Pathogen reduction technology: methods, status of clinical trials, and future prospects.
Transfusion-transmitted infections caused by viruses, bacteria, and protozoa have been extensively reported for the past three decades. In the early 1980s, the HIV epidemic heightened the focus on transfusion safety and demonstrated the potential for new pathogens to enter the donor population and rapidly spread through the transfusion of blood components. The foundation for the prevention of transfusion-transmitted infections has been donor screening and testing, and significant advances have been made to reduce the risk of transfusion-associated infection. However, despite these efforts, transfusion-transmitted infections continue to be reported, and new infectious agents, such as the West Nile virus, continue to enter the donor population with transmission to recipients. For the past decade, several technologies to inactivate infectious pathogens that may contaminate donor blood have been developed and several of these methods have been introduced into clinical practice. These technologies offer the potential for a paradigm shift to further improve the safety of blood transfusion.


A Dual-Masked Deep Structural Clustering Network With Adaptive Bidirectional Information Delivery.
Structured clustering networks, which alleviate the oversmoothing issue by delivering hidden features from autoencoder (AE) to graph convolutional networks (GCNs), involve two shortcomings for the clustering task. For one thing, they used vanilla structure to learn clustering representations without considering feature and structure corruption; for another thing, they exhibit network degradation and vanishing gradient issues after stacking multilayer GCNs. In this article, we propose a clustering method called dual-masked deep structural clustering network (DMDSC) with adaptive bidirectional information delivery (ABID). Specifically, DMDSC enables generative self-supervised learning to mine deeper interstructure and interfeature correlations by simultaneously reconstructing corrupted structures and features. Furthermore, DMDSC develops an ABID module to establish an information transfer channel between each pairwise layer of AE and GCNs to alleviate the oversmoothing and vanishing gradient problems. Numerous experiments on six benchmark datasets have shown that the proposed DMDSC outperforms the most advanced deep clustering algorithms.


The formation of ornithine from proline in animal tissues.
1. Homogenates of liver or kidney from rat, mouse, dog and guinea pig formed ornithine from proline but not from glutamate. Rat kidney was most active in this reaction and was used for further studies. 2. The overall reaction was found to be catalysed by proline oxidase to yield glutamic gamma-semialdehyde, followed by transamination of this product with glutamate as catalysed by ornithine-keto acid aminotransferase. 3. The unfavourable equilibrium of the ornithine-keto acid aminotransferase reaction was overcome chiefly by glutamate dehydrogenase in the tissue, which removed the alpha-oxoglutarate produced, by reduction with endogenous ammonia and NADH. 4. Aspartate aminotransferase in these preparations also aided in the removal of alpha-oxoglutarate. In this case the overall reaction was driven also by the rapid decarboxylation of oxaloacetate. 5. No evidence could be found for a pathway of ornithine synthesis involving acylated intermediates as has been observed in some micro-organisms. 6. The rate of ornithine synthesis in homogenates of several rat tissues paralleled the activity of ornithine-keto acid aminotransferase in these tissues, indicating that this enzyme was rate-determining for the synthesis. 7. The possible influence of these reactions on urea synthesis is discussed.


Ethical issues in nanotechnology.
Nanotechnology is a rapidly developing area in science involved with manipulating matter at the atomic or molecular level. Nanotechnology is typically defined at a scale on the order of less than approximately 100 nm. Matter possesses unique properties at these size levels that are neither Newtonian nor quantum, but between the two regimes.These unique properties have created significant interest and excitement, sparking numerous research investigations. Nanotechnology is a very broad field with many current and potential applications. Some important examples of applications include battlefield activated dynamic armor clothing for soldiers, additives to sunscreens, and diagnostic laboratories on a chip to monitor general personal health. Groundbreaking capabilities often raise new questions. Any new scientific or technological development has the usual concomitant associated ethical issues, specifically regarding containment and regulation. These ethical issues are more pronounced with nanotechnology due to the sharp divide between those who see its great potential and opponents who express fears. Nanotechnology supporters believe that it has the potential to transform our lives dramatically, while opponents of nanotechnology fear that self-replicating "nanobots" could escape from laboratories and reduce all life on earth to "gray goo. "These fears have swayed generally uninformed public opinions via the media and sensational entertainment. A critical discussion of ethical issues surrounding nanotechnology, including the interaction of nanotechnology with the body and the environment--nanobiotechnology--and regulation of nanotechnology, is presented. We advocate strong, uniform regulations for nanotechnology, but only the use of regulations as needed. The limited use of regulations prevents the regulations from becoming burdensome and inhibiting research in the field.


Granulocyte-macrophage colony-stimulating factor produced by splenic T lymphocytes of mice infected with Schistosoma japonicum.
The production of granulocyte-macrophage (GM) colony-stimulating factor (CSF) by splenic lymphocytes was examined in murine schistosomiasis japonica. When splenic lymphocytes obtained at various weeks after infection were cultured with soluble egg antigen, GM-CSF activity in the conditioned medium became detectable at 3 weeks after infection, reached a peak at week 5, and persisted at least up to week 7. Not only soluble egg antigen but also concanavalin A was highly effective in stimulating splenic lymphocytes to produce GM-CSF. When splenic lymphocytes were treated with anti-Thy-1.2 antibody and complement, GM-CSF-producing activity was completely abolished. The molecular weight of this T-cell-derived GM-CSF was estimated to be 30,000 by gel filtration on Sephadex G-150. After isoelectric focusing, GM-CSF activity was detected as two major peaks at pH 3.7 and 5.5. The physicochemical nature of this T-cell-derived GM-CSF was compared with those of known lymphokine GM-CSFs or with that of a previously reported GM-CSF in the serum of S. japonicum-infected mice (M. Owhashi and Y. Nawa, Infect. Immun. 49: 533-537, 1985).


[A case of familial adenomatous polyposis presenting with thyroid cancer].
We report a case of familial adenomatous polyposis( FAP) presenting with thyroid cancer. A 24-year-old woman, on histological examination, was diagnosed as having the cribriform-morular variant of papillary thyroid carcinoma, which is known to be associated with FAP. Therefore, she underwent colonoscopy, and FAP was diagnosed. In addition, abdominal computed tomography( CT) scans revealed a tumor, approximately 12 cm in diameter, in the right lower abdomen. After total thyroidectomy, total proctocolectomy and excision of the tumor arising from the mesentery of the small intestines were performed. The histological diagnosis was FAP with a desmoid tumor arising from the mesentery.


The influence of smoking and non-insulin-dependent diabetes mellitus on periodontal disease.
The periodontal health of smokers and non-smokers with non-insulin-dependent diabetes mellitus (NIDDM) and non-smokers with periodontitis who were not suffering from a systemic disease was assessed. The investigation was carried out on 60 adult subjects. Levels of blood glucose, glycosylated haemoglobin and immunoglobulins G, A and M were determined, together with the plaque index, gingival index, probing pocket depths and clinical attachment level. Periodontitis was more severe in smokers and non-smokers with NIDDM than non-smokers without NIDDM, and the periodontal condition (clinical attachment level, probing pocket depth and gingival bleeding) was better in non-smokers with NIDDM than smokers with NIDDM. The results suggest that diabetes and smoking are high-risk factors for periodontal disease.


Validation of a simple response-time measure of listening effort.
This study compares two response-time measures of listening effort that can be combined with a clinical speech test for a more comprehensive evaluation of total listening experience; verbal response times to auditory stimuli (RT(aud)) and response times to a visual task (RTs(vis)) in a dual-task paradigm. The listening task was presented in five masker conditions; no noise, and two types of noise at two fixed intelligibility levels. Both the RTs(aud) and RTs(vis) showed effects of noise. However, only RTs(aud) showed an effect of intelligibility. Because of its simplicity in implementation, RTs(aud) may be a useful effort measure for clinical applications.


Intestinal absorption of macromolecules and epithelial cell surface glycosylation in suckling rats nursed on mothers fed low-protein diet-I.
The effect of feeding 8% protein (low-protein; LP) diet to lactating rats has been studied on the absorption of macromolecules and the glycosylation of enterocytes in suckling animals. The absorption of 125I-labelled bovine serum albumin, gamma-globulin and alpha-lactalbumin was 24-314% more in pups nursed on mothers fed LP diet compared to the pair-fed controls. The observed enhancement in protein absorption was associated with a significant increase in the binding of these proteins to microvillus membranes (MVM). The sialic acid content of brush borders was unaltered but the fucose level was augmented (p less than 0.01) in pups nursed on rats fed LP diet. The binding of 125I-labelled wheat germ agglutinin and Ulex europeus agglutinin I to MVM was in agreement to the data on sialic acid and fucose levels of the membranes. The binding of peanut agglutinin to MVM was 30% low in pups from LP-diet-fed animals. The incorporation of (14C) D-mannose into MVM was essentially unaffected but that of (14C) N-acetylglucosamine was reduced in pups reared on mothers given LP diet. These findings suggest that the quality of maternal nutrition affects the absorption of macromolecules and the glycosylation in developing rat intestine.


Safety and efficacy of a feed additive consisting of Lacticaseibacillus caseiIDAC 210415-01, Limosilactobacillus fermentumIDAC 210415-02, Levilactobacillus brevisIDAC 051120-02 and Enterococcus faeciumIDAC 181218-03 (K-9 Heritage Probiotic Blend®) for dogs (CanBiocin Inc.).
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of K-9 Heritage Probiotic Blend® when used as a zootechnical additive (functional group: gut flora stabilisers) for dogs. The product under assessment is based on viable cells of Lacticaseibacillus casei IDAC 210415-01, Limosilactobacillus fermentum IDAC 210415-02, Levilactobacillus brevis IDAC 051120-02 and Enterococcus faecium IDAC 181218-03. The FEEDAP Panel was not in the position to conclude on the identification of the strains and, therefore, the safety of the product cannot be based on the presumption of safety of the active agents. The Panel notes that the use of E. faecium IDAC 181218-03 represents a safety concern because it harbours an acquired antimicrobial resistance gene. Moreover, the hazard related to the presence of additional antimicrobial resistance genes in the active agents cannot be excluded. No tolerance trials on the target animals have been provided. Therefore, the Panel is not in the position to conclude on the safety of the additive for dogs. Regarding the user safety, the Panel cannot conclude on the irritant potential of the additive for skin or eyes due to the absence of data. Given the proteinaceous nature of the active agents, the additive should be considered a respiratory sensitiser. No conclusions could be drawn on its potential to be a skin sensitiser. The use of K-9 Heritage Probiotic Blend® in animal nutrition represents a safety concern for the environment due to the potential carryover of at least an antimicrobial resistance gene. The FEEDAP Panel is not in the position to conclude on the efficacy of K-9 Heritage Probiotic Blend® for the target species.


The Power of Analogies for Imagining and Governing Emerging Technologies.
The emergence of new technologies regularly involves comparisons with previous innovations. For instance, analogies with asbestos and genetically modified organisms have played a crucial role in the early societal debate about nanotechnology. This article explores the power of analogies in such debates and how they could be effectively and responsibly employed for imagining and governing emerging technologies in general and nanotechnology in particular. First, the concept of analogical imagination is developed to capture the explorative and anticipatory potential of analogies. Yet analogies do not simply stimulate imagination, they also restrict it by framing emerging technologies in specific ways. Thus, second, the article argues that tracing the rhetorical and persuasive power of analogical arguments is essential for understanding how analogies are constructed to legitimise assessments, funding policies, and governance approaches. Third, the article addresses factors that account for the persuasiveness of analogies in debates about emerging technologies. The article concludes with reflections on how analogical imagination and an enhanced analogical sensibility for framing and persuasive effects can foster responsible research and innovation (RRI).


Extended spectrum beta lactamase producing gram negative bacilli in a tertiary referral hospital of Assam--experience with two methods.
Extended Spectrum Beta Lactamases (ESBL) are enzymes produced in some gram negative bacilli that mediate resistance to extended spectrum cephalosporins. 683 clinical isolates of Escherisia coli and Klebsiella pneumoniae were studied for their capacity to produce ESBL. Isolates showing resistance to at least two of the third generation cephalosporins were studied for ESBL production by Jarlier technique and combination disc methods. Out of the 457 E. Coli and 226 Klebsiella pneumoniae isolated in Assam Medical College, 29.76% and 53.1% were resistant to two cephalosporins of which 29.41% and 29.16% strains showed production of ESBL. However, 6 (4.41%) and 16 (13.34%) strains additionally showed production of ESBL when tested with combination disc method. Though the Jarlier technique is popular, for detection of ESBL, yet false negative results warrants for alternative method. In the absence of molecular detection methods in routine clinical microbiology laboratory, combination disc method appears to be a better option.


Recreational inhalation of butane and propane in adolescents: Two forensic cases of accidental death.
The recreational use of inhalants is a fairly widespread habit among adolescents because of the ease of availability and methods of assumption. Their use is however not free of risks, both for direct toxicity on several target organs and for a mechanism of gas replacement with lack of oxygen. The first case concerns a 12-year-old boy who died suddenly after sniffing a mix of butane and propane contained in a can of air freshener. The second case concerns a 14-year-old boy who died by acute poisoning by the same mixture contained in a refill for lighters. High concentrations of the compounds were found in the tissues by analysis with gas chromatography-mass spectrometry. The compounds found in tissues and biological fluids were perfectly compatible with those contained in the containers used for the inhalation. The mechanisms of death were therefore assessed in a combination of the direct toxicity of the compound and oxygen replacement, thus highlighting the crucial help that toxicological analyses can provide in such cases.


Localization of prolactin in rat kidney tissue using a double-antibody technique.
A fluorescein-labelled double-antibody technique was used for the microscopical localization of ovine prolactin in kidney tissue of rats previously injected intravenously with 50 i.u. of the hormone at varying intervals before death. Thirty seconds after the injection, the hormone could already be visualized in teh lumina of the proximal tubules. After 2 min, discrete praticulate fluorescence appeared on the brush border of the epithelium of the proximal tubules. Three minutes later prolactin was clearly localized in the apical portion of the cytoplasm of these cells as well as on the brush border. Ten minutes after the injection, the hormone appeared exclusively within the cell, highest concentrations being observed in the perinuclear region. After 20 min, however, the hormone appeared evenly distributed throughout the cytoplasm. The distributtion of prolactin was in all cases confined to the proximal tubular region of the nephron. The findings support the suggestion that the site of action of prolactin in the kidney is the epithelium of the proximal tubule. As prolactin was first visualized in the lumen of this portion of the nephron, it appers that the hormone gains access to these cells via the glomerular filtrate.


A potential role for N-cadherin in mediating endothelial cell-smooth muscle cell interactions in the rat vasculature.
The cadherins are a family of calcium-dependent cell adhesion molecules that play a critical role in morphogenetic cell interactions in the embryo. N-cadherin has been identified in neural and non-neural tissues, including developing muscle; however, there are few reports of N-cadherin expression in adult mammals. We attempted to identify N-cadherin in the rat vasculature and to ask whether it has a role in mediating vascular cell interactions. Vascular tissues were isolated from Fischer rats and analyzed immunohistochemically and by Western blotting using pan-cadherin and N-cadherin antibodies. Anti-N-cadherin antibodies were used in an in vitro cell adhesion assay to determine if N-cadherin mediates interactions between smooth muscle cells (SMC) and endothelial cells (EC). Western blot analysis of vascular tissues reveals a 135 kilodalton (kd) band that is recognized by anti-N-cadherin antibodies. N-cadherin localizes in the rat aorta to the endothelium and to the smooth muscle cell layer beneath the internal elastic membrane. A cell adhesion assay demonstrates that rat SMCs and ECs adhere to each other in a Ca(2+)-dependent manner, and an anti-N-cadherin antibody inhibits approximately 25% of this adhesion. Our data indicate that N-cadherin is expressed in large vessels of the rat and is capable of mediating EC-SMC adhesion in vitro. It is noteworthy that N-cadherin localizes to a population of SMCs in the rat aorta adjacent to ECs suggesting that N-cadherin may mediate EC-SMC interactions in vivo.


Serotonin 2A receptor gene (HTR2A) polymorphism in alcohol-dependent patients.
The serotonergic (5-HT) dysfunction has been frequently described in subjects with alcohol dependence (AD). In the present study, a potential relationship between T102C polymorphism in the 5-HT receptor subtype 2Agene (HTR2A) and alcohol dependence was examined. Genotypes were analyzed in 150 AD patients diagnosed with DSM-IV criteria and in 80 healthy controls. The genetic analysis showed that the frequency of 102C allele and C102C genotype in AD subjects was significantly higher than in controls. Moreover, AD patients homozygous for C allele had significantly lower age at onset of alcohol problems than subjects having at least one T allele. The results suggest a potential role of the T102C HTR2A polymorphism in development of alcohol dependence.


Anti-Babesia microti antibodies in foresters highly exposed to tick bites in Poland.
Human babesiosis caused by Babesia microti and Babesia divergens parasites is an emerging tick-borne disease worldwide. The prevalence of infection and frequency of the disease caused by B. microti in Europe is not well known. The aim of our study was to evaluate the frequency of anti-B. microti antibodies in the serum of forest employees (a population highly exposed to tick bites) from 2 different regions of Poland. We studied 114 foresters from 2 separate forest inspectorates in north-eastern and central Poland. Direct immunofluorescence assays (Babesia microti IgM and IgG IFA kits) were used to detect serum IgM and IgG anti-B. microti antibodies. Simultaneously, anti-B. burgdorferi antibodies were detected using an enzyme-linked immunosorbent assay kit, and positive cases were confirmed with immunoblot. Anti-B. microti IgG antibodies were detected in 5 foresters (4.4%), all from the forest inspectorate in Białowieża in the northeast of the country. All persons with anti-B. microti antibodies were also IgG-seropositive for B. burgdorferi. Our results suggest that unrecognized infections with B. microti occur in the Polish population and should be considered in the differential diagnosis of a febrile illness occurring after exposure to ticks, particularly in patients from endemic regions.


Ischemic postconditioning confers cerebroprotection by stabilizing VDACs after brain ischemia.
Ischemic postconditioning provides robust neuroprotection, therefore, determining the molecular events may provide promising targets for stroke treatment. Here, we showed that the expression of functional mitochondrial voltage-dependent anion channel proteins (VDAC1, VDAC2, and VDAC3) reduced in rat vulnerable hippocampal CA1 subfield after global ischemia. Ischemic postconditioning restored VDACs to physiological levels. Stabilized VDACs contributed to the benefits of postconditioning. VDAC1 was required for maintaining neuronal Ca2+ buffering capacity. We found that microRNA-7 (miR-7) was responsible for postischemic decline of VDAC1 and VDAC3. Notably, miR-7 was more highly expressed in the peripheral blood of patients with acute ischemic stroke compared to healthy controls. Inhibition of miR-7 attenuated neuronal loss and ATP decline after global ischemia, but also diminished the infarct volume with improved neurological functions after focal ischemia. Thus, ischemic postconditioning protects against mitochondrial damage by stabilizing VDACs. MiR-7 may be a potential therapeutic target for ischemic stroke.


Identification of MEDAG as a Hub Candidate Gene in the Onset and Progression of Type 2 Diabetes Mellitus by Comprehensive Bioinformatics Analysis.
We conducted the present study to identify novel hub candidate genes in the pathogenesis of type 2 diabetes mellitus (T2DM) and provide potential biomarkers or therapeutic targets for dealing with the disease. We conducted weighted gene coexpression network analysis on a series of the expression profiles of the pancreas islet of T2DM patients obtained from the Gene Expression Omnibus database to construct a weighted coexpression network. After dividing genes into separated coexpression modules, we identified a T2DM-related module using Pearson's correlation analysis. Then, hub genes were identified from the T2DM-related module using the Maximal Clique Centrality method and validated by correlation analysis with clinical traits, differentially expressed gene analysis, validation in other datasets, and single-gene gene set enrichment analysis (GSEA). Genes were divided into 16 coexpression modules, and one module was identified as a T2DM-related module. Four hub candidate genes were identified, and MEDAG was a novel hub candidate gene. The expression level of MEDAG was positively correlated with hemoglobin A1c (HbA1c) and was evidently overexpressed in the pancreas islet tissue of T2DM patients compared with normal control. Analyses on two other datasets supported the results. GSEA verified that MEDAG plays essential roles in T2DM. MEDAG is a novel hub candidate of T2DM, and its irregular expression in the pancreas islet plays vital roles in the pathogenesis of T2DM. MEDAG is a potential target of intervention in the future for the treatment of T2DM.


Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1.
Pancreatic tumours are common in patients with multiple endocrine neoplasia type 1 (MEN1), and close surveillance is needed to detect pancreatic lesions at an early stage. Conventional radiology is inefficient in verifying the small tumours indicated by biochemical screening. During the past decade, endoscopic ultrasonography (EUS) has evolved as a sensitive method for the detection of small pancreatic lesions. EUS was evaluated in 25 patients with MEN1, two of whom had symptoms due to hormonal secretion. Twenty-two patients had biochemical signs of pancreatic tumours, and in five patients lesions were located by either computed tomography (two) or transabdominal ultrasonography (three). EUS visualized pancreatic tumours in the five patients in whom lesions were detected by the other methods and in a further nine patients. Eight of these 14 patients had surgery, and tumours were confirmed histopathologically. No lesion was detected in any of the 11 patients with no tumour detected by EUS. EUS is a more sensitive technique for the detection and localization of potentially malignant lesions in patients with MEN1 than computed tomography or transabdominal ultrasonography.


Structure of vapour deposited adenine on a nanostructured perovskite surface studied by STM.
The structures of vapour deposited layers of adenine on a nanostructured SrTiO3(001) surface have been investigated by scanning tunneling microscopy (STM). The STM images reveal details of self-organization of adenine monolayers in which adsorption is controlled both by substrate nanostructure and by intermolecular H-bonding of adenine molecules. Detailed examination of STM images suggests that at least three different ordering structures are possible and two distinct orientations may exist with opposite chirality.


Synthesis of carbon containing TiO2 nano powders by aerosol flame deposition for photocatalyst.
In-situ carbon-doped-TiO2 nano-powder was prepared by an AFD (aerosol flame deposition) technique using ethanol and isopropanol, and the photocatalytic activity of the prepared powder was examined. There were no significant effect of the solvents on the phase of the prepared TiO2, but the level of carbon in the deposits prepared with ethanol was lower than that prepared with isopropanol. Also, the average sizes of the particles prepared with ethanol were slightly smaller than that formed with isopropanol. All the samples showed excellent photocatalytic activity in the decomposing of methylene blue (MB). We even observed photocatalytic activity of the powder under visible light irradiation, although the decomposition rate of MB under this irradiation was slightly slower than under UV-A light irradiation.


Ouch! My employees' drug therapy costs how much?
In the United States today, most citizens receive their health care through programs sponsored and financed by their employers rather than through primarily government-based funding. With this in mind, 85% of U.S. employer survey respondents indicated their health care programs are an investment in their employees from which they expect a return. With the many new pharmaceutical therapies that have been developed and marketed in this country that treat small populations suffering from rare or previously untreatable diseases such as multiple sclerosis, inflammatory diseases and treatments for various types of cancer, employers have found themselves in an uncomfortable position. The costs of these pharmaceutical therapies can reach $5,000 per month or more, but the long-term benefits may take decades to assess; even increased survival rates or improvement of symptoms is uncertain in some newer oncology therapies. What steps can employers take to manage the availability of these high-cost therapies so their prescription drug plans continue to provide an acceptable return on investment? Prior authorization, step therapy, wellness programs, case management, drug compliance efforts, drug therapy rationing, transparency and cost-sharing techniques are discussed.


Long non-coding RNA THOR promotes cell proliferation and metastasis in hepatocellular carcinoma.
Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the development and progression of multiple cancers by previous studies. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in hepatocellular carcinoma (HCC) is still unclear. In this study, we found that THOR was relatively highly expressed in human HCC tissues and cell lines. Notably, high THOR expression was associated with worse prognosis. THOR depletion resulted in significant inhibition of the growth and metastasis of HCC cells. Mechanistically, THOR drives HCC cell progression via the PTEN/AKT pathway. Moreover, the specific PI3-K inhibitor LY294002 abolished the discrepancy in the growth and metastatic capacity between THOR-silenced HCC cells and control cells, which further confirmed that AKT was required in THOR-driven HCC cell growth and metastasis. Taken together, our results suggest that THOR could promote HCC cell growth and metastasis by amplifying PTEN/AKT signaling and may be a new therapeutic target and predictive factor for HCC.


Bio-accumulation of some trace metals in the short-neck clam Paphia malabarica from Mandovi estuary, Goa.
Monthly collections of the clam Paphia malabarica were made for period of 1 year from May 2002 to April 2003 from Verem, Mandovi estuary, Goa. Clams were categorised into two groups, 25-35 mm (small size) and 35-40 mm (big size). Significant difference was not observed in the accumulation of metals in the whole soft tissue between the two size groups. Irrespective of size, annual mean, metal content recorded as microg/g dry weight in the whole soft tissue was 3.8, 30.3, 13.5, 36.6 and 105.7, respectively, for Cd, Pb, Cu, Zn and Fe. Of the two toxic elements Cd and Pb, Cd content was almost uniform throughout the year except for a rise in September for the small size and October for the big size. Pb, on the other hand, was low from the beginning of the monsoon and exhibited distinct accumulation from December onwards up to April, May and, to some extent, June. The pattern was similar in both the size groups, the values being higher for the bigger size group. The three essential elements Cu, Fe and Zn exhibit trends similar to one another with peaks in September and December-January in both the size groups. Cadmium accumulation was highest in the mantle and adductor muscle, Lead, in foot, Copper, in digestive gland and gonad, and Zn and Fe, in gills. Correlation coefficient between different metal couplings as tested statistically revealed significant coupling for Zn-Fe (r 0.92) in the bigger size group, the same was observed between Cu-Fe (r 0.62) and Cd-Zn (r 0.94). Seasonal difference in Pb accumulation was highly significant.


Effects of nebulized terbutaline on oxygen saturation in acute asthmatic children.
To evaluate the paradoxical effect of oxygen desaturation following beta-2 bronchodilator nebulization treatment in acute asthmatic children, a total of 47 patients, aged between 1.8 and 14 years, 27 males and 20 females, were studied. Twenty ml of nebulized normal saline (NS), followed by 10 mg (4 ml) of terbutaline sulphate solution (TSS) in 20 ml NS, were delivered by an ultrasonic nebulizer in 10 min to each patient through a connecting air tube placed in front of the nose and mouth. Oxygen saturation (SaO2) and pulse rate were monitored, using a pulse oximeter, before study and every two minutes until the end of the study. The clinical severity score and peak expiratory flow rate (PEFR) were checked before the study, at the end of inhalation of NS, and at the end of inhalation of TSS. SaO2 was increased both after nebulized NS and TSS when compared with the pre-study data (p < 0.05 and p < 0.0001, respectively). Twenty two cases (47%) during NS and 12 cases (25%) during TSS nebulization had SaO2 below the pre-study level. The mean decrease of SaO2 for the former was 1.62 +/- 0.95% (range: 1.00% to 4.26%), and 1.64 +/- 0.83% (range: 1.02% to 3.13%) for the latter (p > 0.9). No SaO2 decrease after nebulized TSS was observed in any of the seven severe asthmatic children with a prestudy SaO2 < or = 90%. The clinical severity score and PEFR were also significantly improved both after nebulized NS and TSS (p < 0.0001 and p < 0.001, respectively for NS, and both p < 0.0001 for TSS).(ABSTRACT TRUNCATED AT 250 WORDS)


INFLUENCE OF THE CIVIC COMMUNITY RELIGIOUS ENVIRONMENT ON FAMILY POVERTY: A MULTILEVEL ANALYSIS.
This study integrates research in the civic community tradition and structuralist and individualist perspectives on poverty to assess the relationship between religious-based civic community structures and family poverty in the United States. Using multilevel analyses of 2006-2008 American Community Survey, 2000 Census of Population and Housing, and 2000 Religious Congregations and Membership Survey data, results demonstrate that the presence of Mainline Protestant and Catholics adherents within communities - measured as the percentage of a community's population comprised of Mainline Protestant and Catholic adherents - is significantly and negatively associated with family poverty risks, net of other family and community factors. That is, in communities with a greater presence of Mainline Protestants and Catholics, there were also lower risks of families being in poverty. These findings suggest the importance of the ecology of religion within communities in understanding poverty outcomes for families.


Dissociation cross sections for N2 + N → 3N and O2 + O → 3O using the QCT method.
Cross sections for the homo-nuclear atom-diatom collision induced dissociations (CIDs): N2 + N and O2 + O are calculated using Quasi-Classical Trajectory (QCT) method on ab initio Potential Energy Surfaces (PESs). A number of studies for these reactions carried out in the past focused on the CID cross section values generated using London-Eyring-Polanyi-Sato PES and seldom listed the CID cross section data. A highly accurate CASSCF-CASPT2 N3 and a new O3 global PES are used for the present QCT analysis and the CID cross section data up to 30 eV relative energy are also published. In addition, an interpolating scheme based on spectroscopic data is introduced that fits the CID cross section for the entire ro-vibrational spectrum using QCT data generated at chosen ro-vibrational levels. The rate coefficients calculated using the generated CID cross section compare satisfactorily with the existing experimental and theoretical results. The CID cross section data generated will find an application in the development of a more precise chemical reaction model for Direct Simulation Monte Carlo code simulating hypersonic re-entry flows.


Heart disease prevention for Alaska Native women: a review of pilot study findings.
Although historically Alaska Native women have had a relatively low incidence of cardiovascular disease (CVD), this pattern has changed dramatically in recent years. Alaska Native leaders have identified decreasing cardiovascular risk as an intervention priority. From October 2000 to April 2001, Southcentral Foundation, an Alaska Native-owned and managed health corporation in Anchorage, conducted a pilot randomized controlled trial of a heart disease prevention program tailored for Alaska Native women. The aim was to assess feasibility and cultural acceptability and to develop enrollment procedures. Of 76 women who enrolled, 44 were randomized to the intervention group. Thirty-seven of 44 attended at least two intervention sessions, 23 completed prequestionnaires and postquestionnaires, and 27 returned for 12-month follow-up screening. Thirty of 32 control group participants returned for 12-month follow-up screening. The intervention included 12 weekly sessions on lifestyle change and goal setting. At baseline and 12 months, participants' height, weight, resting blood pressure, fasting lipid levels, and blood glucose were measured. At sessions 1 and 12, participants completed assessments regarding diet, physical activity, tobacco use, and psychosocial status. At 12 weeks, significant improvements were noted in moderate walking and physical activity self-efficacy. Also observed was substantial movement from the contemplation and preparation stages to the action stage regarding physical activity and heart-healthy eating. Although the small sample size precludes drawing conclusions about the intervention's effect, participants reported lifestyle and psychosocial changes. The pilot study resulted in protocol changes that improved the design and implementation of a subsequent large-scale study.


Extraction of mismatch negativity using a resampling-based spatial filtering method.
It is currently a challenge to extract the mismatch negativity (MMN) waveform on the basis of a small number of EEG trials, which are typically unbalanced between conditions. In order to address this issue, a method combining the techniques of resampling and spatial filtering is proposed in this paper. Specifically, the first step of the method, termed 'resampling difference', randomly samples the standard and deviant sweeps, and then subtracts standard sweeps from deviant sweeps. The second step of the method employs the spatial filters designed by a signal-to-noise ratio maximizer (SIM) to extract the MMN component. The SIM algorithm can maximize the signal-to-noise ratio for event-related potentials (ERPs) to improve extraction. Simulation data were used to evaluate the influence of three parameters (i.e. trial number, repeated-SIM times and sampling times) on the performance of the proposed method. Results demonstrated that it was feasible and reliable to extract the MMN waveform using the method. Finally, an oddball paradigm with auditory stimuli of different frequencies was employed to record a few trials (50 trials of deviant sweeps and 250 trials of standard sweeps) of EEG data from 11 adult subjects. Results showed that the method could effectively extract the MMN using the EEG data of each individual subject. The extracted MMN waveform has a significantly larger peak amplitude and shorter latencies in response to the more deviant stimuli than in response to the less deviant stimuli, which agreed with the MMN properties reported in previous literature using grand-averaged EEG data of multi-subjects.


Culture-independent diagnosis of Chlamydia trachomatis using monoclonal antibodies.
To simplify the diagnosis of chlamydial genital infection, we used a fluorescein-conjugated monoclonal antibody in immunofluorescence tests on smears prepared from urethral or cervical secretions obtained directly from patients. This direct test, requiring less than 30 minutes to perform, was based on the detection of extracellular chlamydial elementary bodies. A comparison of the direct test with cultures stained with iodine on specimens from 926 patients demonstrated a sensitivity of 93 per cent and a specificity of 96 per cent. The direct test provides a rapid, simple, and sensitive method for the diagnosis of chlamydial infection, which can be performed in laboratories that do not have tissue-culture capability.


A new Laubieriellus species (Annelida, Spionidae) from Western Australia.
A new annelid species within the Prionospio- complex (Spionidae), Laubieriellus cacatua sp. nov., is described from material collected from the continental slope off the western margin of Australia. Laubieriellus cacatua sp. nov. is distinguished by having dorsal crests from chaetigers 6 to 11 and ventral crests on chaetigers 2 to 11. Neuropodial hooded hooks are present from chaetiger 10, with 2 pairs of apical teeth above the main tooth. Ventral sabre chaetae are present from chaetiger 10. This is the first record of Laubieriellus in Australia.


Structure and Assembly of Escherichia coli Capsules.
The capsule is a cell surface structure composed of long-chain polysaccharides that envelops many isolates of Escherichia coli. It protects the cell against host defenses or physical environmental stresses, such as desiccation. The component capsular polysaccharides (CPSs) are major surface antigens in E. coli. They are named K antigens (after the German word Kapsel). Due to variations in CPS structures, more than 80 serologically unique K antigens exist in E. coli. Despite the hypervariability in CPS structures, only two capsule-assembly strategies exist in E. coli. These have led to the assignment of group 1 and group 2 capsules, and many of the key elements of the corresponding assembly pathways have been resolved. Structural features, as well as genetic and regulatory variations, give rise to additional groups 3 and 4. These employ the same biosynthesis processes described in groups 2 and 1, respectively. Each isolate possesses a distinctive set of cytosolic and inner-membrane enzymes, which generate a precise CPS structure, defining a given K serotype. Once synthesized, a multiprotein complex is needed to translocate the nascent CPS across the Gram-negative cell envelope to the outer surface of the outer membrane, where the capsule structure is assembled. While the translocation machineries for group 1 and group 2 CPSs are fundamentally different from one another, they possess no specificity for a given CPS structure. Each is conserved in all isolates producing capsules belonging to a particular group.


Tree Frog-Derived Cathelicidin Protects Mice against Bacterial Infection through Its Antimicrobial and Anti-Inflammatory Activities and Regulatory Effect on Phagocytes.
Due to excessive use or abuse in the food industry, agriculture, and medicine, many pathogens are developing resistance against conventional antibiotics. Antimicrobial peptides (AMPs) hold promise as effective therapeutic options for the treatment of bacterial infections. Herein, a novel cathelicidin antimicrobial peptide (Zs-CATH) was identified from the tree frog Zhangixalus smaragdinus. Zs-CATH mainly adopted an amphipathic β-sheet structure in a membrane-mimetic environment. It showed broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria in vitro and significantly protected mice from lethal infections induced by Gram-negative bacteria Escherichia coli ATCC 25922 or Gram-positive bacteria Staphylococcus aureus ATCC 25923 in vivo. In addition, Zs-CATH exerted a strong anti-inflammatory effect by neutralizing lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and promoting macrophage M2 polarization, thus inhibiting the secretion of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and enhancing the production of M2 macrophage markers IL-10, IL-4, and CD206. The MAPK and NF-κB inflammatory signaling pathways and transcriptional activator 6 (STAT6) were involved in this effect. In mice, Zs-CATH rapidly recruited neutrophils and monocytes/macrophages to the abdominal cavity but not T and B lymphocytes. Zs-CATH did not exhibit a direct chemoattractant effect on phagocytes but significantly promoted phagocyte migration in the presence of macrophages. Zs-CATH stimulated macrophages to secrete chemokines CXCL1, CXCL2, and CCL2, which mediated the recruitment of phagocytes. Furthermore, Zs-CATH promoted the production of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs), which are oxygen-dependent and oxygen-independent mechanisms of the microbicidal activity of neutrophils, respectively. Zs-CATH exhibited no toxic side effects on mammalian cells and mice. These findings show that in addition to direct antibacterial activity, Zs-CATH also possesses the ability to modulate immune and inflammatory processes during bacterial infection, showing potential for development as anti-infective and/or anti-inflammatory agents.


The COOH-terminal E-F hand structure of calcium-activated neutral protease (CANP) is important for the association of subunits and resulting proteolytic activity.
High-Ca2+-requiring calcium-activated neutral protease (mCANP), a dimeric enzyme composed of large (Mr = 80,000) and small (Mr = 28,000) subunits, is resistant to carboxypeptidase Y (CPase Y) in the absence of NaSCN. In the presence of 0.2 M NaSCN, CPase Y digested mCANP, one or two amino acids being released from the COOH-termini of the large and small subunits, but no change occurred in the activity of the digested mCANP. In the presence of 1 M NaSCN, 8-10 amino acids were released from the subunits by CPase Y, and the COOH-terminal potential Ca2+-binding sites of both subunits were destroyed. On digestion under these conditions, mCANP lost the ability to form a complex, and the proteolytic activity was not recovered even when the digested subunits were mixed with native subunits. These results suggest that the COOH-terminal regions of the two subunits of mCANP, which constitute the helical portions of the COOH-terminal E-F hand structures in both subunits, are essential for the subunit association and resulting proteolytic activity.


Fracture of supracondylar process of the humerus.
The supracondylar process of the humerus is a rare skeletal anomaly, which is usually an incidental finding while an X-ray is done for some other purpose. The process can fracture resulting in pain and tender mobile swelling over the medial aspect of the arm, and consequent neurovascular symptoms, or entrapment neuropathies. The anomaly, which fractured in a clinical situation, is described, followed by a review of the literature.


Screening for alcoholism in general medical patients.
Medical patients (N = 108) were administered a brief screening instrument (LAMSI) and a structured diagnostic interview (SUDDS). Twenty-five patients met DSM-III criteria for an alcohol use disorder, 20 current, five in remission. The four-item scale embedded in the screen identified the alcoholics with 88% sensitivity and 96% specificity.


Invasive fungal disease after remote inoculation in transplant recipients.
We describe 3 cases of invasive fungal disease in the setting of transplantation-associated immunosuppression, developing months to years after clinically resolved penetrating soft-tissue injuries with wood fragments. Invasive fungal disease resulting from remote inoculation is a distinct syndrome in immunocompromised patients presenting with soft-tissue abnormalities in areas of prior trauma.


Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration during kidney injury.
Loss of the microvascular (MV) network results in tissue ischemia, loss of tissue function, and is a hallmark of chronic diseases. The incorporation of a functional vascular network with that of the host remains a challenge to utilizing engineered tissues in clinically relevant therapies. We showed that vascular-bed-specific endothelial cells (ECs) exhibit differing angiogenic capacities, with kidney microvascular endothelial cells (MVECs) being the most deficient, and sought to explore the underlying mechanism. Constitutive activation of the phosphatase PTEN in kidney MVECs resulted in impaired PI3K/AKT activity in response to vascular endothelial growth factor (VEGF). Suppression of PTEN in vivo resulted in microvascular regeneration, but was insufficient to improve tissue function. Promoter analysis of the differentially regulated genes in KMVECs suggests that the transcription factor FOXO1 is highly active and RNAseq analysis revealed that hyperactive FOXO1 inhibits VEGF-Notch-dependent tip-cell formation by direct and indirect inhibition of DLL4 expression in response to VEGF. Inhibition of FOXO1 enhanced angiogenesis in human bio-engineered capillaries, and resulted in microvascular regeneration and improved function in mouse models of injury-repair.


[The effectiveness of psychodynamic therapy. A review using criteria of evidence-based medicine].
The existing studies on the effectiveness of psychodynamic therapy are reviewed. All studies published between 1960 and 2001 were collected. In the first part of this survey, the focus is on short-term psychodynamic therapy, the second part focuses on longer-term psychoanalytic and psychodynamic therapy. The studies are reviewed with regard to forms of disorders. The methodological quality of the studies is judged according to criteria of evidence-based medicine. These criteria themselves are also critically discussed. Although they vary concerning their methodological quality, the studies reveal evidence of the effectiveness of both short-term and long-term psychodynamic therapy. In a meta-analytic evaluation performed by the author, substantial effects were found for psychodynamic therapy of personality disorders, i.e. 1.13 (self-report measures) and 1.57 (observer-rated measures) for short-term psychodynamic therapy and 1.05 (self-report measures) and 2.11 (observer-rated measures) for longer term psychodynamic therapy. Although there is evidence of the effectiveness of psychodynamic therapy, further research of specific forms of psychodynamic therapy in specific disorders is necessary.


Halococcus thailandensis sp. nov., from fish sauce in Thailand.
Fifteen strains of red-pigmented, strictly aerobic, coccoid, extremely halophilic archaea were isolated from fish sauce (nam-pla) produced in Thailand. They grew optimally at 37 degrees C, pH 6-8 and in the presence of 20-30 % (w/v) NaCl. The DNA G+C contents of the isolates were 60.0-61.8 mol%. They had MK-8(H2) as a major menaquinone component and C(20)C(20) and C(20)C(25) derivatives of phosphatidylglycerol, phosphatidylglycerol methylphosphate and a sulfated glycolipid, S-DGA-1, as major polar lipid components. 16S rRNA gene sequence comparisons revealed that a representative strain, HDB5-2(T), was affiliated with Halococcus dombrowskii JCM 12289(T), Halococcus qingdaonensis JCM 13587(T) and Halococcus morrhuae JCM 8876(T) (levels of similarity of 98.2-98.7 %). Based on data from DNA-DNA hybridization experiments, the 15 strains represented a single species, showing hybridization values of >78.9 % to representative strain HDB5-2(T), but were unrelated to either Halococcus dombrowskii JCM 12289(T) or Halococcus morrhuae JCM 8876(T), with levels of relatedness of <50 %. Moreover, a comparison of phenotypic properties discriminated these new isolates from recognized species of the genus Halococcus. The 15 strains are thus considered to represent a novel species of the genus Halococcus, for which the name Halococcus thailandensis sp. nov. is proposed. The type strain is HDB5-2(T) (=BCC 20213(T) =JCM 13552(T) =PCU 278(T)).


Morulustatin, A Disintegrin that Inhibits ADP-Induced Platelet Aggregation, Isolated from the Mexican Tamaulipan Rock Rattlesnake (Crotalus lepidus morulus).
The Tamaulipan rock rattlesnake (Crotalus lepidus morulus) is a montane snake that occurs in the humid pine-oak forest and the upper cloud forest of the Sierra Madre Oriental in southwestern Tamaulipas, central Nuevo Leon, and southeastern Coahuila in Mexico. Venom from this rattlesnake was fractionated by High-Performance Liquid Chromatography for the purpose of discovering disintegrin molecules. Disintegrins are non-enzymatic, small molecular weight peptides that interfere with cell-cell and cell-matrix interactions by binding to various cell receptors. Eleven fractions were collected by anion exchange chromatography and pooled into six groups (I, II, III, IV, V, and VI). Proteins of the six groups were analyzed by SDS-PAGE and western blot using antibodies raised against a disintegrin. The antibodies recognized different protein bands in five (II, III, IV, V, and VI) of six groups in a molecular mass range of 7 to 105 kDa. Western blot analysis revealed fewer protein bands in the higher molecular mass range and two bands in the disintegrin weight range in group II compared with the other four groups. Proteins in group II were further separated into nine fractions using reverse phase C18 chromatography. Fraction 4 inhibited platelet aggregation and was named morulustatin, which exhibited a single band with a molecular mass of approximately 7 kDa. Mass spectrometry analysis of fraction 4 revealed the identification of disintegrin peptides LRPGAQCADGLCCDQCR (MH+ 2035.84) and AGEECDCGSPANCCDAATCK (MH+ 2328.82). Morulustatin inhibited ADP-induced platelet aggregation in human whole blood and was concentration-dependent with an IC50 of 89.5 nM ± 12.


The behaviour of green tea catechins in a full-fat milk system under conditions mimicking the cheesemaking process.
Due to their well-known health benefits, green tea catechins have received recent attention as natural additives in foods such as dairy products. However, they may present some irreversible associations with milk components (e.g. protein and milk fat globules). To investigate the behaviour of two important green tea catechins, (+)-catechin (C) and (-)-epigallocatechin gallate (EGCG), in a standard whole milk system under the conditions of cheesemaking, 250 and 500 ppm of each catechin were added to whole milk (3.3% fat). Although both C and EGCG at either concentration increased both total phenolic content and total antioxidant capacity of the subnatants obtained from the milk system, there was a less linear increase when the concentration of the catechins was doubled, whereas C or EGCG were recovered (measured by HPLC) differently. Overall, these results suggest a degree of associations between green tea catechins with milk proteins and milk fat.


The desert moss Pterygoneurum lamellatum (Pottiaceae) exhibits an inducible ecological strategy of desiccation tolerance: effects of rate of drying on shoot damage and regeneration.
Bryophytes include clades that incorporate constitutive desiccation tolerance, especially terrestrial species. Here we test the hypothesis that the opposing ecological strategy of desiccation tolerance, inducibility, is present in a desert moss, and address this hypothesis by varying rates of drying in a laboratory study. Desiccation tolerance is arguably the most important evolutionary innovation relevant to the colonization of land by plants; increased understanding of the ecological drivers of this trait will eventually illuminate the responsible mechanisms and ultimately open doors to the potential for the application of this trait in cultivated plants. Plants were cloned, grown in continuous culture (dehardened) for several months, and subjected to rates of drying (drying times) ranging from 30 min to 53 h, rehydrated and tested for recovery using chlorophyll fluorescence, leaf damage, and regeneration of protonema and shoots. Rate of drying significantly affected all recovery responses, with very rapid drying rates severely damaging the entire shoot except the shoot apex and resulting in slower growth rates, fewer regenerative shoots produced, and a compromised photosynthetic system as inferred from fluorescence parameters. For the first time, a desert moss is shown to exhibit an ecological strategy of desiccation tolerance that is inducible, challenging the assumption that arid-land bryophytes rely exclusively on constitutive protection. Results indicate that previous considerations defining a slow-dry event in bryophytes need reevaluation, and that the ecological strategy of inducible desiccation tolerance is probably more common than currently understood among terrestrial bryophytes.


Emergency Neurologic Life Support: Spinal Cord Compression.
There are many causes of acute myelopathy including multiple sclerosis, systemic disease (SD), and acute spinal cord compression (SCC). SCC should be among the first potential causes considered given the significant permanent loss of neurologic function commonly associated with SCC. This impairment can occur over a short period of time, and may be avoided through rapid and acute surgical intervention. Patients with SCC typically present with a combination of motor and sensory dysfunction that has a distribution referable to a spinal level. Bowel and bladder dysfunction and neck or back pain may also be part of the clinical presentation, but are not uniformly present. Because interventions are critically time-sensitive, the recognition and treatment of SCC was chosen as an ENLS protocol.


A case of anaphylaxis after the ingestion of yacon.
Anaphylaxis is a potentially life-threatening systemic allergic reaction, often with an explosive onset; the symptoms range from mild flushing to upper respiratory obstruction, with or without vascular collapse. Foods are common offending allergens and remain the leading cause of outpatient anaphylaxis in most surveys. Yacon (Smallanthus sonchifolius) is a plant native to the Andes region, where its root is cultivated and consumed mainly as food. Unlike most edible roots, yacon contains large amounts of ructooligosaccharides. Traditionally, yacon tubers have been used as a source of natural sweetener and syrup for people suffering from various disorders. We report the case of a 55-year-old woman who developed syncope and generalized urticaria after ingesting yacon roots. The patient had positive skin prick and intradermal tests to yacon extract. An open food challenge test was performed to confirm food anaphylaxis and was positive 10 minutes after the consumption of yacon roots. To our knowledge, this is the first reported case of anaphylaxis after the ingestion of yacon roots.


Loudness predicts prominence: fundamental frequency lends little.
We explored a database covering seven dialects of British and Irish English and three different styles of speech to find acoustic correlates of prominence. We built classifiers, trained the classifiers on human prominence/nonprominence judgments, and then evaluated how well they behaved. The classifiers operate on 452 ms windows centered on syllables, using different acoustic measures. By comparing the performance of classifiers based on different measures, we can learn how prominence is expressed in speech. Contrary to textbooks and common assumption, fundamental frequency (f0) played a minor role in distinguishing prominent syllables from the rest of the utterance. Instead, speakers primarily marked prominence with patterns of loudness and duration. Two other acoustic measures that we examined also played a minor role, comparable to f0. All dialects and speaking styles studied here share a common definition of prominence. The result is robust to differences in labeling practice and the dialect of the labeler.


[The experience of a blood-bank doctor in Chile].
Director of a blood transfusion service in Concepción, Chili, Dr. Christina Martinez reports on her experience in this centre and the actions undertaken in order to find resources and supports, to guarantee the operation of the centre and to enhance voluntary blood donation.


Early two-dimensional echocardiographic measurement of left ventricular ejection fraction in acute myocardial infarction.
Left ventricular volume and ejection fraction were measured by 2-dimensional echocardiography from 2 orthogonal apical long axis views in 90 patients admitted with acute transmural myocardial infarction. Results were correlated with worst Killip class during hospital stay, enzymatic infarct size (peak CK-MB) and mortality. We used two algorithms, a biplane area-length algorithm and a modification of Simpson's rule. Both algorithms yielded essentially the same results: there were statistically significant trends towards higher end-diastolic and end-systolic volumes and lower ejection fraction with higher Killip -class. Ejection fraction was lower (P less than 0.01) in the 6 patients dying from cardiogenic shock (28.0 +/- 7.8% v. 46.6 +/- 10.1% in survivors with the area--length algorithm; 28.1 +/- 6.2% v. 48.1 +/- 10.2% with modified Simpson's rule). In 5 patients dying from other causes ejection fraction was 46.0 +/- 14.9% with the area-length method or 46.2 +/- 14.5% with Simpson's rule (not different from survivors). Correlation with peak CK-MB was only modest, though statistically significant: the regression equation was: y = -0. 39x + 54 (r = -0.35; P less than 0.01) with the area-length method; and y = -0. 41x + 55 (r = -0.37; P less than 0.01) with Simpson's rule. Left ventricular ejection fraction measured at the bedside in patients with acute myocardial infarction, can provide useful clinical information. Patients likely to develop shock can be identified shortly after admission.


A multidimensional investigation of the relationship between skin-mediated somatosensory signals, emotion regulation and behavior problems in autistic children.
Autistic children may have abnormal sensory perception, emotion dysregulation and behavior problems. The aim of this cross-sectional study was to explore the relationship between skin-mediated somatosensory signals and emotion/behavior difficulties in autistic children and adolescents, in comparison typically developing peers (TDP). Thirty-eight autistic children and adolescents and 34 TDP completed a multidimensional assessment consisting of the measurement of somatosensory thresholds of touch, pain and temperature, a task on emotion knowledge and parent-reported questionnaires on sensory reactivity, emotion regulation and behavior. Autistic children had higher pain sensitivity, less sensory reactive behaviors and more behavior problems than their TDP. In contrast to TDP, several somatosensory thresholds of autistic children correlated with emotion regulation and behavior problems. Sensory dysfunction may affect the development of emotional processing and behavior in autistic children and adolescents. This knowledge can lay the foundation for future studies on co-occurring alterations in corresponding neural networks and for the implementation of early interventions, including sensory rehabilitation therapy, for promoting regulated behaviors in autistic children and adolescents.


Endobronchial ultrasound-guided transbronchial needle aspiration for lymph node staging in patients with non-small cell lung cancer in non-operable patients pursuing radiotherapy as a primary treatment.
Carbon ion radiotherapy (CIRT) is a promising modality with excellent localization and significant biologic effects on tumors. Nevertheless, success depends primarily on accurate staging before radiotherapy. Surgical interventions should be avoided in patients considered for CIRT because they usually have multiple comorbidities. The aim of this study was to evaluate the effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in patients with non-small cell lung cancer before CIRT. From April 2005 to December 2007, 49 patients with non-small cell lung cancer considered for CIRT with abnormal positron emission tomography-computed tomography (PET-CT) accumulations in the mediastinum and/or hilum were evaluated by EBUS-TBNA. The convex probe EBUS was used for EBUS-TBNA. There were 38 men and 11 women. Their mean age was 75.2 years (range: 55-87). Based on PET-CT, clinical staging was four with N1 disease, 42 with N2 disease, and three with N3 disease. By histology, 26 patients had adenocarcinoma, 19 had squamous cell carcinoma, and four had other histologies. All positive lymph nodes on PET-CT were aspirated (range: 1-5; average 2.55 lymph nodes/patient). EBUS-TBNA diagnosed 43 cases as N0 disease and as a result underwent CIRT. Forty of the 43 cases remained in stable condition without local recurrences (follow-up 6-46 months). The diagnostic accuracy of EBUS-TBNA for lymph node staging was 93.9%. EBUS-TBNA offers accurate minimally invasive lymph node staging in patients who are candidates for CIRT. EBUS-TBNA can be safely performed with a high diagnostic accuracy before CIRT.


Adaptation and gain pool summation: alternative models and masking data.
Foley [J. Opt. Soc. Am. A 11 (1994) 1710] has proposed an influential psychophysical model of masking in which mask components in a contrast gain pool are raised to an exponent before summation and divisive inhibition. We tested this summation rule in experiments in which contrast detection thresholds were measured for a vertical 1 c/deg (or 2 c/deg) sine-wave component in the presence of a 3 c/deg (or 6 c/deg) mask that had either a single component oriented at -45 degrees or a pair of components oriented at +/-45 degrees. Contrary to the predictions of Foley's model 3, we found that for masks of moderate contrast and above, threshold elevation was predicted by linear summation of the mask components in the inhibitory stage of the contrast gain pool. We built this feature into two new models, referred to as the early adaptation model and the hybrid model. In the early adaptation model, contrast adaptation controls a threshold-like nonlinearity on the output of otherwise linear pathways that provide the excitatory and inhibitory inputs to a gain control stage. The hybrid model involves nonlinear and nonadaptable routes to excitatory and inhibitory stages as well as an adaptable linear route. With only six free parameters, both models provide excellent fits to the masking and adaptation data of Foley and Chen [Vision Res. 37 (1997) 2779] but unlike Foley and Chen's model, are able to do so with only one adaptation parameter. However, only the hybrid model is able to capture the features of Foley's (1994) pedestal plus orthogonal fixed mask data. We conclude that (1) linear summation of inhibitory components is a feature of contrast masking, and (2) that the main aftereffect of spatial adaptation on contrast increment thresholds can be assigned to a single site.


Autonomic impairment in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor neurones, but it is increasingly recognized to be a more disseminated disease. The autonomic nervous system may also be involved. Here we review the literature with specific emphasis on autonomic functions in ALS. Ample evidence exists for subclinical dysfunction of cardiovascular, sudomotor, gastrointestinal, salivary and lacrimal regulation, even in early ALS cases. Autonomic disturbances may lead to circulatory collapse or sudden death in respirator dependent patients. Several studies suggest the existence of sympathetic hyperactivity in ALS. We discuss some possible pathophysiological mechanisms of the subtle abnormalities and some clinical and treatment implications. The wide range of autonomic involvement, together with results suggesting cognitive and extrapyramidal dysfunction, supports the view that ALS is a multisystem degenerative disease.


Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds.
A human leukemic cell line (designated HL-60) has recently been established from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. This cell line displays distinct morphological and histochemical commitment towards myeloid differentiation. The cultured cells are predominantly promyelocytes, but the addition of dimethyl sulfoxide to the culture induces them to differentiate into myelocytes, metamyelocytes, and banded and segmented neutrophils. All 150 clones developed from the HL-60 culture show similar morphological differentiation in the presence of dimethyl sulfoxide. Unlike the morphologically immature promyelocytes, the dimethyl sulfoxide-induced mature cells exhibit functional maturity as exemplified by phagocytic activity. A number of other compounds previously shown to induce erythroid differentiation of mouse erythroleukemia (Friend) cells can induce analogous maturation of the myeloid HL-60 cells. The marked similarity in behavior of HL-60 cells and Friend cells in the presence of these inducing agents suggests that similar molecular mechanisms are involved in the induction of differentiation of these human myeloid and murine erythroid leukemic cells.


[Reducing dietary salt intake: an important public health strategy in Switzerland].
Current dietary salt (sodium chloride) intake largely exceeds physiological needs (about 1.5 g salt per day, or 550 mg sodium per day) in most countries (> 8 g salt per day). The main sources of dietar salt intake are breads, cheeses, products derived from meat and ready-to-eat meals. On average, a high-salt diet is associated with higher blood pressure levels. In Switzerland, one out of three adults suffers from arterial hypertension. Half of cerebrovascular events and ischaemic cardiac events are attributable to elevated blood pressure. The Swiss Federal Office of Public Health is currently running a strategy aiming at reducing dietary salt intake in the Swiss population to less than 5 g per day on the long run (Salz Strategie 2008-2012).


A confirmatory factor analysis of the PTSD checklist 5 in veteran and college student samples.
An important change in the conceptualization of posttraumatic stress disorder (PTSD) has been the shift from a three-factor model used in the DSM-IV-TR to the current four-factor model used in DSM-5. Early research initially supported the three-factor model, but most recent data suggest a four-factor model provides the best fit. Still other research has examined evidence for a five-factor model that would include depression sequelae. By way of a confirmatory factor analysis, we demonstrate the reliability of DSM-5 PTSD criteria clustering in a sample of 124 OEF/OIF/OND Veterans treated at a VAMC (49% white, 89% men) and a sample of 737 college students (48% white, 78% women). All participants were trauma-exposed, and completed the PTSD Checklist for DSM-5. The current study shows both samples best support a five-factor model over two four factor models considered for the DSM-5, though none provided better than moderate fit. Implications of the current findings regarding the reliability of the new DSM-5 criteria of PTSD will be discussed.


Autotransfusion by cell saver technique in surgery of lumbar and thoracic spinal fusion with instrumentation.
The authors used a modern cell saver technique to perform autotransfusion in patients undergoing instrument-assisted lumbar and/or thoracic spinal fusion, in whom significant blood loss was anticipated. The safety and benefits of this procedure as well as its cost effectiveness were analyzed. The authors studied 50 patients who underwent lumbar and/or thoracic spinal fusion in which instrumentation was placed between January 1998 and June 2000 and in whom an estimated blood loss of 500 ml or more was expected. All surgeries were conducted by a single neurosurgeon (D.R.S.). During surgery, the Brat 2 cell saver system was used to salvage the autologous blood. The anesthesiologist and surgeon jointly decided, on the basis of hematocrit and clinical stability, whether transfusion was necessary in each patient. Various parameters (hematocrit, plasma and urine hemoglobin, platelet counts, coagulation profile, and serum bilirubin) were measured pre-, intra-, and postoperatively. Thirty-three patients (66%) required transfusion. The mean blood loss in these patients was 1046 ml. The most important factor affecting blood loss was the number of levels fused (p < 0.0001). Only two patients required postoperative homologous transfusion. The mean decrease in hematocrit was 7.82%. The maximum reduction of platelet count was limited to 80,000/mm3. Major complications such as hemoglobinuria, coagulopathy, cardiopulmonary problems, air embolism, and major sepsis were not observed in this study. Autotransfusion performed using a modern cell saver technique is safe and has many advantages over homologous transfusion. It conserves the homologous blood resources. The costs of the two modes are statistically comparable when greater than 500 ml of red blood cell transfusion is necessary.


Technology-based assessment in patients with disorders of consciousness.
A number of studies highlight the difficulty in forming a diagnosis for patients with disorders of consciousness when this is established merely on behavioral assessments. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and electroencephalography combined with transcranial magnetic stimulation (TMS-EEG) techniques are promoting the clinical characterization of this challenging population. With such technology-based "objective" tools, patients are also differentially able to follow simple commands and in some cases even communicate through modified brain activity. Consequently, the vegetative state and minimally conscious state have been revised and new nosologies have been proposed, namely the unresponsive wakefulness syndrome, the minimally conscious state plus and minus, and the functional locked-in syndrome. To our mind, an integration of different technical modalities is important to gain a holistic vision of the underlying pathophysiology of disorders of consciousness in general and to promote single-patient medical management in particular.


Relationship of disease-associated gene expression to cardiac phenotype is buffered by genetic diversity and chromatin regulation.
Expression of a cohort of disease-associated genes, some of which are active in fetal myocardium, is considered a hallmark of transcriptional change in cardiac hypertrophy models. How this transcriptome remodeling is affected by the common genetic variation present in populations is unknown. We examined the role of genetics, as well as contributions of chromatin proteins, to regulate cardiac gene expression and heart failure susceptibility. We examined gene expression in 84 genetically distinct inbred strains of control and isoproterenol-treated mice, which exhibited varying degrees of disease. Unexpectedly, fetal gene expression was not correlated with hypertrophic phenotypes. Unbiased modeling identified 74 predictors of heart mass after isoproterenol-induced stress, but these predictors did not enrich for any cardiac pathways. However, expanded analysis of fetal genes and chromatin remodelers as groups correlated significantly with individual systemic phenotypes. Yet, cardiac transcription factors and genes shown by gain-/loss-of-function studies to contribute to hypertrophic signaling did not correlate with cardiac mass or function in disease. Because the relationship between gene expression and phenotype was strain specific, we examined genetic contribution to expression. Strikingly, strains with similar transcriptomes in the basal heart did not cluster together in the isoproterenol state, providing comprehensive evidence that there are different genetic contributors to physiological and pathological gene expression. Furthermore, the divergence in transcriptome similarity versus genetic similarity between strains is organ specific and genome-wide, suggesting chromatin is a critical buffer between genetics and gene expression.


A Review of mTOR Pathway Inhibitors in Gynecologic Cancer.
The treatment of advanced gynecologic cancers remains palliative in most of cases. Although systemic treatment has entered into the era of targeted drugs the antitumor efficacies of current therapies are still limited. In this context there is a great need for more active treatment and rationally designed targeted therapies. The PI3K/AKT/mTOR is a signaling pathway in mammal cells that coordinates important cell activities. It has a critical function in the survival, growth, and proliferation of malignant cells and was object of important research in the last two decades. The mTOR pathway emerges as an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli and, through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including endometrial, cervical, and ovarian cancers. The present study reviewed the available evidence regarding the potential impact of some mTOR pathway inhibitors in the treatment of gynecological cancer. Few advances in medical management have occurred in recent years in the treatment of advanced or recurrent gynecological malignancies, and a poor prognosis remains. Rationally designed molecularly targeted therapy is an emerging and important option in this setting; then more investigation in PI3K/AKT/mTOR pathway-targeted therapies is warranted.


Uptake rate of phenol by Pseudomonas putida grown in unsteady state.
The uptake rate of phenol by washed cells of Pseudomonas putidagrown on phenol in fermenter in an un steady state, caused by the step increase of dilution rate and/or phenol concentration in the feed, was studied. The Monod-Haldane type equation was applied to fit the data and the best kinetic parameters were calculated by nonlinear least-square techniques. It was found that the minimum period of unsteady state required for induction of the phenol metabolic pathway was approximately 30 min. The values of kinetic parameters in an unsteady state varied according to each parameter. The values of u(m) first monotonically increased to reach their highest value after about 120 min and then monotonically decreased to equal the u(m) in new steady state after about five residence times. No regularity in changing of K(s) and K(i), in unsteady state was observed. However, the greatest change in the values of K(i), was 45% while the change in values of K(s) was as much as two times compared to K(i) and K(s) in steady state prior to disturbance.


[Malignant lymphoproliferative neoplasms and chronic hepatitis C virus infection].
It has been suggested that chronic hepatitis C virus (HCV) infection predisposes to the development of benign and malignant lymphoproliferative disorders. We present 2 cases of malignant lymphoproliferative neoplasias (a non-Hodgkin lymphoma [NHL] and a chronic lymphoid leukemia [CLL]) associated to chronic hepatitis C virus (HCV). The possible etiological role of HCV in the development of these tumors is discussed.


The endocannabinoid system as a target for addiction treatment: Trials and tribulations.
Addiction remains a major public health concern, and while pharmacotherapies can be effective, clinicians are limited by the paucity of existing interventions. Endocannabinoid signaling is involved in reward and addiction, which raises the possibility that drugs targeting this system could be used to treat substance use disorders. This review discusses findings from randomized controlled trials evaluating cannabinergic medications for addiction. Current evidence suggests that pharmacotherapies containing delta-9-tetrahydrocannabinol, such as dronabinol and nabiximols, are effective for cannabis withdrawal. Dronabinol may also reduce symptoms of opioid withdrawal. The cannabinoid receptor 1 (CB1) inverse agonist rimonabant showed promising effects for smoking cessation but also caused psychiatric side effects and currently lacks regulatory approval. Few trials have investigated cannabinergic medications for alcohol use disorder. Overall, the endocannabinoid system remains a promising target for addiction treatment. Development of novel medications such as fatty acid amide hydrolase inhibitors and neutral CB1 antagonists promises to extend the range of available interventions. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".


Zinc inhibits UV radiation-induced apoptosis but fails to prevent subsequent cell death.
Zinc ions inhibit the morphological and DNA fragmentation features of apoptosis in a number of systems. HL-60 cells pretreated with zinc and exposed to UV irradiation maintained their normal morphology for up to 8 h, whereas non-zinc-treated cells underwent extensive apoptosis. Zinc pretreatment also inhibited both single and double-stranded DNA fragmentation, which is characteristic of apoptosis. The most effective zinc concentration that blocked apoptosis over short incubation periods (up to 8 h) was also the most toxic over extended time periods (> or = 12 h). The mechanism of cell death at these longer time periods was akin to necrosis, but occurred in the absence of any DNA fragmentation. The effects of the nuclease inhibitor aurintricarboxylic acid (ATA) was also examined on UV-induced apoptosis in HL-60 cells. ATA had no toxic effects over the concentration range tested, but also failed to prevent DNA fragmentation in whole cells. Further analysis showed that it effectively inhibited DNA fragmentation in isolated nuclei.


Construction of the First High-Density Genetic Linkage Map and Analysis of Quantitative Trait Loci for Growth-Related Traits in Sinonovacula constricta.
The razor clam (Sinonovacula constricta) is an important aquaculture species, for which a high-density genetic linkage map would play an important role in marker-assisted selection (MAS). In this study, we constructed a high-density genetic map and detected quantitative trait loci (QTLs) for Sinonovacula constricta with an F1 cross population by using the specific locus amplified fragment sequencing (SLAF-seq) method. A total of 315,553 SLAF markers out of 467.71 Mreads were developed. The final linkage map was composed of 7516 SLAFs (156.60-fold in the parents and 20.80-fold in each F1 population on average). The total distance of the linkage map was 2383.85 cM, covering 19 linkage groups with an average inter-marker distance of 0.32 cM. The proportion of gaps less than 5.0 cM was on average 96.90%. A total of 16 suggestive QTLs for five growth-related traits (five QTLs for shell height, six QTLs for shell length, three QTLs for shell width, one QTL for total body weight, and one QTL for soft body weight) were identified. These QTLs were distributed on five linkage groups, and the regions showed overlapping on LG9 and LG13. In conclusion, the high-density genetic map and QTLs for S. constricta provide a valuable genetic resource and a basis for MAS.


Antipsychotic Use and Mortality in Persons with Alcohol-Related Dementia or Wernicke-Korsakoff Syndrome: A Nationwide Register Study in Finland.
Research on the use of psychotropic drugs in people with alcohol-related neurocognitive disorders is virtually nonexistent. We examined the prevalence of antipsychotic drug use and its effect on mortality among patients with Wernicke-Korsakoff syndrome (WKS) or alcohol-related dementia (ARD). In this nationwide register study, we collected data on the medication use and mortality of all persons aged ≥40 diagnosed with WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the prevalence of antipsychotic use within one year of diagnosis and the adjusted cumulative mortality of antipsychotic users versus non-users in relation to the age-, sex-, and calendar year-matched general population. Of the WKS and ARD patients, 35.9% and 38.5%, respectively, purchased one or more antipsychotic drugs in the year following diagnosis. The adjusted cumulative mortality of the antipsychotic users was significantly lower than that of non-users in both the WKS and ARD groups, where the adjusted hazard ratios (95% CI) were 0.85 (0.72-0.99) and 0.73 (0.65-0.81), respectively. WKS and ARD patients using antipsychotics were less likely to die of alcohol-related causes than antipsychotic non-users, but the difference was significant only in the ARD group. This population-based study shows that antipsychotic use is common in patients with WKS or ARD. In contrast to other dementia studies, our results indicate that the mortality of antipsychotic users is significantly lower than that of non-users. The lower mortality could be explained by decreased alcohol use and better healthcare coverage in antipsychotic users.


Pluripotent stem cell-derived neural stem cells: From basic research to applications.
Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed.


Neural-Network-Based Adaptive Tracking Control for Nonlinear Multiagent Systems: The Observer Case.
This article focuses on the neural-network (NN)-based adaptive tracking control issue for a class of high-order nonlinear multiagent systems both subjected to the immeasurable state variables and unknown external disturbance. Combining with the radial basis function NNs (RBF NNs), the composite disturbance observer and state observer for each follower are established, respectively. The purpose of this work is to develop NN-based adaptive tracking control schemes such that the output of each follower ultimately tracks that of the leader and all the signals of the closed-loop systems are semiglobally uniformly ultimately bounded by utilizing the backstepping technique. Furthermore, so as to cope with the sparsity of the control resources, the proposed method is extended to the event-triggered case and the adaptive event-triggered tracking control protocol is formulated for nonlinear multiagent systems. Finally, the numerical example is performed to verify the efficacy of the proposed approach.


Lectin binding sites on the plasma membranes of Orthoptera Tettigonioidea spermatodesms.
In many Vertebrate and invertebrate, the interaction mechanisms among gametes are based on a high affinity and specificity of recognition and link between specific saccharidic residues and receptors present on the surface of gametes. Literature data also suggest that Insects could use this strategy. In particular, Orthoptera Tettigoniidae spermatodesms and sperms undergo radical changes passing through the male to the female genital tracts that may be interpreted as well as a capacitation process. These changes could also concern the presence and distribution of surface glycoconjugates. Our study aims to highlight the presence and distribution of saccharide residues on the spermatozoa surface in five species of Orthoptera Tettigoniidae using a battery of lectins Fluorescein Isothiocyanate Conjugated and Gold Conjugated. The results of this investigation have shown that on the surface of the male gametes are present saccharide residues whose nature and distribution are species-specific, during their transfer to the female genital tract, they significantly undergo a change. These results let us hypothesize that also for this group of Insects, the glycoconjugates play a significant role in the process of interaction between gametes.


Progression of carotid stenosis detected by duplex ultrasonography predicts adverse outcomes in cardiovascular high-risk patients.
The progression of carotid stenosis reflects the activity of atherosclerotic disease and may indicate a risk for systemic atherothrombotic complications. We investigated whether progressive carotid stenosis determined by duplex ultrasonography predicts adverse outcomes in cardiovascular high-risk patients. We prospectively studied 1065 of 1268 consecutive patients initially asymptomatic with respect to carotid disease. Carotid ultrasound investigations at baseline and after a median of 7.5 months (range, 6 to 9 months) were performed to identify patients with progressive stenosis as defined by Doppler velocity criteria. Patients were then followed up clinically for a median of 3.2 years for the occurrence of major adverse cardiovascular events (composite MACEs: myocardial infarction, percutaneous coronary or peripheral interventions, coronary or vascular surgery, amputation, stroke, and all-cause mortality). We found progressive carotid stenosis in 93 patients (9%) by ultrasound and thereafter recorded 495 MACEs in 421 patients (40%) during clinical follow-up. Patients with progressive carotid stenosis had a significantly increased risk for cardiovascular events compared with patients with nonprogressive disease: adjusted hazard ratios and confidence intervals were 2.01 for composite MACEs (95% CI, 1.48 to 2.67, P<0.001), 2.38 for myocardial infarction (95% CI, 1.07 to 5.35, P=0.044), 1.59 for any coronary event (95% CI, 1.10 to 2.28, P=0.011), 2.00 for stroke (95% CI, 1.02 to 4.11, P=0.035), 2.42 for any peripheral vascular event (95% CI, 1.61 to 3.62, P<0.001), and 1.75 for cardiovascular death (95% CI, 1.03 to 2.97, P=0.039). Progression of carotid stenosis within a 6- to 9-month interval detected by duplex ultrasound predicts midterm clinical adverse events of atherosclerosis in high-risk patients affecting the coronary, cerebrovascular, and peripheral circulations.


Spectrum of mitochondrial genome instability and implication of mitochondrial haplogroups in Korean patients with acute myeloid leukemia.
Mitochondrial DNA (mtDNA) mutations may regulate the progression and chemosensitivity of leukemia. Few studies regarding mitochondrial aberrations and haplogroups in acute myeloid leukemia (AML) and their clinical impacts have been reported. Therefore, we focused on the mtDNA length heteroplasmies minisatellite instability (MSI), copy number alterations, and distribution of mitochondrial haplogroups in Korean patients with AML. This study investigated 74 adult patients with AML and 70 controls to evaluate mtDNA sequence alterations, MSI, mtDNA copy number, haplogroups, and their clinical implications. The hypervariable (HV) control regions (HV1 and HV2), tRNAleu1 gene, and cytochrome b gene of mtDNA were analyzed. Two mtDNA minisatellite markers, 16189 poly-C (16184CCCCCTCCCC16193, 5CT4C) and 303 poly-C (303CCCCCCCTCCCCC315, 7CT5C), were used to examine the mtDNA MSI. In AML, most mtDNA sequence variants were single nucleotide substitutions, but there were no significant differences compared to those in controls. The number of mtMSI patterns increased in AML. The mean mtDNA copy number of AML patients increased approximately 9-fold compared to that of controls (P<0.0001). Haplogroup D4 was found in AML with a higher frequency compared to that in controls (31.0% vs. 15.7%, P=0.046). None of the aforementioned factors showed significant impacts on the outcomes. AML cells disclosed more heterogeneous patterns with the mtMSI markers and had increased mtDNA copy numbers. These findings implicate mitochondrial genome instability in primary AML cells. Therefore, mtDNA haplogroup D4 might be associated with AML risk among Koreans.


Decellularized scaffold of cryopreserved rat kidney retains its recellularization potential.
The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ.


Shewanella infection of snake bites: a twelve-year retrospective study.
Infections of snake bite wounds by Shewanella are rarely discussed in the medical literature. This study aims to characterize the presentation and management of Shewanella infections in snake bite wounds. We retrospectively investigated the microbiology, clinical features, and outcomes of patients with Shewanella infected snake bite wounds admitted to a tertiary medical center from January 1998 to December 2009. Ten patients with Shewanella-infected snake bite wounds were identified. All of the snake bites were caused by cobras. The majority of patients had moderate to severe local envenomation and polymicrobial infections. Shewanella isolates are susceptible to ampicillin-sulbactam, piperacillin-tazobactam, third-and fourth-generation cephalosporins, carbapenems, aminoglycosides, and quinolones but are resistant to penicillin and cefazolin. All of the patients examined had favorable outcomes. It is recommended that Shewanella infection be considered in snake bite patients, especially when patients present with moderate to severe local envenomation.


Consensus on Initiation and Intensification of Premix Insulin in Type 2 Diabetes Management.
Premix insulin is the most commonly used insulin preparation in India. The first Indian premix guidelines were developed in 2009 and thereafter were updated in 2013. There is a need to revisit the Indian premix insulin guidelines, in view of emerging evidence and introduction of newer co-formulations. The present consensus has been developed to evaluate available premix formulations, examine existing evidence related to premix formulations, and evolve consensus statement of recommendations on the topic. A meeting of experts from across India was conducted at Chennai in July 2016. The expert committee evaluated each premix insulin regimen with reference to 1) Current recommendations by various guidelines, 2) Approved pack inserts and 3) Published scientific literature. The information was debated and discussed within the expert group committee, to arrive at seven consensus-based recommendations for initiation and intensification with premix insulin. Recommendations based on consensus on initiation and intensification of premix insulin in type 2 diabetes mellitus (T2DM) management were developed for the following situations. 1) Initiation of premix insulin co-formulation at diagnosis, 2) Initiation of once daily (OD) premix insulin/co-formulation, 3) Initiation of twice daily (BID) premix insulin/co-formulation 4) Intensification with BID and thrice daily (TID) premix insulin/co-formulation. Three recommendations pertained to the use of premix insulin in other forms of diabetes, or in specific situations: 5) Use of premix insulin in gestational diabetes mellitus 6) Use of premix insulin in type 1 Diabetes Mellitus (T1DM) 7) Premix insulin use during Ramadan. In the setting of high carbohydrate consumption in India, or in patients with predominant post prandial hyperglycemia, premix insulin/co-formulation can offer effective and convenient glycemic control. This paper will help healthcare practitioners initiate and intensify premix insulin effectively.


Refractive index of silicon at γ ray energies.
For x rays the real part of the refractive index, dominated by Rayleigh scattering, is negative and converges to zero for higher energies. For γ rays a positive component, related to Delbrück scattering, increases with energy and becomes dominating. The deflection of a monochromatic γ beam due to refraction was measured by placing a Si wedge into a flat double crystal spectrometer. Data were obtained in an energy range from 0.18 MeV to 2 MeV. The data are compared to theory, taking into account elastic and inelastic Delbrück scattering as well as recent results on the energy dependence of the pair creation cross section. Probably a new field of γ optics with many new applications opens up.


Simultaneous surgical treatment of aortic coarctation and aortic root disease: a report of case series.
Aortic coarctation (CoA) is a common congenital aortic disease, which is often accompanied by aortic root disease. This study aimed to explore the simultaneous surgical treatment of aortic root replacement and ascending-abdominal aortic bypass grafting for patients with CoA and aortic root disease. From June 2014 to December 2019, nine patients with CoA and aortic root disease underwent simultaneous surgical treatment involving ascending-abdominal aortic bypass grafting and aortic root replacement (Bentall operation in eight patients and Wheat's operation in one patient). The degree of constriction, cardiopulmonary bypass time, ascending aorta occlusion time, operation time, artificial vessel diameter, ventilator support time and blood loss were recorded and analyzed. The blood pressure data of the limbs were measured pre- and postoperatively. All patients were followed up for 24±7 months. The mean extracorporeal circulation time was 130±17 minutes. The mean duration of the aortic clamp occlusion was 85±14 minutes. The mean operation time was 6.2±1.9 hours. The mean blood loss during and after surgery was 1,958±849 mL. The mean ventilator support time after operation was 20.3±11.6 hours. There were no operative mortalities. The arterial pressure gradient in the upper and lower limbs significantly improved. Postoperative computer-enhanced transvenous angiograms showed that the grafts were open with fluent flow. None of the patients experienced gastrointestinal complications, and no adverse events were observed during the follow-up. Simultaneous surgical treatment with ascending-to-abdominal aorta bypass grafting and aortic root replacement is feasible for patients with CoA and aortic root disease.