A preliminary report on transplantation of microskin autografts overlaid with sheet allograft in the treatment of large burns.
The technique of transplantation of autologous microskin grafts (MG) with overlays of split-thickness skin allografts was used in the treatment of nine extensively burned patients. Preparation of MG includes: 1) mincing small pieces of split-thickness skin autografts into skin particles (SPs); 2) dispersing the SPs evenly on a piece of silk cloth; 3) transferring SPs to the dermal surface of an allograft sheet (20/1000 in.); 4) transplanting the allograft with SPs to the excised wound. The mean burn area (total/3 degrees, mean +/- SEM) of this group was 74.9 +/- 16.6/62.1 +/- 18.1% TBSA (range 40 to 94/28 to 90%). The mean age was 27 years (range 19 to 38). Early staged excisions followed immediately by MG applications were performed on 35 large body sites, including extremities, chests plus abdomens and backs. The mean area excised and grafted with MG was 41.7 +/- 11.0% TBSA (range 26 to 62%). The average time for complete healing was about six to seven weeks postgrafting. Eight patients survived; one died of overwhelming pulmonary infection 22 days postburn. Advantages of this technique are: 1) the great potential of MG to provide a large expansion ratio of 8:1 to 15:1, average greater than 10:1 in this series; 2) good maintenance of the healed graft to withstand trauma except in areas of repeated flexion; 3) ease of preparation and application with less cost compared to cultured epidermal sheet grafts; 4) prevention of infection in extremely large burns by providing continuous epidermal coverage following sheet allograft application.


Impact of Out-of-pocket Costs on Varenicline Utilization and Persistence.
Background: Varenicline is a smoking cessation medication. Objectives: We analyzed patients' out-of-pocket costs and utilization of and persistence with varenicline. Methods: De-identified claims data in the MarketScan® Commercial Claims and Encounters Database were analyzed retrospectively. Participants were all patients at least 18 years of age continuously enrolled in plans during 2009. Plans were categorized according to restriction (no coverage; prior authorization; smoking cessation program requirement; no restrictions) and out-of-pocket cost for a 30-day supply (low: <US$12; medium: US$12-24.99; high: ≥US$25). The main outcome measures were utilization (defined as presence of a drug claim) and persistence (according to days' supply and number of days to discontinuation). Generalized linear models and time-to-event analyses were conducted. Results: There were 142,251, 458,966 and 222,241 individuals in the low, medium and high out-of-pocket cohorts, respectively. The reference group for all comparisons was the cohort with no access restrictions and low out-of-pocket costs. Higher out-of-pocket cost was associated with a lower likelihood of varenicline initiation for both the prior authorization (odds ratio [OR]=0.10, p<0.001) and smoking cessation program requirement (OR=0.19, p<0.001) groups, versus the no restriction cohort. Within the no access restriction cohort, subjects in the high out-of-pocket group were half as likely to complete a varenicline course versus the low out-of-pocket group (OR=0.47; p<0.002). Conversely, for the smoking cessation program requirement cohort, compared to the low out-of-pocket no restriction cohort, subjects who were in the high out-of-pocket group were more likely to complete a varenicline course (OR=0.70; p=0.13) than those in the low out-of-pocket group (OR=0.38; p=0.04). Conclusions: Higher varenicline out-of-pocket costs were generally associated with lower utilization of and persistence with treatment. These findings have implications for coverage policies in health plans and employers seeking to encourage smoking cessation.


In vitro assessment of platelet function.
With the realization that the skin bleeding time is often an unreliable measure of platelet function, efforts have been made to identify ways to assess qualitative platelet dysfunction. Currently available techniques measure platelet adhesion, platelet aggregation, the ability of platelets to retard or stop flow through fibers, and the contribution of platelets to in vitro clot formation. Glass bead adhesion, which continues to be performed in some laboratories, is gradually being replaced by measures of platelet adhesion to filters composed of glass fibers, Dacron fibers, or collagen. In each instance, anticoagulated platelet-rich plasma or whole blood flows through the filter under a regulated pressure gradient. The amount of blood flowing through the filter versus time and/or the time to filter occlusion are measured. Recent developments in platelet aggregation have focused on whole blood and stagnation point flow aggregation techniques. Whole blood aggregation does not require blood sample processing and accommodates blood obtained from citrated vacutainer tubes. Stagnation point flow measures both platelet adhesion and aggregation and may be able to detect pathologically-enhanced platelet function. Global measures of hemostasis attempt to simultaneously evaluate the adequacy of fluid phase coagulation and platelet function. Currently available techniques include Thromboelastography, SonoClot Analyzer, Hemodyne Hemostasis Analyzer, PITT, and Hemostatometry. Although each of these technologies have been shown to provide interesting data in the research setting, the ability of any of these techniques to detect abnormal or clinical inadequate platelet function remains to be established.


An Overview of Image Caption Generation Methods.
In recent years, with the rapid development of artificial intelligence, image caption has gradually attracted the attention of many researchers in the field of artificial intelligence and has become an interesting and arduous task. Image caption, automatically generating natural language descriptions according to the content observed in an image, is an important part of scene understanding, which combines the knowledge of computer vision and natural language processing. The application of image caption is extensive and significant, for example, the realization of human-computer interaction. This paper summarizes the related methods and focuses on the attention mechanism, which plays an important role in computer vision and is recently widely used in image caption generation tasks. Furthermore, the advantages and the shortcomings of these methods are discussed, providing the commonly used datasets and evaluation criteria in this field. Finally, this paper highlights some open challenges in the image caption task.


Semantic vs. syntactic subject: a comprehension test based on control constructions.
The test presented here is made of 32 + 32 complex sentences that are submitted with two different tasks: one to prove comprehension of the event denoted by their embedded clause and the other to prove the corret interpretation of this clause, whose null subject is syntactically controlled. The tasks have been administered to four stabilized aphasic patients of medium severity to see whether their comprehension could be considered asyntactic with respect to the specific Control module of Universal Grammar (Chomsky, 1981).


Effects of electro-acupuncture on corticotropin-releasing factor in rats with experimentally-induced polycystic ovaries.
The aims of the present study were to investigate corticotropin-releasing factor (CRF) concentrations in the brain, the adrenal glands, and the ovaries in rats with estradiol valerate (EV) induced polycystic ovaries (PCO). The effect of 12 electro-acupuncture (EA) treatments on CRF concentrations was also investigated. The CRF concentrations in the median eminence (ME) were significantly increased in rats with PCO (both the PCO control group and the PCO group receiving EA) compared with the healthy control group (veichle control group), indicating increased activity in the hypothalamus-pituitary axis. The CRF concentrations in the ovaries were significantly reduced in the PCO group receiving EA compared with the PCO control group. Also, there was a decrease in comparison withthe healthy control group but the decrease was not as significant. This finding indicates that repeated EA treatments change the neuroendocrinological state in the ovaries, which may play an important role in reproductive failure.


Effect of diet supplemented with quinoa seeds on oxidative status in plasma and selected tissues of high fructose-fed rats.
Oxidative stress plays an important role as a mediator of damage produced by fructose metabolism. This work was designed to investigate the effect of diet supplemented with quinoa seeds on oxidative stress in plasma, heart, kidney, liver, spleen, lung, testis and pancreas of fructose administered rats. Fructose administration (310 g/kg fodder for 5 weeks) caused oxidative stress that was manifested by the increase in plasma malondialdehyde (MDA) (p<0.05), and by the non-significant changes in the enzymatic antioxidant potential in plasma and most of tissues. Co-administration of quinoa seeds (310 g/kg fodder) maintained normal activities of some enzymes. It also influenced the oxidative stress as was evidenced by decreasing MDA in plasma, and decreasing the activities of antioxidant enzymes (erythrocyte superoxide dismutase - eSOD, catalase -CAT, plasma glutathione peroxidase - pGPX). These findings demonstrate that quinoa seeds can act as a moderate protective agent against potential of fructose-induced changes in rats by reducing lipid peroxidation and by enhancing the antioxidant capacity of blood (plasma) and heart, kidney, testis, lung and pancreas.


Cutaneous vasculitis--a dynamic process posing diagnostic challenge.
To characterize the clinicopathologic features and to assess the therapeutic outcome in cutaneous vasculitis. Fifty biopsy proven cases of cutaneous vasculitis seen between January 1998 and July 1999 were studied. The commonest presentation was palpable purpura. The site most commonly affected was the extremity, irrespective of the age (adults - 40 and children - 10) and sex. The histopathologic picture ranged from an acute to chronic process, which besides the classic picture included bullous presentation, granulomatous histology and nonspecific features. Clinical correlation and investigations including direct immunofluorescence (DIF) were required to differentiate primary from secondary vasculitis (SLE-4, dermatomyositis-2, rheumatoid artritis-1, HIV-1, septicaemia-1 and drug reaction 2). DIF was diagnostic in 13 out of 21 cases providing evidence of an immune-mediated pathogenesis. Drugs used in the treatment included dapsone, colchicine, pentoxyphiline and steroids. The clinical picture and outcome of primary cutaneous vasculitis were benign while the prognosis of secondary vasculitis depended on the primary disease, irrespective of the histopathological picture.


Intravitreal bevacizumab (Avastin) injection for neovascular glaucoma: a survey on 23 cases throughout 12-month follow-up.
Neovascular glaucoma (NVG) represents one of the most severe forms of secondary glaucoma, caused by a number of ocular and systemic conditions, which share the common element of retinal ischaemia/hypoxia that initiates the subsequent release of angiogenesis factors, with consequent development of new abnormal vessels through the ciliary body. The aim was to examine the potential efficacy and safety of intravitreal injection of bevacizumab (IVB) (Avastin) in the treatment of NVG in patients who had already undergone the standard retinal ablative procedure. This was a prospective pilot trial. Clinical data of 26 eyes from 23 patients, including diagnosis, visual acuity, iris fluorescein angiography stage and intraocular pressure (IOP), were collected. Three injections of bevacizumab were scheduled for each recruited eye at 4-week intervals from the start. All investigations were repeated the day before the IVB (1.25 mg/0.05 ml) and at the 1-, 3-, 6-, 9- and 12-month follow-up. Regression of corneal oedema together with significant pain reduction was achieved in all eyes already after the first IVB, without any noteworthy improvement of visual acuity. At the end of the scheduled protocol (three IVB), regression of iris neovascularization was documented in all patients, together with significant improvement of visual acuity. The IOP reduction from baseline ranged from 30 to 0 mmHg (12.1 +/- 8 mmHg). Intravitreal bevacizumab, as adjunctive treatment to the standard retinal ablative procedure, seems promising for the management of conditions responsible of retinal ischaemia/hypoxia associated with NVG.


Preliminary Anti-Fungal Activity of the Aqueous Bark Extract of Calotropis procera (ASCLEPIADACEAE).
Calotropis procera is a species of flowering plant which belongs to the Asclepiadaceous family. Its other names are Apple of Sodom, Giant Milkweed and Swallow-wort. It's native to Africa and Asian countries where they exist as a spreading shrub or small tree with height of about 4m. They. exude copious milky sap when cut or broken. It has a broad grey-green leaves with a pointed tip, two rounded basal lobes and no leaf stalk. Their flowers are waxy white. The different part of this plant has been used for different medicinal purposes such as cure of leprosy, eczema, inflammation, cutaneous infections, syphilis, malarial and low hectic fevers, and as abortifacient. The extract of the bark of the plant Calotropis procera used locally by people in Sokoto to treat ringworm infection was investigated for the claimed activity by subjecting the extract collected to both phytochemical and antifungal screening. The extracts of water, n-hexane, petroleum ether and chloroform of the bark of the plant Calotropis procera were evaluated for the presence of alkaloids, tannins, glycosides, saponins, steroids and flavonoids. And the water extract which is often used by the local people was tested for antifungal activity using Sabouraud Dextrose Agar (SDA) in Kirby-Bauer disc diffusion method developed by Kirby et al. Fulcin tablet was used as a standard and two petridishes that does not contain the extracts were used as control. In the phytochemical study using extracts of n-hexane, petroleum ether, chloroform and water, the presence of alkaloids, tannins, saponins and steroids (cardiac glycoside) were confirmed. Also, for the antifungal activity of the plant, there was a complete inhibition of Microsporum specie and Trichophyton specie in the sample after 10 days of inoculation when water extract at different concentrations (i.e. 20 mg/L, 30 mg/L and 40 mg/L) were applied. The tablet only completely inhibited Trichophyton specie. Epidermophyton specie was not found in the sample. The inhibitory effect of this extract was significant (p < 0.05) when compared with fulcin tablet. The research confirmed that the extract of the bark of the plant Calotropis procera has some antifungal activity.


Spinal cord injury. An overview.
Advancements in the management of urologic complications such as the neurogenic bladder have been essential to improving the quality of life and longevity of patients with spinal cord injury. These advances are discussed in greater detail in the subsequent articles in this issue. Despite the many improvements that have been made in post-trauma care, spinal cord injury remains a devastating lesion of the nervous system. Current therapies have not proved to be particularly effective in preventing or reversing damage to the spinal cord. Still, every effort should be made to preserve remaining function and to prevent complications. The care of these patients has been significantly improved with the development of specialized multidisciplinary centers. The emphasis in current treatment focuses on rehabilitation and adaptation to the disability and on prevention of secondary disabilities. Research in basic and clinical neuroscience will result in better, more useful care and treatment for those with spinal cord injury. However, even then, a neurorehabilitation team will be essential to care for these patients. Continuing efforts must be made to ensure that people with spinal cord injury lead full and productive lives.


CC-chemokine ligand 2 inhibition in idiopathic pulmonary fibrosis: a phase 2 trial of carlumab.
The objective of this study was to determine the safety and efficacy of carlumab in the treatment of idiopathic pulmonary fibrosis (IPF).A phase 2, randomised, double-blind placebo-controlled dose-ranging study was conducted in patients with IPF (n=126). Patients were randomised to carlumab (1 mg·kg(-1), 5 mg·kg(-1), or 15 mg·kg(-1)) or placebo every 4 weeks. The primary endpoint was the rate of percentage change in forced vital capacity (FVC). Secondary endpoints were time to disease progression, absolute change in FVC, relative change in diffusing capacity of the lung for carbon monoxide (DLCO), and St George's Respiratory Questionnaire (SGRQ) total score.Due to a pre-planned, unfavourable interim benefit-risk analysis, dosing was suspended. The rate of percentage change in FVC showed no treatment effect (placebo -0.582%, 1 mg·kg(-1) -0.533%, 5 mg·kg(-1) -0.799% and 15 mg·kg(-1) -0.470%; p=0.261). All active treatment groups showed a greater decline in FVC (1 mg·kg(-1) -290 mL, 5 mg·kg(-1) -370 mL and 15 mg·kg(-1) -320 mL) compared with placebo (-130 mL). No effect on disease progression, DLCO, infection rates or mortality was observed. SGRQ scores showed a nonsignificant trend toward worsening with active treatment. Unexpectedly, free CC-chemokine ligand 2 levels were elevated above baseline at both 24 and 52 weeks. A higher proportion of patients with one or more serious adverse events was observed in the 5 mg·kg(-1) group (53.1%) compared with 1 mg·kg(-1) (15.2%), 15 mg·kg(-1) (21.9%) and placebo (46.4%), although no unexpected serious adverse events were noted.Although dosing was stopped prematurely, it is unlikely that carlumab provides benefit to IPF patients.


Co-occurrence of Jalili syndrome and muscular overgrowth.
Jalili syndrome is a rare disorder inherited in an autosomal recessive pattern manifesting as a combination of cone-rod dystrophy including progressive loss of visual acuity, color blindness, photophobia, and amelogenesis imperfecta with hypoplastic, immature, or hypocalcified dental enamel. It is caused by mutations in CNNM4, which encodes the ancient conserved domain protein 4. Here we report three brothers with Jalili syndrome and muscle overgrowth of the legs. Myopathic changes were found in needle electromyography. Mutational analysis showed in all three brothers a novel likely pathogenic homozygous missense substitution in exon 1 (c.1076T>C, p.(Leu359Pro)) of CNNM4. Both parents were carriers for the variant. In order to exclude other causative variants that could modify the patients' phenotype we performed exome sequencing and MLPA analysis of the DMD gene in Patient 1. These analyses did not identify any additional variants. Our results expand the mutational spectrum associated with Jalili syndrome and suggest that mild myopathy with muscle overgrowth of the legs could be a newly identified manifestation of the disorder.


A systematic review of emerging feature selection optimization methods for optimal text classification: the present state and prospective opportunities.
Specialized data preparation techniques, ranging from data cleaning, outlier detection, missing value imputation, feature selection (FS), amongst others, are procedures required to get the most out of data and, consequently, get the optimal performance of predictive models for classification tasks. FS is a vital and indispensable technique that enables the model to perform faster, eliminate noisy data, remove redundancy, reduce overfitting, improve precision and increase generalization on testing data. While conventional FS techniques have been leveraged for classification tasks in the past few decades, they fail to optimally reduce the high dimensionality of the feature space of texts, thus breeding inefficient predictive models. Emerging technologies such as the metaheuristics and hyper-heuristics optimization methods provide a new paradigm for FS due to their efficiency in improving the accuracy of classification, computational demands, storage, as well as functioning seamlessly in solving complex optimization problems with less time. However, little details are known on best practices for case-to-case usage of emerging FS methods. The literature continues to be engulfed with clear and unclear findings in leveraging effective methods, which, if not performed accurately, alters precision, real-world-use feasibility, and the predictive model's overall performance. This paper reviews the present state of FS with respect to metaheuristics and hyper-heuristic methods. Through a systematic literature review of over 200 articles, we set out the most recent findings and trends to enlighten analysts, practitioners and researchers in the field of data analytics seeking clarity in understanding and implementing effective FS optimization methods for improved text classification tasks.


Optimal Imaging Parameters for Readout-segmented EPI of the Temporal Bone.
Readout-segmented echo planar imaging (rs-EPI) is a form of multi-shot EPI. rs-EPI is affected less by susceptibility artifacts than single-shot EPI (ss-EPI), which is widely used for diffusion-weighted imaging, so rs-EPI is expected to produce less image distortion. In this study, we compared rs-EPI and conventional ss-EPI of the temporal bone region, which contains abundant amounts of air and frequently exhibits changes in magnetic susceptibility. In addition, we used a phantom to determine the optimum rs-EPI acquisition conditions for clinical use and investigated the clinical utility of rs-EPI in 20 patients (8 men, 12 women, mean age, 54.3 ± 16.7-years-old) with cholesteatoma (mean apparent diffusion coefficient on ss-EPI, 0.88 × 10(-3) ± 0.18 mm(2)/s). The images of the temporal bone region produced using rs-EPI exhibited less distortion than those obtained with ss-EPI (P < 0.05).


Exploring the 'January effect' at a university hospital in Pakistan: a retrospective cohort study investigating the impact of trainee turnover on patient care quality outcomes.
There are reports of a potential rise in a teaching hospital's morbidity and mortality rates during the trainee turnover period, i.e., with the induction of new residents and house staffs, and the changeover of clinical teams. The published literature displays mixed reports on this topic with lack of reproducible observations. The current study was conducted to explore existence of any such phenomenon (January effect) in Pakistan. This retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan. Five-year (2013-2018) record of all the patients in all age groups related to these outcomes was retrieved and recorded in specifically designed questionnaire. Different outcome measures were used as indicators of patient care and change in these outcomes at the time of new induction was related to possible January effect. During the five-year study period, more than 1100 new trainees were inducted into the post graduate medical education program (average of 237 per year) with more than 22,000 inpatient admissions (average of 45,469 per year). Some patterns were observed in frequencies of surgical site infections, medication errors, sentinel events, patient complaints, and adverse drug reactions. However, these were not consistently reproducible and could not be directly attributed to the trainee turnover. All other indicators did not show any pattern and were considered inconclusive. No effect of overlap was observed. Inconsistency in the patient care quality indicators do not favor existence of January effect in our study. Further research is recommended to establish our results.


Tumor necrosis factor (TNF)-induced cutaneous necrosis is mediated by TNF receptor 1.
Tumor necrosis factor (TNF) is a central mediator of immune and inflammatory responses. Its activities have been shown to be mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75). The cytoplasmic domains of both TNF receptors are unrelated, suggesting that they link to different intracellular signaling pathways. To determine their role in vivo in lipopolysaccharide (LPS)- and TNF-induced skin inflammatory necrosis, TNFR1-, TNFR2-, and TNF lymphotoxin-alpha (LT alpha)-deficient mice were used. Skin abscesses were experimentally induced with local application of TNF or LPS. Large macroscopic ulcerations were observed in TNF-injected wild-type animals and to a slightly lesser extent in TNFR2-deficient mice with tissue destruction in both cases extending deep into the dermis. Tissue destruction was accompanied by an intense immune infiltrate composed mainly of neutrophils, lymphocytes, and macrophages. TNFR1-deficient and TNFR1/TNFR2-double-deficient mice, however, did not exhibit any ulceration and showed only a very mild inflammatory infiltrate. In TNF/LT alpha-double ligand0-deficient animals, a moderate epidermal necrosis was observed with a reduced inflammatory infiltrate compared to wild-type animals. As with TNF injections, subcutaneous injection of LPS induced a comparable pattern of skin necrosis in wild-type and TNF receptor mutant mice, yet a slightly more acute inflammatory level was observed regardless of the type of animal tested. As found for TNF-induced skin necrosis, the extent of LPS-induced skin necrosis was reduced in TNF/LT alpha-deficient mice compared to wild-type animals. The present data strongly suggest that TNFR1, rather than TNFR2, is engaged in LPS- and TNF-induced skin necrosis and highlight the predominant role played by TNF in LPS-induced inflammatory diseases.


Aortic valve stenosis: an active atheroinflammatory process.
To summarize the current understanding of the pathobiology of aortic valve stenosis and portray the major advances in this field. Stenotic aortic valves are characterized by atherosclerosis-like lesions, consisting of activated inflammatory cells, including T lymphocytes, macrophages, and mast cells, and of lipid deposits, calcific nodules, and bone tissue. Active mediators of calcification and cells with osteoblast-like activity are present in diseased valves. Extracellular matrix remodeling, including collagen synthesis and elastin degradation by matrix metalloproteinases and cathepsins, contributes to leaflet stiffening. In experimental animals, hypercholesterolemia induces calcification and bone formation in aortic valves, which can be inhibited by statin treatment. The potential of statins to retard progression of aortic valve stenosis has also been recognized in clinical studies; however, further prospective trials are needed. Angiotensin II-forming enzymes are upregulated in stenotic valves. Angiotensin II may participate in profibrotic progression of aortic valve stenosis and may serve as a possible therapeutic target. Recent findings regarding the interaction of inflammatory cells, lipids, mediators of calcification, and renin-angiotensin system in stenotic valves support the current opinion of aortic valve stenosis being an actively regulated disease, potentially amenable to targeted molecular therapy. Evidence from prospective clinical studies is eagerly awaited.


A posteriori healthy dietary patterns may decrease the risk of central obesity: findings from a systematic review and meta-analysis.
Central obesity is a pivotal component of metabolic syndrome, and several studies have investigated the association of dietary patterns and central obesity. However, findings of studies are inconclusive. Therefore, we aimed to conduct the present study to summarize the available data regarding the association of a posteriori dietary patterns and central obesity in adults to test the hypothesis of whether a highly healthy dietary pattern is associated with decreased risk of central obesity. We searched all published English studies to identify related articles in MEDLINE, EMBASE, and Google Scholar databases up to December 2015. The meta-analysis was conducted on 13 studies including 12 cross-sectional studies and 1 case-control study that reported odds ratios (ORs), relative risks, or hazard ratios for risk of central obesity. The between-study variance was assessed using Cochran Q test and I2. Subgroup analysis was applied to define possible sources of heterogeneity. The highest category of healthy/prudent patterns compared with those in the lowest category resulted in significant decrease in the risk of central obesity (pooled OR was 0.81 [95% confidence interval 0.66-0.96]). Pooled results indicated a higher nonsignificant increase in the risk of central obesity (OR was 1.16 [95% confidence interval 0.96-1.35]) in the highest category of Unhealthy/Western pattern compared with those in the lowest category. There was also a significant heterogeneity in the observed associations. We found that sex, country, and continent were the potential sources of heterogeneity. The results of the present meta-analysis showed that a posteriori healthy dietary patterns may decrease the risk of central obesity, whereas no significant association was found between unhealthy dietary patterns and central obesity. Together, the results highlight the need for well-designed and carefully carried out clinical trials based on dietary patterns in future research.


The remaining barriers to normalcy in CF: Advances in assessment of CF lung disease.
Despite early diagnosis of cystic fibrosis (CF) through newborn screening, a substantial proportion of infants and young children with CF still demonstrate physiologic and structural evidence of lung disease progression, such as obstructive airway disease and bronchiectasis. The growing availability of highly effective CF transmembrane conductance regulatory modulator therapy to the vast majority of people with CF has led to the potential to alter the natural history of CF lung disease, but to assess the full impact of these therapies on CF lung disease and to help guide treatment, sensitive measures of early and mild disease are needed. Chest imaging using computed tomography or magnetic resonance imaging is one approach, but technologic barriers and/or concern about exposure to ionizing radiation may limit its use. However, advances in physiologic measurement techniques and exhaled breath analysis offer another option for assessment of CF lung disease.


The utility of motion parallax information for the perception and control of heading.
Two experiments in which participants were given control over the direction of computer-simulated self-motion were conducted. Environments were designed to evaluate the functionality of simple and multiple motion parallax as well as a separation ratio (sigma; indexing the separation of 2 objects in depth) for the perception and control of heading. Results provide a 1st indication of optimizing performance in the top end of the global optical flow velocity range available during human bipedal self-motion. The introduction of sigma, developed to explain performance improvements with decreasing distance to the target, was able to account for most of the performance differences among all simulated environments. The rate of change in horizontal optical separation between at least 2 discontinuities was identified as a likely candidate for the optical foundation of the perception and control of heading during target approach.


Symmetry-specific characterization of bond orientation order in DNA-assembled nanoparticle lattices.
Bond-orientational order in DNA-assembled nanoparticles lattices is explored with the help of recently introduced Symmetry-specific Bond Order Parameters (SymBOPs). This approach provides a more sensitive analysis of local order than traditional scalar BOPs, facilitating the identification of coherent domains at the single bond level. The present study expands the method initially developed for assemblies of anisotropic particles to the isotropic ones or cases where particle orientation information is unavailable. The SymBOP analysis was applied to experiments on DNA-frame-based assembly of nanoparticle lattices. It proved highly sensitive in identifying coherent crystalline domains with different orientations, as well as detecting topological defects, such as dislocations. Furthermore, the analysis distinguishes individual sublattices within a single crystalline domain, such as pair of interpenetrating FCC lattices within a cubic diamond. The results underscore the versatility and robustness of SymBOPs in characterizing ordering phenomena, making them valuable tools for investigating structural properties in various systems.


Production of maize-bambara groundnut complementary foods fortified pre-fermentation with processed foods rich in calcium, iron, zinc and provitamin A.
Maize-bambara groundnut complementary foods are deficient in calcium, iron, zinc and vitamin A. Food-to-food fortification could be cheaper, safer and more easily adopted by local communities compared to the use of chemically pure compounds and vitamins to enrich such foods. Maize-bambara groundnut complementary foods fortified for iron, zinc, calcium and vitamin A by blending with a multi-mix (1.41:1:2.25, w/w) of processed roselle calyces, cattle bones, and red palm oil in a 1:2.1 (w/w) ratio showed significant increases in calcium, iron, zinc and vitamin A contents of 3.26-4.225, 0.083-0.134 and 0.015-0.017 g kg(-1) and 4855.3-7493.7 microgRE kg(-1), respectively. The maize-bambara groundnut foods had calcium, iron, zinc and vitamin A contents that satisfy the proposed nutrient requirements for infants. Only the maize-bambara groundnut and maize-bambara groundnut malt fermented by backslopping [(MB)(b) and (MB(m))(b)] containing red palm oil emulsified with Brachystegia eurycoma had calcium contents significantly (P < 0.05) higher than Nutrend, a complementary food produced by Nestle (Nigeria) PLC. These products are from raw materials produced in commercial quantities by rural farmers using household level technologies which the rural and urban poor can more easily access in order to reduce micronutrient malnutrition.


State diabetes prevention and control program participation in the Health Disparities Collaborative: evaluating the first 5 years.
Approximately 20.8 million people in the United States, or 7% of the population, have diabetes mellitus. Treatment for this disease costs Americans more than 130 billion dollars yearly, and it is the sixth leading cause of death. The prevalence of diabetes has grown substantially in recent decades and is expected to continue to rise. The medically underserved and poor are at greater risk of developing diabetes and its complications than are other members of the U.S. population. The Health Resources and Services Administration makes health care resources and services available to economically disadvantaged populations through the Health Disparities Collaborative (HDC), a consortium formed to pool resources and services from state- and community-level donors. Since 1999, many of the Centers for Disease Control and Prevention's Division of Diabetes Translation State Diabetes Prevention and Control Programs (DPCPs) have joined the HDC to leverage resources and services. The purpose of a 2004 evaluation was to examine the impact that DPCP involvement with the Collaborative had on aspects of diabetes care at Federally Qualified Health Centers (FQHCs). An electronic survey was administered to DPCP coordinators. They were asked about 1) their roles and experience as participants in the Collaborative; 2) the skills and expertise most useful in developing and maintaining an effective collaboration for improved health care for diabetes; 3) which DPCP contributions were viewed as being routine and which were perceived to be essential; 4) the effects of DPCP contributions on the use of the chronic care model under which FQHCs operate; and 5) which health systems improvements played the greatest role in enhancing components of the chronic care model. Most respondents identified themselves as DPCP coordinators with 3 years of experience in that position. Organizational skills, such as communication, leadership, conflict resolution, negotiation, and meeting management, were cited as necessary to develop and maintain collaborative partnerships. DPCP contributions to FQHCs were perceived to be training, technical assistance with clinical care and patient education, financial resources, linkages to other diabetes partners, educational materials, and improved linkages with community resources. DPCPs contribute resources, skills, knowledge, and varied perspectives to the Collaborative that FQHCs may not have otherwise.


Diversity of a wall-associated kinase gene in wild and cultivated barley.
Domestication of barley and other cereals was accompanied by an increase in seed size which has been ascribed to human selection, large seeds being preferred by early farmers or favoured by cultivation practices such as deep sowing. An alternative suggestion is that the increase in seed size was an indirect consequence of selection for plants with more vigorous growth. To begin to address the latter hypothesis we studied the diversity of HvWAK1, a wall-associated kinase gene involved in root proliferation, in 220 wild barley accessions and 200 domesticated landraces. A 3655-bp sequence comprising the gene and upstream region contained 69 single nucleotide polymorphisms (SNPs), one indel and four short tandem repeats. A network of 50 haplotypes revealed a complex evolutionary relationship, but with landraces largely restricted to two parts of the topology. SNPs in the HvWAK1 coding region resulted in nonsynonymous substitutions at nine positions in the translation product, but none of these changes were predicted to have a significant effect on the protein structure. In contrast, the region upstream of the coding sequence contained five SNPs that were invariant in the domesticated population, fixation of these SNPs decreasing the likelihood that the upstream of a pair of TATA boxes and transcription start sites would be used to promote transcription of HvWAK1. The sequence diversity therefore suggests that the cis-regulatory region of HvWAK1 might have been subject to selection during barley domestication. The extent of root proliferation has been linked with traits such as above-ground biomass, so selection for particular cis-regulatory variants of HvWAK1 would be consistent with the hypothesis that seed size increases during domestication were the indirect consequence of selection for plants with increased growth vigour.


Pharmacodynamic effects of buspirone and clobazam.
1. The pharmacodynamic effects of buspirone and clobazam were compared in two volunteer studies. Acute doses of buspirone 5 mg, 10 mg and clobazam 10 mg were contrasted with placebo and a verum (lorazepam 1 mg), in a repeated measures design with 10 subjects assessed on a battery of psychometric tests at 1.5, 3.5, and 5.5 h post dose. For the combined results clobazam and the lower dose of buspirone (5 mg) were significantly contrasted with lorazepam on measures of subjective sedation, memory and choice reaction time (CRT). The higher dose of buspirone was not statistically different from lorazepam for all measures except memory; whilst contrasting significantly with placebo and clobazam on movement and total reaction time components respectively. Though failing to achieve significance, a similar trend was seen for critical flicker fusion (CFF) with buspirone 10 mg and lorazepam producing the lowest scores indicative of increased sedation. 2. Repeated doses of buspirone 5 mg twice daily, clobazam 10 mg twice daily, or placebo twice daily for 8 consecutive days were compared on the same battery of psychometric tests in a repeated measures design. Nine subjects were assessed on days 1, 3, and 8 of the study. Overall, memory performance significantly decreased with buspirone 5 mg in contrast to both clobazam and placebo whilst the opposite trend was seen with CFF. Clobazam significantly improved TRT in contrast to both placebo and buspirone. 3. These results indicate improved reaction time and memory performance with repeated dosing of clobazam in contrast to buspirone. Impairment following acute administration of buspirone appears limited to the higher (10 mg) dose.


Bioavailability of dexamethasone. II. Dexamethasone phosphate.
Plasma levels of dexamethasone phosphate (DP) and dexamethasone free alcohol (DA) were determined by a modification of existing radioimmunoassay methodology following intravenous administration of DP in man. Areas under DA plasma profiles were a linear function of DP dosage over the 40-fold range 0.05 to 2.0 mg/kg, and, by comparison with values obtained after DA was intravenously administered, indicated an overall conversion of DP to DA of 90%. The first-order rate constant for the conversion, 4.03 hr-1, was approximately 25 times that for hydrolysis in whole blood incubated in vitro. This relationship as well as disposition kinetics suggested that the major component of DP hydrolysis occurs within highly perfused organ(s) comprising the central kinetic compartment. Eighteen subjects were studied in a crossover experiment, and no significant differences were observed in best-fit parameters for the 4 mg/ml parenteral solution of DP in current use and an experimental high potency preparation of 24 mg/ml.


Comprehensive Characterization of RNA Processing Factors in Gastric Cancer Identifies a Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses.
RNA processing converts primary transcript RNA into mature RNA. Altered RNA processing drives tumor initiation and maintenance, and may generate novel therapeutic opportunities. However, the role of RNA processing factors in gastric cancer (GC) has not been clearly elucidated. This study presents a comprehensive analysis exploring the clinical, molecular, immune, and drug response features underlying the RNA processing factors in GC. This study included 1079 GC cases from The Cancer Genome Atlas (TCGA, training set), our hospital cohort, and two other external validation sets (GSE15459, GSE62254). We developed an RNA processing-related prognostic signature using Cox regression with the least absolute shrinkage and selection operator (LASSO) penalty. The prognostic value of the signature was evaluated using a multiple-method approach. The genetic variants, pathway activation, immune heterogeneity, drug response, and splicing features associated with the risk signature were explored using bioinformatics methods. Among the tested 819 RNA processing genes, we identified five distinct RNA processing patterns with specific clinical outcomes and biological features. A 10-gene RNA processing-related prognostic signature, involving ZBTB7A, METTL2B, CACTIN, TRUB2, POLDIP3, TSEN54, SUGP1, RBMS1, TGFB1, and PWP2, was further identified. The signature was a powerful and robust prognosis factor in both the training and validation datasets. Notably, it could stratify the survival of patients with GC in specific tumor-node-metastasis (TNM) classification subgroups. We constructed a composite prognostic nomogram to facilitate clinical practice by integrating this signature with other clinical variables (TNM stage, age). Patients with low-risk scores were characterized with good clinical outcomes, proliferation, and metabolism hallmarks. Conversely, poor clinical outcome, invasion, and metastasis hallmarks were enriched in the high-risk group. The RNA processing signature was also involved in tumor microenvironment reprogramming and regulating alternative splicing, causing different drug response features between the two risk groups. The low-risk subgroup was characterized by high genomic instability, high alternative splicing and might benefit from the immunotherapy. Our findings highlight the prognostic value of RNA processing factors for patients with GC and provide insights into the specific clinical and molecular features underlying the RNA processing-related signature, which may be important for patient management and targeting treatment.


Posting edited photos of the self: Increasing eating disorder risk or harmless behavior?
Social media use has been implicated as a correlate and a cause of increased disordered eating (DE), but little is known about the impact of specific aspects of social media use, such as posting edited photos of the self. Utilizing a two-stage design, the present study sought to determine how posting edited photos relates to DE, as well as anxiety and depression symptoms, in male and female college students. Stage 1 examined concurrent associations between posting edited photos and mental health measures in 2,485 undergraduates (76% female). Stage 2 examined causal associations between posting edited photos and eating disorder (ED) risk factors in 80 undergraduates (93% female) who endorsed posting edited photos in Stage 1 and volunteered for the experimental portion of the study. In Stage 1, those who endorsed posting edited photos (n = 660; 27%) reported greater eating pathology and anxiety than those who did not, but no differences were found for depressive symptoms. In Stage 2, posting edited photos caused increased weight/shape concerns. Posting photos reinforced urges to exercise and restrict food intake and anxiety. Editing photos without posting caused an immediate decrease in weight/shape concerns and a delayed decrease in sadness. Results support a consistent and direct link between posting edited photos and ED risk factors, suggesting that this is not a harmless behavior. Future work should explore the cumulative effects of this link to determine how specific uses of social media contribute to clinically meaningful outcomes.


The Masseter Muscle and Its Role in Facial Contouring, Aging, and Quality of Life: A Literature Review.
Masseter muscle hypertrophy manifests itself as enlargement of the masseter muscle. It can be associated with a square-angled lower face, pain, dental attrition, maxillary and mandibular bone resorption, and accelerated aging process of the lower face. The objective of this study was to assess the efficacy and safety of botulinum toxin type A in contouring the masseter and its impact on quality of life and the aging process of the lower face, and its role in full face rejuvenation. A PubMed search was conducted for articles on masseter treatment with botulinum toxin type A, masseter muscle hypertrophy, and the aging process of the lower face. Key studies are reviewed and findings are summarized. Botulinum toxin type A can be injected into the lower posterior aspect of the masseter muscle. Treatment decreases muscle bulk and reshapes the lower face. Furthermore, patient quality-of-life measures, including pain and symptoms of grinding and clenching, are improved. Treatment can decrease shear stress on maxillary and mandibular bones and can possibly prevent tooth loss and progressive bone resorption of the lower face. Adverse effects are minimal and short lasting. Botulinum toxin type A is a safe and effective treatment of masseter hypertrophy. The treatment results in improvement of functionality and cosmesis, and restoration of facial harmony.


PET and PET-CT. State of the art and future prospects.
Fluoro-deoxyglucose positron emission tomography (FDG PET) enables the in vivo study of tissue metabolism, and thus is able to identify malignant tumours as hypermetabolic lesions by an increase in tracer uptake. Many papers have demonstrated both the relevant impact of FDG PET on staging of many cancers and the superior accuracy of the technique compared with conventional diagnostic methods for pre-treatment evaluation, therapy response evaluation and relapse identification. In particular PET was found useful in identifying lymph nodal and metastatic spread, thus altering patient management in more than 30% of cases. PET images, however, provide limited anatomical data, which in regions such as the head and neck, mediastinum and pelvic cavity is a significant drawback. The exact localization of lesions may also be difficult in some cases on the basis of PET images alone. The introduction of combined PET-computed tomography (PET-CT) scanners enables the almost simultaneous acquisition of transmission and emission images, thus obtaining optimal fusion images in a very short time. PET-CT fusion images enable lesions to be located, reducing false positive studies and increasing accuracy; the overall duration of the examination may also be reduced. On the basis of both literature data and our experience we established the clinical indications when PET-CT may be particularly useful, in comparison with PET alone. It should also be underlined that the use of PET-CT is almost mandatory for new tracers such as 11C-choline and 11C-methionine; these new tracers may be applied for studying tumours not assessable with FDG, such as prostate cancer. In conclusion PET-CT is at present the most advanced method for metabolic imaging, and is capable of precisely localizing and assessing tumours; fusion images reduce false positive and inconclusive studies, thus increasing diagnostic accuracy.


Treatment Considerations of Myelodysplastic Syndromes/Neoplasms for Pathologists.
The diagnosis of myelodysplastic syndromes/neoplasms (MDS) has evolved over the years with the incorporation of genetic abnormalities to establish a diagnosis, their impact on risk stratification, prognostication, and therapeutic options. Hematopathologists are the cornerstone to establish an accurate diagnosis and ensure patients receive the best available treatment option. Hematopathologists and clinicians must work closely together to establish the best disease subclassification, by combining pathologic findings with the clinical presentation. This will ensure patients receive the best therapeutic approach by better understanding the disease entity. In this review, we discuss how we approach a bone marrow biopsy report in the management of MDS.


Transgenic hairy roots. recent trends and applications.
Agrobacterium rhizogenes causes hairy root disease in plants. The neoplastic roots produced by A. rhizogenes infection is characterized by high growth rate and genetic stability. These genetically transformed root cultures can produce higher levels of secondary metabolites or amounts comparable to that of intact plants. Hairy root cultures offer promise for production of valuable secondary metabolites in many plants. The main constraint for commercial exploitation of hairy root cultures is their scaling up, as there is a need for developing a specially designed bioreactor that permits the growth of interconnected tissues unevenly distributed throughout the vessel. Rheological characteristics of heterogeneous system should also be taken into consideration during mass scale culturing of hairy roots. Development of bioreactor models for hairy root cultures is still a recent phenomenon. It is also necessary to develop computer-aided models for different parameters such as oxygen consumption and excretion of product to the medium. Further, transformed roots are able to regenerate genetically stable plants as transgenics or clones. This property of rapid growth and high plantlet regeneration frequency allows clonal propagation of elite plants. In addition, the altered phenotype of hairy root regenerants (hairy root syndrome) is useful in plant breeding programs with plants of ornamental interest. In vitro transformation and regeneration from hairy roots facilitates application of biotechnology to tree species. The ability to manipulate trees at a cellular and molecular level shows great potential for clonal propagation and genetic improvement. Transgenic root system offers tremendous potential for introducing additional genes along with the Ri T-DNA genes for alteration of metabolic pathways and production of useful metabolites or compounds of interest. This article discusses various applications and perspectives of hairy root cultures and the recent progress achieved with respect to transformation of plants using A. rhizogenes.


Changes in Volatile Compounds of Chinese Luzhou-Flavor Liquor during the Fermentation and Distillation Process.
The aim of this study was to investigate the dynamic of volatile compounds in the Zaopei during the fermentation and distillation process by headspace solid-phase microextraction-gas chromatography mass spectrometry (HS-SPME-GCMS). Physicochemical properties analysis of Zaopei (fermented grains [FG], fermented grains mixed with sorghum [FGS], streamed grains [SG], and streamed grains mixed with Daqu [SGD]) showed distinct changes. A total number of 66 volatile compounds in the Zaopei were identified, in which butanoic acid, hexanoic acid, ethyl hexanoate, ethyl lactate, ethyl octanoate, hexyl hexanoate, ethyl hydrocinnamate, ethyl oleate, ethyl hexadecanoate, and ethyl linoleate were considered to be the dominant compounds due to their high concentrations. FG had the highest volatile compounds (112.43 mg/kg), which significantly decreased by 17.05% in the FGS, 67.12% in the SG, and 73.75% in the SGD. Furthermore, about 61.49% of volatile compounds of FGS were evaporated into raw liquor, whereas head, heart, and tail liquor accounted for 29.84%, 39.49%, and 30.67%, respectively. Each volatile class generally presented a decreasing trend, except for furans. Especially, the percentage of esters was 55.51% to 67.41% in the Zaopei, and reached 92.60% to 97.67% in the raw liquor. Principal component analysis based ordination of volatile compounds data segregated FGS and SGD samples. In addition, radar diagrams of the odor activity values suggested that intense flavor of fruit was weakened most from FG to SGD. The dynamic of volatile compounds in the Zaopei during the fermentation and distillation process was tested by SPME-GCMS. The result of this study demonstrated that both volatile compounds of Zaopei and thermal reaction during distillation simply determined the unique feature of raw liquor. This study was conducted based on the real products from liquor manufactory, so it is practicable that the method can be used in an industry setting.


Heart-cutting two-dimensional gas chromatography-isotope ratio mass spectrometry analysis of monoaromatic hydrocarbons in complex groundwater and gas-phase samples.
Compound-specific isotope analysis (CSIA) is increasingly used to evaluate the origin and fate of petroleum hydrocarbons in the environment. However, as samples often contain a complex mixture of compounds and the method requires a full chromatographic separation, it can be challenging to obtain accurate and precise isotope values. In this study, in order to develop a method to analyze carbon isotopes in benzene, toluene, ethylbenzene, and xylenes (BTEX) in complex environmental samples, a two-dimensional heart-cutting gas chromatograph (GC) was hyphenated to an isotope ratio mass spectrometer (IRMS). The focus was placed on benzene and toluene, which are the main compounds of concern in contaminated sites. A full separation for BTEX was successfully achieved using a 60m polar column in the first dimension and a 30m non-polar column in the second dimension. Accuracy and precision of carbon isotope measurements of standards were not impacted by the new setup compared to classic one-dimensional (1D) GC-C-IRMS. For benzene and toluene, precision remained very good (≤0.2‰) for concentrations comprised between 5 and 20μg/L. A high matrix load did not influence the precision and accuracy of isotope measurements. The method was tested on several samples from two different field sites. For all samples tested, full chromatographic baseline resolution was achieved for benzene and toluene. Spatial variability of isotopes values linked to biodegradation was evidenced for one field site. This new 2D-GC-C-IRMS method will broaden the spectrum of samples suitable for isotope analysis and will be therefore able to give new insights into attenuation processes of BTEX in contaminated sites or source fingerprinting.


Rhabdomyosarcoma: Advances in Molecular and Cellular Biology.
Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.


Dual-task attention deficits in dysphoric mood.
The attentional functioning of nondysphoric, mildly dysphoric, and moderately to severely dysphoric college students was tested using the attentional blink (AB) paradigm. These groups performed equally well at reporting a single target appearing in a rapidly presented stream of stimuli. All groups showed an AB, with report sensitivity for a 2nd target being reduced when the 2 targets were presented less than 0.5 s apart. Nondysphoric and mildly dysphoric participants showed the same size ABs, but the ABs for moderately to severely dysphoric participants were larger and longer. As predicted, the results showed that moderately to severely dysphoric individuals have attentional impairments. These impairments, however, were evident only in the more demanding dual-task condition.


[PCR analysis of DNA in paraffin sections of malignant lymphomas].
The polymerase chain reaction was used to detect the clonal rearrangement of immunoglobulin heavy chain gene in paraffin embedded samples of human lymph nodes. We developed a sensitive and reliable method of the DNA isolation from 4-5 tissue sections, which enabled us to perform 50-100 PCR reactions. We compared the reactive lymph nodes and non-Hodgkin's malignant lymphomas using framework 3 and J region primers. PCR products were examined by agarose gel electrophoresis. The dominant 80-120 bp amplification product was found in all lymphoma samples. The samples of reactive nodes were negative.


Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study.
Few studies have reported on the clinical utility of targeted next-generation sequencing (NGS) for breast cancer in Korea. We retrospectively reviewed the targeted NGS data of 219 patients with breast cancer who underwent surgical resection between August 2018 and April 2021. Here, we described the mutational profiles of breast cancer and examined their prognostic implications. The most frequently mutated gene was PIK3CA (n = 97/219, 44.3%), followed by TP53 (n = 79/219, 36.1%), AKT1 (n = 23/219, 10.5%), and GATA3 (n = 20/219, 9.1%). TP53 mutations were associated with aggressive histologic features. We followed up for 31 (range, 1-39) months and observed 11 (5.0%) recurrences: nine were TP53 mutant and two were TP53 wild-type. Multivariable analysis revealed that TP53 mutation was an independent prognostic factor for recurrence (p = 0.012). Although no drug is currently available for TP53 mutations, it is valuable to know the mutational status of TP53 for the precise management of breast cancer.


Inhibition of neutrophil-mediated cytotoxicity by alpha 2 macroglobulin.
Highly purified human alpha 2 macroglobulin (1.2--10 mg/ml) was shown to inhibit phytohemagglutinin-induced or antibody-induced lysis of chicken erythrocytes by polymorphonuclear neutrophils. Inhibition was not associated with impaired contact between effector and target cells but rather with the antiprotease activity of alpha 2 macroglobulin.


Overcoming treatment resistance in HER2-positive breast cancer: potential strategies.
Human epidermal growth factor receptor (HER)-2 overexpression or amplification occurs in about 20% of all breast cancers and results in a worse prognosis. Nevertheless, anti-HER2 treatments have recently been developed, resulting in dramatic improvements in the clinical outcome of patients with HER2-positive breast cancer. Trastuzumab has shown efficacy in early and advanced breast cancer treatment and lapatinib is currently approved for the treatment of advanced disease. Other anti-HER2 agents are being investigated. Mechanisms of resistance to trastuzumab treatment include crosstalk with heterologous receptors and amplification of HER2 signalling; amplification of the phosphoinositide 3-kinase (PI3K)/AKT pathway; alteration in binding of trastuzumab to HER2; and loss of HER2 expression. Proposed mechanisms of resistance to lapatinib involve derepression and/or activation of compensatory survival pathways through increased PI3K/AKT or estrogen receptor (ER) signalling. Several strategies to overcome resistance to anti-HER2 treatment are in different phases of development and include treatment with pertuzumab, T-DM1 and mammalian target of rapamycin (mTOR) inhibitors.


A new kinetic mechanism for the concomitant hydrolysis and transfer reactions catalyzed by bacterial DD-peptidases.
In the presence of an adequate nucleophilic acceptor substrate (A) and ester and thiolester donor substrates (S), the Streptomyces R61 soluble DD-peptidase catalyzes both hydrolysis and acyl group transfer reactions. Simple bisubstrate models do not explain the variation of the transfer to hydrolysis ratios with the donor and acceptor concentrations. A new kinetic mechanism for the concomitant hydrolysis and transfer reactions is proposed which involves an acceptor and a second, nonproductive donor substrate binding site. In this model, the acceptor essentially binds to the acyl-enzyme, and the second donor molecule only binds to the ternary ES*A complex. Hydrolysis can then proceed from the quaternary ES*AS complex. The values of all of the parameters involved in the reaction of a thiolester substrate with D-alanine as the acceptor substrate were determined at 15 and 37 degrees C. The results obtained with a protein modified by site-directed mutagenesis, and with which the transpeptidation reaction appeared to be specifically impeded, are discussed on the basis of the new kinetic mechanism. The data obtained with the soluble form of the high molecular weight penicillin binding protein 2X from Streptococcus pneumoniae are also in agreement with this model.


Infantile spasms as an epileptic feature of DEND syndrome associated with an activating mutation in the potassium adenosine triphosphate (ATP) channel, Kir6.2.
Activating mutations in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium (KATP) channel is a cause of neonatal diabetes associated with various neurological disorders that include developmental delay, epilepsy, and neonatal diabetes (known together as DEND syndrome). This article reports a girl who developed infantile spasms and early onset diabetes mellitus at the age of 3 months and revealed DEND syndrome with a heterozygous activating mutation in Kir6.2. Infantile spasms with hypsarrhythmia on the electroencephalogram were severe and refractory to steroids. Steroids combined with oral sulfonylurea, a drug that closes the ATP-sensitive potassium channel by an independent mechanism, allowed partial and transitory control of the epilepsy. However, the child still exhibited severe encephalopathy and died of aspiration pneumonia. The role of oral sulfonylurea as an anticonvulsant in DEND syndrome associated with Kir6.2 mutation is discussed.


Colloid cyst of the third ventricle.
A colloid cyst is a malformation composed of an amorphous, gelatinous material surrounded by epithelial and connective tissue. It is typically located in the third ventricle, leading to signs of increased intracranial pressure and hydrocephalus. In this case report, we discuss a classic presentation of a patient presenting with a colloid cyst of the third ventricle. This includes the patient's symptoms before arriving at the emergency department and presentation upon arrival and during their hospital stay. We also discuss the diagnostic approach to colloid cysts, providing radiographic imaging to support the diagnosis. Finally, we discuss the approach to treatment of a colloid cyst, including temporizing measures to relieve symptoms and definitive measures for removal of the colloid cyst. The overall approach from diagnosis to management to definitive treatment of a colloid cyst requires an interdisciplinary approach but prompt recognition of the signs and symptoms in the ED can decrease both morbidity and mortality associated with this potentially fatal diagnosis.


Spontaneous perforation--a rare complication of choledochal cyst.
We report a 2-year-old girl with spontaneous perforation of choledochal cyst. Preoperative diagnosis was possible by hepatobiliary scintigraphy. In view of emergency presentation and bile peritonitis, management was a staged procedure with peritoneal lavage and T-tube drainage of the biliary system, followed by excision of the cyst and Roux-en-Y hepatico-jejunostomy 3 months later.


Nanoscale film formation of recombinant azurin variants with various cysteine residues on gold substrate for bioelectronic device.
Nanoscale film fabrication of recombinant azurin variants with various cysteine residues on gold substrate was developed without any surface modification for bioelectronic device. We have modified azurin with different number of cysteine residues at its amino acid chain based on site-directed mutagenesis. The resulting recombinant protein, azurin, retained its original redox property in the same manner as native azurin. Recombinant azurin was immobilized on Au substrate by strong affinity between thiol of cysteine and gold. The orientations of recombinant azurin with various cysteine residues immobilized on the Au substrate were analyzed by fluorescence microscope, scanning tunneling microscope, and surface plasmon resonance. Our data revealed that binding activity of recombinant azurin with three cysteine residues on the Au substrate significantly increased in comparison to single residue azurin. Immobilization method of highly oriented recombinant azurin based on cysteine-modification could be useful for the nanoscale film fabrication of nanobiochip.


Quantum computations in heavy noble-gas hydride cations: Reference energies and new spectroscopic data.
Computational quantum chemistry has become a powerful tool with a wide range of possibilities to solve chemical-physical problems. As a result of this, the interest in the applications of computational quantum chemistry has expanded considerably, and has opened up novel research opportunities. In particular, those related to the characterization of heavy-atoms complexes, as most electronic structure calculations for such systems struggle with the problem posed by the large number of electrons present in them, and consequently, the introduction of relativistic effects. The present study performed an exhaustive assess to characterized the uncommon NgH+ (Ng = Kr, Xe, and Rn) hydride cations in order to provide accurate rovibrational data of their isotopes to assist in the laboratory characterization or even their astronomical detection. Scalar relativistic effects were included, and the ground and first electronically exited states potential curves were obtained from benchmark ab initio CCSD(T)/CBS and MRCI+Q electronic structure calculations. Next, such interaction potentials, correctly extended to long-range asymptotic regions, were employed in quantum bound state calculations and molecular spectroscopic constants were determined for the most abundance 84Kr, 132Xe, and 222Rn isotopes. Our results were discussed in comparison with available experimental and previous theoretical estimates, aiming to treat accuracy issues. The new sets provide reference data that could serve for spectroscopic characterization of such low abundance and high radioactive species.


[The benefits of treatment with recombinant human erythropoietin in cancer patients].
IMPROVED QUALITY OF LIFE WITH EPOETIN BETA: In a study against a placebo, there was evidence that the quality of life scores were significantly improved in patients treated with epoetin beta, whether they exhibited a solid tumour or a malignant lymphoma. The same was noted in children with cancer exhibiting severe neoplasia and treated with chemotherapy. The efficacy and tolerance to treatment were equivalent, whatever the administration regimen. IN PATIENTS SUFFERING FROM MYELODYSPLASTIC SYNDROMES: A particular entity among malignant blood diseases, myelodysplastic syndromes are at the origin of anaemia against which repeated transfusions and growth factors are proposed with varying results and disadvantages, and against which erythropoietin may be moderately effective (a mean of 25% in non-selected cohorts of patients). DEPENDING ON THE PROTOCOLS OF ERYTHROPOIETIN ADMINISTRATION IN CASES OF MYELODYSPLASTIC SYNDROMES: Recombinant human erythropoietin, irrespective of its concentration in myelodysplastic cell culture, does not appear capable of restoring normal erythropoiesis. The influence of prolonged treatment is not admitted by all. The effects of the addition of growth factors (notably G-CSF) are obvious but some are controversial because of the costs and the prolonged duration of such treatments.


Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity: nitric oxide induces phosphorylation of initiation factor eIF-2 alpha.
Nitric oxide (NO) is cytostatic for proliferating cells, inhibits microbial growth, and down-regulates the synthesis of specific proteins. Studies were undertaken to determine the mechanism by which NO inhibits total protein synthesis and whether the inhibition correlates with established cytostatic activities of NO. In in vitro experiments, various cell types were exposed to NO using either donors or expression of inducible NO synthase (iNOS). The capacity of NO to suppress total protein synthesis, measured by incorporation of 35S-methionine into protein, was correlated with the capacity of NO to suppress cell proliferation, viral replication, or iNOS expression. Phosphorylation of eIF-2 alpha was examined as a possible mechanism for the suppressed protein synthesis by NO. Both NO donors and expression of the iNOS suppressed total protein synthesis in L929 cells and A2008 human ovarian tumor cells in parallel with decreased cell proliferation. Suppressed protein synthesis was also shown to correlate with decreased vaccinia virus proliferation in murine peritoneal macrophages in an iNOS-dependent manner. Furthermore, iNOS expression in pancreatic islets or RAW264.7 cells almost completely inhibited total protein synthesis, suggesting that nonspecific inhibition of protein synthesis may be the mechanism by which NO inhibited the synthesis of specific proteins such as insulin or iNOS itself. This possibility was confirmed in RAW264.7 cells where the inhibition of total protein synthesis correlated with the decreased iNOS protein. The decrease in protein levels occurred without changes in iNOS mRNA levels, implicating an inhibition of translation. Mechanistic studies revealed that iNOS expression in RAW264.7 cells resulted in the phosphorylation of eIF-2 alpha and inhibition of the 80S ribosomal complex formation. These results suggest that NO suppresses protein synthesis by stimulating the phosphorylation of eIF-2 alpha. Furthermore, our observations indicate that nonspecific inhibition of protein synthesis may be a generalized response of cells exposed to high levels of NO and that inhibition of protein synthesis may contribute to many of the described cytostatic actions of NO.


Dolphin "packet" use during long-range echolocation tasks.
When echolocating, dolphins typically emit a single broadband "click," then wait to receive the echo before emitting another click. However, previous studies have shown that during long-range echolocation tasks, they may instead emit a burst, or "packet," of several clicks, then wait for the packet of echoes to return before emitting another packet of clicks. The reasons for the use of packets are unknown. In this study, packet use was examined by having trained bottlenose dolphins perform long-range echolocation tasks. The tasks featured "phantom" echoes produced by capturing the dolphin's outgoing echolocation clicks, convolving the clicks with an impulse response to create an echo waveform, and then broadcasting the delayed, scaled echo to the dolphin. Dolphins were trained to report the presence of phantom echoes or a change in phantom echoes. Target range varied from 25 to 800 m. At ranges below 75 m, the dolphins rarely used packets. As the range increased beyond 75 m, two of the three dolphins increasingly produced packets, while the third dolphin instead utilized very high click repetition rates. The use of click packets appeared to be governed more by echo delay (target range) than echo amplitude.


The criterion of subscale sufficiency and its application to the relationship between static capillary pressure, saturation and interfacial areas.
Modern imaging techniques, increased simulation capabilities and extended theoretical frameworks, naturally drive the development of multiscale modelling by the question: which new information should be considered? Given the need for concise constitutive relationships and efficient data evaluation; however, one important question is often neglected: which information is sufficient? For this reason, this work introduces the formalized criterion of subscale sufficiency. This criterion states whether a chosen constitutive relationship transfers all necessary information from micro to macroscale within a multiscale framework. It further provides a scheme to improve constitutive relationships. Direct application to static capillary pressure demonstrates usefulness and conditions for subscale sufficiency of saturation and interfacial areas.


Release of alien populations in Sweden.
Introduction of alien species is a major threat to biological diversity. Although public attention typically focuses on the species level, guidelines from the Convention of Biological Diversity define alien species to include entities below species level. This inclusion recognizes that release of nonlocal populations of native species may also result in negative effects on biodiversity. In practice, little is known about the extent, degree of establishment, or the effects on natural gene pools of such releases. Existing information on the releases in Sweden shows that alien populations are spread to a great extent. The most commonly released species include brown trout, Atlantic salmon, Arctic char, common whitefish, Scots pine, Norway spruce, mallard duck, gray partridge, and pheasant. Although millions of forest trees, fish, and birds are released annually, poor documentation makes the geographic and genetic origin of these populations, as well as the sites where they have been released, largely unclear. We provide recommendations for urgently needed first steps relating to the risks and problems associated with release of alien populations.


The Pathophysiology and New Advancements in the Pharmacologic and Exercise-Based Management of Heart Failure With Reduced Ejection Fraction: A Narrative Review.
Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome whose management has significantly evolved based on the pathophysiology and disease process. It is widely prevalent, has a relatively high mortality rate, and is comparatively more common in men than women. In HFrEF, the series of maladaptive processes that occur lead to an inability of the muscle of the left ventricle to pump blood efficiently and effectively, causing cardiac dysfunction. The neurohormonal and hemodynamic adaptations play a significant role in the advancement of the disease and are critical to guiding the treatment and management of HFrEF. The first-line therapy, which includes loop diuretics, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, hydralazine/isosorbide-dinitrate, and mineralocorticoid receptor antagonists (MRAs), has been proven to provide symptomatic relief and decrease mortality and complications. The newly recommended drugs for guideline-based therapy, angiotensin receptor/neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors, soluble guanylate cyclase, and myosin activators and modulators have also been shown to improve cardiac function, reverse cardiac remodeling, and reduce mortality rates. Recent studies have demonstrated that exercise-based therapy has resulted in an improved quality of life, exercise capacity, cardiac function, and decreased hospital readmission rates, but it has not had a considerable reduction in mortality rates. Combining multiple therapies alongside holistic advances such as exercise therapy may provide synergistic benefits, ultimately leading to improved outcomes for patients with HFrEF. Although first-line treatment, novel pharmacologic management, and exercise-based therapy have been shown to improve prognosis, the existing literature suggests a need for further studies evaluating the long-term effects of MRA and ARNI.


The Maryland State Board of Dental Examiners and the chemically dependent dentist.
The Maryland State Board of Dental Examiners (SBDE) has adopted the disease model in dealing with chemically dependent dentists. SBDE has found that a punitive attitude toward chemical dependence is not productive. The SBDE works closely with the Dentists' Well-Being Committee of the Maryland State Dental Association to help dentists regain productive lives while observing its responsibility to protect the public. The SBDE's concern for patient welfare is a top priority, but it does not lessen SBDE's compassion for dentists who may be suffering from this illness.


Strategies for recombinant production of antimicrobial peptides with pharmacological potential.
The need to develop new drugs for the control of pathogenic microorganisms has redoubled efforts to prospect for antimicrobial peptides (AMPs) from natural sources and to characterize its structure and function. These molecules present a broad spectrum of action against different microorganisms and frequently present promiscuous action, with anticancer and immunomodulatory activities. Furthermore, AMPs can be used as biopharmaceuticals in the treatment of hospital-acquired infections and other serious diseases with relevant social and economic impacts.Areas covered: The low yield and the therefore difficult extraction and purification process in AMPs are problems that limit their industrial application and scientific research. Thus, optimized heterologous expression systems were developed to significantly boost AMP yields, allow high efficiency in purification and structural optimization for the increase of therapeutic activity.Expert opinion: This review provides an update on recent developments in the recombinant production of ribosomal and non-ribosomal synthesis of AMPs and on strategies to increase the expression of genes encoding AMPs at the transcriptional and translational levels and regulation of the post-translational modifications. Moreover, there are detailed reports of AMPs that have already reached marketable status or are in the pipeline under advanced stages of preclinical testing.


Identifying mutations in sd1, Pi54 and Pi-ta, and positively selected genes of TN1, the first semidwarf rice in Green Revolution.
Taichung Native 1 (TN1) is the first semidwarf rice cultivar that initiated the Green Revolution. As TN1 is a direct descendant of the Dee-geo-woo-gen cultivar, the source of the sd1 semidwarf gene, the sd1 gene can be defined through TN1. Also, TN1 is susceptible to the blast disease and is described as being drought-tolerant. However, genes related to these characteristics of TN1 are unknown. Our aim was to identify and characterize TN1 genes related to these traits. Aligning the sd1 of TN1 to Nipponbare sd1, we found a 382-bp deletion including a frameshift mutation. Sanger sequencing validated this deleted region in sd1, and we proposed a model of the sd1 gene that corrects errors in the literature. We also predicted the blast disease resistant (R) genes of TN1. Orthologues of the R genes in Tetep, a well-known resistant cultivar that is commonly used as a donor for breeding new blast resistant cultivars, were then sought in TN1, and if they were present, we looked for mutations. The absence of Pi54, a well-known R gene, in TN1 partially explains why TN1 is more susceptible to blast than Tetep. We also scanned the TN1 genome using the PosiGene software and identified 11 genes deemed to have undergone positive selection. Some of them are associated with drought-resistance and stress response. We have redefined the deletion of the sd1 gene in TN1, a direct descendant of the Dee-geo-woo-gen cultivar, and have corrected some literature errors. Moreover, we have identified blast resistant genes and positively selected genes, including genes that characterize TN1's blast susceptibility and abiotic stress response. These new findings increase the potential of using TN1 to breed new rice cultivars.


Mechanism of Fibril and Soluble Oligomer Formation in Amyloid Beta and Hen Egg White Lysozyme Proteins.
Assembly and deposition of insoluble amyloid fibrils with a distinctive cross-β-sheet structure is the molecular hallmark of amyloidogenic diseases affecting the central nervous system as well as non-neuropathic amyloidosis. Amyloidogenic proteins form aggregates via kinetic pathways dictated by initial solution conditions. Often, early stage, cytotoxic, small globular amyloid oligomers (gOs) and curvilinear fibrils (CFs) precede the formation of late-stage rigid fibrils (RFs). Growing experimental evidence suggests that soluble gOs are off-pathway aggregates that do not directly convert into the final stage RFs. Yet, the kinetics of RFs aggregation under conditions that either promote or suppress the growth of gOs remain incompletely understood. Here we present a self-assembly model for amyloid fibril formation in the presence and absence of early stage off-pathway aggregates, driven by our experimental results on hen egg white lysozyme (HewL) and beta amyloid (Aβ) aggregation. The model reproduces a range of experimental observations including the sharp boundary in the protein concentration above which the self-assembly of gOs occurs. This is possible when both primary and secondary RFs nucleation rates are allowed to have a nonlinear dependence on initial protein concentration, hinting toward more complex prenucleation and RFs assembly scenarios. Moreover, analysis of RFs lag period in the presence and absence of gOs indicates that these off-pathway aggregates have an inhibitory effect on RFs nucleation. Finally, we incorporate the effect of an Aβ binding protein on the aggregation process in the model that allows us to identify the most suitable solution conditions for suppressing gOs and RFs formation.


[Effect of enhanced ultrasound guiding on brachial plexus block].
To assess whether the enhanced imaging technology can improve the needle visibility during ultrasound-guided auxillary brachial plexus block. After obtaining informed consent, 60 ASA (American Society of Anesthesiologists) I-II patients undergoing forearm or hand surgery were enrolled in this prospective, randomized, double-blind study. The patients were randomly assigned to two groups, the common image group (n=30) and enhanced image group (n=30). Ultrasound was used in guiding the block of the four branches of brachial plexus, i.e. the median, radial, ulnar and musculocutaneous nerves. In the enhanced image group a special function key "Multi-beam enhance" (MBe) was turned on during the needle insertion. After the nerve stimulator identification of the median, radial, ulnar and musculocutaneous nerves, 10 mL of 0.5% ropivacaine was injected near each nerve. The operating time, the visibility of the needle, the depth of each nerve, the onset time of the block, and the complications related to the block were assessed and recorded. The operating time was significantly shorter in the enhanced image group compared with the common image group [(2.63±0.81) min vs. (5.07±1.89) min, P=0.01]. The visibility of the needle was better in enhanced image group when the radial and musculocutaneous nerve blocks were performed (P<0.05). The enhanced image technology can reduce the operating time and improve the visibility of the needle during the peripheral nerve block for the nerve which is relatively deep.


Transition-Metal-Free Desulfinative Cross-Coupling of Heteroaryl Sulfinates with Grignard Reagents.
A mild cross-coupling reaction of heteroaryl sulfinates with Grignard reagents has been developed under transition-metal-free conditions. This study provides an example of the SO22- as a leaving group in an aromatic system and an effective methodology for the construction of C-C bond.


Spring-mass behaviour during the run of an international triathlon competition.
We investigated the changes in step temporal parameters and spring-mass behaviour during the running phase of a major international triathlon competition. 73 elite triathletes were followed during the 2011 World Championships Grand Final. The running speed, ground contact and flight times were assessed over a 30 m flat section at the beginning of the 4 running laps and towards the finish line, by using a high-frequency camera (300 Hz). The leg and vertical stiffness, and vertical displacement of the mass centre were calculated from step temporal characteristics. A concomitant decrease in running speed, vertical stiffness and leg stiffness was reported during the 4 running laps, except towards the finish line, where these parameters increased. Running biomechanics was not affected between the beginning and the end of the 10 km run, when triathletes were compared for the same running speed (1.68±0.16 m vs. 1.70±0.17 m for step length, 3.18±0.11 Hz vs. 3.16±0.15 Hz for step rate, 12.87±3.14 kN.m - 1 vs.12.76±3.05 kN.m - 1 for Kleg, 31.18±4.71 kN.m - 1 vs.30.74±3.88 kN.m - 1 for Kvert, at lap1 and finish, respectively). Multiple regression models revealed that both step rate change and step length change were correlated with running speed change and that the standardized partial regression coefficient was higher for step length change than for step rate. Independent of the cofounding effect of speed and despite the neuromuscular fatigue previously shown after long-duration events, the lower limb mechanical stiffness and the overall spring-mass regulation were not altered over the 10 km triathlon run in elite competitors. This study showed also that step length explained, to a greater extent than step frequency, the running speed variance in elite triathletes.


Risk factors and prediction of preeclampsia.
Inadequate trophoblast invasion of the spiral arteries in early pregnancy, an increased inflammatory response and changes in the immune answer to paternal antigens are considered aetiological factors in preeclampsia. Searching for factors related to these angiogenic, anti-angiogenic, immunologic and inflammatory mechanisms may provide methods to determine which patient will develop preeclampsia predating the onset of the clinical manifestations of the disease. Screening for preeclampsia in the first trimester has had Limited success. Currently, maternal characteristics, clinical history, maternal serum biochemistry and uterine artery Doppler sonography before 14 weeks are being investigated. Preeclampsia in a previous pregnancy is still the strongest predictor. In the second trimester, uterine artery Doppler has a detection rate around 60% but also a high false positive rate of 25%. First trimester uterine artery Doppler studies have high sensitivity but poor specificity with a high false positive rate. Combination of first trimester uterine artery Doppler with patient characteristics and maternal serum biochemistry, specifically placental protein 13 holds promise but further evaluation is needed. Maternal serum markers including inhibin A, activin A, soluble FMS-Like tyrosine kinase 1, endoglin, pregnancy associated plasma protein A and others, when used alone have proved poor predictors of preeclampsia. Most studies have been performed by a limited group of researchers in a population with a high risk and no validation studies of any method in other populations are available. Results are difficult to compare due to differences in methodology, and differences in the end point studied.There are still no good methods of preventing preeclampsia once a high risk has been determined.


Lady with 'lobster claw' feet.
A 94-year-old woman admitted with confusion secondary to a urinary tract infection exhibited deformities in all four limbs that were present from birth. Her appearance was suggestive of split hand/split foot malformation a rare congenital condition that affects the central rays of the distal limb portion. She had no syndromic features and had lived without support or assistance of her daily activities. A keen knitter, she regularly knitted for her three grandchildren, all of which, along with her son, were unaffected by this condition.


[The effect of benzydamine on the generation and interaction of reactive oxygen species and cyclo- and lipoxygenase].
Pharmacological mechanisms of benzydamine (Tantum) are studied which are of relevance for the antiinflammatory properties of this non-steroidal antiinflammatory drug (NSAID). Benzydamine most effectively inhibits the generation of reactive oxygen species by murine neutrophils (IC50 1.7 X 10(-5) mol/l). Piroxicam, indomethacin and acetylsalicylic acid are ineffective. Benzydamine, however, does not interfere with xanthine oxidase-dependent superoxide anion radical formation or epinephrine oxidation. The other tested NSAID are as well inactive. The findings confirm the missing cyclooxygenase inhibition of benzydamine (IC50 greater than 10(-3) mol/l), contrary to the other NSAID which are strong (indomethacin IC50 6 X 10(-8) mol/l; piroxicam IC50 2 X 10(-7) mol/l) or moderate cyclooxygenase inhibitors (acetylsalicylic acid IC50 10(-5) mol/l). LTB4 generation via the lipoxygenase is only inhibited by indomethacin (EC50 3.6 X 10(-5) mol/l). Benzydamine appears unique among other NSAID by its relatively strong interference with the generation of reactive oxygen radicals and the lack of cyclooxygenase inhibition.


Diagnosis of extrapulmonary tuberculosis by smear, culture, and PCR using universal sample processing technology.
Definitive and rapid diagnosis of extrapulmonary tuberculosis is challenging since conventional techniques have limitations. We have developed a universal sample processing (USP) technology for detecting mycobacteria in clinical specimens. In this study, this technology was evaluated blindly on 99 extrapulmonary specimens collected from 87 patients. USP-processed specimens were submitted to smear microscopy for detection of acid-fast bacilli (AFB), culture, and two PCR tests targeting devR (Rv3133c) and IS6110 gene sequences. On the basis of clinical characteristics, histology and cytology, conventional microbiology results, and response to antitubercular therapy, 68 patients were diagnosed with tuberculosis. Although USP smear and culture were significantly superior to conventional microbiology, which was not optimized (P < 0.0001), these approaches fell short of PCR tests (P < 0.0001). The low yields by smear and culture are attributed to the paucibacillary load in the specimens. The highest sensitivity in PCR was achieved when devR and IS6110 test results were combined; the sensitivity and specificity values were 83 and 93.8%, 87.5 and 100%, and 66.7 and 75%, respectively, in pleural fluid, needle-biopsied pleural tissue, and lymph node specimens. In conclusion, the application of USP technology, together with clinicopathological characteristics, promises to improve the accuracy and confidence of extrapulmonary tuberculosis diagnosis.


Fuzzy logic assisted control of inspired oxygen in ventilated newborn infants.
The control of oxygen delivery to mechanically ventilated newborn infants is a time intensive process that must balance adequate tissue oxygenation against possible toxic effects of oxygen exposure. Investigation in computer assisted control of mechanical ventilation is increasing, although very few studies involve newborn infants. We have implemented a fuzzy controller for the adjustment of inspired oxygen concentration (FIO2) in ventilated newborns. The controller utilizes rules produced by neonatologists, and operates in real-time. A clinical trial of this controller is currently taking place in the neonatal intensive care unit (NICU) of Children's Hospital, Boston, MA.


Effects of pelvic floor muscle training during pregnancy.
The objective of the present study was to evaluate the effect of pelvic floor muscle training in 46 nulliparous pregnant women. The women were divided into 2 groups: an exercise group and a control group. Functional evaluation of the pelvic floor muscle was performed by digital vaginal palpation using the strength scale described by Ortiz and by a perineometer (with and without biofeedback). The functional evaluation of the pelvic floor muscles showed a significant increase in pelvic floor muscle strength during pregnancy in both groups (P < .001). However, the magnitude of the change was greater in the exercise group than in the control group (47.4% vs. 17.3%, P < .001). The study also showed a significant positive correlation (Spearman's test, r = 0.643; P < .001) between perineometry and digital assessment in the strength of pelvic floor muscles. Pelvic floor muscle training resulted in a significant increase in pelvic floor muscle pressure and strength during pregnancy. A significant positive correlation between functional evaluation of the pelvic floor muscle and perineometry was observed during pregnancy.


Mature Luffa Leaves (Luffa cylindrica L.) as a Tool for Gene Expression Analysis by Agroinfiltration.
We exploited the potential of cucurbits for ectopic gene expression. Agroinfiltration is a simple and commonly used method to obtain transient expression of foreign genes in plants. In contrast to in vitro transformation techniques, agroinfiltration can be used for genetic modification of mature plant tissues. Although the cucurbits are commonly used as model plants for molecular biology and biotechnology studies, to date there are no literature sources on the possibility of transient gene expression in mature cucurbit tissues. Our research has shown that mature leaves of Luffa cylindrica L. (luffa), in contrast to other cucurbit species, can be successfully transiently transformed with Agrobacterium tumefaciens. We efficiently transformed luffa leaves with a reporter gene encoding β-glucuronidase (GUS). The GUS activity in transiently transformed leaf tissues was detected within 24 h after the infiltration with bacteria. Additionally, we have shown that the activity of a transiently expressed the GUS gene can be monitored directly in the EDTA-exudates collected from the cut petioles of the agroinfiltrated leaves. The results suggest that luffa leaves can be useful as a plant expression system for studies of physiological and biochemical processes in cucurbits.


Experimental verification of twin photonic nanojets from a dielectric microcylinder.
In this Letter, the direct generation of twin photonic nanojets (PNJs) through two coherent illuminations of a microcylinder is investigated theoretically and experimentally. The dielectric microcylinder (polydimethylsiloxane) with 5 μm diameter and 6 μm height is employed to generate symmetric twin PNJs. The finite-difference time-domain calculation is used to simulate the electric field distributions inside and outside the microcylinder. The scanning optical microscope system is performed for experimental verification of twin photonic nanojets. In both theory and in practice, the intensity null of electric field creates two separate PNJs. Compared to a single PNJ, twin PNJs have a smaller subwavelength waist and more complex intensity distribution. The focal distance, interval, and full width at half-maximum of twin PNJs are a function of the offset angle. The twin PNJs will provide novel applications in nanolithography, optical trapping, biophotonic sensing, and therapy.


Is It Barrett's Esophagus or Gastric Heterotopia?
Columnar epithelium in the distal part of the esophagus is generally related to Barrett's esophagus. Barrett's esophagus is a well-known premalignant lesion for adenocarcinoma of the esophagus. Therefore, its diagnosis and surveillance are important. Columnar epithelium in the esophagus other than Barrett's esophagus can be gastric heterotopia, which generally takes place in the upper part of the esophagus and is named inlet patch. The presence of gastric metaplasia in the distal part of the esophagus is rare and can cause misdiagnosis. Therefore, its differentiation from Barrett's esophagus is important. Here we present a case of gastric heterotopia located in the distal part of the esophagus that caused reflux-like symptoms and needed differentiation from Barrett's esophagus.


Hydrogen-bonding controls the solid-state and enantiomeric conformations of the amino alcohol ligand 2-[(2-hydroxyethyl)amino]cyclohexanol.
The crystal structure of the title compound, C(8)H(17)NO(2), consists of (R,R) and (S,S) enantiomeric pairs packed in adjacent double layers which are characterized by centrosymmetric hydrogen-bonded dimers, generated via N-H...O and O-H...O interactions, respectively. Intermolecular interactions, related to acceptor and donor molecule chirality, link the achiral double layers into tubular columns, which consist of a staggered hydrophilic inner core surrounded by a hydrophobic cycloalkyl outer surface and extend in the [011] direction.