Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and Histopathology in Kidney of Wistar Rat.
Cadmium (Cd) is a non-essential metal whose dispersion in the environment has increased recently, Cd may enhance cell oxidative stress that leads to DNA damage and apoptotic cell death. The study aimed to evaluate the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced oxidative stress and histopathology of the kidney of Wistar rats. Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1) for five weeks with two groups pre-treated with 'Arctium lappa' administration, 100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test to determine the difference among means using the JMP version 12. Results revealed that cadmium induced a significant disorganization (p<0.05) of renal structure with collapsed tubular lamina and 76 μm tail length of the cells was observed, while histological sections of kidney pre-treated with 100 mg Arctium lappa kg-1 b.wt., showed a slightly less hypercellularity of glomerulus and reduction in the cell tail (59 μm). Furthermore, histological sections of kidney of rats pre-treated with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules and glomerulus with a prominent urinary space beside tail length of cells was recorded as 39 μm which was lower in comparison to other groups. Moreover, cadmium induced cellular destruction of the kidney was resumed with the pre-treatment of the secondary metabolites as an antioxidant compounds that produced from plant extracts. Arctium lappa leaf extract was efficient at both applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative effect.


Contributing Factors to Heterogeneity in the Timing of the Onset of Nonfatal Suicidal Behavior: Results From a Nationally Representative Study.
It remains unclear whether specific clinical factors contribute to heterogeneity in the timing of the onset of nonfatal suicidal behavior. This knowledge could have important implications for suicide prevention. Using a nationally representative US adult sample, the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005; n = 34,629), we compared the characteristics of 4 different suicide attempter groups: those who first attempted (1) before 18 years, (2) from 18 to 34 years, (3) from 35 to 49 years, and (4) at 50 years or older. Specifically, DSM-IV psychiatric disorders that occurred before the first suicide attempt, childhood maltreatment experiences, parental history of psychiatric disorders, and sociodemographic characteristics were examined. Most first nonfatal suicide attempts (85.3%) occurred before age 35 years. Compared with suicide attempts occurring from 18 to 34 years, suicide attempts occurring before 18 years were more strongly associated with childhood maltreatment and less strongly linked to lifetime prior psychiatric disorders, whereas first suicide attempts occurring at 35 years and older were more strongly associated with a prior lifetime history of substance use disorders, including alcohol use disorder and nicotine dependence, and mood disorders, including mania/hypomania and dysthymic disorder between 35 and 49 years and major depressive episode at 50 years and older (all P < .05). These results suggest age differences in risk factors for first nonfatal suicide attempt. Improving early detection and treatment of psychiatric disorders and preventing childhood maltreatment may have broad benefits to reduce the burden of suicidal behavior at all ages.


Effect of noxythiolin on experimental peritonitis.
The intraperitoneal instillation of noxythiolin in the treatment of peritonitis is widespread in clinical practice despite contradictory evidence as to its efficacy. In this light the value of noxythiolin was reappraised by studying its effect in guinea-pigs and mice with induced bacterial peritonitis. Treatment with a 1% solution of noxythiolin reduced the mortality rate of mice by 14% (P less than 0.1). The guinea-pig model proved unreliable giving inconsistent mortality rates throughout. Further studies are required to determine the optimum dose and concentration of noxythiolin while the search for more effective intraperitoneal antiseptics should continue.


Age calculation using X-ray microfocus computed tomographical scanning of teeth: a pilot study.
To correlate dental age with an individual's chronological age based on the calculated volume ratio of pulp versus tooth volume measured, an X-ray microfocus computed tomography unit (microCT) with 25 microm spatial resolution was used to non-destructively scan 43 extracted single root teeth of 25 individuals with well-known chronological age. Custom-made analysis software was used by two examiners to obtain numerical values for pulpal and tooth volume. The ratio of both was calculated and statistically processed. No significant intra- or inter-examiner differences were found. In fact, a very strong concordance correlation coefficient was found. Linear regression analysis showed a coefficient of determination (r) of 0.31 which suggests that there is a rather weak correlation between the volume ratio of pulp versus tooth and biological age. Although rather time consuming, this technique shows promising results for dental age estimation in a non-destructive manner using X-ray microfocus computed tomography.


Eye motion correction algorithm for OCT-based corneal topography.
With its sequential image acquisition, OCT-based corneal topography is often susceptible to measurement errors due to eye motion. We have developed a novel algorithm to detect eye motion and minimize its impact on OCT topography maps. We applied the eye motion correction algorithm to corneal topographic scans acquired using a 70 kHz spectral-domain OCT device. OCT corneal topographic measurements were compared to those from a rotating Scheimpflug camera topographer. The motion correction algorithm provided a 2-4 fold improvement in the repeatability of OCT topography and its agreement with the standard Scheimpflug topographer. The repeatability of OCT Zernike-based corneal mean power, cardinal astigmatism, and oblique astigmatism after motion detection was 0.14 D, 0.28 D, and 0.24 D, respectively. The average differences between the two devices were 0.19 D for simulated keratometry-based corneal mean power, 0.23 D for cardinal astigmatism, and 0.25 D for oblique astigmatism. Our eye motion detection method can be applied to any OCT device, and it therefore represents a powerful tool for improving OCT topography.


Effect of Oscillation on Perineal Pressure in Cyclists: Implications for Micro-Trauma.
Genital numbness and erectile dysfunction in cyclists may result from repeated perineal impacts on the bicycle saddle (micro-trauma) that occur during routine cycling. To evaluate the relationship between oscillation forces and perineal pressures among cyclists in a simulated laboratory setting. Participants were fit to a study bicycle to ensure all cyclists had the same torso angle (60 ± 1 degree) and maximum knee angle (150 ± 1 degree). A lever system was used to generate oscillation events of 3 progressively increasing magnitudes. Perineal pressure was continuously measured using a pressure sensor on the bicycle saddle. This process was carried out in each of the following conditions: (1) stationary (not pedaling) with the standard seatpost, (2) pedaling with standard seatpost, (3) stationary with seatpost shock absorber, and (4) pedaling with seatpost shock absorber. We compared perineal pressure changes during oscillation events in the stationary and pedaling states, with and without the seatpost shock absorber. A total of 39 individuals were recruited (29 men and 10 women). As the amount of oscillation increased from an average of 0.7g (acceleration due to Earth's gravity) to 1.3g, the perineal pressure increased from 10.3% over baseline to 19.4% over baseline. There was a strong linear relationship between the amount of oscillation and increase in pressure (r2 = 0.8, P < .001). A seatpost shock absorber decreased the impact of oscillation by 53% in the stationary condition. Men and women absorbed the majority of shock in areas corresponding to pelvic bony landmarks. This study represents one of the first characterizations of cycling-associated perineal micro-trauma in a laboratory setting. We found a strong linear relationship between oscillation magnitude and perineal pressure during cycling, which was mitigated by a seatpost shock absorber. The use of shock absorption in bicycle design may reduce perineal micro-trauma and potentially improve cycling-associated perineal numbness and erectile dysfunction. Sanford T, Gadzinski AJ, Gaither T, et al. Effect of Oscillation on Perineal Pressure in Cyclists: Implications for Micro-Trauma. Sex Med 2018;6:239-247.


Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients.
Two patients (brother and sister, 41 and 39 yr of age, respectively) have been shown to have marked elevation of plasma triglycerides and chylomicrons, decreased low density lipoproteins (LDL) and high density lipoproteins (HDL), a type I lipoprotein phenotype, and a deficiency of plasma apolipoprotein C-II (apo C-II). The male patient had a history of recurrent bouts of abdominal pain often accompanied by eruptive xanthomas. The female subject, identified by family screening, was asymptomatic. Hepatosplenomegaly was present in both subjects. Analytical and zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins including chylomicrons and very low density lipoproteins, a reduction in LDL, and the presence of virtually only the HDL3 subfraction. LDL were heterogeneous with the major subfraction of a higher hydrated density than that observed in plasma lipoproteins of normal subjects. Apo C-II levels, quantitated by radioimmunoassay, were 0.13 mg/dl and 0.12 mg/dl, in the male and female proband, respectively. A variant of apo C-II (apo C-IIPadova) with lower apparent molecular weight and more acidic isoelectric point was identified in both probands by two-dimensional gel electrophoresis. The marked hypertriglyceridemia and elevation of triglyceride-rich lipoproteins were corrected by the infusion of normal plasma or the injection of a biologically active synthesized 44-79 amino acid residue peptide fragment of apo C-II. The reduction in plasma triglycerides after the injection of the synthetic apo C-II peptide persisted for 13-20 d. These results definitively established that the dyslipoproteinemia in this syndrome is due to a deficiency of normal apo C-II. A possible therapeutic role for replacement therapy of apo C-II by synthetic or recombinant apo C-II in those patients with severe hypertriglyceridemia and recurrent pancreatitis may be possible in the future.


The evolution of AGHE as a global leader in education on aging: Why, how, and what's next.
The scope of AGHE's responsibility to gerontology and geriatrics extends worldwide, as reflected in its tag line, "Global Leaders in Education on Aging." Optimal responses to worldwide demographic transitions can only come from persons well versed in the dimensions of aging and trained and globally situated to translate that knowledge into effective and culturally appropriate solutions. This article reviews the evolution of AGHE's role in initiating and fostering global networks of educators in gerontology and geriatrics, including collaborative efforts with major international organizations (e.g., WHO, UN, IAGG) to increase the visibility and appreciation of aging-related issues among world leaders; sponsoring national and international meetings and publications to promote the exchange of ideas and refinement of teaching methodologies; initiating and adapting new models of gerontological training enhanced by advances in information and communication technology; and supporting world-wide cohorts of emerging scholars to assume leadership roles within the organization. Recommendations for next steps are considered.


Delayed diagnosis of thoracolumbar fractures in multiple-trauma patients.
To determine the frequency of delayed diagnosis of major thoracolumbar vertebral fractures (T-L Fxs) in ED multiple-trauma patients, and to determine the differences between cases of delayed and nondelayed diagnoses of T-L Fx. A retrospective chart review was conducted of 181 trauma patients with 310 major T-L Fxs (compression, burst, or chance Fxs or dislocations). Data collected included the time of the diagnosis of T-L Fx, the patient's clinical presentation in the ED, the mechanism of injury, and the outcome. Of the 181 patients with major T-L Fxs, 138 were diagnosed in the ED (nondelayed group), and 43 were diagnosed after the patient left the ED (delayed group). Of these, 33 cases occurred in unstable patients requiring emergent medical imaging and/or operation, 7 occurred when emergency physicians failed to detect subtle compression Fxs on ED radiographs, and 3 occurred in stable patients who were not radiographed in the ED. The delayed group were more often critical, and hypotensive, and had lower Glasgow Coma Scale (GCS) scores than did the nondelayed group. The delayed group patients also had more cervical spine injuries, multiple noncontiguous spinal Fxs, high-energy mechanisms of injury, and direct blunt assaults to the back than did the nondelayed group patients. There were 13 patients with T-L Fxs, GCS scores = 15, and normal back examinations. There were 43 patients who had neurologic deficits associated with their injuries; 11 patients with incomplete cord lesions progressed, including 3 in the delayed group. A delay in the diagnosis of T-L Fx in hospitalized trauma patients is frequently associated with an unstable patient condition that necessitates higher-priority procedures than ED T-L spine radiographs. Such patients should receive spinal precautions until more complete evaluation can be performed. The decision to selectively radiograph T-L spines in multiple-trauma patients should consider the mechanism of injury, the presence of possible confounders to physical examination, and clinical signs and symptoms of back injury.


Effects of short-term second language learning on the development of individual semantic networks in written and spoken language.
Previous studies have primarily focused on the relationship between native language (L1) and second language (L2) in the brain, specifically in one language modality, such as written or spoken language. However, there is limited research on how L2 proficiency impacts both modalities. This study aimed to investigate the functional networks involved in reading and speech comprehension for both L1 and L2, and observe changes in these networks as L2 proficiency improves. The dataset used in this study was obtained from a previous research conducted by Gurunandan et al., which involved Spanish-English bilingual participants undergoing a three-month English training program. Participants underwent fMRI scanning and performed a semantic animacy judgment task in both spoken and written language before and after training. Through analysis, distinct neural networks associated with spoken and written language were found between individuals' L1 and L2, both before and after training. Moreover, as L2 proficiency improved, the spoken and written networks for L2 remained distinct from those of the L1. These findings suggest that short-term L2 learning experiences can modify neural networks, but may not be enough to achieve native-like proficiency, supporting the accommodation hypothesis. These results have important implications for language learning and education, indicating that additional short-term training and exposure alone may not bridge the gap between L1 and L2 processing networks.


DETECTing Merkel Cell Polyomavirus in Merkel Tumors.
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCV) T antigen expression, post-integration (~80% cases), or by UV-mediated DNA damage. Interestingly, overall survival of MCV-positive Merkel cell carcinoma patients is better, making this differential information of significant diagnostic and prognostic value. Also, MCV provides a direct target for therapy in MCC patients. Currently, the methods used for diagnosis of MCV in tumors are often discordant and unreliable. Here we used a guided molecular scissors based-DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) technique to develop an in vitro molecular diagnostic tool for MCV-positive MCC. DETECTR couples recombinase polymerase based amplification of target MCV DNA with Cas12a mediated detection. CRISPR diagnostics couple specific detection followed by cutting of the pathogenic DNA by the Cas enzyme-gRNA complex, with non-specific cutting of ssDNA that provides a measurable visual cue. To detect MCV DNA in MCC, we designed Cas12a gRNAs targeting the MCV DNA and tested their targeting efficiency, and sensitivity using a fluorophore quencher labeled reporter assay. We show that MCV DETECTR system can detect MCV integrated in Merkel tumor rapidly, specifically and with femto-molar sensitivity. Our study is a preliminary, proof-of-principle analysis showing the use of CRISPR for MCV diagnosis. Further validation in human tumor samples is needed for its clinical use in the near future. This new system is promising and we hope it can be coupled with immunohistochemical studies to diagnose the viral status of MCC in clinics soon.


A new technique for reduction of atlantoaxial subluxation using a simple tool during posterior segmental screw fixation: clinical article.
The authors introduce a simple technique and tool to facilitate reduction of atlantoaxial subluxation during posterior segmental screw fixation. Two types of reduction tool have been designed: T-type and L-type. A T-shaped levering tool was used when a pedicle or pars screw was used for C-2, and an L-shaped tool was used when a laminar screw was used for C-2. Twenty-two patients who underwent atlantoaxial segmental screw fixation and fusion for the treatment of anteroposterior instability or subluxation, using either of these new types of reduction tool, were enrolled. Demographic, clinical, and surgical data, which had been prospectively collected in a database, were analyzed. The atlantodens interval was measured on lateral radiographs, and the space available for the spinal cord was measured on CT scans. The authors could attain reduction of the atlantoaxial subluxation without difficulty using either type of tool. The preoperative atlantodens interval ranged from -16.9 to 10.9 mm in a neutral position, and the postoperative interval ranged from -2.8 to 3.0 mm, with negative values due to extension-type or mixed-type instability. The mean space available for the spinal cord significantly increased, from 9.5 mm preoperatively to 15.4 mm postoperatively (p < 0.001). This technique allowed for controlled manipulation and reduction of the atlantoaxial subluxation without difficulty.


An overview and performance evaluation of classification-based least squares trained filters.
An overview of the classification-based least squares trained filters on picture quality improvement algorithms is presented. For each algorithm, the training process is unique and individually selected classification methods are proposed. Objective evaluation is carried out to single out the optimal classification method for each application. To optimize combined video processing algorithms, integrated solutions are benchmarked against cascaded filters. The results show that the performance of integrated designs is superior to that of cascaded filters when the combined applications have conflicting demands in the frequency spectrum.


Development of optokinetic neuronal responses in the pretectum and horizontal optokinetic nystagmus in unilaterally enucleated rats.
Responses of single units to constant-velocity rotations of the visual surround (0.25-10 degrees/s) were studied in the pretectum of unilateral enucleated rats at different ages. Enucleation was performed either in the first postnatal week ("early" enucleated rats) or in the adult stage ("late" enucleated rats). Pretectal unitary responses were recorded in early enucleated animals at postnatal day 20-21, 36-49 and, in both experimental groups, in the adult stage. Optokinetic ocular nystagmus was studied in early and late enucleated rats in the adult stage. Gain of optokinetic nystagmus in temporo-nasal stimulus direction was not changed for visual surround rotations of up to 20 degrees/s compared to controls in monocular viewing conditions. At higher stimulus velocities, however, the gain dropped. In naso-temporal stimulus direction, optokinetic nystagmus was improved in gain for optokinetic pattern motions of up to 5-10 degrees/s. There were only minor differences in the gain behaviour of optokinetic nystagmus obtained from early or late enucleated rats. The optokinetic responses of pretectal neurons obtained from early and late enucleated rats were reduced in sensitivity by more than 50%. The response patterns of neurons recorded in the contralateral pretectum relative to the intact eye were shifted by a large amount from directional selective to directional nonselective response types. No such changes were obtained in the ipsilateral pretectum. In contrast to normal rats, there were very few directional selective units responding to temporo-nasal pattern motion. On the other hand, a large proportion of directional selective units responded to naso-temporal pattern motion. These latter units were found in both early and late enucleated rats. A similar response type has previously been described for intact young rats but not for adult rats. The velocity tuning curve of pretectal units studied in the adult stage was similar in shape in early and late enucleated rats and resembled that obtained from enucleated or intact young animals. Our results show that response sensitivity, direction and velocity tuning of pretectal units depend crucially on retinal afferent input originating from both eyes. The data suggest that the response characteristics of many of the pretectal units that are considered to be important for mediating optokinetic reflexes depend on interpretectal signal processing using commissural connections. There is very little evidence for an adaptative structural plasticity of the optokinetic system following loss of one eye. The reduced asymmetry observed in gain of optokinetic responses correlated in both early and late enucleated rats with the shifts observed in the distribution of pretectal unitary response patterns.


'A contradiction between our state and the tobacco company': conflicts of interest and institutional constraints as barriers to implementing Article 5.3 in Bangladesh.
Bangladesh has not yet adopted measures to implement Article 5.3 of the WHO Framework Convention on Tobacco Control. The National Tobacco Control Cell (NTCC) has drafted a guideline for implementation, but progress has stalled amid high levels of tobacco industry interference in public policy. This paper examines the barriers to minimising industry interference in a context of close relationships between government officials and tobacco companies. In-depth interviews were conducted with government officials, representatives from civil society, think tank and media organisations, and academic researchers. The data were analysed using a '3 Is' framework developed within the political sciences, emphasising the interactive role of ideas, interests and institutions in policy change. The findings indicate that policy ideas about protecting public health policy making from tobacco industry interests are largely restricted to the Ministry of Health and Family Welfare, and the NTCC specifically. Both individual and institutional conflicts of interest emerge as key barriers to progress to minimising industry interference and for tobacco control governance more broadly. The data also suggest that development of an Article 5.3 guideline has been shaped by the perceived interests of political actors and institutions, and the institutional position of the NTCC, constrained by limits on its resources, authority and isolation from other ministries. NTCC's initiatives towards implementing Article 5.3 constitute an important opportunity to address conflicts of interest that restrict tobacco control in Bangladesh. Progress in minimising industry interference is essential to realising the commitment to being smoke free by 2040.


[Financial capital versus medical-industrial complex: challenges for the regulatory agencies].
This article presents the structural processes that consolidated under the hegemony of the financial capital in the 90s; the dispute between the financial capital operating in the health sector and the medical-industrial complex; the strategies used by the medical-industrial complex for regaining positions; and the challenges all these processes pose for the regulatory agencies. The problems the regulatory agencies are facing lie in two central processes: 1) the hegemony the financial capital reached in the 90s in the health sector through reforms aimed at deregulating the sector in order to facilitate its entrance; and 2) the repositioning of the medical-industrial complex since the mid 90s by radicalizing medicalization. This article is based on several studies conducted by the author using qualitative methods and quantitative secondary data for understanding the historical-situational context. The theoretical approach was based on Marx, Gramsci, Benasayag, Badiou, Testa and Merhy. The analyses of the most recent reforms induced by the medical-industrial complex were the result of a bibliographic and document review.


Improving covalent cell encapsulation with temporarily reactive polyelectrolytes.
Calcium alginate/poly-L-lysine beads were coated with either 50% hydrolyzed poly(methyl vinyl ether-alt-maleic anhydride) (PMM(50)), or with poly(vinyl dimethyl azlactone-co-methacrylic acid) (50:50, PMV(50)), to form covalently shell-crosslinked capsules, and compared with analogous capsules coated with sodium alginate. All capsule types were prepared with and without C2C12 murine myoblast cells, and implanted into mice for up to 6 weeks. Cell viability, capsule integrity, fibrotic overgrowth, and mechanical strength of the capsules were assessed, and correlated with inflammatory cytokine marker levels in tail vein blood samples taken at different time points. AP-PMM(50) capsules displayed the least amount of fibrotic overgrowth, were found to be the strongest, and showed the lowest levels of TNF-α in tail vein serum samples taken at 4 h, 24 h, 1 and 6 weeks post transplantation. The results for APA and AP-PMV(50) capsules were more variable and depended on the presence or absence of encapsulated cells.


Validity of field assessments to predict peak muscle power in preschoolers.
Field-based fitness assessments are time- and cost-efficient. However, no studies to date have reported the predictive value of field-based musculoskeletal fitness assessments in preschoolers. The purpose of this study was to determine the validity of 2 field assessments to predict peak muscle power in preschool-aged children. Four-hundred and nineteen 3- to 5-year olds participated (208 girls, 211 boys; mean age: 4.5 ± 0.9 years). Peak power (PP) was evaluated using a modified 10-s Wingate protocol as the criterion standard. Standing long-jump was measured in inches to the back of the heel using a 2-footed takeoff and landing. Shuttle-run time was measured using a shuttle-run protocol, which required children to sprint 50 feet (15.2 m), pick up a small block, and sprint back, with time measured to the closest tenth of a second. Regression modelling was used to calculate the predictive power of each field-based measurement, adjusting for weight (kg), age, and sex. Both standing long-jump distance and shuttle-run time were significantly correlated with PP (r = 0.636, p < 0.001, and r = -0.684, p < 0.001, respectively). Linear regression analysis determined that a child's PP can be predicted from the child's weight, age, and sex and either standing long-jump or shuttle-run time (adjusted R2 = 0.79, p < 0.001, and 0.81, p < 0.001, respectively). The standing long-jump and the Bruininks Oseretsky Test of Motor Proficiency 2nd Edition shuttle-run are both significant predictors of peak muscle power in preschool children. Either measure can be used as a cost- and time-efficient estimate of musculoskeletal fitness in preschoolers.


Inhibition of Human Y Chromosome Gene, SRY, Promotes Naïve State of Human Pluripotent Stem Cells.
Although males and females have a variety of sexually dimorphic features related to hormonal effects, the genetic basis of dimorphism relies on early embryo development. Two pluripotent states, naïve and primed, emerge during early mammalian development. Identification of signaling pathways that induce differences between these two states can help to modulate conversion of primed cells to naïve cells. Naïve cells have a shorter doubling time and longer survival than their primed counterparts when passaged as single cells. In this study, we sought to explore the role of Y chromosome genes on human pluripotent stem cells (hPSCs) by investigating differential expressions of the male-specific region of the Y chromosome (MSY) genes in primed and naïve cells. Interestingly, we found that several MSY genes, including SRY, showed higher expression levels in primed compared to naïve human embryonic stem cells (hESCs). We hypothesize that SRY prevents WNT/β-catenin signaling by its interaction and inhibition of β-catenin activation in the nucleus. Results of the loss-of-function approach conducted by depletion of SRY indicated increased expressions of pluripotency marker genes and alkaline phosphatase (ALP) activity in the primed cells. SRY reduction was associated with overexpression of WNT signaling target genes AXIN2, Brachury, TCF1, TBX2, and TBX3. We suggest that inhibition of SRY may result in activation of β-catenin and up-regulation of the WNT signaling pathway, both of which are important to naïve conversion.


The hematologist and radiation casualties.
Since the terrorist attack of September 11, 2001, preparation by the health care system for an act of terrorism has been mandated by leaders of governments. Scenarios for terrorist acts involving radioactive material have been identified, and approaches to management (based on past experience from atomic weapons detonations and radiation accidents) have been developed. Because of their experience in managing patients with profound cytopenia and/or marrow aplasia, hematologists will be asked to play a significant role in evaluating and treating victims of mass accidental or deliberate exposure to radiation. This review provides a framework for understanding how radiation levels are quantified, how radiation alters the function of hematopoietic (and nonhematopoietic) cells and tissues, and how victims receiving a significant radiation dose can be identified and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the Acute Radiation Syndrome: the hematopoietic, neurovascular, gastrointestinal and cutaneous subsyndromes. Clinical signs and symptoms are discussed for exposed individuals at the time of initial presentation (the prodromal phase) and during their course of disease (the manifest illness). In Section II, he presents clinical and laboratory methods to assess radiation doses, including time to onset and severity of vomiting, rate of decline in absolute blood lymphocyte count and the appearance of chromosome aberrations such as dicentrics and ring forms. Potential scenarios of a radiation terrorist event are reviewed, and methods for initial clinical assessment, triage, and early management of the acute radiation syndrome and its component subsyndromes are summarized. In Section III, Dr. Jamie Waselenko reviews the hematopoietic syndrome, and presents guidelines for the use of cytokine therapy, antibiotics, and supportive care that have been developed by the Strategic National Pharmaceutical Stockpile Working Group. Results of preclinical and clinical growth factor therapy studies with G-CSF, GM-CSF, pegylated G-CSF, SCF, and IL-3 are summarized. When and how potassium iodide should be used after exposure to radioiodines is also reviewed. In Section IV, Dr. James Armitage describes a narrow "window" of 7 to 10 Gy where therapy with stem cell transplantation may be appropriate. Victims who are candidates for allotransplantation should not have major trauma or significant injury to other (nonhematopoietic) tissues. Rarely, victims may have an identical sibling or autologous stored marrow or blood stem cells, in which case the threshold for transplantation is 4 Gy. In Section V, Dr. Thomas MacVittie describes new directions for therapy, using cytokines such as IL-7, keratinocyte growth factor, and FLT-3. The potential for combinations of cytokines to enhance hematopoietic recovery is also reviewed.


Metabolic engineering of Ralstonia eutropha for the production of polyhydroxyalkanoates from sucrose.
A sucrose utilization pathway was established in Ralstonia eutropha NCIMB11599 and R. eutropha 437-540 by introducing the Mannheimia succiniciproducens MBEL55E sacC gene that encodes β-fructofuranosidase. These engineered strains were examined for the production of poly(3-hydroxybutyrate) [P(3HB)] and poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)], respectively, from sucrose as a carbon source. It was found that β-fructofuranosidase excreted into the culture medium could hydrolyze sucrose to glucose and fructose, which were efficiently used as carbon sources by recombinant R. eutropha strains. When R. eutropha NCIMB11599 expressing the sacC gene was cultured in nitrogen-free chemically defined medium containing 20 g/L of sucrose, a high P(3HB) content of 73.2 wt% could be obtained. In addition, R. eutropha 437-540 expressing the Pseudomonas sp. MBEL 6-19 phaC1437 gene and the Clostridium propionicum pct540 gene accumulated P(3HB-co-21.5 mol% LA) to a polymer content of 19.5 wt% from sucrose by the expression of the sacC gene and the Escherichia coli ldhA gene. The molecular weights of P(3HB) and P(3HB-co-21.5 mol%LA) synthesized in R. eutropha using sucrose as a carbon source were 3.52 × 10(5) (Mn ) and 2.19 × 10(4) (Mn ), respectively. The engineered R. eutropha strains reported here will be useful for the production of polyhydroxyalkanoates (PHAs) from sucrose, one of the most abundant and relatively inexpensive carbon sources.


Intussusception of the bowel in adults: two different cases.
Intussusception in adults is considered an unusual condition accounting for 5% of all cases of intussusceptions and almost 1%-5% of all cases of bowel obstruction. We present two cases of patients with a complaint of abdominal discomfort and concomitant vomiting who are 43 and 44 years old. Ileocecal intussusception was diagnosed by computed tomography. One patient underwent open whereas the other underwent laparoscopic right hemicolectomy and ileotransversostomy. A histopathological study revealed lipoma in the first case and adenocarcinoma in the second. We described the diagnosis and treatment of intestinal intussusception in adults.


Effect of sedimentation on ice-sheet grounding-line stability.
Sedimentation filling space beneath ice shelves helps to stabilize ice sheets against grounding-line retreat in response to a rise in relative sea level of at least several meters. Recent Antarctic changes thus cannot be attributed to sea-level rise, strengthening earlier interpretations that warming has driven ice-sheet mass loss. Large sea-level rise, such as the approximately 100-meter rise at the end of the last ice age, may overwhelm the stabilizing feedback from sedimentation, but smaller sea-level changes are unlikely to have synchronized the behavior of ice sheets in the past.


European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis.
To validate enhanced liver fibrosis (ELF) test and its components-amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an independent, international, multicentre cohort. Two hundred and fifty-four SSc patients from six Rheumatology Centres were included. Sera were collected and stored according to EUSTAR biobanking recommendations and analysed through automated high throughput diagnostics. Statistical analysis was performed with SPSS software. Two hundred and forty-seven SSc patients (mean age 55.7 ± 13.9 years, 202 F) were analysed. ELF score, TIMP-1 and PIIINP levels were higher in males (P = 0.0197, P = 0.0107, P = 0.0108 respectively) and in dcSSc (P = 0.001, P = 0.0008, P < 0.0001 respectively). ELF score and the single markers significantly correlated with modified Rodnan skin score (r = 0.37, P < 0.0001), disease activity and severity (P < 0.0001 for all markers, except for HA P = 0.0001) and inversely with forced vital capacity, (FVC) % (TIMP-1, r = -0.21, P = 0.0012; PIIINP, r = -0.26, P = 0.0001), TLC% (ELF score, r = -0.20, P = 0.0036; TIMP-1, r = -0.32, P < 0.0001; PIIINP, r = -0.28, P < 0.0001), diffusion capacity of the lung for carbon monoxide (DLCO) % (P < 0.0001 for all markers, except for HA P = 0.0115). Multivariate analysis indicated that age (P < 0.001), modified Rodnan skin score (P < 0.001) and DLCO% (P = 0.005) were independently associated with ELF score. Between the first and this validation studies, the value of the ELF score as independent marker of skin and lung involvement in SSc is confirmed in 457 patients. A longitudinal study is on-going to identify an SSc specific algorithm with predictive value for skin and lung progression.


Subtypes of major depression: latent class analysis in depressed Han Chinese women.
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally? Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾ 30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus. RESULTS; Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct. MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.


Alpha and beta band event-related desynchronization reflects kinematic regularities.
The short-lasting attenuation of brain oscillations is termed event-related desynchronization (ERD). It is frequently found in the alpha and beta bands in humans during generation, observation, and imagery of movement and is considered to reflect cortical motor activity and action-perception coupling. The shared information driving ERD in all these motor-related behaviors is unknown. We investigated whether particular laws governing production and perception of curved movement may account for the attenuation of alpha and beta rhythms. Human movement appears to be governed by relatively few kinematic laws of motion. One dominant law in biological motion kinematics is the 2/3 power law (PL), which imposes a strong dependency of movement speed on curvature and is prominent in action-perception coupling. Here we directly examined whether the 2/3 PL elicits ERD during motion observation by characterizing the spatiotemporal signature of ERD. ERDs were measured while human subjects observed a cloud of dots moving along elliptical trajectories either complying with or violating the 2/3 PL. We found that ERD within both frequency bands was consistently stronger, arose faster, and was more widespread while observing motion obeying the 2/3 PL. An activity pattern showing clear 2/3 PL preference and lying within the alpha band was observed exclusively above central motor areas, whereas 2/3 PL preference in the beta band was observed in additional prefrontal-central cortical sites. Our findings reveal that compliance with the 2/3 PL is sufficient to elicit a selective ERD response in the human brain.


Leptospirosis and dengue fever: a predictive model for early differentiation based on clinical and biochemical parameters.
Leptospirosis and dengue fever are increasingly seen as causes of tropical febrile illness and often are clinically indistinguishable. This two-year prospective study from a tertiary care centre comprised 200 patients including 68 men (mean 34.8 years) with dengue and 73 (mean 46.19 years) with leptospirosis. Oliguria, icterus, muscle tenderness, anaemia, leukocytopenia, thrombocytopenia, elevated erythrocyte sedimentation rate (ESR), acute renal failure (ARF) and hypoalbuminaemia appeared more commonly in leptospirosis in comparison to dengue. Eighteen per cent mortality was observed in leptospirosis compared to one per cent in dengue. ARF, hyperbilirubinaemia, acute respiratory distress syndrome (ARDS), creatine kinase (CK) elevation and thrombocytopenia were predictors of death in leptospirosis and thrombocytopenia, ARDS and ARF predictors of death in dengue. On receiver operating characteristics (ROC) analysis, leucocytosis >11000/mm(3), ESR >40 mm, serum creatinine >2 mg/dL, total serum bilirubin >2 mg/dL, CK >500 U/L and serum albumin <3 mg/dL were more likely to be an indication of leptospirosis at presentation compared to dengue.


Expression Patterns of Nrf2 and Keap1 in Ovarian Cancer Cells and their Prognostic Role in Disease Recurrence and Patient Survival.
This study evaluated the expression patterns of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) and assessed their clinical value as prognostic indicators in ovarian cancer. The expression patterns of Nrf2 and Keap1 were determined in 100 epithelial ovarian cancers by immunohistochemistry analyses. The associations of Nrf2 and Keap1 expression with clinicopathological characteristics of patients were evaluated. All patients received platinum-based chemotherapy. Chemoresistance was defined as recurrence within 6 months of first-line chemotherapy. Cytoplasmic expression of Nrf2 and Keap1 was observed in 95% and 72%, respectively, of all 100 epithelial ovarian cancers examined. Low Keap1 expression (intensity < 1) was strongly associated with disease recurrence (P = 0.046) and death (P = 0.002). Chemoresistance was associated with high Nrf2 expression (intensity = 3) (P = 0.833; hazard ratio [HR], 1.202; 95% confidence interval [CI], 0.217-6.667) and low Keap1 expression (P = 0.862; HR, 0.899; 95% CI, 0.270-2.994). However, these associations were not statistically significant. Survival analysis indicated that high Keap1 expression (intensity ≥ 1) was strongly predictive of better overall survival (P = 0.049) and disease-free survival (P = 0.004). Cox regression analysis indicated that Keap1 expression was an independent prognostic factor for overall survival (P = 0.012; HR, 0.349; 95% CI, 0.153-0.797). Although patients with high Nrf2 expression displayed better overall survival and disease-free survival, the association was not statistically significant. High cytoplasmic Keap1 expression, which might prevent nuclear translocation of Nrf2 in ovarian cancer cells, was associated with lower disease recurrence and death rate. Survival analysis suggested a probable role of Keap1 expression in predicting the prognosis of ovarian cancer.


Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.
Previous studies have suggested that hyperhomocysteinemia may be a risk factor for venous thrombosis. To assess the risk of venous thrombosis associated with hyperhomocysteinemia, we studied plasma homocysteine levels in patients with a first episode of deep-vein thrombosis and in normal control subjects. We measured plasma homocysteine levels in 269 patients with a first, objectively diagnosed episode of deep-vein thrombosis and in 269 healthy controls matched to the patients according to age and sex. Hyperhomocysteinemia was defined as a plasma homocysteine level above the 95th percentile in the control group (18.5 micromol per liter). Of the 269 patients, 28 (10 percent) had plasma homocysteine levels above the 95th percentile for the controls, as compared with 13 of the controls (matched odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.2). The association between elevated homocysteine levels and venous thrombosis was stronger among women than among men and increased with age. The exclusion of subjects with other established risk factors for thrombosis (e.g., a deficiency of protein C, protein S, or antithrombin; resistance to activated protein C; pregnancy or recent childbirth; or oral-contraceptive use) did not materially affect the risk estimates. High plasma homocysteine levels are a risk factor for deep-vein thrombosis in the general population.


Acute carotid artery stenting in symptomatic high-grade cervical carotid artery stenosis.
The safety and efficacy of emergency carotid artery stenting (CAS) for patients with acute ischemic stroke resulting from internal carotid artery stenosis are not established. In this retrospective study, we evaluated outcomes for CAS performed within 2 weeks of acute ischemic stroke for 16 patients treated between December 2009 and February 2014. Cases of internal carotid artery occlusion, internal carotid dissection, or intracranial major arterial trunk occlusion were excluded. Five patients were treated with CAS during the hyperacute phase (within 24 h of stroke onset), three in the advanced phase (within 24 h of stroke-in-evolution after admission), and eight in the acute phase (24 h to 2 weeks after onset). We evaluated modified Rankin scale (mRS) scores 90 days after CAS. For patients treated during the hyperacute phase without intravenous tissue-type plasminogen activator (IV-tPA), two had mRS scores of 2 and one had a score of 3. Two patients treated in the hyperacute phase with IV-tPA had scores of 5: one with symptomatic intracerebral hemorrhage and the other with acute brain swelling. For patients treated in the advanced phase, mRS scores were 1, 3, and 5; the patient with 5 had contralateral cerebral infarction. All patients treated in the acute phase had scores of 2 or lower. Patients treated with IV-tPA in advanced or acute phases had no severe post-CAS complications. CAS was effective and safe for treating ischemic stroke within 2 weeks of onset. However, IV-tPA treatment may be a risk factor for CAS treatment during the hyperacute phase.


[Activity of antioxidative enzymes of the myocardium during ischemia].
Activation of lipid peroxidation during myocardial ischemia may be determined by the reduction of the enzymatic antioxidant cell protection. Such a conclusion has been drawn on the basis of an analysis of variation in the activity of superoxide dismutase, glutathion peroxidase and catalase in experimental myocardial ischemia in rats, induced by ligation of the left descending artery of the heart. In the early period of ischemia (1-3 h) the activity of superoxide dismutase and glutation peroxidase markedly decreases. In the periischemic zone, the fall in the enzymatic activity is not so pronounced. The activity of the enzymes does not reach the basic level 5 days after the operation.


Chitosan-GSNO nanoparticles: a positive modulator of drought stress tolerance in soybean.
Chitosan biopolymer is an emerging non-toxic and biodegradable plant elicitor or bio-stimulant. Chitosan nanoparticles (CSNPs) have been used for the enhancement of plant growth and development. On the other hand, NO is an important signaling molecule that regulates several aspects of plant physiology under normal and stress conditions. Here we report the synthesis, characterization, and use of chitosan-GSNO nanoparticles for improving drought stress tolerance in soybean. The CSGSNONPs released NO gas for a significantly longer period and at a much lower rate as compared to free GSNO indicating that incorporation of GSNO in CSNPs can protect the NO-donor from rapid decomposition and ensure optimal NO release. CS-GSNONPs improved drought tolerance in soybean plants reflected by a significant increase in plant height, biomass, root length, root volume, root surface area, number of root tips, forks, and nodules. Further analyses indicated significantly lower electrolyte leakage, higher proline content, higher catalase, and ascorbate peroxidase activity, and reduction in MDA and H2O2 contents after treatment with 50 μM CS-GSNONPs under drought stress conditions. Quantitative real-time PCR analysis indicated that CS-GSNONPs protected against drought-induced stress by regulating the expression of drought stress-related marker genes such as GmDREB1a, GmP5CS, GmDEFENSIN, and NO-related genes GmGSNOR1 and GmNOX1. This study highlights the potential of nano-technology-based delivery systems for nitric oxide donors to improve plant growth, and development and protect against stresses.


Mechanisms of craniofacial pain.
Aim To provide an overview of mechanisms underlying craniofacial pain; to highlight peripheral and central adaptations that may promote chronification of pain in craniofacial pain states such as migraine and temporomandibular disorders (TMD). Background Pain is a common symptom associated with disorders involving craniofacial tissues including the teeth and their supporting structures, the temporomandibular joint and the muscles of the head. Most acute painful craniofacial conditions are easily recognized and well managed, but others, especially those that are chronic (e.g., migraine, TMD and trigeminal neuropathies), present clinical challenges. Preclinical studies have provided substantial information about the anatomical and physiological mechanisms related to the initiation and modulation of nociceptive signals in the trigeminal system. While knowledge of the mechanisms underlying chronic craniofacial pain remains limited, both clinical and preclinical investigations suggest that changes in afferent inputs to the brain as well as in brain structure and modulatory pathways occur in chronic pain. Collectively, these changes result in amplification of nociception that promotes and sustains craniofacial chronic pain states. Conclusions The increased understanding gained of the physiological and pathological processing of nociception in the trigeminal system has provided new perspectives for the mechanistic understanding of acute craniofacial pain conditions and the peripheral and central adaptations that are related to pain chronification. Such knowledge may contribute to improvements in currently available treatments as well as to the development of novel analgesic therapies.


Direction controllable linearly polarized laser from a dye-doped cholesteric liquid crystal.
We demonstrate a direction controllable linearly polarized laser from a dye-doped cholesteric liquid crystal (CLC) in a homogeneous cell coated with a metallic mirror on the inner side of a glass substrate. Due to coherent superposition of two orthogonal polarization states, the output laser light becomes linearly polarized and its output energy is greatly enhanced. Moreover, the linear polarization direction angle is proportional to the product of the CLC effective birefringence and cell gap. Hence direction tunable laser devices can be demonstrated by controlling the cell gap and the operating temperature.


More evidence on the impact of India's conditional cash transfer program, Janani Suraksha Yojana: quasi-experimental evaluation of the effects on childhood immunization and other reproductive and child health outcomes.
In 2005, India established a conditional cash transfer program called Janani Suraksha Yojana (JSY), to increase institutional delivery and encourage the use of reproductive and child health-related services. To assess the effect of maternal receipt of financial assistance from JSY on childhood immunizations, post-partum care, breastfeeding practices, and care-seeking behaviors. We use data from the latest district-level household survey (2007-2008) to conduct a propensity score matching analysis with logistic regression. We conduct the analyses at the national level as well as separately across groups of states classified as high-focus and non-high-focus. We carry out several sensitivity analyses including a subgroup analysis stratified by possession of an immunization card. Receipt of financial assistance from JSY led to an increase in immunization rates ranging from 3.1 (95%CI 2.2-4.0) percentage points for one dose of polio vaccine to 9.1 (95%CI 7.5-10.7) percentage points in the proportion of fully vaccinated children. Our findings also indicate JSY led to increased post-partum check-up rates and healthy early breastfeeding practices around the time of childbirth. No effect of JSY was found on exclusive breastfeeding practices and care-seeking behaviors. Effect sizes were consistently larger in states identified as being a key focus for the program. In an analysis stratified by possession of an immunization card, there was little to no effect of JSY among those with vaccination cards, while the effect size was much larger than the base case results for those missing vaccination cards, across nearly all immunization outcomes. Early results suggest the JSY program led to a significant increase in childhood immunization rates and some healthy reproductive health behaviors, but the structuring of financial incentives to pregnant women and health workers warrants further review. Causal interpretation of our results relies on the assumption that propensity scores balance unobservable characteristics.


Phage display-selected single-chain antibodies confer high levels of resistance against Tomato spotted wilt virus.
Rational design of antibodies targeting essential viral proteins can complement the palette of antiviral resistance strategies. Here, stable and high expression of single-chain monoclonal antibodies targeting the nucleoprotein of the economically important plant virus Tomato spotted wilt virus, a protein that is involved in multiple steps in the viral infection cycle, is reported. High cytoplasmic expression levels of three selected phage display-derived anti-viral single-chain antibodies were established. Of these antibodies, two led to high levels of resistance against this plant virus. Protoplast experiments provided evidence that the two resistance-conferring antibodies may have a different mode of action and could be combined for higher durability of resistance in the field.


Neoplastic pericardial disease: Old and current strategies for diagnosis and management.
The prevalence of neoplastic pericardial diseases has changed over time and varies according to diagnostic methods. The diagnostic factor is usually the detection of neoplastic cells within the pericardial fluid or in specimens of pericardium, but the diagnosis may be difficult. Accurate sampling and cytopreparatory techniques, together with ancillary studies, including immunohistochemical tests and neoplastic marker dosage, are essential to obtain a reliable diagnosis. The goals of treatment may be simply to relieve symptoms (cardiac tamponade or dyspnea), to prevent recurrent effusion for a long-term symptomatic benefit, or to treat the local neoplastic disease with the aim of prolonging survival. Immediate relief of symptoms may be obtained with percutaneous drainage or with a surgical approach. For long term prevention of recurrences, various approaches have been proposed: extended drainage, pericardial window (surgical or percutaneous balloon pericardiostomy), sclerosing local therapy, local and/or systemic chemotherapy or radiation therapy (RT) (external or with intrapericardial radionuclides). The outcomes of various therapeutic approaches vary for different tumor types. Lymphoma and leukemias can be successfully treated with systemic chemotherapy; for solid tumors, percutaneous drainage and the use of systemic and/or local sclerosing and antineoplastic therapy seems to offer the best chance of success. The use of "pure" sclerosing agents has been replaced by agents with both sclerosing and antineoplastic activity (bleomycin or thiotepa), which seems to be quite effective in breast cancer, at least when associated with systemic chemotherapy. Local chemotherapy with platinum, mitoxantrone and other agents may lead to good local control of the disease, but the addition of systemic chemotherapy is probably relevant in order to prolong survival. The surgical approach (creation of a pericardial window, even with the mini-invasive method of balloon pericardiostomy) and RT may be useful in recurring effusions or in cases that are refractory to other therapeutic approaches.


Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC6803. I. Sequence features in the 1 Mb region from map positions 64% to 92% of the genome.
The contiguous sequence of 1,003,450 bp spanning map positions 64% to 92% of the genome of Synechocystis sp. strain PCC6803 has been deduced. Computer analysis of the sequence predicts that this region contains at least 818 potential ORFs, in which 255 (31%) were either genes that had already been identified or their homologues, 84 (10%) were homologues to registered hypothetical genes, and 149 (18%) showed weak similarities to reported genes. The remaining 330 ORFs showed no apparent similarity to any reported genes or carried no significant protein motifs. The potential ORFs as a whole occupied 86% of the sequenced region, implying compact arrangement of genes in the genome. As to the structural RNA genes, one rRNA operon consisting of 5,028 bp and at least 11 species of tRNA genes were identified. It is noteworthy that 10 out of the 11 tRNA species showed significant sequence similarities to tRNAs reported in plant chloroplasts. As other notable unique sequences, three classes of IS-like elements each with characteristics typical of IS elements were identified, and a typical unit of WD(Trp-Asp)-repeats which have only been detected in the regulatory proteins of eukaryotes was identified within the large 5,079-bp ORF located at map position 69%.


Monosaccharide sequence of protein-bound glycans of Uukuniemi virus.
Uukuniemi virus, a member of the Bunyaviridae family, was grown in BHK-21 cells in the presence of [(3)H]mannose. The purified virions were disrupted with sodium dodecyl sulfate and digested with pronase. The [(3)H]mannose-labeled glycopeptides of the mixture of the two envelope glycoproteins G1 and G2 were characterized by degrading the glycans with specific exo-and endoglycosidases, by chemical methods, and by analyzing the products with lectin affinity and gel chromatography. The glycopeptides of Uukuniemi virus fell into three categories: complex, high-mannose type, and intermediate. The complex glycopeptides probably contained mainly two NeuNAc-Gal-GlcNAc branches attached to a core (Man)(3)(GlcNAc)(2) peptide. The high-mannose-type glycans were estimated to contain at least five mannose units attached to two N-acetylglucosamine residues. Both glycan species appeared to be similar to the asparagine-linked oligosaccharides found in many soluble and membrane glycoproteins. The results suggested that the intermediate glycopeptides contained a mannosyl core. In about half of the molecules, one branch appeared to be terminated in mannose, and one appeared to be terminated in N-acetylglucosamine. Such glycans are a novel finding in viral membrane proteins. They may represent intermediate species in the biosynthetic pathway from high-mannose-type to complex glycans. Their accumulation could be connected with the site of maturation of the members of the Bunyaviridae family. Electron microscopic data suggest that the virions bud into smooth-surfaced cisternae in the Golgi region. The relative amounts of [(3)H]mannose in the complex, high-mannose-type, and intermediate glycans were 25, 62, and 13%, respectively, which corresponded to the approximate relative number of oligosaccharide chains of 2:2.8:1, respectively, in the roughly equimolar mixture of G1 and G2. Endoglycosidase H digestion of isolated [(35)S]methionine-labeled G1 and G2 proteins suggested that most of the complex and intermediate chains were attached to G1 and that most of the high-mannose-type chains were attached to G2.


Radiographers' perceptions on the quality of managing general radiographic paediatric examinations through the use of a reflective tool.
Paediatric patients are a vulnerable population that require additional care by healthcare professionals. Quality managing these examinations ensures that effective and quality care is provided to individual patients, whilst encouraging consistency within the medical imaging department. This study explored radiographers' perspectives on quality management strategies of general radiographic paediatric examinations using a paediatric imaging reflective checklist. A quantitative descriptive research design with qualitative questions was used through a purposive sampling method from both public and private Australian diagnostic imaging qualified radiographers who had experience in paediatric imaging examinations. The paediatric imaging service reflective tool consisted of 65 items in total. Data analysis entailed Microsoft Excel version 16.16.6 and Jamovi version 2.3.21 for the closed-ended questions and for the open-ended responses a thematic analysis. The participation rate was 13.2% and the most significant findings were: lead shielding was still being used at their organisation, despite recent recommendations to suspend its use; access to paediatric patient related information resources is limited; there was no involvement of families and communities regarding policy development or quality improvement measures as advocated in literature; and there was a need for enhanced specialised paediatric education, training and protocols. Using the paediatric patient-centred imaging reflective checklist, radiographers had an opportunity to identify quality improvement indicators as well as issues that could further enhance best practice principles. Further studies could inform on the validity of this reflective tool.


Alcohol consumption and the incidence of type II diabetes.
This study examines the relation between alcohol and type II diabetes and the possible mediating effects of HDL-cholesterol and serum insulin. Prospective study of 5221 men aged 40-59 years with no history of coronary heart disease, diabetes, or stroke drawn from general practices in 18 British towns. During the mean follow up of 16.8 years there were 198 incident cases of type II diabetes. Occasional drinkers were the reference group. A non-linear relation was seen between alcohol intake and age adjusted risk of diabetes, with risk lowest in light and moderate drinkers and highest in heavy drinkers (quadratic trend p=0.03). Further adjustment for body mass index decreased risk in heavy drinkers. After additional adjustment for physical activity, smoking, and (undiagnosed) pre-existing coronary heart disease, only moderate drinkers showed significantly lower risk than occasional drinkers (RR=0.66 95% CI 0.44 to 0.99). Alcohol intake was inversely associated with serum insulin and positively associated with HDL-cholesterol. Adjustment for these factors reduced the "protective" effect in moderate drinkers (adjusted RR=0.73 95% CI 0.48 to 1.10) but the quadratic trend remained significant (p=0.02). There is a non-linear relation between alcohol intake and the risk of type II diabetes. Serum insulin and HDL-cholesterol explained a small amount (20%) of the reduction in risk of type II diabetes associated with moderate drinking. The adverse effect of heavy drinking seemed to be partially mediated through its effect on body weight.


Iridium-Catalyzed Borylation of Primary Benzylic C-H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity.
Primary benzylic boronate esters are useful intermediates in organic synthesis, but these reagents cannot be prepared by hydroboration. The benzylic C-H borylation of methylarenes would be a method to form these products, but such reactions without neat methylarene or a directing group are unknown. We report an approach to divert the borylation of methylarenes from aromatic positions to benzylic positions with a silylborane as reagent and a new iridium catalyst containing an electron-deficient phenanthroline as ligand. This system forms benzylic boronate esters selectively over the corresponding aryl boronate esters. An Ir diboryl monosilyl complex ligated by the phenanthroline was isolated and determined to be the resting state of the catalyst. Mechanistic studies show that this complex is kinetically competent to be an intermediate in the catalytic process. Kinetic studies of benzylic and aryl C-H borylation catalyzed by various Ir complexes show that the rate of aryl C-H borylation decreases with decreasing electron density at the metal center of the Ir catalyst, but that the rate of benzylic C-H borylation is less sensitive to the degree of electron density at the metal center of the Ir catalyst. Kinetic and computational studies suggest that the two borylation reactions respond differently to the degree of electron density at the metal center because they occur with different turnover-limiting steps. The turnover-limiting step in the borylation of aryl C-H bonds is known to be C-H oxidative addition, but the turnover-limiting step of the borylation of benzylic C-H bonds appears to be an isomerization prior to C-B reductive elimination.


Diffuse alveolar hemorrhage in pediatric hematopoietic cell transplant patients.
Diffuse alveolar hemorrhage (DAH) is defined as a syndrome of hypoxia, dyspnea, infiltrates on chest radiograph, and bloody fluid on successive bronchoalveolar lavages without apparent infection. Minimal experience has been reported with DAH after hematopoietic cell transplant (HCT) in children. We reviewed the incidence, management and outcome of DAH in a pediatric HCT population. Retrospective review of 138 patients undergoing allogeneic (n = 89) or autologous (n = 49) HCT at a referral children's medical center between January 1996 and April 2000. Seven (5.1%) of 138 patients met criteria for DAH; all were allogeneic recipients. Mean age of DAH patients was 11 years (range: 1.4-15.2). Median onset of DAH following HCT was day 24 (range: 10-50), median day of engraftment day 20 and white blood cell count 0.54 x 10(9)/L (range: < 0.1-7.03), with no difference between survivors and nonsurvivors. All patients developed clinical respiratory failure and 6 required intubation, with PaO(2)/fraction of inspired oxygen <200. Patients were intubated a median of 12 days (range: 1-75). All patients experienced >1 episode of bleeding and 3 patients required reintubation after successful extubation resulting from recurrent DAH. Bronchoalveolar lavage fluid cultures were negative for viruses, bacteria and fungi. All DAH patients received steroids. Three patients died with progressive pulmonary failure and other organ system involvement. Four of 7 DAH patients (57%) survived to discharge, but 3 died from disease relapse at days 116, 138, and 273 post-HCT. DAH occurred more frequently in allogeneic HCT recipients compared with autologous recipients. Onset of DAH coincided closely with white blood cell engraftment. Although associated with significant respiratory failure and need for mechanical ventilation, HCT patients can survive DAH.


NiMoO4@NiWO4 honeycombs as a high performance electrode material for supercapacitor applications.
In this study, we report a facile two-step fabrication of honeycomb-like NiMoO4@NiWO4 nanocomposites on Ni foam as the electrode for high-performance supercapacitor applications. Structural characterization and compositional analysis of the as-prepared NiMoO4@NiWO4 nanocomposites was performed using scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, cyclic voltammetry, galvanostatic charge-discharge cycling, and electrochemical impedance spectroscopy. The electrochemical properties of the as-synthesized NiMoO4@NiWO4 nanocomposites were studied in a 3 M KOH electrolyte solution for application as electrode material of supercapacitors. A maximum specific capacitance of 1290 F g-1 was achieved for NiMoO4@NiWO4 at a current density of 2 A g-1. This electrode exhibits excellent long cycle-life stability with 93.1% specific capacitance retention after 3000 cycles at a current density of 6 A g-1. Our studies indicate that the as-synthesized NiMoO4@NiWO4 nanocomposites could be a promising candidate as the electrode material in high-performance electrochemical energy storage applications.


Intestinal atresia and stenosis: analysis of survival in 120 cases.
This report reviews the clinical presentation, operative management, and survival in 120 infants with intestinal atresia and stenosis treated from 1972 to 1984. Duodenal atresia occurred in 39 neonates and duodenal stenosis in 19. Thirty-two infants had severe associated anomalies. Operative management included duodenoduodenostomy in 47 infants, duodenotomy and web excision in four, and duodenojejunostomy in seven. Jejunoileal atresia occurred in 49 infants and stenosis in three. Six infants had cystic fibrosis and nine had gastroschisis. Operative therapy included wide proximal resection and end-to-end anastomosis in 18 infants, minimal resection with antimesenteric tapering enteroplasty and anastomosis in 14 neonates, and resection with temporary enterostomies in 20 infants. Twenty-nine infants (56%) required total parenteral nutrition. Colon atresia occurred in 11 infants and stenosis in one. Initial end-colostomy with subsequent resection and anastomosis was performed in 11 infants while one underwent a primary resection. The survival rate was 91% for duodenal defects, 87% for jejunoileal cases, and 100% for colonic anomalies. Death is currently caused by severe associated anomalies in infants with duodenal atresia and sepsis and total parenteral nutrition-related cholestasis with progressive liver failure in instances of jejunoileal atresia.


[Combined radiation exposures and their immediate and late sequelae].
The author reviews correlations between the general and local processes and criteria for the diagnosis of acute radiation sickness (acute radiation syndrome) /ARS/ as well as other clinical sequels of radiation injury (radiation burns, abnormalities of critical organ function, stochastic sequels) induced by total even and uneven radiation and concomitant radiation effects. Based on the own observations the coefficients were defined of private correlations of the doses of the total gamma- and high-absorbable ("soft") components of concomitant radiation effects on the content of neutrophil leukocytes in peripheral blood seen during successive transformations of the development of ARS and the subclinical forms of radiation injury. The main characteristic features of ARS induced by concomitant radiation injury as a result of nuclear reactor break down have been formulated.


Observation of confined current ribbon in JET plasmas.
We report the identification of a localized current structure inside the JET plasma. It is a field-aligned closed helical ribbon, carrying current in the same direction as the background current profile (cocurrent), rotating toroidally with the ion velocity (corotating). It appears to be located at a flat spot in the plasma pressure profile, at the top of the pedestal. The structure appears spontaneously in low density, high rotation plasmas, and can last up to 1.4 s, a time comparable to a local resistive time. It considerably delays the appearance of the first edge localized mode.


Synergistic effect of hydrogen peroxide on polyploidization during the megakaryocytic differentiation of K562 leukemia cells by PMA.
The human myelogenous cell line, K562 has been extensively used as a model for the study of megakaryocytic (MK) differentiation, which could be achieved by exposure to phorbol 12-myristate 13-acetate (PMA). In this study, real-time PCR analysis revealed that the expression of catalase (cat) was significantly repressed during MK differentiation of K562 cells induced by PMA. In addition, PMA increased the intracellular reactive oxygen species (ROS) concentration, suggesting that ROS was a key factor for PMA-induced differentiation. PMA-differentiated K562 cells were exposed to hydrogen peroxide (H2O2) to clarify the function of ROS during MK differentiation. Interestingly, the percentage of high-ploidy (DNA content >4N) cells with H2O2 was 34.8±2.3% at day 9, and was 70% larger than that without H2O2 (21.5±0.8%). Further, H2O2 addition during the first 3 days of PMA-induced MK differentiation had the greatest effect on polyploidization. In an effort to elucidate the mechanisms of enhanced polyploidization by H2O2, the BrdU assay clearly indicated that H2O2 suppressed the division of 4N cells into 2N cells, followed by the increased polyploidization of K562 cells. These findings suggest that the enhancement in polyploidization mediated by H2O2 is due to synergistic inhibition of cytokinesis with PMA. Although H2O2 did not increase ploidy during the MK differentiation of primary cells, we clearly observed that cat expression was repressed in both immature and mature primary MK cells, and that treatment with the antioxidant N-acetylcysteine effectively blocked and/or delayed the polyploidization of immature MK cells. Together, these findings suggest that MK cells are more sensitive to ROS levels during earlier stages of maturation.


Antioxidant Activity and Inhibitory Potential of Cistus salviifolius (L.) and Cistus monspeliensis (L.) Aerial Parts Extracts against Key Enzymes Linked to Hyperglycemia.
Cistus genus (Cistaceae) comprises several medicinal plants used in traditional medicines to treat several pathological conditions including hyperglycemia. These include Cistus salviifolius L. (CS) and Cistus monspeliensis L. (CM), still not fully explored as a source of metabolites with therapeutic potential for human diseases. In this study, the antioxidant α-amylase and α-glucosidase enzyme inhibitory effects of aqueous and hydromethanolic extracts from the aerial parts of Moroccan CS and CM were investigated. Antioxidant activity has been assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals and ferric reducing/antioxidant power (FRAP) methods. The α-amylase and α-glucosidase inhibitory activity has been assessed using an in vitro model. Moreover, mineral and phenolic contents of CS and CM were analyzed. The extracts of both species exhibited potent antioxidant activity in all used systems and possess strong inhibitory effect towards α-glucosidase (IC50: 0.95 ± 0.14 to 14.58 ± 1.26 μg/mL) and significant inhibitory potential against α-amylase (IC50: 217.10 ± 0.15 to 886.10 ± 0.10 μg/mL). Furthermore, the result showed high levels of phenolic content and unexpectedly some higher levels of mineral content in CS. The results suggest that the phenolic rich extracts of CS and CM may have a therapeutic potential against diseases associated with oxidative stress and may be useful in the management of hyperglycemia in diabetic patients.


L-type voltage-sensitive calcium channels mediate synaptic activation of immediate early genes.
Although L-type voltage-sensitive calcium channels (VSCCs) have been well characterized electrophysiologically, their role in synaptic physiology has remained unclear. To assess their involvement in synaptic regulation of gene expression, we have examined the effects of selective VSCC antagonists on basal, synaptically mediated activation of several transcription factor genes in cultured cortical neurons. Basal expression of c-fos, jun-B, zif268, and fos-B is rapidly suppressed by exposure to L-type VSCC antagonists and increased by (-)BayK-8644, a VSCC agonist. Although VSCC antagonists block kainate-induced rises in intracellular calcium and gene expression, these agents have little effect on spontaneous electrical activity or synaptically induced calcium transients in these neurons. These findings suggest that even though L-type VSCCs contribute a relatively minor component of synaptic calcium transients, they appear to play a key role in coupling synaptic excitation to activation of transcriptional events thought to contribute to neuronal plasticity.


Phosphatidylserine and phosphatidylethanolamine regulate the structure and function of FVIIa and its interaction with soluble tissue factor.
Cell membranes have important functions in many steps of the blood coagulation cascade, including the activation of factor X (FX) by the factor VIIa (FVIIa)-tissue factor (TF) complex (extrinsic Xase). FVIIa shares structural similarity with factor IXa (FIXa) and FXa. FIXa and FXa are regulated by binding to phosphatidylserine (PS)-containing membranes via their γ-carboxyglutamic acid-rich domain (Gla) and epidermal growth-factor (EGF) domains. Although FVIIa also has a Gla-rich region, its affinity for PS-containing membranes is much lower compared with that of FIXa and FXa. Research suggests that a more common endothelial cell lipid, phosphatidylethanolamine (PE), might augment the contribution of PS in FVIIa membrane-binding and proteolytic activity. We used soluble forms of PS and PE (1,2-dicaproyl-sn-glycero-3-phospho-l-serine (C6PS), 1,2-dicaproyl-sn-glycero-3-phospho-ethanolamine (C6PE)) to test the hypothesis that the two lipids bind to FVIIa jointly to promote FVIIa membrane binding and proteolytic activity. By equilibrium dialysis and tryptophan fluorescence, we found two sites on FVIIa that bound equally to C6PE and C6PS with Kd of ∼ 150-160 μM, however, deletion of Gla domain reduced the binding affinity. Binding of lipids occurred with greater affinity (Kd∼70-80 μM) when monitored by FVIIa proteolytic activity. Global fitting of all datasets indicated independent binding of two molecules of each lipid. The proteolytic activity of FVIIa increased by ∼50-100-fold in the presence of soluble TF (sTF) plus C6PS/C6PE. However, the proteolytic activity of Gla-deleted FVIIa in the presence of sTF was reduced drastically, suggesting the importance of Gla domain to maintain full proteolytic activity.


24/7 pediatric radiology attending coverage: times are changing.
The job of the pediatric radiologist long ago ceased to be an 8-to-5 role. Many practices have adopted evening shifts of in-house attending radiologists to cover the busy evening activity. With the ever-increasing role of imaging in clinical decisions and patient management, there is a need - if not a demand - to further extend attending pediatric radiology coverage. In this article, we discuss the needs and justification for extending pediatric radiology coverage at a tertiary-care children's hospital. We also describe the approach we took toward implementing 24/7 attending in-house coverage of pediatric radiology.


Latex allergy: an update for the otolaryngologist.
To describe the clinical manifestations of latex allergy in otolaryngology patients. Descriptive case series. Tertiary academic otolaryngology practice. Otolaryngology patients with documented allergic reactions to latex during surgery and confirmatory laboratory test results for latex allergy. Clinical description of latex reactions; identification of risk factors for latex allergy. We describe 3 patients, 2 children and 1 young adult, with severe latex allergy manifested by intraoperative cardiorespiratory changes and confirmed by positive latex-specific IgE test results. A 9-year-old boy with a tracheotomy and a history of multiple procedures for laryngeal stenosis developed a rash and unexplained bronchospasm during an open laryngeal procedure. Surgery was aborted, and subsequent surgery was performed uneventfully 4 weeks later using a latex-safe environment. A 13-year-old boy with recurrent respiratory papillomatosis and a ventriculoperitoneal shunt had sudden unexplained arterial oxygen desaturation and a rash during laser endoscopy. He was then treated successfully using latex-safe protocols. A 23-year-old man with a parotid malignancy developed unexplained hypotension and ventilatory difficulties in the operating room during preparation for surgery. He responded to medical treatment for anaphylaxis. The otolaryngologist should share in the increased awareness of latex allergy. Our patients who have had multiple surgical procedures or who are exposed to latex on a long-term basis may be at increased risk. Latex allergy should be considered when unexplained cardiorespiratory compromise occurs during surgery.


Transmembrane current imaging in the heart during pacing and fibrillation.
Recently, we described a method to quantify the time course of total transmembrane current (Im) and the relative role of its two components, a capacitive current (Ic) and a resistive current (Iion), corresponding to the cardiac action potential during stable propagation. That approach involved recording high-fidelity (200 kHz) transmembrane potential (Vm) signals with glass microelectrodes at one site using a spatiotemporal coordinate transformation via measured conduction velocity. Here we extend our method to compute these transmembrane currents during stable and unstable propagation from fluorescence signals of Vm at thousands of sites (3 kHz), thereby introducing transmembrane current imaging. In contrast to commonly used linear Laplacians of extracellular potential (Ve) to compute Im, we utilized nonlinear image processing to compute the required second spatial derivatives of Vm. We quantified the dynamic spatial patterns of current density of Im and Iion for both depolarization and repolarization during pacing (including nonplanar patterns) by calibrating data with the microelectrode signals. Compared to planar propagation, we found that the magnitude of Iion was significantly reduced at sites of wave collision during depolarization but not repolarization. Finally, we present uncalibrated dynamic patterns of Im during ventricular fibrillation and show that Im at singularity sites was monophasic and positive with a significant nonzero charge (Im integrated over 10 ms) in contrast with nonsingularity sites. Our approach should greatly enhance the understanding of the relative roles of functional (e.g., rate-dependent membrane dynamics and propagation patterns) and static spatial heterogeneities (e.g., spatial differences in tissue resistance) via recordings during normal and compromised propagation, including arrhythmias.


The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ.
The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases.


Improved model adaptation approach for recognition of reduced-frame-rate continuous speech.
In distributed speech recognition applications, the front-end device that stands for any handheld electronic device like smartphones and personal digital assistants (PDAs) captures the speech signal, extracts the speech features, and then sends the speech-feature vector sequence to the back-end server for decoding. Since the front-end mobile device has limited computation capacity, battery power and bandwidth, there exists a feasible strategy of reducing the frame rate of the speech-feature vector sequence to alleviate the drawback. Previously, we proposed a method for adjusting the transition probabilities of the hidden Markov model to enable it to address the degradation of recognition accuracy caused by the frame-rate mismatch between the input and the original model. The previous model adaptation method is referred to as the adapting-then-connecting approach that adapts each model individually and then connects the adapted models to form a word network for speech recognition. We have found that this model adaption approach introduces transitions that skip too many states and increase the number of insertion errors. In this study, we propose an improved model adaptation approach denoted as the connecting-then-adapting approach that first connects the individual models to form a word network and then adapts the connected network for speech recognition. This new approach calculates the transition matrix of a connected model, adapts the transition matrix of the connected model according to the frame rate, and then creates a transition arc for each transition probability. The new approach can better align the speech feature sequence with the states in the word network and therefore reduce the number of insertion errors. We conducted experiments to investigate the effectiveness of our new approach and analyzed the results with respect to insertion, deletion, and substitution errors. The experimental results indicate that the proposed new method obtains a better recognition rate than the old method.


[Pharmacokinetics and clinical studies of ceftizoxime in newborn and premature infants].
Serum concentrations and urinary recovery rates of ceftizoxime (CZX) were investigated in 13 mature newborns and 16 premature newborns (with ages 1-17 days) after one shot intravenous injection of 10 and 20 mg/kg, respectively, for treatment and prophylaxis of various infections. Obtained data were studied comparatively among the 3 groups, i.e. the 1st group (age: 0-3 days), 2nd group (age: 4-7 days) and 3rd group (age: 8 days or older). The clinical investigation was made in 9 male and 6 female newborns aged 3-34 days including 4 pediatrics patients with septicemia (1 with purulent meningitis, 1 with urinary tract infection, 1 with Staphylococcal pneumonia and 1 without complication), 1 with maxillary sinusitis, 5 with bronchopneumonia and 5 with urinary tract infections. 1. Serum concentrations and urinary recovery rates (1) Mature newborns given one shot intravenous injection of 10 mg/kg Serum concentrations of the drug in the 1st, 2nd and 3rd groups in 30 minutes after one shot intravenous injection of 10 mg/kg peaked at 18.9-23.3 micrograms/ml, without any significant differences, and thereafter gradually declined to 2.10-4.99 micrograms/ml at 8 hours. Serum half-lives were shorter in older subjects and values in the 3 groups were 3.89, 2.99 and 2.35 hours, respectively. Urinary recovery rates ranged from 55.5% to 70.0% at 8-6 hours in the 3 patients. (2) Mature newborns given one shot intravenous injection of 20 mg/kg Serum concentrations of the drug in the 3 groups peaked in 30 minutes after one shot intravenous injection of 20 mg/kg at, respectively, 36.9, 41.4 and 38.4 micrograms/ml, and thereafter they gradually declined to 9.0, 7.3 and 4.5 micrograms/ml at 8 hours, respectively. Serum half-lives were shorter in older subjects and values in the 3 groups were 3.59, 2.93 and 2.49 hours, respectively. Urinary recovery rates ranged from 43.5 to 78.2% within 12 hours in 2 patients, within 8 hours in 2 patients and within 6 hours in 1 patient. (3) Premature newborns given one shot intravenous injection of 10 mg/kg Serum concentrations of the drug in the 3 groups peaked in 30 minutes after one shot intravenous injection of 10 mg/kg at, respectively, 27.9, 21.5 and 23.0 micrograms/ml, and they gradually declined thereafter to 10.8, 6.2 and 6.5 micrograms/ml at 8 hours, respectively. Serum half-lives were shorter in older subjects and values in the 3 groups were 5.28, 4.43 and 4.24 hours, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term results of arterial counterpulsation in acute severe cardiac failure complicating myocardial infarction.
Thirty patients were discharged from hospital after treatment with arterial counterpulsation for acute severe heart failure complicating myocardial infarction. Seventeen patients had been in cardiogenic shock--13 with power failure alone, and 4 with a mechanical complication which required corrective surgery. Thirteen patients were in impending or 'preshock'. The follow-up period after infarction averaged 13-1 months. Results were good in 'preshock' patients, and in shocked patients with a surgically correctable mechanical complication. Results were poor in shocked patients with power failure alone. Counterpulsation has an important supportive role in the treatment of complicated myocardial infarction, provided that intervention is prompt and mechanical complications, if present, are corrected early.


Signatures of somatic mutations and gene expression from p16INK4A positive head and neck squamous cell carcinomas (HNSCC).
Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA- and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified from 35- formalin fixed and paraffin embedded (FFPE) HNSCC tumor samples. Immuno-histochemical evaluation of tumors was performed to determine the expression levels of p16INK4A and classified tumor samples either p16+ or p16-. Using ClearSeq Comprehensive Cancer panel, we examined the distribution of somatic mutations. Somatic single-nucleotide variants (SNV) were called using GATK-Mutect2 ("tumor-only" mode) approach. Using RNA-seq, we identified a catalog of 1,044 and 8 genes as significantly expressed between p16+ and p16-, respectively at FDR 0.05 (5%) and 0.1 (10%). The clinicopathological characteristics of the patients including anatomical site, smoking and survival were analyzed when comparing p16+ and p16- tumors. The majority of tumors (65%) were p16+. Population sequence variant databases, including gnomAD, ExAC, COSMIC and dbSNP, were used to identify the mutational landscape of somatic sequence variants within sequenced genes. Hierarchical clustering of The Cancer Genome Atlas (TCGA) samples based on HPV-status was observed using differentially expressed genes. Using RNA-seq in parallel with targeted DNA-seq, we identified mutational and gene expression signatures characteristic of p16+ and p16- HNSCC. Our gene signatures are consistent with previously published data including TCGA and support the need to further explore the biologic relevance of these alterations in HNSCC.


New glycine substitution mutations in type VII collagen underlying epidermolysis bullosa pruriginosa but the phenotype is not explained by a common polymorphism in the matrix metalloproteinase-1 gene promoter.
Epidermolysis bullosa (EB) pruriginosa is an unusual variant of dystrophic EB in which intense itching can lead to striking skin changes resembling acquired skin disorders such as nodular prurigo or hypertrophic lichen planus. The molecular pathology involves mutations in the COL7A1 gene, but the nature of the mutations is similar to those seen in other non-pruritic forms of dystrophic EB. The mechanism of the dramatic phenotypic differences is currently unknown. In this study we assessed the incidence of a common functional polymor-phism in the matrix metalloproteinase-1 gene promoter (1G or 2G at nucleotide -1607) in individuals with EB pruriginosa (n = 27) compared with non-itchy dominant dystrophic EB (n = 23), recessive dystrophic EB (n = 25) and normal controls (n = 50). The hypothesis is that the 2G allele, which was previously shown to increase matrix metalloproteinase-1 activity and lead to increased degradation of type VII collagen, could explain the phenotypic heterogeneity encountered in dominant forms of EB, particularly the itchy EB pruriginosa phenotype. The rationale is that increased type VII collagen degradation could trigger an inflammatory response leading to itchy skin characteristic of EB pruriginosa. All 27 individuals with EB pruriginosa were heterozygous for dominant-negative glycine substitution mutations in the COL7A1 gene, six of which have not been reported previously. The frequency of the 2G allele in these subjects (46.3%) was greater than in the controls (42.0%), but less than in non-itchy dominant dystrophic EB (52.2%) or recessive dystrophic EB (62.0%), indicating that variants of a common functional polymorphism in the matrix metalloproteinase-1 gene promoter do not account for the itchy skin phenotype. The pathophysiology of EB pruriginosa remains unexplained.


[Dilatation technique with the TNS (transcutaneous nail insertion system) for minimally invasive implantation of intramedullary nails at the proximal femur].
A new technique of a minimally invasive approach to the proximal femur was developed for the management of per- and subtrochanteric fractures using intramedullary nail blade systems. For creating the entry portal at the proximal femur a transcutaneously applied Kirschner-wire is used. Subsequently, a new developed trocar system (TNS) for the protection of the soft tissue during reaming procedures is placed via a small cutaneous incision. The reaming of the femoral shaft can be performed through this trocar system. A new targeting jig especially adapted to the gliding nail was used in this first series. From December 1998 to June 1999 12 patients were treated with this new technique in the Department of Trauma Surgery of the Philipps-University in Marburg. The mean age of the 8 female and 4 male patients was 78 (+/- 12) years. The majority of the total group were old patients with a mean ASA score of 3-4. Relevant intraoperative complications using the new dilatation approach were not observed. All patients were mobilised after few days. Postoperative complications or infections were not found. In the clinical practice of the management of per- and subtrochanteric femoral fractures the new dilatation approach has proved to be more comfortable and minimally invasive than the standard technique existing to date.


[The afferent control of the cortically evoked reactions of the interneurons in the spinal cord ventral horn].
Responses of spinal interneurons of the ventral horn (L6, 7) to stimulation of motor cortex and hindlimbs' afferents, were studied in cats. The cortically induced responses were shown to be modulated by a preceding afferent wave. Three types of effects were revealed: facilitation, depression, and biphasic changes. The facilitation was rather short (not over 30-35 msec) whereas the depression varied from 60-100 to 300-400 msec. The facilitation was commonly observed for the short-latency responses whereas the long-latency ones were rather depressed. The depression was more obvious for ipsilateral responses, when conditioning contralateral afferents rather than ipsilateral ones, high-threshold afferents rather than low-threshold ones. The data obtained suggest the mechanism of presynaptic inhibition to play a major part in the depression of descending activity, as well as the defacilitation in the interneurons themselves due to a blocking of the background afferent inflow from other inputs.


[Tobacco- and alcohol-associated cancer risk of the upper respiratory and digestive tract].
A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in the ENT Departments of the University hospitals of Heidelberg and Giessen (FRG) provided information on the role of chronic tobacco and alcohol consumption as risk factors in 200 patients and 800 control subjects (4:1 matched design).--Only 4.5% of the tumour patients were non-smokers in contrast to 29.5% in the control group. The average tobacco and alcohol consumption in the patients was more than twice that high than in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer.--It could be demonstrated that tobacco as well as alcohol increased the risk for head and neck cancer, in a dose-dependent fashion, as separate risk factors. In heavy smokers (greater than 60 pack years) a relative risk of 23.4 (alcohol-adjusted) was calculated. For heavy drinkers (greater than 100 g ethanol/day) a relative risk of 21.4 (tobacco-adjusted) was documented. Combined alcohol and tobacco consumption showed a synergistic effect and increased the cancer risk more in an multiplicative than in an additive manner: A daily ethanol consumption of more than 75 g/day combined with more than 50 pack years caused a risk value of 146.2.