecular weight of about 29,000, and hydrolyzed beta-lactam antibiotics such as penicillin G, ampicillin, oxacillin, carbenicillin, piperacillin, cephalothin, cefoxitin, cefotaxime, ceftazidime, and aztreonam. Toho-1 was markedly inhibited by beta-lactamase inhibitors such as clavulanic acid and tazobactam. Resistance to beta-lactams, streptomycin, spectinomycin, sulfamethoxazole, and trimethoprim was transferred by conjugational transfer from E. coli TUH12191 to E. coli ML4903, and the transferred plasmid was about 58 kbp, belonging to incompatibility group M. The cefotaxime resistance gene for Toho-1 was subcloned from the 58-kbp plasmid by transformation of E. coli MV1184. The sequence of the gene for Toho-1 was determined, and the open reading frame of the gene consisted of 873 or 876 bases (initial sequence, ATGATG). The nucleotide sequence of the gene (DDBJ accession number D37830) was found to be about 73% homologous to the sequence of the gene encoding a class A beta-lactamase produced by Klebsiella oxytoca E23004. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 290 or 291 amino acid residues, which contained amino acid motifs common to class A beta-lactamases (70SXXK, 130SDN, and 234KTG). Toho-1 was about 83% homologous to the beta-lactamase mediated by the chromosome of K. oxytoca D488 and the beta-lactamase mediated by the plasmid of E. coli MEN-1. Therefore, the newly isolated beta-lactamase Toho-1 produced by E. coli TUH12191 is similar to beta-lactamases produced by K. oxytoca D488, K. oxytoca E23004, and E. coli MEN-1 rather than to mutants of TEM or SHV enzymes. Toho-1 has shown the highest degree of similarity to K. oxytoca class A beta-lactamase. Detailed comparison of Toho-1 with other beta-lactamases implied that replacement of Asn-276 by Arg with the concomitant substitution of Thr for Arg-244 is an important mutation in the extension of the substrate specificity.


Validation of in vitro cell-based human blood-brain barrier model using clinical positron emission tomography radioligands to predict in vivo human brain penetration.
We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [(18)F] and [(11)C]-compounds in humans by PET imaging. The in vivo plasma-brain exchange parameters used for comparison were determined in humans by PET using a kinetic analysis of the radiotracer binding. For each radiotracer, the parameters were determined by fitting the brain kinetics of the radiotracer using a two-tissue compartment model of the ligand-receptor interaction. Bidirectional transport studies with the same compounds as in in vivo studies were carried out using the in vitro cell-based human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model has important features of the BBB in vivo and is suitable for discriminating between CNS and non-CNS marketed drugs. A very good correlation (r(2) = 0.90; P < 0.001) was demonstrated between in vitro BBB permeability and in vivo permeability coefficient. In contrast, a poor correlation (r(2) = 0.17) was obtained between Caco-2 data and in vivo human brain penetration. This study highlights the potential of this in vitro cell-based human BBB model in drug discovery and shows that it can be an extremely effective screening tool for CNS programs.


Dynamical Slowing-Down in an Ultrafast Photoinduced Phase Transition.
Complex systems, which consist of a large number of interacting constituents, often exhibit universal behavior near a phase transition. A slowdown of certain dynamical observables is one such recurring feature found in a vast array of contexts. This phenomenon, known as critical slowing-down, is well studied mostly in thermodynamic phase transitions. However, it is less understood in highly nonequilibrium settings, where the time it takes to traverse the phase boundary becomes comparable to the timescale of dynamical fluctuations. Using transient optical spectroscopy and femtosecond electron diffraction, we studied a photoinduced transition of a model charge-density-wave (CDW) compound LaTe_{3}. We observed that it takes the longest time to suppress the order parameter at the threshold photoexcitation density, where the CDW transiently vanishes. This finding can be captured by generalizing the time-dependent Landau theory to a system far from equilibrium. The experimental observation and theoretical understanding of dynamical slowing-down may offer insight into other general principles behind nonequilibrium phase transitions in many-body systems.


Single-cell transcriptional analysis of human endothelial colony-forming cells from patients with low VWF levels.
von Willebrand factor (VWF) plays a key role in normal hemostasis, and deficiencies of VWF lead to clinically significant bleeding. We sought to identify novel modifiers of VWF levels in endothelial colony-forming cells (ECFCs) using single-cell RNA sequencing (scRNA-seq). ECFCs were isolated from patients with low VWF levels (plasma VWF antigen levels between 30 and 50 IU/dL) and from healthy controls. Human umbilical vein endothelial cells were used as an additional control cell line. Cells were characterized for their Weibel Palade body (WPB) content and VWF release. scRNA-seq of all cell lines was performed to evaluate for gene expression heterogeneity and for candidate modifiers of VWF regulation. Candidate modifiers identified by scRNA-seq were further characterized with small-interfering RNA (siRNA) experiments to evaluate for effects on VWF. We observed that ECFCs derived from patients with low VWF demonstrated alterations in baseline WPB metrics and exhibit impaired VWF release. scRNA-seq analyses of these endothelial cells revealed overall decreased VWF transcription, mosaicism of VWF expression, and genes that are differentially expressed in low VWF ECFCs and control endothelial cells (control ECs). An siRNA screen of potential VWF modifiers provided further evidence of regulatory candidates, and 1 such candidate, FLI1, alters the transcriptional activity of VWF. In conclusion, ECFCs from individuals with low VWF demonstrate alterations in their baseline VWF packaging and release compared with control ECs. scRNA-seq revealed alterations in VWF transcription, and siRNA screening identified multiple candidate regulators of VWF.


Differences and similarities in the treatment of diffuse goiter in Europe and the United States.
In two separate studies, members of the American Thyroid Association (ATA), and the European Thyroid Association (ETA) were surveyed by questionnaire on their management of Graves' disease. The aim was to determine how expert clinical thyroidologists employ three different therapies which are available for this disorder. Herein we summarize, compare and contrast similarities and differences in the results of these surveys. For the index patient, radioiodine (RAI) was the therapy of choice for 69% of ATA respondents but only 22% of ETA respondents. In contrast, only 30.5% of ATA respondents chose antithyroid drugs as first line therapy compared to 77% of ETA respondents. There was consensus on the relative lack of a role for thyroidectomy. The implications of these differing approaches to the treatment of hyperthyroidism due to Graves' disease are discussed.


Identification of cortical landmarks based on structural connectivity to subcortical regions.
Quantitative assessment of structural connectivities between cortical and subcortical regions has been of increasing interest in recent years. This paper proposes an algorithmic pipeline for identification of reliable cortical landmarks based on the consistent structural connectivity patterns between cortical and subcortical regions. Our experimental results of eight healthy subjects show that reliable and meaningful cortical landmarks can be extracted by using our approaches. Furthermore, subcortical regions can serve as reliable reference points for the identification of consistent corresponding cortical regions across individuals.


Synthesis of Cyclopenta[ b]piperazinones via an Azaoxyallyl Cation.
A new and efficient reaction sequence between 2-furylcarbinols, anilines, and α-haloamides has been developed to afford highly functionalized cyclopenta[ b]piperazinones. This transformation was accomplished through an aza-Piancatelli cyclization/azaoxyallyl cation trapping with a complete control of the diastereoselectivity.


Involvement of TCR-V beta 8.3+ cells in the cure of mice bearing a large MOPC-315 tumor by low dose melphalan.
We have previously shown that the curative efficacy of low dose melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large s.c. MOPC-315 tumor requires the participation of CD8+ (but not CD4+) T cell-dependent antitumor immunity. Here we show that CD8+ T cells obtained from regressing tumors on day 4 or 5 after low dose L-PAM therapy of MOPC-315 tumor bearers (L-PAM TuB mice) display a preferential enhancement in the utilization of the TCR-V beta 8.3 gene segment as compared to CD8+ T cells from normal lymph nodes. Treatment of L-PAM TuB mice with mAb F23.1, which leads to the depletion of V beta 8.3+ cells, as well as V beta 8.1 and 8.2+ cells, led to a significant reduction in the ability of their tumor-infiltrating lymphocytes as well as their spleen cells to lyse MOPC-315 tumor cells in vitro in a short term assay. In addition, the mAb F23.1 treatment almost completely abrogated the lytic activity of the tumor-infiltrating lymphocytes against another syngeneic, antigenically related plasmacytoma (the MOPC-104E). Moreover, the mAb F23.1 treatment significantly reduced the curative effectiveness of low dose L-PAM for mice bearing a large MOPC-315 tumor. In contrast, mAb KJ16 treatment, which leads to the depletion of V beta 8.1 and 8.2+ cells (but not V beta 8.3+ cells), did not reduce significantly the curative effectiveness of low dose L-PAM for such MOPC-315 tumor bearers. Thus, V beta 8.3+ T cells are important for the curative effectiveness of low dose L-PAM therapy for MOPC-315 tumor bearers, and it is conceivable that the V beta 8.3+ cells mediate their effect (at least in part) by contributing to the acquisition of CTL activity against plasmacytoma-shared Ag.


Oral-recombinant Methioninase Converts an Osteosarcoma from Methotrexate-resistant to -sensitive in a Patient-derived Orthotopic-xenograft (PDOX) Mouse Model.
Osteosarcoma is the most common bone sarcoma. Although surgery and chemotherapy are initially effective, the 5-year survival is approximately 60% to 80%, and has not improved over three decades. We have previously shown that methionine restriction (MR) induced by oral recombinant methioninase (o-rMETase), is effective against osteosarcoma in patient-derived orthotopic xenograft (PDOX) nude-mouse models. In the present report, the efficacy of the combination of oral o-rMETase and methotrexate (MTX) was examined in an osteosarcoma PDOX mouse model. An osteosarcoma-PDOX model was previously established by implanting tumor fragments into the proximal tibia of nude mice. The osteosarcoma PDOX models were randomized into four groups: control; o-rMETase alone; MTX alone; combination of o-rMETase and MTX. The mice were sacrificed after 4 weeks of treatment. The combination of o-rMETase and MTX showed significantly higher efficacy compared to the control group (p=0.04). The combination also showed significantly higher efficacy compared to MTX alone (p=0.04). No significant efficacy of o-rMETase alone or MTX alone compared to control was shown (p=0.21, 1.00, respectively). Only the combination of o-rMETase and MTX reduced the cancer-cell density in the osteosarcoma tumor. rMETase converted an osteosarcoma PDOX from MTX-resistant to MTX-sensitive and thereby shows future clinical potential.


Novel MSH2 splice-site mutation in a young patient with Lynch syndrome.
Lynch Syndrome (LS) is associated with germline mutations in one of the mismatch repair (MMR) genes, including MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6, PMS1 homolog 2, mismatch repair system component (PMS2), MLH3 and MSH3. The mutations identified in MMR genes are point mutations or large rearrangements. The point mutations are certainly pathogenetic whether they determine formation of truncated protein. The mutations that arise in splice sites are classified as 'likely pathogenic' variants. In the present study, a novel splicing mutation was identified, (named c.212‑1g>a), in the MSH2 gene. This novel mutation in the consensus splice site of MSH2 exon 2 leads to the loss of the canonical splice site, without skipping in‑frame of exon 2; also with the formation of 2 aberrant transcripts, due to the activation of novel splice sites in exon 2. This mutation was identified in a young patient who developed colon cancer at the age of 26 years and their belongs to family that met the 'Revised Amsterdam Criteria'. The present study provided insight into the molecular mechanism determining the pathogenicity of this novel MSH2 mutation and it reaffirms the importance of genetic testing in LS.


Diagonal-free 3D/4D HN,HN-TROSY-NOESY-TROSY.
Structural biology by NMR spectroscopy relies on measuring interproton distances via NOE cross-signals in nuclear Overhauser effect spectroscopy (NOESY) spectra. In proteins, the subset of H(N)-H'(N) NOE contacts is most important for deriving initial structural models and for spectral assignment by "NOE walking". Here we present a fully optimized NMR experiment for measuring these pivotal contacts: diagonal-free 3D/4D HN,HN-TROSY-NOESY-TROSY. It combines all of the critical requirements for extracting the optimal H(N)-H'(N) distance information: the highest resolution by consistent transverse relaxation-optimized spectroscopy (TROSY) evolution, the largest spectral dispersion in two (15)N dimensions, and maximal coverage and purity through specific suppression of the intense diagonal signals that are the main source of overlap, artifacts, and bias in any NOESY spectrum. Most notably, diagonal suppression here comes without compromising the NOE cross-signal intensities. This optimized experiment appears to be ideal for a broad range of structural studies, particularly on large deuterated, partially unfolded, helical, and membrane proteins.


Family veto in organ donation in Canada: framing within English-language newspaper articles.
Because organ transplantation relies on public support for donation, an analysis of public discourse around organ donation is essential. We investigated the portrayal of family veto - when a family overrides the deceased person's prior legally executed wishes to donate - in Canadian news media. Using the Canadian Newsstream database, we identified articles published in English-language newspapers addressing family veto between 2000 and 2016. Guided by the theoretical perspectives of framing of media effects, we conducted a systematic content analysis of the articles to examine how the Canadian media framed family veto. An initial in-depth analysis of the data set in which themes and patterns were captured and recorded identified coding categories, including primary framing of family veto, prevalence, reasons, ethical or legal concerns and overall tone of the article. Two coders analyzed the data set to ensure intercoder reliability. A total of 133 relevant articles were identified. Family veto was framed predominantly as something that should not be allowed (81 articles [60.9%]) and as a reality that is little understood outside the transplantation community (45 [33.8%]). One-quarter of the articles (32 [24.1%]) highlighted ethical principles of autonomy and justice associated with family veto. Family veto was represented as a stumbling block in the present organ donation system, with most publications (107 [80.4%]) calling for change. There were differing interpretations of organ donation legislation, with 82 articles (61.6%) erroneously stating or suggesting that existing legislation permits family veto. Family veto in organ donation was portrayed predominantly negatively. Many publications reflected a misunderstanding of the law concerning this issue. Although the framing of family veto highlighted important ethical and legal concerns as well as practice and policy considerations, research is needed to enhance the understanding of family veto in organ donation.


Effects of Social Stories on Increasing Social Interaction and Engagement of Deaf and Hard of Hearing Students with Autism Spectrum Disorder in Inclusive Settings.
d/Deaf or hard of hearing (d/Dhh) students with autism spectrum disorder (ASD) may require specific approaches to promote social inclusion. The purpose of this study was to investigate the effects of reading social stories with American Sign Language vocabulary to students who are d/Dhh with ASD (d/Dhh-ASD) and their peers in inclusive settings, using a non-concurrent multiple baseline design across participants. To examine the effectiveness of the intervention, the frequency of four communicative social behaviors and the duration of social engagement with peers were recorded for each participant during lunchtime and recess. The results did not show an immediate effect across all participants. Implications for promoting social inclusion for students who are d/Dhh-ASD in general education classrooms are discussed.


[Association of the calpain-10 gene polymorphism with glucose metabolism disorder in pregnant women].
To study three single nucleotide polymorphisms (SNP), SNP-43, -19 and -63 of calpain-10 (CAPN10) gene in pregnant women with glucose metabolism disorders and their relationship with the risk of these disorders. Totally, 270 pregnant women including 156 with an abnormal oral glucose tolerance test (study group) and 114 healthy controls were selected among those delivered at the Department of Obstetrics and Gynecology, Peking University First Hospital from Jan. 2005 to Dec. 2006. The SNP of CAPN10 gene at positions 43, 19, and 63 were analyzed by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR). (1) The frequencies CAPN10 SNP-19 2R/2R genotype (26.9%, 42/156) and 2R allele (48.9%, 152/312) were higher than those in controls (12.3%, 14/114 and 36.8%, 84/228, respectively; P=0.012, 0.006). (2) Stratified analysis according to family history of diabetes mellitus showed the proportion of the CAPN10 SNP-19 2R/2R+2R/3R genotypes (83%, 47/57) in the study group were significantly higher than that of control group (52%, 11/21; P=0.009), and the proportion of SNP-63 T/T+T/C genotypes (47%, 27/57) in study group were significantly higher than that of control group (14%, 3/21; P=0.026) among those with positive family history. (3) The combined effect of CAPN10 SNP-43, -19 and -63 on glucose metabolism disorders was analyzed by comparing with the other haplotypes and showed that the haplotype 121 distribution in study group was significantly higher than those in controls (P=0.036), and 221 haplotype was significantly lower than controls (P=0.042). (1) CAPN10 SNP-19 is associated with glucose metabolism disorders in pregnant women. And 2R allele might be the risk factor. CAPN10 SNP-19 2R/2R+2R/3R and SNP-63 T/T+T/C genotypes might increase the risk of glucose metabolism disorders in women with positive family history. Haplotype 121 might increase the risk of glucose metabolism disorders in pregnant women and 221 be a protective factor.


Early experience with SILS port laparoscopic sleeve gastrectomy.
Ever since single-incision laparoscopic surgery was introduced 12 years ago, it has undergone many attempts to improve its feasibility and accessibility. We herein are reporting our early experience with SILS Port as a multichannel single-port access to perform laparoscopic sleeve gastrectomy. Six morbidly obese patients underwent laparoscopic sleeve gastrectomy using the SILS Port as a common point of entry for 3 trocars. The same perioperative protocol was implemented for all 6 patients. All 6 SILS Port laparoscopic sleeve gastrectomies were successfully performed using this technique. The 3 super-obese male patients with central obesity required the insertion of a 5-mm subxiphoid trocar. The mean operating time was 123 minutes. There were no mortalities or postoperative complications noted during the immediate follow-up period of all 6 patients. SILS gastrectomy using SILS Port is safe and feasible.


Pulmonary Tuberculosis.
This review on pulmonary tuberculosis includes an introduction that describes how the lung is the portal of entry for the tuberculosis bacilli to enter the body and then spread to the rest of the body. The symptoms and signs of both primary and reactivation tuberculosis are described. Routine laboratory tests are rarely helpful for making the diagnosis of tuberculosis. The differences between the chest X ray in primary and reactivation tuberculosis is also described. The chest computed tomography appearance in primary and reactivation tuberculosis is also described. The criteria for the diagnosis of pulmonary tuberculosis are described, and the differential is discussed. The pulmonary findings of tuberculosis in HIV infection are described and differentiated from those in patients without HIV infection. The occurrence of tuberculosis in the elderly and in those patients on anti-tumor necrosis factor alpha inhibitors is described. Pleural tuberculosis and its diagnosis are described. Efforts to define the activity of tuberculosis and the need for respiratory isolation are discussed. The complications of pulmonary tuberculosis are also described.


Strengths and challenging behaviors in children and adolescents with Prader-Willi syndrome: Two sides to the coin.
Prader-Willi Syndrome (PWS) is a rare genetic disorder associated with emotional/behavioral disturbances. These difficulties are well documented in the literature, but the positive attributes of these individuals are not described. Taking a strengths-based approach, the aim of this study was to describe the emotional/behavioral strengths and difficulties in children and young people with PWS from their parent caregivers' perspectives. Parent caregivers of 52 individuals with PWS aged 4-24 years (median = 12.1 years; including 22 males) completed the parent form of the Developmental Behavior Checklist (DBC-P), including its original two open-ended questions regarding positive traits. Prevalences of emotional/behavioral disturbances were comparable to those reported in previous literature: common behaviors of concern across studies being skin-picking (75%), impulsivity (69%), poor sense of danger (67%), lying (67%), and tantrums (54%). Total DBC-P scores showed that just over half (n = 28, 54%) had scores indicative of clinically significant behavior problems. However, thematic analysis of caregivers' written comments regarding their children's strengths resolved into three themes: warmth (94%), persistence (41%), and skills (41%). Warmth encompassed friendliness, happiness, and empathy. A strength-based approach to behavioral difficulties in PWS provides a more balanced view of the children and a more holistic foundation for interventions.


Extrapyramidal side effects, tardive dyskinesia, and the concept of atypicality.
The most frequent problems associated with the older generation of antipsychotic agents are extrapyramidal side effects (EPS) and tardive dyskinesia. Neuroleptic-induced EPS are thought to be caused by blockade of nigrostriatal dopamine tracts resulting in a relative increase in cholinergic activity; tardive dyskinesia is less well understood but is thought to be a supersensitivity response to chronic dopamine blockade. The leading hypothesis for the mechanism of action of the newer generation of atypical antipsychotics is the presence of a high serotonin-to-dopamine receptor blockade ratio in the brain. When serotonergic activity is blocked-as is the case with atypical antipsychotics-dopamine release increases and balances out the dopamine blockade effect at postsynaptic receptor sites, which results in few or no EPS. Prospective data indicate that the risk of tardive dyskinesia in patients taking atypical antipsychotics is less than that for those taking typical antipsychotics. This article reviews the mechanisms of neuroleptic-induced EPS and tardive dyskinesia and discusses the relationship between these movement disorders and atypical antipsychotic agents.


Effect of management interventions on the helminth parasites recovered from donkeys in South Africa.
The helminth burdens and biodiversity of 9 randomly selected donkeys (Equus asinus) were examined after necropsy. Prior to necropsy, 8 of the animals were subjected to 1 of 3 management interventions (monthly fecal removal, prewinter moxidectin treatment, and a combination of both treatments) or a control for a 16-mo period. The remaining animal was killed earlier in the study. Quantitative samples were collected from the gastrointestinal tract for helminth recovery. The intestinal walls were examined with transmural illumination and thereafter digested with a HCl-peptic method for identification of the mucosal larval stages of cyathostomes. In this study, 37 helminth species belonging to the Ascarididae, Atractidae, Dictyocaulidae. Habronematidae, Onchocercidae, Oxyuridae, Strongylidae, and Trichostrongylidae, 1 cestode species of the Anoplocephalidae, and 1 trematode species in the Paramphistomatidae were recovered. In addition, 1 species of oestrid fly of the Gasterophilidae was identified. The results obtained in the present study support the application of several intervention methods to reduce the helminth burdens in donkeys.


Polyamines Disrupt the KaiABC Oscillator by Inducing Protein Denaturation.
Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles in cells by stabilizing chromatin structure, regulating DNA replication, modulating gene expression, etc., and they also affect the structure and function of proteins. A few studies have investigated the impact of polyamines on protein structure and function previously, but no reports have focused on a protein-based biological module with a dedicated function. In this report, we investigated the impact of polyamines (putrescine, spermidine, and spermine) on the cyanobacterial KaiABC circadian oscillator. Using an established in vitro reconstitution system, we noticed that polyamines could disrupt the robustness of the KaiABC oscillator by inducing the denaturation of the Kai proteins (KaiA, KaiB, and KaiC). Further experiments showed that the denaturation was likely due to the induced change of the thermal stability of the clock proteins. Our study revealed an intriguing role of polyamines as a component in complex cellular environments and would be of great importance for elucidating the biological function of polyamines in future.


Factors associated with implant survival following total hip replacement surgery: A registry study of data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man.
Nearly 100,000 people underwent total hip replacement (THR) in the United Kingdom in 2018, and most can expect it to last at least 25 years. However, some THRs fail and require revision surgery, which results in worse outcomes for the patient and is costly to the health service. Variation in the survival of THR implants has been observed between units and reducing this unwarranted variation is one focus of the "Getting it Right First Time" (GIRFT) program in the UK. We aimed to investigate whether the statistically improved implant survival of THRs in a high-performing unit is associated with the implants used or other factors at that unit, such as surgical skill. We analyzed a national, mandatory, prospective, cohort study (National Joint Registry for England, Wales, Northern Ireland and the Isle of Man [NJR]) of all THRs performed in England and Wales. We included the 664,761 patients with records in the NJR who have received a stemmed primary THR between 1 April 2003 and 31 December 2017 in one of 461 hospitals, with osteoarthritis as the only indication. The exposure was the unit (hospital) in which the THR was implanted. We compared survival of THRs implanted in the "exemplar" unit with THRs implanted anywhere else in the registry. The outcome was revision surgery of any part of the THR construct for any reason. Net failure was calculated using Kaplan-Meier estimates, and adjusted analyses employed flexible parametric survival analysis. The mean age of patients contributing to our analyses was 69.9 years (SD 10.1), and 61.1% were female. Crude analyses including all THRs demonstrated better implant survival at the exemplar unit with an all-cause construct failure of 1.7% (95% CI 1.3-2.3) compared with 2.9% (95% CI 2.8-3.0) in the rest of the country after 13.9 years (log-rank test P < 0.001). The same was seen in analyses adjusted for age, sex, and American Society of Anesthesiology (ASA) score (difference in restricted mean survival time 0.12 years [95% CI 0.07-0.16; P < 0.001]). Adjusted analyses restricted to the same implants as the exemplar unit show no demonstrable difference in restricted mean survival time between groups after 13.9 years (P = 0.34). A limitation is that this study is observational and conclusions regarding causality cannot be inferred. Our outcome is revision surgery, and although important, we recognize it is not the only marker of success of a THR. Our results suggest that the "better than expected" implant survival results of this exemplar center are associated with implant choice. The survival results may be replicated by adopting key treatment decisions, such as implant selection. These decisions are easier to replicate than technical skills or system factors.


Impact of an osteopathic presence in a large categorical pediatric residency training program.
Nationwide Children's Hospital (NCH) has a large pediatric residency program with 43 residents in the categorical pediatric program and 10 residents in the Internal Medicine-Pediatrics (IM-Peds) program per class. Of the 43 categorical pediatric residents, four are in the osteopathic recognition track (ORT) and continue their osteopathic education throughout residency. There is currently a lack of data examining the effect of an ORT, and specifically a pediatric ORT, on a residency program. To evaluate the impact of an ORT osteopathic recognition track on an overall residency program's perceptions of osteopathic manipulative treatment (OMT) and to evaluate allopathic (MD) resident perception of osteopathic educational sessions. An anonymous survey was conducted in June 2017 and distributed to 141 residents (both categorical and IM-Peds) to gather baseline information regarding perceptions and knowledge of OMT. Based on the initial results, a four-part case-based educational series was implemented during the 2018-2019 academic year to teach osteopathic principles to MD residents. A second survey was distributed following each session. For the initial survey, 59 (41.8%) residents responded. Survey results demonstrated that resident perceptions of OMT as an efficacious treatment option increased after starting their residency at NCH (p=0.04), and 25 of 43 (58.1%) MD residents stated an interest in learning OMT skills. A total of 140 attendees were present at the four educational sessions. One hundred and thirty-eight residents (98.5%) found the educational sessions beneficial and 132 (94.2%) stated they would refer a patient for OMT. ORT residents make a significant impact on their colleagues' perceptions and knowledge of OMT. This study suggests that further efforts to highlight the clinical applications of OMT in pediatric patients would be welcomed by residents.


Electronic spectrum of the UO and UO(+) molecules.
Electronic theory calculations are applied to the study of the UO molecule and the UO(+) ion. Relativistic effective core potentials are used along with the accompanying valence spin-orbit operators. Polarized double-ς and triple-ς basis sets are used. Molecular orbitals are obtained from state-averaged multiconfiguration self-consistent field calculations and then used in multireference spin-orbit configuration interaction calculations with a number of millions of terms. The ground state of UO has open shells of 5f(3)7s(1), angular momentum Ω = 4, and a spin-orbit-induced avoided crossing near the equilibrium internuclear distance. Many UO excited states are studied with rotational constants, intensities, and experimental comparisons. The ground state of UO(+) is of 5f(3) nature with Ω = 9/2. Many UO(+) excited states are also studied. The open-shell nature of both UO and UO(+) leads to many low-lying excited states.


Focusing on a nickel hydrocorphinoid in a protein matrix: methane generation by methyl-coenzyme M reductase with F430 cofactor and its models.
Methyl-coenzyme M reductase (MCR) containing a nickel hydrocorphinoid cofactor, F430, is an essential enzyme that catalyzes anaerobic methane generation and oxidation. The active Ni(I) species in MCR converts methyl-coenzyme M (CH3S-CoM) and coenzyme B (HS-CoB) to methane and heterodisulfide (CoM-S-S-CoB). Extensive experimental and theoretical studies focusing on the substrate-binding cavity including the F430 cofactor in MCR have suggested two principally different reaction mechanisms involving an organonickel CH3-Ni(III) species or a transient methyl radical species. In parallel with research on native MCR itself, the functionality of MCR has been investigated in the context of model complexes of F430 and recent protein-based functional models, which include a nickel complex. In the latter case, hemoproteins reconstituted with tetradehydro- and didehydrocorrinoid nickel complexes have been found to represent useful model systems that are responsible for methane generation. These efforts support the proposed mechanism of the enzymatic reaction and provide important insight into replicating the MCR-like methane-generation process. Furthermore, the modeling of MCR described here is expected to lead to understanding of protein-supported nickel porphyrinoid chemistry as well as the creation of MCR-inspired catalysis.


Critical role of actin bundling in plant cell morphogenesis.
Actin microfilaments form highly-organized structures, such as arrays, meshwork and bundles, and are involved in cell division, organelle motility and intracellular transport in plants. Such organization is indicative of their vital role in directing plant cell morphogenesis. However, the physiological impact of changes in actin bundling level has been unclear until recently, despite progress in our understanding of their roles following actin microfilament disruption. Recent advances have shown that actin bundling levels can be modified through expression of actin binding proteins, or by using auxin transport inhibitors or auxin itself. The technical aspects of these findings have underscored the importance of actin bundling levels in plant cell morphogenesis, including cell division, cell elongation/expansion and stomatal movements. Based on such progress, we discuss the possible mechanisms that connect the actin microfilaments status with cellular dynamics.


Functional Microarray Platform with Self-Assembled Monolayers on 3C-Silicon Carbide.
Currently available bioplatforms such as microarrays and surface plasmon resonators are unable to combine high-throughput multiplexing with label-free detection. As such, emerging microelectromechanical systems (MEMS) and microplasmonics platforms offer the potential for high-resolution, high-throughput label-free sensing of biological and chemical analytes. Therefore, the search for materials capable of combining multiplexing and label-free quantitation is of great significance. Recently, interest in silicon carbide (SiC) as a suitable material in numerous biomedical applications has increased due to its well-explored chemical inertness, mechanical strength, bio- and hemocompatibility, and the presence of carbon that enables the transfer-free growth of graphene. SiC is also multifunctional as both a wide-band-gap semiconductor and an efficient low-loss plasmonics material and thus is ideal for augmenting current biotransducers in biosensors. Additionally, the cubic variant, 3C-SiC, is an extremely promising material for MEMS, being a suitable platform for the easy micromachining of microcantilevers, and as such capable of realizing the potential of real time miniaturized multiplexed assays. The generation of an appropriately functionalized and versatile organic monolayer suitable for the immobilization of biomolecules is therefore critical to explore label-free, multiplexed quantitation of biological interactions on SiC. Herein, we address the use of various silane self-assembled monolayers (SAMs) for the covalent functionalization of monocrystalline 3C-SiC films as a novel platform for the generation of functionalized microarray surfaces using high-throughput glycan arrays as the model system. We also demonstrate the ability to robotically print high throughput arrays on free-standing SiC microstructures. The implementation of a SiC-based label-free glycan array will provide a proof of principle that could be extended to the immobilization of other biomolecules in a similar SiC-based array format, thus making potentially significant advances to the way biological interactions are studied.


The way ahead for Wodonga.
In this adapted version of an article from The Australian Hospital Engineer, Kim Bruton, MIHEA, the magazine's editor, and chief engineer at the Wodonga Hospital campus of the newly-formed Albury Wodonga Health Service in Victoria, Australia, describes a project to both analyse the impact of regular maintenance on plant performance, and significantly reduce energy consumption across the hospital estate in the future.


[Syncope in childhood: not always vasovagal in origin].
Two healthy children, a 10-year-old boy and a 13-year-old girl, both presented with a history of collapse. The boy had had multiple episodes of syncope over a 7-year period. He was diagnosed with reflex syncope on the basis of case history and diagnostic tests. The girl collapsed at school while resting. She was diagnosed with long QT syndrome and was treated with beta-blockers. After DNA-testing both her mother (who had, in retrospect, been wrongly diagnosed with epilepsy), and her brother were also diagnosed with long QT syndrome. Syncope is a common complaint in children and adolescents. In most cases the cause is a benign reflex syncope, but potentially life threatening syncope caused by rare cardiac conditions does occur and needs to be recognized in both the patient and their family members (who may be asymptomatic). Benign reflex syncope and cardiac syncope can be distinguished by performing a thorough medical and family history, physical examination and ECG.


Pediatric infection and sepsis in five age subgroups: single-center registry.
Sepsis is, worldwide, one of the leading causes of death among infants and children. Over the past two decades, mortality rates have declined due to advanced treatment options; however, the incidence of sepsis and septic shock is still on the rise in many hospital settings. The objective of this study was to evaluate the course of this disease in pediatric intensive care patients. An evaluation of pediatric patients in the intensive care unit diagnosed with infections or sepsis between 2005 and 2015 was performed via a retrospective exploratory data analysis. During the observational period, 201 patients were diagnosed with infection or sepsis. The study population was divided into five age subgroups. The majority of patients were newborns, infants, and toddlers. Forty percent had sepsis; 6% had septic shock. Viral infection was the most prevalent (59%). The overall survival rate was 83%; newborns and adolescents had the lowest survival rates. With this registry, children divided into five age subgroups with infection or sepsis were evaluated and treatment strategies were examined. We have shown that our findings on children treated in our pediatric intensive care unit conform with current literature about pediatric sepsis. In addition to maintaining strict hygiene standards, optimal aspects of sepsis care should be stringently observed, such as the quick administration of empirical broad-spectrum antibiotics, initial adequate fluid resuscitation, and a reliable and frequent routine of source control.


Approach to the forgetful patient.
Singapore has an ageing population with a projected 53,000 people aged ≥ 60 years living with dementia by 2020. Primary care doctors have the opportunity to initiate early work-up for reversible causes of cognitive dysfunction, allowing identification of comorbidities and discussion of medical therapy options. Early diagnosis confers the sick role on the patient, which allays frustration and explains events and behaviour that may have strained relationships with family and friends. The patient can be encouraged to plan for future health and personal care options with a Lasting Power of Attorney and/or Advance Care Planning. Objective cognitive tests (e.g. abbreviated mental test and Mini-Mental State Examination) and brain imaging are adjuncts that help in formulating the diagnosis. Referral to a hospital memory clinic activates a multidisciplinary team approach to dementia, including clinical consultation, dementia counselling, physiotherapy sessions on gait/fall prevention, occupational therapy sessions on cognitive stimulation and caregiver training.


When typical is atypical: mycobacterial infection mimicking cutaneous vasculitis.
Patients with systemic lupus erythematosus (SLE) who present with skin disease pose the clinician with diagnostic challenges. The skin disease can reflect an increase in systemic disease activity suggested by other features of active lupus and, as such, usually responds well to more aggressive immunosuppressive therapy. Other possibilities of skin disease include drug eruptions, skin disease unrelated to SLE and, more rarely, opportunistic skin infection. In patients who show a poor response to more aggressive immunosuppressive therapy, consideration must be given to the possibility of opportunistic infection. A high index of suspicion will allow prompt treatment. We describe two patients with SLE who developed cutaneous atypical mycobacterial infection during immunosuppressive therapy. The diagnosis of cutaneous vasculitis was considered in both cases, but subsequent skin biopsy revealed the correct diagnosis. This report illustrates the importance of skin biopsy in patients with suspected cutaneous lupus who are not responding to immunosuppressive therapy.


A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp.
Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the corneodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin. To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene. The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed. By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation co-segregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI. A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins.


Effects of the dialectical behavioral therapy-mindfulness module on attention in patients with borderline personality disorder.
It is known that patients with borderline personality disorder (BPD) show attention deficits and impulsivity. The main aim of this study was to explore the effects of Dialectical Behavioral Therapy-Mindfulness training (DBT-M), used as an adjunct to general psychiatric management (GPM), on attention variables in patients diagnosed with BPD. A second objective was to assess the relation of mindfulness formal practice on clinical variables. A sample of 60 patients with BPD was recruited. Forty of them were allocated to GPM + DBT-M treatment and the other 20 received GPM alone. At the termination of the mindfulness training, DBT-M + GPM group showed a significant improvement on commissions, hit reaction time, detectability scores from the CPT-II neuropsychological test, and also on the composite scores of inattention and impulsivity. Further, the more minutes of mindfulness practice were correlated to greater improvement in general psychiatric symptoms and affective symptomatology, but not in CPT-II measures. This is probably the first study so far assessing the effects of this single DBT module in patients with BPD. The results suggest a positive effect of such intervention on attention and impulsivity variables.


Preventable hospitalizations and emergency department visits for angina, United States, 1995-2010.
Preventable hospitalizations for angina have been decreasing since the late 1980s - most likely because of changes in guidance, physician coding practices, and reimbursement. We asked whether this national decline has continued and whether preventable emergency department visits for angina show a similar decline. We used National Hospital Discharge Survey data from 1995 through 2010 and National Hospital Ambulatory Medical Care Survey data from 1995 through 2009 to study preventable hospitalizations and emergency department visits, respectively. We calculated both crude and standardized rates for these visits according to technical specifications published by the Agency for Healthcare Research and Quality, which uses population estimates from the US Census Bureau as the denominator for the rates. Crude hospitalization rates for angina declined from 1995-1998 to 2007-2010 for men and women in all 3 age groups (18-44, 45-64, and ≥65) and age- and sex-standardized rates declined in a linear fashion (P = .02). Crude rates for preventable emergency department visits for angina declined for men and women aged 65 or older from 1995-1998 to 2007-2009. Age- and sex-standardized rates for these visits showed a linear decline (P = .05). We extend previous research by showing that preventable hospitalization rates for angina have continued to decline beyond the time studied previously. We also show that emergency department visits for the same condition have also declined during the past 15 years. Although these declines are probably due to changes in diagnostic practices in the hospitals and emergency departments, more studies are needed to fully understand the reasons behind this phenomenon.


Somatic Embryogenesis in the Medicago truncatula Model: Cellular and Molecular Mechanisms.
Medicago truncatula is now widely regarded as a legume model where there is an increasing range of genomic resources. Highly regenerable lines have been developed from the wild-type Jemalong cultivar, most likely due to epigenetic changes. These lines with high rates of somatic embryogenesis (SE) can be compared with wild-type where SE is rare. Much of the research has been with the high SE genotype Jemalong 2HA (2HA). SE can be induced from leaf tissue explants or isolated mesophyll protoplasts. In 2HA, the exogenous phytohormones 1-naphthaleneacetic acid (NAA) and 6-benzylaminopurine (BAP) are central to SE. However, there are interactions with ethylene, abscisic acid (ABA), and gibberellic acid (GA) which produce maximum SE. In the main, somatic embryos are derived from dedifferentiated cells, undergo organellar changes, and produce stem-like cells. There is evidence that the SE is induced as a result of a stress and hormone interaction and this is discussed. In M. truncatula, there are connections between stress and specific up-regulated genes and specific hormones and up-regulated genes during the SE induction phase. Some of the transcription factors have been knocked down using RNAi to show they are critical for SE induction (MtWUSCHEL, MtSERF1). SE research in M. truncatula has utilized high throughput transcriptomic and proteomic studies and the more detailed investigation of some individual genes. In this review, these studies are integrated to suggest a framework and timeline for some of the key events of SE induction in M. truncatula.


The death drive: conceptual analysis and relevance in the Spanish psychoanalytic community.
Based on a six-year doctoral research, the author carries out a historical, epistemological and paradigmatic assessment of the controversial concept of the death instinct. The author analyses this notion's speculative nature; its relation with the second principle of thermodynamics; the feasibility of a return to an inorganic state; the death drive's metaphorical and isomorphic uses, as well as its theoretical and doctrinaire approaches; its relationship with repetition compulsion and masochism; the influence of Freud 's scientific background on its formulation; and its context-dependent meaning. Although this paper stems mainly from the theoretical aspects of the study, it also offers some clinical thoughts on the basis of a clinical vignette. The author stresses the underlying healing aspects of repetition in the analytic situation. Next, he presents concise comments on his empirical research on the current professional usage of the death drive in the Spanish psychoanalytical community. This research covered more than 27% of Spanish psychoanalysts (IPA) and psychotherapists (EFPP). The essay's conclusions point to the ambiguous character of the death drive concept and its literal unacceptability and the absence of consistent arguments for its acceptance.


The Neurophysiological Index in ALS.
The Neurophysiological Index (NI) consists of a mathematical derivation of three standardised neurophysiological measurements. Since these measurements are part of routine practice in any clinical neurophysiology laboratory, calculation of the NI is within the capability of any laboratory. The NI is derived from the CMAP, the DML and the F-wave frequency (CMAP amplitude/DML) x F frequency %), representing aspects of the effects of denervation and reinnervation, of degeneration of the terminal part of the motor axons, and of the excitability of anterior horn cells. We have shown that this simple index is reproducible in consecutive studies of normal subjects and of patients with ALS (intra-rater reliability), and is sensitive to change. In ALS, the NI differentiates rapidly and slowly progressive disease at least as sensitively as other measures in common use, including the ALS-FRS. We propose that the NI could be used as a sensitive measure of change during the course of ALS and its treatment. In combination with relevant measures of clinical benefit, such as ALS-FRS and a QoL measure, this could simplify trial design and allow more rapid determination of the efficacy of putative new therapies in clinical trials.


Limited tryptic modification stimulates activation of Ca2+ release from isolated sarcoplasmic reticulum vesicles.
Tryptic modification appears to potentiate activation of the Ca2+ channels of isolated sarcoplasmic reticulum vesicles. In the presence of 1 mM free Mg2+ we observe that: 1) cAMP and doxorubicin activation of passive efflux from tryptically modified vesicles is approximately 20-fold greater than from native SR. 2) Ruthenium red inhibits Ca2+ efflux from modified vesicles. 3) The binding affinities and Hill coefficients of activation of efflux by cAMP and doxorubicin are the same in modified vesicles as in native vesicles. 4) Proteolysis stimulates passive efflux from heavy SR much more than from light SR. 5) Stimulation of cAMP- and doxorubicin-activated Ca2+ release is biphasic, whereas Hg2+-activated Ca2+ efflux is monophasic. 6) In the absence of Mg2+, the Ca2+ dependence of cAMP-activated efflux from tryptically modified vesicles is similar to that of native vesicles, with peak efflux rates occurring between approximately 1 and 10 microM Ca2+. 7) The Mg2+ dependence of efflux from modified vesicles is similar to that of native vesicles. 8) SDS-polyacrylamide gels indicate that the Ca2+, Mg2+-ATPase and the high molecular weight ryanodine receptor are both cleaved faster than the stimulation of efflux.


HIV vaccines. Controversy continues in Nigeria over supposed preventive and curative vaccine.
The Nigerian government is butting heads with Dr. Jeremiah Abalaka over Abalaka's AIDS vaccine, with the government taking the latest hit. Abalaka claims to have successfully produced a vaccine that can reduce or cure HIV. The vaccine has been administered to infected people, with adverse results, the government claims. According to a report in Nigeria's Post Express newspaper ("Nigeria: Why We Stopped Use of the Vaccines-Atiku", Post Express (Lagos) July 25, 2000, by Obiorah Ifo), the country's vice president, Alhaji Atiku Abubakar, said the government has stepped in to stop Abalaka from administering the vaccine "because it has killed more people than it has cured". The newspaper quoted him saying that it was only in Nigeria that "somebody can go and manufacture vaccine without permission and authorization of the drug administration of the country before he can begin to administer it on Nigerians". Then on July 31, 2000, the Federal Court of Appeal backed Abalaka and ordered that the government stop investigating the vaccine. "The court, presided over by Justice Muntaka Coomassie, also granted an interim order restraining the defendant from taking any action on Dr. Abalaka pending the hearing of the motion on notice", said an article in the Vanguard Daily newspaper ("Court halts federal government over Abalaka's HIV vaccine", Vanguard Daily (Lagos) July 31, 2000, by Bukola Ojeme). The government's primary complaint is that Abalaka reportedly would not back his claims for the vaccine with proper scientific data. A team of medical experts found "the vaccine could not pass through any acceptable criteria", the Post Express report said, and so the government had ordered that use of the vaccine cease. According to Abubakar, the vaccine "has caused more havoc, it has killed people, and it will kill more. That is when the government decided to intervene. Meanwhile, the man is busy administering the vaccine and people are dying", the Post Express quoted him as saying. Nigerian go


Scutellariabarbata D. Don extraction selectively targets stemness-prone NSCLC cells by attenuating SOX2/SMO/GLI1 network loop.
Scutellariabarbata D. Don extraction (SBE), a traditional Chinese medicine, has been proved effective against various malignant disorders in clinics with tolerable side-effects when administered alone or in combination with conventional chemotherapeutic regimens. Multi-drug resistance of cancer is attributed to existence of cancer stemness-prone cells that harbor aberrantly high activation of Sonic Hedgehog (SHH) cascade. Our previous study has demonstrated that SBE sensitized non-small cell lung cancer (NSCLC) cells to Cisplatin (DDP) treatment by downregulating SHH pathway. Yet, whether SBE could prohibit proliferation of cancer stemness-prone cells and its underlying molecular mechanisms remain to be investigated. In this article, we further investigated intervention of SBE on NSCLC cell stemness-associated phenotypes and its potential mode of action. CCK-8 and clonal formation detection were used to measure the anti-proliferative potency of SBE against NSCLC and normal epithelial cells. Sphere formation assay and RQ-PCR were used to detect proliferation of cancer stemness cells and associated marker expression upon SBE incubation. Mechanistically, DARTS-WB and SPR were used to unveil binding target of SBE. Immunodeficient mice were implanted with patient derived tumor bulk for in vivo validation of anti-cancer effect of SBE. SBE selectively attenuated proliferation and stemness-like phenotypes of NSCLC cells rather than bronchial normal epithelial cells. Drug-protein interaction analysis revealed that SBE could directly bind with stem cell-specific transcription factor sex determining region Y-box 2 (SOX2) and interfere with the SOX2/SMO/GLI1 positive loop. In vivo assay using patient-derived xenografts (PDXs) model further proved that SBE diminished tumor growth and SOX2 expression in vivo. Our data indicate that SBE represses stemness-related features of NSCLC cells via targeting SOX2 and may serve as an alternative therapeutic option for clinic treatment.


Sleep Architecture in Response to a Late Evening Competition in Team-Sport Athletes.
The aim of this study was to assess the effect of a late evening competition on sleep characteristics and perceived recovery in team-sport players using a validated self-applicable and portable polysomnographic device. Sixteen team-sport players (age: 25.4 [1.4] y; body mass index: 23.6 [0.5] kg/m2) completed the study. Objective and subjective sleep data were collected for 4 consecutive nights: 2 nights before (PRE2 and PRE1) and the 2 nights after an evening match (POST1), performed between 6:00 PM and 9:00 PM. Total quality of recovery values were also collected in the morning. A significantly delayed bedtime (P < .0001; ηp2=.68, large) was observed in the first night after the competition (2 h 29 min [1 h 15 min]) compared both to PRE2 (+88 min; P < .0001), PRE1 (+98 min; P < .0001), and POST1 (+100 min; P < .0001), and similar results were observed for wake-up time (P = .033; ηp2=.39, large): Players woke up significantly later in evening match (9 h 20 min [1 h 55 min]) compared with PRE2 (+85 min; P = .050) and POST1 (+85 min; P = .049). Conversely, total sleep time; sleep efficiency; sleep onset latency; wake after sleep onset; cortical arousals; N1, N2, N3, and REM (rapid eye movement) percentages; total quality of recovery values; and scores of subjective sleep quality did not vary among the 4 study nights. Team-sport players had delayed bedtime and wake-up time following an evening competition; however, sleep quality, duration, and subjective scores of recovery were not affected by the evening match. The delayed wake-up time seems to protect athletes' sleep efficiency/duration against the evening-match-induced delayed bedtime.