Application of TDA AAS to Direct Mercury Determination in Postmortem Material in Forensic Toxicology Examinations.
Mercury is a heavy metal with high toxicity, the level of which depends on the form of the metal. One of the newer techniques for determining trace amounts of total mercury in various materials, including biological samples, is thermal decomposition, amalgamation and atomic absorption spectrometry (TDA AAS). The TDA AAS method was optimized and validated using a mercury analyzer (DMA-80). The limits of detection for mercury were 0.10 and 0.20 μg/L (nickel and quartz boats, respectively). The working range of the calibration curve was at least from 0.6 to 200 ng Hg/mL; the intra-day precision in samples (RSD)-in the range of: 1.66-6.86% (blood), 0.82-1.47% (urine) and 2.01-3.44% (hair); the inter-day precision (over 8 days): 2.51%, and 2.5% (blood spiked with 2.5 and 10 ng Hg, respectively), 5.10% and 3.16% (urine spiked with 2.0 and 6.0 ng Hg, respectively). The accuracy (as relative error, mean value) determined on the basis of the study of reference materials of blood (Seronorm Trace Elements Whole Blood L-1, L-2, L-3), urine (Seronorm Trace Elements Urine, Urine L-2), and hair (Human Hair NIES CRM No. 13) was: 2.00% (blood), 0.50% (urine) and 0.86% (hair); recovery of 2.5 ng Hg (blood): 93-97%. The method was used for the determination of mercury in 76 samples of various biological matrices, including samples of whole blood, urine, hair, bile and vitreous humor. Mercury concentrations in postmortem blood (n = 24) were in the range: 0.61-12.4 μg/L (median 3.02 μg/L); urine (n = 12): 0.16-2.19 μg/L (median 0.81 μg/L); hair (n = 14): 0.08-0.53 μg/g (median 0.22 μg/g); bile (n = 12): 1.15-7.11 μg/L (median 2.41 μg/L and vitreous humor (n = 13): 0.22-1.01 μg/L (median 0.47 μg/L). The method is suitable for the purposes of forensic toxicology analysis.


Enhancing Classification of liquid chromatography mass spectrometry data with Batch Effect Removal Neural Networks (BERNN).
Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful method for profiling complex biological samples. However, batch effects typically arise from differences in sample processing protocols, experimental conditions and data acquisition techniques, significantlyimpacting the interpretability of results. Correcting batch effects is crucial for the reproducibility of proteomics research, but current methods are not optimal for removal of batch effects without compressing the genuine biological variation under study. We propose a suite of Batch Effect Removal Neural Networks (BERNN) to remove batch effects in large LC-MS experiments, with the goal of maximizing sample classification performance between conditions. More importantly, these models must efficiently generalize in batches not seen during training. Comparison of batch effect correction methods across three diverse datasets demonstrated that BERNN models consistently showed the strongest sample classification performance. However, the model producing the greatest classification improvements did not always perform best in terms of batch effect removal. Finally, we show that overcorrection of batch effects resulted in the loss of some essential biological variability. These findings highlight the importance of balancing batch effect removal while preserving valuable biological diversity in large-scale LC-MS experiments.


Nanotopography alters nuclear protein expression, proliferation and differentiation of human mesenchymal stem/stromal cells.
Mesenchymal stem/stromal cells respond to physical cues present in their microenvironment such as substrate elasticity, geometry, or topography with respect to morphology, proliferation, and differentiation. Although studies have demonstrated the role of focal adhesions in topography-mediated changes of gene expression, information linking substrate topography to the nucleus remains scarce. Here we show by two-dimensional gel electrophoresis and western blotting that A-type lamins and retinoblastoma protein are downregulated in mesenchymal stem/stromal cells cultured on 350 nm gratings compared to planar substrates; these changes lead to a decrease in proliferation and changes in differentiation potential.


Testing a Military Family Stress Model.
The current study examines a military family stress model, evaluating associations between deployment-related stressors (i.e., deployment length/number, posttraumatic stress disorder [PTSD] symptoms) and parent, child, parenting, and dyadic adjustment among families in which a parent had previously deployed to Iraq or Afghanistan in the recent conflicts. Married families (N = 293) with at least one child between the ages of 4 and 12 were recruited from a Midwestern state. Service members were from the Reserve Component (National Guard or Reserves); fathers (N = 253) and/or mothers had deployed (N = 45) to the recent conflicts in the Middle East. Multiple-method (observations of parenting and couple interactions; questionnaires) and multiple informant measures were gathered online and in the homes of participants, from parents, children, and teachers. Findings demonstrated associations between mothers' and fathers' PTSD symptoms and a latent variable of child adjustment comprising teacher, parent, and child report. Mothers' but not fathers' PTSD symptoms were also associated with dyadic adjustment and parenting practices; parenting practices were in turn associated with child adjustment. The results are discussed in terms of their implications for military family stress research and interventions to support and strengthen parents and families after deployment.


Nurses' views about cancer.
To examine the impression of cancer the nurse in likely to convey to the public, 785 female hospital nurses were asked by means of postal questionnaire to give their opinion of the curability and treatment of cancer and the extent to which they regard the disease as alarming. Seven out of ten nurses disagreed with the statement that a patient who had had cancer can never really be cured. Characteristics leading to a better appreciation of the curability of cancer included training, increasing age and length of service and accurate knowledge of survival rates. Positive, personal experience of cancer was more important than professional experience of cancer nursing, suggesting it is the nature of the experience that is important. Young learners had a very poor understanding of the curability of cancer. The majority of nurses considered it at least sometimes true that treatment could do more harm than good and this conclusion is reached very early on in the nurse's career. Trained nurses had a better appreciation of palliative treatment. Nurses, like women generally, tend to regard cancer as the most alarming condition, although this view is less prevalent among trained or experienced nurses. While characterizing nurses' views about cancer as optimistic or pessimistic is not necessarily helpful, it is clear that the minority of nurses would find it difficult to present anything other than a negative view of cancer to their social network.


High prevalence of fibromyalgia among Israeli school teachers.
Fibromyalgia syndrome (FM), characterised by widespread pain and fatigue, has frequently been associated with stress in various models, including workplace related stress. In the current study we have evaluated the prevalence of FM symptoms among Israeli school teachers and have attempted to correlate such symptoms with work-related stress. Individuals, all currently employed as school teachers in Israel, were recruited to the study. Participants were asked to answer a questionnaire evaluating symptoms of FM, based on the current diagnostic criteria, which include the widespread pain index (WPI) and the symptom severity scale (SSS). Participants were further questioned regarding stressful experiences during their work and about post-traumatic symptoms as well as regarding work performance and motivation. 321 participants were recruited (79.4% female, 20.6 male). 30 individuals (9.3%) of the sample fulfilled current criteria for a diagnosis of FM, with a rate of 11.4% among females and 1.5% among males. While specific symptoms such as fatigue and irritable bowel symptoms were negatively correlated with work performance, no significant difference was found between teachers with or without fibromyalgia regarding work attendance and performance. FM symptoms were strongly correlated with work-related stress and were strongly correlated with post-traumatic stress disorder (PTSD) related symptoms. Motivation to work was significantly lower among teachers fulfilling FM criteria, but other performance-related parameters did not differ between teachers fulfilling or not fulfilling FM criteria. Fibromyalgia symptoms are highly prevalent among Israeli school teachers, and may be related to stress encountered in the classroom. These results are relevant both for physicians treating individuals involved in educational careers as well as for educators and decision-makers involved in planning and managing educational strategies.


Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus.
Medication nonadherence may reduce the effectiveness of therapies. To our knowledge, the association between medication nonadherence and mortality remains unexplored outside the context of clinical trials. A retrospective cohort study of 11 532 patients with diabetes mellitus in a managed care organization. Medication adherence was calculated as the proportion of days covered for filled prescriptions of oral hypoglycemics, antihypertensives, and statin medications. The primary outcomes of interest were all-cause hospitalization and all-cause mortality. Multivariable regression analyses were performed to assess the independent association between medication adherence and outcomes. Nonadherent patients (proportion of days covered, <80%; prevalence, 21.3%) were younger and had fewer comorbidities compared with adherent patients. During follow-up, nonadherent patients had higher glycosylated hemoglobin, systolic and diastolic blood pressure, and low-density lipoprotein cholesterol levels. In unadjusted analyses, nonadherent patients had higher all-cause hospitalization (23.2% vs 19.2%, P<.001) and higher all-cause mortality (5.9% vs 4.0%, P<.001). In multivariable analyses, medication nonadherence remained significantly associated with increased risks for all-cause hospitalization (odds ratio, 1.58; 95% confidence interval, 1.38-1.81; P<.001) and for all-cause mortality (odds ratio, 1.81; 95% confidence interval, 1.46-2.23; P<.001). The findings were consistent across patient subgroups and using different cutoffs for the proportion of days covered. Medication nonadherence is prevalent among patients with diabetes mellitus and is associated with adverse outcomes. Interventions are needed to increase medication adherence so that patients can realize the full benefit of prescribed therapies.


Monitoring of temephos (abate) application as a cyclopicide under the guineaworm eradication programme in India.
Temephos application in unsafe water sources at a dose of 1ppm, which started in 1986, is an important activity of the guineaworm eradication programme in India. During March 1989, monitoring of temephos application was carried out in six villages in each of the five guineaworm endemic districts: Kurnool (Andhra Pradesh), Gulbarga (Karnataka), Dhar (Madhya Pradesh), Thane (Maharashtra) and Jhalawar (Rajasthan), selected for the study. Out of 62 unsafe water sources targeted in the sampled villages for temephos treatment, 43 were treated during 1989 in the five districts (coverage 69.35 per cent). Out of these 43 treated sources 79.1 per cent were free of cyclops and the rest 20.93 per cent showed a variable cyclops count. 117 adult cyclops identified from these sources included Mesocyclops byalinus (82) and M. leuckarti (35). People's perception of utility of chemical treatment of water sources varied from negligibly low to moderate levels. Those areas which received timely application of temephos during the preceding year, al sharp decline in the number of cases in 1989 was observed. However, in those villages where no temephos was applied or where application was started as late as April or May, there was no impact on prevalence of the disease.


Value-Based Care in the Worldwide Battle Against Cancer.
Globally, an increasing and aging population is contributing to the prevalence of cancer. To be effective, cancer care needs to involve the coordination of multidisciplinary specialties, and also needs to be affordable, accessible, and capable of producing optimal patient outcomes. Porter and Teisberg (2006) have postulated that shifting current healthcare strategies from volume-based to patient-centric care redirects economic competition to providing treatments which promote the best patient outcomes while driving down costs. Therefore, the value in value-based healthcare (VBH) is defined as patient outcome per currency spent on providing care. Based on the experiences of healthcare organizations currently transitioning to the value-based system, this review details actionable guidelines to transition current cancer care practices to the value-based system in four main steps: by defining universal clinical and patient-reported measures, creating cancer-specific units that provide the full care cycle, establishing a data capture model to routinely determine the value of the care delivered, and continually improving treatment strategies through research. As healthcare providers in more developed countries move to value-based care, those located in less developed countries should also be assisted in their transition to relieve the cancer burden globally.


Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in the cholesterol metabolism and is synthesized by the liver. It interacts with the LDL-receptor to promote its degradation. The model of end-stage liver disease (MELD) score is a well-established tool to estimate the risk of mortality in patients with end-stage chronic liver disease. The study aims to assess the associations between PCSK9, hypocholesterinemia, liver synthesis, cholestasis, MELD score and mortality in patients with end-stage liver disease. Serum samples were obtained from 74 patients with severe liver disease. The study participants were aged between 23 and 70 y (mean: 55.8 y; 47 males [63.5%], 27 females [36.5%]). Samples were selected from those with a wide range of MELD scores (7 to 40). Patients that underwent liver transplantation (17 / 74) were censored at the time of transplantation for mortality analysis. PCSK9 values ranged from 31.47 ng/mL to 261.64 ng/mL. The median value was 106.39 ng/ml. PCSK9 was negatively correlated with markers of liver function and cholestasis (INR, bilirubin). Over a 90-d follow-up, 15 of 57 (26,3%) patients died within the 90-d follow-up without receiving liver transplantation. Thirteen of 31 (42%) patients with PCSK9 levels below the median died compared to 2/26 (8%) patients with higher PCSK9 levels (p = 0.006). In this cohort, there were no significant correlations between PCSK9, cholesterol, its precursors and several phytosterols. Low PCSK9 serum concentrations were associated with higher mortality in patients with end-stage liver disease. The mean PCSK9 levels in the study population were much lower than those found in normal or healthy populations. Further studies are required to acquire a more detailed understanding of the role of PCSK9 in liver-related mortality.


Association between BDNF rs6265 and obesity in the Boston Puerto Rican Health Study.
Brain-derived neurotrophic factor (BDNF) has been associated with regulation of body weight and appetite. The goal of this study was to examine the interactions of a functional variant (rs6265) in the BDNF gene with dietary intake for obesity traits in the Boston Puerto Rican Health Study. BDNF rs6265 was genotyped in 1147 Puerto Rican adults and examined for association with obesity-related traits. Men (n = 242) with the GG genotype had higher BMI (P = 0.009), waist circumference (P = 0.002), hip (P = 0.002), and weight (P = 0.03) than GA or AA carriers (n = 94). They had twice the risk of being overweight (BMI ≥ 25) relative to GA or AA carriers (OR = 2.08, CI = 1.02-4.23, and P = 0.043). Interactions between rs6265 and polyunsaturated fatty acids (PUFA) intake were associated with BMI, hip, and weight, and n-3 : n-6 PUFA ratio with waist circumference in men. In contrast, women (n = 595) with the GG genotype had significantly lower BMI (P = 0.009), hip (P = 0.029), and weight (P = 0.027) than GA or AA carriers (n = 216). Women with the GG genotype were 50% less likely to be overweight compared to GA or AA carriers (OR = 0.05, CI = 0.27-0.91, and P = 0.024). In summary, BDNF rs6265 is differentially associated with obesity risk by sex and interacts with PUFA intake influencing obesity traits in Boston Puerto Rican men.


Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts.
The influence of cell dose and human leukocyte antigen (HLA) match on double-unit cord blood (CB) engraftment is not established. Therefore, we analyzed the impact of cell dose and high-resolution HLA match on neutrophil engraftment in 84 double-unit CB transplant recipients. The 94% sustained engraftment rate was accounted for by 1 unit in nearly all patients. Higher CD3(+) cell doses (P = .04) and percentage of CD34(+) cell viability (P = .008) were associated with unit dominance. After myeloablative conditioning, higher dominant unit total nucleated cell (TNC), CD34(+) cell, and colony-forming unit doses were associated with higher sustained engraftment and faster neutrophil recovery (P = .07, P = .0008, and P < .0001, respectively). Total infused TNC (P = .0007) and CD3(+) cell doses (P = .001) also significantly influenced engraftment. At high-resolution extensive donor-recipient HLA disparity was frequent, but had no influence on engraftment (P = .66), or unit dominance (P = .13). Although the unit-unit HLA match also did not affect sustained engraftment (P = 1.0), recipients of units closely (7-10 to 10-10) HLA-matched to each other were more likely to demonstrate initial engraftment of both units (P < .0001). Our findings have important implications for unit selection and provide further insight into double-unit biology.


Active tuberculosis in a healthcare worker: are you ready?
We describe a healthcare worker with a previously positive tuberculin skin test result who developed active tuberculosis. An investigation revealed 280 potential contacts, 3 of whom had positive tuberculin skin test results. Our experience demonstrates the potential benefits of therapy for latent tuberculosis infection as a component of a tuberculosis-control program.


Fish odor syndrome (trimethylaminuria) supporting the possible FMO3 down expression in childhood: a case report.
Trimethylaminuria is a rare inherited disorder due to decreased metabolism of dietary-derived trimethylamine by flavin-containing monooxygenase 3. Several single nucleotide polymorphisms of the flavin-containing monooxygenase 3 gene have been described and result in an enzyme with decreased or abolished functional activity for trimethylamine N-oxygenation thus leading to trimethylaminuria. Here we investigated an Italian family in which the proband was a 7-year-old girl with suspected trimethylaminuria, by flavin-containing monooxygenase 3 gene direct sequencing and urinary determination of trimethylamine and trimethylamine N-oxide. Genetic analysis found that, as with her parents and one of her two brothers, the proband carried three polymorphisms: c.472 G>A p. E158K (rs 2266782) in exon 4, c.627+10 C>G (IVS5+10G>C) (rs 2066534) and c.485-21 G>A (IVS4-22G>A) (rs 1920149) in intronic regions. Despite the same genotypic condition only the girl had symptoms attributable to the trimethylaminuria. The suspicion is that she has transient childhood trimethylaminuria. Therefore, we bring attention to the importance of genetic testing and eventual determination of urinary trimethylamine and trimethylamine N-oxide as instruments to offer to clinicians in the management of these pediatric patients.


Numerical simulation of leaflet flexure in bioprosthetic valves mounted on rigid and expansile stents.
Recent studies suggest that flexural stresses induced during the opening phase may be responsible for much of the mechanical failures of bioprosthetic heart valves. Sharp leaflet bending is promoted by the mounting of valves on rigid stents that do not mimic the systolic expansion of the natural aortic root. We, therefore, hypothesized that flexural stresses could be significantly reduced by incorporating a flexible or expansile supporting stent into the valve design. Using our own non-linear finite element code (INDAP) and the pre- and post-processor modules of a commercial finite element package (PATRAN), we simulated the opening and closing behaviour a trileaflet bovine pericardial valve. The leaflets of this valve were assumed to be of uniform thickness, with a non-linear elastic behaviour adapted from experimentally obtained bending stiffness data. Our simulations have shown that during maximal systolic valve opening, sharp curvatures are induced in the leaflets near their commissural attachment to the supporting stent. These areas of sharp flexure experience compressive stresses of similar magnitude to the tensile stresses induced in the leaflets during valve closure. By incorporating a stent with posts that pivot about their base, such that a 10% expansion at the commissures is realized, we were able to reduce the compressive commissural stressing from 250 to 150 kPa. This was a reduction of 40%. Conversely, a simple pliable stent with stent posts that deflect inward and outward under load did not achieve a significant reduction of compressive stresses. This numerical analysis, therefore, supports the theory that (i) high flexural and compressive stresses exist at sites of sharp leaflet bending and may promote bioprosthetic valve failure, and (ii) that proper design of the supporting stent can significantly reduce such flexural stresses.


alpha-Tocopherol intake and plasma concentration of Hispanic and non-Hispanic white elders is associated with dietary intake pattern.
alpha-Tocopherol from foods has been associated with protection against several chronic diseases and maintenance of immune function. However, most people do not meet current recommendations for intake. We examined alpha-tocopherol intake and plasma concentration in a representative sample of Puerto Rican and Dominican older adults (n = 447) and in neighborhood-matched non-Hispanic whites (n = 155). A validated food frequency questionnaire was used to assess dietary intake. Mean dietary intakes of alpha-tocopherol were 6 mg in both ethnicities. Only 4.7% of women and 7.9% of men met the estimated average requirement (12 mg/d) for vitamin E from food alone. Top sources of alpha-tocopherol for Hispanics included oils and milk, and for non-Hispanic whites they were ready-to-eat breakfast cereal and sweet baked products. Mean plasma alpha-tocopherol concentrations were 24.5 micromol/L for Hispanics and 25.8 micromol/L for non-Hispanic whites (P > 0.05). Plasma alpha-tocopherol was positively associated with alpha-tocopherol intake (P = 0.003), and significance remained after adjusting covariates and after exclusion of supplement users (P for trend = 0.008). We identified the following 5 dietary patterns by cluster analysis: 1) fruit and breakfast cereal, 2) starchy vegetables, 3) rice, 4) milk and milk products, and 5) sweets. Those following the sweets pattern had the lowest plasma alpha-tocopherol relative to those following the fruit and breakfast cereal or milk patterns (P < 0.05 for all), although they had similar intakes. A large proportion of these elders (>90%) have inadequate intake of alpha-tocopherol, and plasma concentrations were associated with intake patterns.


Gender disparities in common sense models of illness among myocardial infarction victims.
Symptom attributions were contrasted between male and female myocardial infarction victims (N = 157) who were comparable on age, cardiac risk status, medical history, symptom presentation, and other variables. Women were less likely than men to attribute their prehospital symptoms to cardiac causes. In the context of hearing symptom attributions or advice from support persons, women were less likely than men to report receiving a cardiac attribution or advice to seek medical attention. Results have implications for how victim gender influences the lay interpretation of cardiac symptoms.


Histiocytic lesions and proliferations in the lung.
Pulmonary lesions encountered by the pathologist in which histiocytes are the dominant finding histologically are reviewed. Lesions discussed include neoplasms of histiocytes and nonneoplastic processes. The nonneoplastic processes are divided into those that present as nodular histiocytic proliferations in the lung, those that present as diffuse proliferations of histiocytes in the lung, and those with a mixed pattern. Entities discussed include pulmonary Langerhans' cell histiocytosis, pneumonoconioses, infections, diffuse panbronchiolitis, crystal storing histiocytosis, respiratory bronchiolitis, alveolar hemorrhage, eosinophilic pneumonia, obstructive pneumonia, exogenous lipoid pneumonia, some drug reactions, and some metabolic/storage diseases. Entities of uncertain histogenesis, including Rosai-Dorfman disease and Erdheim-Chester disease, are also discussed. Qualitative features of the histiocytes are addressed, including the presence of foreign dust, hemosiderin, foamy change, and histiocytes showing features of Langerhans' cells.


Expressive suppression tendencies, projection bias in memory of negative emotions, and well-being.
The current research extends prior research linking negative emotions and emotion regulation tendencies to memory by investigating whether (a) naturally occurring negative emotions during routine weekly life are associated with more negatively biased memories of prior emotional experiences-a bias called projection; (b) tendencies to regulate emotions via expressive suppression are associated with greater projection bias in memory of negative emotions; and (c) greater projection bias in memory is associated with poorer future well-being. Participants (N = 308) completed a questionnaire assessing their general tendencies to engage in expressive suppression. Then, every week for 7 weeks, participants reported on (a) the negative emotions they experienced across the current week (e.g., "This week, I felt 'sad'"), (b) their memories of the negative emotions they experienced the prior week (e.g., "Last week, I felt 'sad'"), and (c) their well-being. First, participants demonstrated significant projection bias in memory: Greater negative emotions in a given week were associated with remembering emotions in the prior week more negatively than those prior emotions were originally reported. Second, projection bias in memory of negative emotions was greater for individuals who reported greater tendencies to regulate emotions via expressive suppression. Third, greater projection bias in memory of negative emotions was associated with reductions in well-being across weeks. These 3 novel findings indicate that (a) current negative emotions bias memory of past emotions, (b) this memory bias is magnified for people who habitually use expressive suppression to regulate emotions, and (c) this memory bias may undermine well-being over time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Direct S0→T Excitation of a Conjugated Polymer Repeat Unit: Unusual Spin-Forbidden Transitions Probed by Time-Resolved Electron Paramagnetic Resonance Spectroscopy.
A detailed understanding of the electronic structure of semiconducting polymers and their building blocks is essential to develop efficient materials for organic electronics. (Time-resolved) electron paramagnetic resonance (EPR) is particularly suited to address these questions, allowing one to directly detect paramagnetic states and to reveal their spin-multiplicity, besides its clearly superior resolution compared to optical methods. We present here evidence for a direct S0→T optical excitation of distinct triplet states in the repeat unit of a conjugated polymer used in organic photovoltaics. These states differ in their electronic structure from those populated via intersystem crossing from excited singlet states. This is an additional and so far unconsidered route to triplet states with potentially high impact on efficiency of organic electronic devices.


Parallel synthesis and in vitro activity of novel anthranilic hydroxamate-based inhibitors of the prostaglandin H2 synthase peroxidase activity.
Currently available non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin are directed at the cyclooxygenase (COX) site, but not the peroxidase (POX) activity of prostaglandin H2 synthase (PGHS). They are thus unable to inhibit the free-radical induced tissue injury associated with PGHS peroxidase activity, which can occur independently of the COX site. A lead compound, anthranilic hydroxamic acid (AHA) was found to have significant PGHS-POX inhibitory activity (IC50= 72 microM). To define the critical parameters for PGHS-POX inhibition, we investigated 29 AHA derivatives, synthesised from their acid precursors, using solid phase synthesis. In vitro analysis demonstrated a ten-fold improvement in inhibition with 3,5-diiodoanthranilic hydroxamic acid (IC50= 7 microM).


Controlled release minocycline-lipid-complex extrudates for the therapy of periodontitis with enhanced flexibility.
We describe the development of flexible minocycline-lipid-complex extrudates with optimized mechanical and drug release properties. These extrudates contain a minocycline - magnesium stearate chelate complex with a higher stability in aqueous media, which has now been incorporated in a PEG-PLGA (polyethylene glycol - poly(lactic-co-glycolic acid)) matrix. PEG 1500 has been utilized in different concentrations to serve as plasticizer. The novel formulations have been characterized by texture analysis, X-Ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Extrudates with a reduced diameter of 300 µm (previously 600 µm) were introduced, and a more sensitive quantification method with a tandem-mass spectrometry detector was developed. From all tested formulations, the extrudates consisting of Expansorb DLG 50 - 6P (PEG-PLGA, molar weight 30-60 kDa) paired with 10% PEG 1500 emerged as best formulation. These extrudates feature a drug content of 11.5% and a controlled release over at least 42 days. The release profile is without a lag time and shows initially a slightly higher release rate, which is desired. Compared to previous developments, the extrudates now offer a high flexibility combined with a large mechanical resilience, which will ease the handling and administration.


Quantification of greenhouse gas emissions from a biological waste treatment facility.
Whole-site emissions of methane and nitrous oxide, from a combined dry anaerobic digestion and composting facility treating biowaste, were quantified using a tracer dispersion technique that combines a controlled tracer gas release from the treatment facility with time-resolved concentration measurements downwind of the facility. Emission measurements were conducted over a period of three days, and in total, 80 plume traverses were obtained. On-site screening showed that important processes resulting in methane emissions were aerobic composting reactors, anaerobic digester reactors, composting windrows and the site's biofilter. Average whole-site methane emissions measured during the three days were 27.5±7.4, 28.5±6.1 and 30.1±11.4kg CH4 h-1, respectively. Turning the windrows resulted in an increase in methane emission from about 26.3-35.9kg CH4 h-1. Lower emissions (21.5kg CH4 h-1) were measured after work hours ended, in comparison to emissions measured during the facility's opening hours (30.2kg CH4 h-1). Nitrous oxide emission was too small for a downwind quantification. Direct on-site measurements, however, suggested that the main part of the emitted nitrous oxide came from the biofilter (about 1.4kg N2O h-1). Whole-site emissions were compared to emissions previously measured at different point sources on-site. Whole-site fugitive emissions were three to eight times higher than the sum of emissions measured at on-site sources. The magnitude of the emissions had a significant influence on the overall environmental impact of the treatment facility, assessed by consequential life cycle assessment. Including the higher whole-site fugitive emissions led to an increase in global warming potential, from a saving of 97kgCO2-eq.tonne-1 of treated waste (wet weight) to a loading of 71kg CO2-eq. tonne-1, ultimately flipping the environmental profile of the treatment facility.


Ring-opening iodo- and bromosilation of lactones for the formation of silyl haloalkanoates.
Ring-opening halosilation of lactones with two types of reagents, Et(3)SiH/MeI(PdCl(2)) (1a) and Et(3)SiH/AllylBr(PdCl(2)) (1b), was studied. Cyclic esters such as gamma-butyrolactones, delta-valerolactone, and 6-hexanolide reacted with 1 equiv of 1a,b to give triethylsilyl omega-iodo- and omega-bromoalkanoates in good yields. Reaction of an acyclic ester, methyl benzoate, with 1a afforded triethylsilyl benzoate. O-Silyl-protected amino acids could be obtained by amination of the halosilation products, triethylsilyl omega-bromoalkanoates.


Mucosal cryobiopsies: a new method for studying airway pathology in asthma.
In vivo studies of airway pathology in obstructive lung disease are limited by poor quality of specimens obtained with forceps. Obtainment of cryobiopsies has increased diagnostic yield in cancer and interstitial lung disease but has not been used in patients with asthma. In a recent pilot study, we found mucosal cryobiopsies to be larger and more intact than conventional forceps biopsies. The aim of the present study was to compare quality and safety of mucosal cryobiopsies versus conventional forceps biopsies in patients with asthma. Endobronchial biopsies were obtained with forceps and cryoprobe from patients with asthma not currently treated with inhaled steroids and evaluated histologically. A total of 240 cryobiopsies and 288 forceps biopsies were obtained from 48 patients. Bleeding from the biopsy site was common but self-limiting. No major complications related to the procedure were seen. Cryobiopsy cross areas were four times larger compared with forceps. Stretches of intact epithelium were detected in all cryobiopsies compared to 33% in forceps biopsies. Further, the length of intact epithelium was on average four times longer in the cryobiopsies. Importantly, there was a good preservation of both antigens and mRNA in the cryobiopsies ensuring a suitability and robustness for immunohistochemistry and in situ hybridisation. Obtainment of mucosal cryobiopsies in patients with asthma is safe and yields biopsies that are significantly larger and morphologically better preserved compared with traditional forceps biopsies. The cryotechnique thus seems to be a promising tool for future in vivo studies of airway pathology.


Community-based surveillance of cardiovascular risk factors in Geneva: methods, resulting distributions, and comparisons with other populations.
This paper presents the results of an ongoing community-based surveillance program of cardiovascular risk factors in Geneva, Switzerland, using percentiles with their associated 95% confidence intervals and compares the Genevan results with published data from international surveys reporting percentiles. A random survey of adults ages 35 to 74 years was conducted from 1993 to 1994. Confidence intervals for percentiles based on parametric and non-parametric methods are given. The distribution of total cholesterol was shifted upward with increasing age. The median reached a maximum at 55-64 years among men (5.7 mmol/L) and at 65-74 years among women (5.9 mmol/L), and remained relatively stable thereafter. In both genders, systolic and, less so, diastolic blood pressure increased progressively with advancing age. The median daily energy intake among men declined from 2,390 kcal at age 35-44 years to 2,169 kcal at age 65-74 years, while among women it remained stable at about 1,900 kcal. In both males and females, the relative intake of saturated fat was stable throughout life (14 to 13%). The median body mass index (BMI) was about 25 kg/m2 across all age groups among men, but increased with age among women, with a peak of 23.6 kg/m2 occurring at ages 65-74 years. Compared with U.S. and western European surveys, Genevan men and women had lower total plasma cholesterol and Genevan women tended to have lower BMIs. Percentiles with their associated precision appear particularly well suited for international comparison of surveillance data. They could be used in the future to monitor shifts in distributions resulting from mass prevention strategies.


Differential staining of apoptotic nuclei in living cells: application to macronuclear elimination in Tetrahymena.
Acridine orange (AO) has been used as a vital fluorescent stain to identify apoptotic cells in Drosophila, but little is known about what structures are stained. We explored the specificity of AO staining while studying nuclear apoptosis in Tetrahymena. Using AO alone or together with the vital nuclear stain Hoechst 33342 (HO), we find that lysosomes are generally clustered around the degenerating nucleus and that such nuclei are stained an orange-red color, like lysosomes. Significantly, the combined dyes, more so than with AO alone, distinguish between apoptotic and normal (or necrotic) nuclei by a clear color difference. Moreover, these dyes differentially stain apoptotic and normal nuclei in avian chondrocytes. The differential staining results are nullified in fixed cells or in cytoskeletal preparations treated with RNAse. Similarly, lysosomotrophic agents eliminate the differential staining. Our results are consistent with acidification of the apoptotic nucleus, possibly by fusion with lysosomes. However, even under basic conditions, the macronucleus condenses and is eliminated, suggesting that, if the nucleus is becoming acidified, acidification by itself is not essential for nuclear elimination. The differential staining procedure may provide a useful method for specifically identifying apoptotic cells and separating them for further analysis.


Classical Swine Fever Virus Infection and Its NS4A Protein Expression Induce IL-8 Production through MAVS Signaling Pathway in Swine Umbilical Vein Endothelial Cells.
Classical swine fever virus (CSFV) infection causes a severe disease of pigs, which is characterized by hemorrhage, disseminated intravascular coagulation, and leucopenia. IL-8, a main chemokine and activator of neutrophils, regulates the permeability of endothelium, which may be related to the hemorrhage upon CSFV infection. Until now, the molecular mechanisms of IL-8 regulation during CSFV infection are poorly defined. Here, we showed that CSFV infection induced IL-8 production and the upregulation of IL-8 required virus replication in swine umbilical vein endothelial cells (SUVECs). Additionally, MAVS expression was increased and was required for IL-8 production upon CSFV infection. Moreover, ROS was involved in CSFV-induced IL-8 production. Subsequent studies demonstrated that ROS was involved in MAVS-induced IL-8 production and CSFV induced ROS production through MAVS pathway. These results indicate that CSFV induces IL-8 production through MAVS pathway and production of ROS. The role of NS4A in the pathogenesis of CSFV is not well-understood. In this study, we further demonstrated that CSFV NS4A induced IL-8 production through enhancing MAVS pathway and promoted CSFV replication. In addition, we discovered that CSFV NS4A was localized in the cell nucleus and cytoplasm, including endoplasmic reticulum (ER) and mitochondria. Taken together, these results provide insights into the mechanisms of IL-8 regulation and NS4A functions during CSFV infection.


[Non-opioid analgesics and co-analgesics in therapy of chronic pain].
Efficacy and side effects of non-opioid-analgesics were analysed in a standardized review of placebo-controlled or double-blind studies. In rheumatoid arthritis, ibuprofen showed the best ratio of effectiveness and side-effects. Naproxen, diclofenac and meloxicam may serve as alternatives. In osteoarthritis, naproxen seems to be superior to diflunisal, meloxicam and diclofenac. In cancer pain, ibuprofen is the treatment of the first choice followed by naproxen and diclofenac. No sufficient data on non-opioids in neuropathic pain were available. The dose administered in the management of chronic pain should be low in order to reduce the incidence of side-effects. The frequency of side-effect-related discontinuation of chronic pain medication was calculated as follows: ibuprofen 3.8%, aspirin 4.7%, piroxicam 4.8%, naproxen 7.4%, meloxicam 13.0% and diclofenac 17.8%. Since differences in efficacy were not clinically relevant, the indication for a special non-opioid-analgesic medication should focus on the prevention of side-effects.


From the bench to the bedside: dipeptidyl peptidase IV inhibitors, a new class of oral antihyperglycemic agents.
New therapeutic agents are needed to combat the ever-increasing prevalence of diabetes. The two incretins glucagon-like peptide-1 (7-36) (GLP-1(7-36)) amide and glucose-dependent insulinotropic peptide (GIP) are released from the small intestine in response to the ingestion of nutrients and regulate glucose homeostasis in a glucose-dependent fashion; however, the action of both incretins is terminated by the rapid N-terminal cleavage of two amino acid residues of GLP-1 and GIP by dipeptidyl peptidase-IV (DPP-IV). The preservation of active GLP-1 and GIP by inhibiting DPP-IV activity is an attractive strategy for the treatment of diabetes in patients who exhibit a reduced incretin response. This strategy has resulted in the launch of two DPP-IV inhibitor drugs; sitagliptin in North America, several European territories, and various other countries, and vildagliptin in the EU as well as various countries. This article provides an overview of the recent advances in and the lessons learned from the design of potent and selective small-molecule inhibitors of DPP-IV for the treatment of type 2 diabetes.


Characterization of a new genotype of avian bornavirus from wild ducks.
Avian bornaviruses (ABV) are a recently described group of intranuclear negative-stranded RNA viruses (Order Mononegavirales, Family Bornaviridae). At least 13 different ABV genotypes have been described. One genotype, the Canada goose genotype (ABV-CG), has been isolated from geese and swans and is widely distributed across North America. We have isolated and characterized a previously undescribed genotype of avian bornavirus from the brains of wild ducks. This new genotype, provisionally designated ABV genotype MALL, was detected in 12 of 83 mallards, and 1 of 8 wood ducks collected at a single location in central Oklahoma. The virus was cultured on primary duck embryo fibroblasts, fragments were cloned, and its genome sequence of 8904 nucleotides determined. This new genotype has 72% nucleotide identity and 83% amino acid identity with the ABV-CG genotype previously shown to be present in geese and swans. Histologic and immunohistochemical examination of the brains and eyes of four positive ducks indicated the presence of virus-infected neurons and glia in their cerebrums and retinas in the absence of inflammation. More than one genotype of ABV is circulating in North American waterfowl. While the infected ducks were not observed to be suffering from overt disease, based on the immunohistochemistry, we speculate that they may have suffered some visual impairment.


Physical stability of albinterferon-α(2b) in aqueous solution: effects of conformational stability and colloidal stability on aggregation.
Controlling aggregation in protein therapeutics is a significant challenge. In this study, the aggregation behavior of albinterferon-α(2b) , a genetic fusion protein combining human serum albumin and α-interferon, was examined as a function of solution conditions. The stability was monitored during agitation and during storage at elevated temperature, where the extent of aggregation was determined using size-exclusion chromatography. The osmotic second virial coefficient and the free energy of unfolding were measured for each sample. This study demonstrates that both increasing conformational stability and maximizing colloidal stability help to maintain the physical stability of albinterferon-α(2b).


Independent dose per monitor unit review of eight U.S.A. proton treatment facilities.
Compare the dose per monitor unit at different proton treatment facilities using three different dosimetry methods. Measurements of dose per monitor unit were performed by a single group at eight facilities using 11 test beams and up to six different clinical portal treatment sites. These measurements were compared to the facility reported dose per monitor unit values. Agreement between the measured and reported doses was similar using any of the three dosimetry methods. Use of the ICRU 59 ND,w based method gave results approximately 3% higher than both the ICRU 59 NX and ICRU 78 (TRS-398) ND,w based methods. Any single dosimetry method could be used for multi-institution trials with similar conformity between facilities. A multi-institutional trial could support facilities using both the ICRU 59 NX based and ICRU 78 (TRS-398) ND,w based methods but use of the ICRU 59 ND,w based method should not be allowed simultaneously with the other two until the difference is resolved.


Formulation and pharmacokinetics of thermosensitive stealth® liposomes encapsulating 5-Fluorouracil.
We optimize the encapsulation and investigate the pharmacokinetics of 5-Fluorouracil (5-FU) delivered by thermosensitive stealth(®) liposomes (TSLs) designed to trigger drug release upon hyperthermia using focused ultrasound (FUS). 5-FU was encapsulated into liposomes made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 either as a free molecule or complexed with copper-polyethylenimine. Heat-triggered drug release was evaluated using either a water bath or FUS. Formulation cytotoxicity was assessed on HT-29 cell line by MTS assay. Pharmacokinetics and biodistribution of 5-FU were evaluated in HT-29-tumor bearing mice. 5-FU was easily encapsulated using the lipid hydration method (encapsulation efficacy of 13%) but poorly retained upon dilution. 5-FU complexation with copper-polyethylenimine improved 5-FU retention into liposomes and allowed to obtain an encapsulation efficacy of 37%. At 42°C, heat-triggered 5-FU release from TSLs was 63% using a water bath and 68% using FUS, within 10 min, whereas it remained below 20% for the non-thermosensitive formulation. The MTS assay revealed that formulation toxicity arose from 5-FU and not from the excipients. In addition, 5-FU complex encapsulation into TSLs induces a reduction of the IC50 from 115 down to 49 μM. Pharmacokinetics reveals a longer circulation of encapsulated 5-FU and a more important body exposure, although tumor passive targeting is not significantly higher than free 5-FU. Complexation of 5-FU with copper-polyethylenimine appears an interesting strategy to improve 5-FU retention into TSLs in vitro and in vivo. TSLs allow heat-triggered release of the drug within 10 min at 42°C, a reasonable time for future in vivo experiments.


A mouse model of conditional lipodystrophy.
Lipodystrophies are syndromes of adipose tissue degeneration associated with severe defects in lipid and glucose homeostasis. We report here the generation and analysis of Pparg(ldi), a targeted allele that confers conditional dominant lipodystrophy in mice. The Pparg(ldi) allele was generated by insertion of the Tet activator (tTA) and a tTA-regulated Flag-Pparg1 transgene into the Pparg gene. Unexpectedly, tTA elicits mild lipodystrophy, insulin resistance, and dyslipidemia, and the Flag-PPARgamma1 transgene surprisingly exacerbates these traits. Doxycycline can both completely prevent and reverse these phenotypes, providing a mouse model of inducible lipodystrophy. Embryonic fibroblasts from either Pparg(ldi/+) or the phenotypically similar aP2-nSrebp1c (Sr) transgenic mice undergo robust adipogenesis, suggesting that neither strain develops lipodystrophy because of defective adipocyte differentiation. In addition, Pparg(ldi/+) adipose tissue shares extensive gene expression aberrations with that of Sr mice, authenticating the phenotype at the molecular level and revealing a common expression signature of lipodystrophic fat. Thus, the Pparg(ldi/+) mouse provides a conditional animal model for studying lipodystrophy and its associated physiology and gene expression.


Lifetime of evaporating two-dimensional sessile droplets.
Prevailing diffusion-limited analyses of evaporating sessile droplets are facilitated by a quasisteady model for the evolution of vapor concentration in space and time. When attempting to employ that model in two dimensions, however, one encounters an impasse: the logarithmic growth of concentration at large distances, associated with the Green's function of Laplace's equation, is incompatible with the need to approach an equilibrium concentration at infinity. Observing that the quasisteady description breaks down at large distances, the diffusion problem is resolved using matched asymptotic expansions. Thus the vapor domain is conceptually decomposed into two asymptotic regions: one at the scale of the drop, where vapor transport is indeed quasisteady, and one at a remote scale, where the drop appears as a point singularity and transport is genuinely unsteady. The requirement of asymptotic matching between the respective regions furnishes a self-consistent description of the time-evolving evaporation process. Its solution provides the droplet lifetime as a universal function of a single physical parameter. Our scheme avoids the use of a remote artificial boundary, which introduces a nonremovable dependence upon a nonphysical parameter.


Short-term outcomes of reconstruction subsequent to intercalary resection of femoral diaphyseal metastatic tumor with pathological fracture: Comparison between segmental allograft and intercalary prosthesis.
Reconstruction of bone defects following femoral diaphyseal tumor resection is challenging. Segmental allograft (SA) and intercalary prosthesis (IP) are the most common reconstruction methods for femoral diaphyseal metastatic tumors with pathological fracture. However, whether the complications and functional outcomes differ between SA and IP remains unclear. To compare the clinical outcomes and complications for patients treated with SA reconstruction or IP replacement for femoral shaft tumors, 34 patients who had undergone intercalary resection for metastatic tumor with pathological fracture in the femoral diaphysis were evaluated. Of these, 18 had received SA and 16 IP. There were 11 males, and 24 females, with a mean age of 64.5±11.3 years. The most common sites of primary metastases were lung (26.5%), breast (17.6%) and liver (14.7%). The visual analog scale (VAS), implant-related complications and the Musculoskeletal Tumor Society (MSTS) scores for each patient were collected. The follow-up period for patients ranged from 2 to 27 months. At the most recent follow-up, 28 patients had succumbed to mortality, with a mean survival time of 6.9±3.7 months for the IP group and 7.4±3.0 months for the SA group. Patients with IP had a significantly shorter time to full weight bearing and hospitalization time than those who received SA (P=0.003 and P=0.002, respectively). The rates of overall complications and implant-related complications were significantly lower for IP as compared with SA (18.8 vs. 66.7%, P=0.007; 12.5 vs. 55.6%, P=0.013). The reoperation rate of the SA group was higher than that of the IP group (38.9 vs. 12.5%), however the difference between the two groups was statistically insignificant (P=0.125). MSTS scores were significantly higher for the IP group as compared with the SA group at one month after surgery (IP, 26.7±1.6 vs. SA, 20.3±1.5; P<0.05), without a significant difference at the final follow-up. There were no statistically significant differences in age, sex, length of resection, follow-up time, operative time or blood loss between the two groups. In summary, IP reconstruction may provide improved early functional outcomes and fewer early complications, particularly for patients with a shorter life expectancy due to femoral metastatic tumors with pathological fracture.


Analysis of the opinions of individuals on the COVID-19 vaccination on social media.
The COVID-19 pandemic continues to threaten public health globally. To develop effective interventions and campaigns to raise vaccination rates, policy makers need to understand people's attitudes towards vaccination. We examine the perspectives of people in India, the United States, Canada, and the United Kingdom on the administration of different COVID-19 vaccines. We analyse how public opinion and emotional tendencies regarding the COVID-19 vaccines relate to popular issues on social media. We employ machine learning algorithms to forecast thoughts based on the social media posts. The prevailing emotional tendency indicates that individuals have faith in immunisation. However, there is a likelihood that significant statements or events on a national, international, or political scale influence public perception of vaccinations. We show how public health officials can track public attitudes and opinions towards vaccine-related information in a geo-aware manner, respond to the sceptics, and increase the level of vaccine trust in a particular region or community.


Cognitive Performance during a 24-Hour Cold Exposure Survival Simulation.
Survivor of a ship ground in polar regions may have to wait more than five days before being rescued. Therefore, the purpose of this study was to explore cognitive performance during prolonged cold exposure. Core temperature (T c) and cognitive test battery (CTB) performance data were collected from eight participants during 24 hours of cold exposure (7.5°C ambient air temperature). Participants (recruited from those who have regular occupational exposure to cold) were instructed that they could freely engage in minimal exercise that was perceived to maintaining a tolerable level of thermal comfort. Despite the active engagement, test conditions were sufficient to significantly decrease T c after exposure and to eliminate the typical 0.5-1.0°C circadian rise and drop in core temperature throughout a 24 h cycle. Results showed minimal changes in CTB performance regardless of exposure time. Based on the results, it is recommended that survivors who are waiting for rescue should be encouraged to engage in mild physical activity, which could have the benefit of maintaining metabolic heat production, improve motivation, and act as a distractor from cold discomfort. This recommendation should be taken into consideration during future research and when considering guidelines for mandatory survival equipment regarding cognitive performance.


Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance.
To measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing. Beat-to-beat arterial pressure was monitored by Finapres. Orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing. Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria of chronic fatigue without orthostatic intolerance.


[Recurrent collapse of one lung (author's transl)].
A case of recurrent collapse of one lung is reported. It developed within 90 minutes after reexpansion of a completely collapsed lung induced by pneumothorax. There was no demonstrable cause for the recurrence of the atelectasis. Treatment was by means of a bird respirator (ventilation via a mouthpiece) with respiratory resistance. Factors possibly responsible for the secondary atelectasis are discussed.


[Effect of sevoflurane postconditioning on spinal cord ischemia reperfusion injury via the release of oxygen free radicals in rabbits].
To investigate whether postconditioning with sevoflurane could alleviate spinal cord ischemia reperfusion injury in rabbits, and whether the beneficial effect is dependent on oxygen free radicals. In Experiment 1, 48 male New Zealand white rabbits were randomly assigned to six groups (n=8 each). Animals in the sham group only underwent sham-operation. Animals in the control group underwent spinal cord ischemia for 20 min without postconditioning. Animals in 02 postconditioning group (Group O2) inhaled 100% O2 from 5 min before reperfusion and lasted 13 min. Animals in sevoflurane postconditioning groups (Group Sevo0.5, Sevo1.0 and Sevo1.5) inhaled 0.5, 1.0, 1.5 minimum alveolar concentration (MAC) sevoflurane in 100% O2 from 5 min before reperfusion and lasted 10 min, then inhaled 100% O2 for 3 min to wash out the remaining sevoflurane. In Experiment 2, 36 male New Zealand White rabbits were randomly assigned to four groups (n=9 each). Animals in O2 and Sevo groups received normal saline (5 ml/kg intravenously) 1 h before postconditioning with 100% O2 and 1.0 MAC sevoflurane, respectively. In the DMTU + Sevo and DMTU + O2 groups, 5 ml/kg of 10% dimethylthiourea (DMTU, a potent oxygen free radical scavenger, dissolved in saline) was administered intravenously at the same time. Spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, hind-limb motor function and histopathology of the spinal cord were examined in a blinded fashion. (1) The neurologic and histopathologic outcomes in the sevoflurane postconditioning groups were better than those in the control group (P < 0.05), the histopathologic outcomes in Sevo1.0 group were better than that in Sevo0.5 and Sevo1.5 groups (P < 0.05). (2) The neurologic and histopathologic outcomes in Sevo, DMTU + Sevo and DMTU + O2 groups were better than those in the O2 group (P < 0.05), the histopathologic outcomes in Sevo group were better than that in the DMTU + Sevo and DMTU + O2 groups (P < 0.05). Our study demonstrates that sevoflurane postconditioning against spinal cord ischemia injury via the release of oxygen free radicals in rabbits.


[A randomized trial of single and multifraction radiation therapy for bone metastasis: a preliminary report].
From April, 1989 through January, 1990, a randomized trial was conducted to investigate the efficacy of single fraction radiation treatment (8, 10, 12, 15Gy) compared to a multifraction dose schedule (5Gy x 4, 5Gy x 5, 5Gy x 6) as a therapy for a bone metastasis. Both subjective and objective pain scores were used to measure the therapeutic results. A total of 31 patients participated in the trial and, for analysis, 27 of these patients were follow-up for more than 8 weeks after the start of the radiation therapy. The following statistics resulted. Of the single fraction series, symptomatic pain relief was obtained in 86% of the patients (12/14 treatment areas), and of the multifraction series, 92% (12/13). Further, a complete response was achieved in 57% (8/14) of the single fraction patients and 31% (4/13) of the multifraction patients, respectively. Between the two treatment regimens, no difference was found in the incidence of pain relief, speed of onset, or acute morbidity. Finally, no severe morbidity was seen in either arm.


Enhanced Adsorption Performance of Oxytetracycline by Desugared Reed Residues.
The performance of oxytetracycline adsorption by untreated reed roots, stems and leaves, as well as the desugared reed roots, stems and leaves, was investigated with scanning electron microscopy, Fourier-transform infrared spectroscopy, elemental analysis and surface area analysis to understand the adsorption mechanism. The results showed that the adsorption capacities of untreated reed were 416.35 mg/kg for roots, 341.92 mg/kg for stems and 280.21 mg/kg for leaves, and can be increased significantly by a factor of 8⁻12 after desugarization. The pseudo-first-order kinetic model was more suitable for describing the adsorption kinetics of reed residues, and the isothermal adsorption process was fitted well by both the Langmuir and Freundlich models. The thermodynamic process suggested that the adsorption was a spontaneous endothermic reaction, and mainly physical adsorption-dominated. The desugared reed tissues had a larger surface area and smaller pore area, and the aromaticity of reed residues increased; on the other hand, the polarity and hydrophilicity decreased after desugarization, thus revealing the mechanism of enhanced OTC(oxytetracycline) adsorption by desugared reed residues. This study suggests that the reed residues contribute the complex adsorption ability for both inorganic and organic contaminates. Corruption of the reed can enhance the adsorption; thus, protecting the natural reed residue and letting it naturally corrupt, rather than artificially cleaning it up, can effectively promote the adsorption of pollutants in the environment and protect environmental and public health.


Pancreatic intraductal tubulopapillary neoplasm with associated invasive cancer successfully treated by total pancreatectomy: A case report.
A 74-year-old male was admitted to Departments of Surgery, Toyonaka Municipal Hospital (Osaka, Japan) for treatment of a pancreatic tumor. Contrast enhanced computed tomography (CT) revealed a mass with small cystic lesions in the pancreatic head and body. Fluorodeoxyglucose-positron emission tomography/CT revealed an abnormal uptake of fluorodeoxyglucose, corresponding to the mass lesions. Upper gastrointestinal endoscopy revealed rough mucosa near the opening of the accessory pancreatic duct, and the mucosa biopsy exhibited adenocarcinoma with no mucin observed. The preoperative diagnosis was pancreatic intraductal tubulopapillary neoplasm (ITPN) with cancerous lesions, and a total pancreatectomy with splenectomy was performed. The resected tissue specimen revealed a solid tumor occupying the entire pancreas with intraductal growth into the main pancreatic duct. Histological examination revealed high-grade dysplastic cells in a tubulopapillary growth pattern without overt mucin production beyond the pancreatic duct. Immunohistochemical staining analysis of the tumor was positive for cytokeratin (CK)7, CK19 and mucin (MUC)1, and negative for MUC2, MUC5AC, MUC6 and caudal type homeobox 2. The tumor was finally diagnosed as pancreatic ITPN with associated invasive cancer. The patient remains well without evident recurrence nine months post-surgery. ITPN is a rare type of epithelial neoplasm of the pancreas, and is characterized by intraductal tubulo-papillary growth, ductal differentiation, limited intracellular mucin production, and cellular dysplasia. The present case report may contribute to improved understanding of how to effectively treat patients with ITPN.


Event-specific qualitative and quantitative polymerase chain reaction analysis for genetically modified canola T45.
Polymerase chain reaction (PCR) methods have been the main technical support for the detection of genetically modified organisms (GMOs). To date, GMO-specific PCR detection strategies have been developed basically at four different levels, such as screening-, gene-, construct-, and event-specific detection methods. Event-specific PCR detection method is the primary trend in GMO detection because of its high specificity based on the flanking sequence of exogenous integrant. GM canola, event T45, with tolerance to glufosinate ammonium is one of the commercial genetically modified (GM) canola events approved in China. In this study, the 5'-integration junction sequence between host plant DNA and the integrated gene construct of T45 canola was cloned and revealed by means of TAIL-PCR. Specific PCR primers and TaqMan probes were designed based upon the revealed sequence, and qualitative and quantitative TaqMan real-time PCR detection assays employing these primers and probe were developed. In qualitative PCR, the limit of detection (LOD) was 0.1% for T45 canola in 100 ng of genomic DNA. The quantitative PCR assay showed limits of detection and quantification (LOD and LOQ) of 5 and 50 haploid genome copies, respectively. In addition, three mixed canola samples with known GM contents were detected employing the developed real-time PCR assay, and expected results were obtained. These results indicated that the developed event-specific PCR methods can be used for identification and quantification of T45 canola and its derivates.


Status, equity and social identification during an intergroup merger: a longitudinal study.
Using an intergroup perspective, this longitudinal study (N=215) examined the adjustment patterns of employees from low vs. high status pre-merger organizations. The first questionnaire was distributed 3 months after the implementation of the merger, whereas the second was completed 2 years later. As predicted, members of the low status group perceived the merger to be implemented in a less fair manner at the start of the merger and reported a decreased adjustment to the merger over time. Members of the high status group showed an increase in adjustment over time, lower in-group bias and a stronger identification with the new merged organization. Path analyses further confirmed that identification with the new merged organization mediated the associations between perceptions of fairness and in-group bias as well as changes in adjustment over time. With its longitudinal design, this study replicates and extends past results by revealing the predictors of adjustment for members of low vs. high status groups involved in an intergroup merger.


Serial high-resolution computed tomography imaging in patients with Wegener granulomatosis: differentiation between active inflammatory and chronic fibrotic lesions.
To evaluate pulmonary pathologies in Wegener granulomatosis with sequential computed tomography (CT) in order to differentiate active inflammatory lesions from chronic fibrotic lesions. Serial CT findings in 38 patients with Wegener granulomatosis were retrospectively analyzed (mean follow-up period, 21 months). The presence, extension, and distribution of the following findings were evaluated with CT: parenchymal nodules, masses, ground-glass attenuation, airspace consolidation, bronchial wall-thickening, bronchiectasis, linear areas of attenuation, pleural irregularities, pleural effusions, hilar and mediastinal lymphadenopathy. Observed in 92% of patients, nodules were the most common CT pathology. Areas of ground-glass attenuation, consolidation, masses of linear attenuation, and tracheal/bronchial wall-thickening were detected in 24%, 26%, 32%, 39%, and 68% of patients. At follow-up, the clearance of lesions was most consistent for areas of ground-glass attenuation (89%), masses (87%), and cavitated nodules (85%). In the follow-up scan, 58% of all nodules, 47% of pulmonary consolidations, and 66% of bronchial wall-thickening were completely resolved. Areas of bronchiectasis and septal/non-septal lines remained stable in 70% and 71% of patients. The majority of the lesions decreased or resolved completely with or without areas of linear attenuation. Ground-glass attenuation, cavitated nodules and masses appear to represent active inflammatory lesions. In most probability, areas of bronchiectasis and septal/non-septal lines more often represent chronic fibrotic changes rather than active inflammatory changes. In combination with clinical evaluation and bronchoscopy, CT assists in the assessment of disease activity.


Akinesia and axial rigidity without limb rigidity: an intermediate form between progressive supranuclear palsy and pure akinesia of Imai and Narabayashi.
We report five patients with atypical parkinsonism characterized by freezing phenomenon, akinesia and axial rigidity without limb rigidity or tremor. These patients were selected from 252 patients with parkinsonism who were referred to our clinic from 1986 to 1993. They have common clinical features consisting of freezing phenomena involving all four extremities, especially in the initiation of walking, and marked axial rigidity; otherwise, neither supranuclear ophthalmoparesis nor nuchal dystonia was noted. Their clinical features did not change over several years except in one patient who later developed typical manifestations of progressive supranuclear palsy (PSP). Levodopa was of no effect on their symptoms. After excluding other possibilities, it is our conclusion that they represent an atypical form of PSP lying between the pure akinesia of Imai and Narabayashi and the typical form of PSP.


Semantic Fluency Predicts Gait Velocity in PSP.
Progressive supranuclear palsy (PSP) is a large-scale network disease resulting in variable signs and symptoms including gait impairment and higher order cognitive dysfunction. Despite few studies showing the association of falls and cognitive dysfunction, the existing literature is yet to establish the exact relationship of discrete characteristics of gait with cognitive function in PSP. In this cross-sectional study, we aimed to characterize and explore the relationship of these two apparently distinct physiological phenomena in patients with PSP and across its different variants. Quantitative assessment of two-dimensional gait parameters was measured using an electronic walkway (GAITRite®). Dementia Rating Scale-2 was used to assess global as well as higher order cognitive functions. A regression model was used to interpret results. We observed that the variability domain of gait was significantly impaired in PSP patients with severe cognitive impairment compared to that of intact cognition. Moreover, initiation/perseveration (I/P), a higher order cognitive process, and one of its specific components, i.e., complex verbal task (β = 2.39, P < 0.001), significantly predict gait velocity in PSP [F (1, 40) = 16.102, P < 0.001]. Our findings indicate that the severity of cognitive functions affects gait variability, which might lead to frequent falls as observed in PSP. Furthermore, semantic fluency task of I/P function may act as a predictor of gait velocity. We suspect that higher order cognitive dysfunction through the damage of frontal lobe structure including dorsolateral prefrontal cortex or related network may influence gait in PSP.


Genes and Musculoskeletal Soft-Tissue Injuries.
There is mounting evidence suggesting a genetic contribution to the susceptibility of sustaining a musculoskeletal soft-tissue injury. To date, more than 70 loci have been implicated in several injury profiles. The genes implicated through these loci encode a broad spectrum of matrix proteins including collagens and non-collagens. The large majority of these studies have followed a candidate gene case-control study design. A small proportion of these loci have been repeated in independent studies, of which some have included different musculoskeletal injuries. However, the large majority of these studies are underpowered to detect contributions of small effect sizes (odds ratio <2.0). It is therefore critical that large data sets are collected and that consortia are established to effectively pool resources to understand the biological significance of these genetic loci and risk susceptibility. We are in the era of omics and high-throughput technologies but it is only through collaborations that we will realize the clinical significance of the genomic revolution and its application to musculoskeletal soft-tissue injury susceptibility.


Olfactory ensheathing glia transplantation combined with LASERPONCTURE in human spinal cord injury: Results measured by electromyography monitoring.
Preliminary results were measured by electromyography monitoring (electromyoscan) on three subjects suffering from spinal cord injury and who underwent a double therapy. The aim of this study was to evaluate regained voluntary activity below the injury in subjects who received a double therapy: 1) an olfactory ensheathing glia (OEG) transplantation using procedures developed by Dr. Hongyun Huang at the Xishan Hospital and Rehabilitation Centre, Beijing, China, and 2) LASERPONCTURE developed by Albert Bohbot, Laboratoire de Recherches sur le LASERPONCTURE, La Chapelle Montlinard, France. Materials uses were the LASERPONCTURE device developed by Albert Bohbot; the PROCOMP5 equipment with softwares BIOGRAPH INFINITI 5 and REHAB SUITE; the sensors MYOSCAN-PRO EMG (SA9401M-50) to record muscle activity, and FLEX/PRO-SA9309M to record skin conductance were fixed on the skin. An infrared laser, whose frequencies and power settings cannot be disclosed due to its proprietary nature, was applied after an OEG injection performed according to Dr. Hongyun Huang's procedures. Three cases, two males and one female, were selected for this study. Presentation and comments of the graphs recordings of voluntary muscle activity below the injury are provided. This preliminary study suggests that the double therapy restores some voluntary muscle activity as measured by electromyography monitoring.


Protein electrostatics: rapid multigrid-based Newton algorithm for solution of the full nonlinear Poisson-Boltzmann equation.
A new method for solving the full nonlinear Poisson-Boltzmann equation is outlined. This method is robust and efficient, and uses a combination of the multigrid and inexact Newton algorithms. The novelty of this approach lies in the appropriate combination of the two methods, neither of which by themselves are capable of solving the nonlinear problem accurately. Features of the Poisson-Boltzmann equation are fully exploited by each component of the hybrid algorithm to provide robustness and speed. The advantages inherent in this method increase with the size of the problem. The efficacy of the method is illustrated by calculations of the electrostatic potential around the enzyme Superoxide Dismutase. The CPU time required to solve the full nonlinear equation is less than half that needed for a conjugate gradient solution of the corresponding linearized Poisson-Boltzmann equation. The solutions reveal that the field around the active sites is significantly reduced as compared to that obtained by solving the corresponding linearized Poisson-Boltzmann equation. This new method for the nonlinear Poisson-Boltzmann equation will enable fast and accurate solutions of large protein electrostatics problems.


Serratia proteamaculans Strain AGR96X Encodes an Antifeeding Prophage (Tailocin) with Activity against Grass Grub (Costelytra giveni) and Manuka Beetle (Pyronota Species) Larvae.
A highly virulent Serratia proteamaculans strain, AGR96X, exhibiting specific pathogenicity against larvae of the New Zealand grass grub (Costelytra giveni; Coleoptera: Scarabaeidae) and the New Zealand manuka beetle (Pyronota festiva and P. setosa; Coleoptera: Scarabaeidae), was isolated from a diseased grass grub larva. A 12-day median lethal dose of 4.89 × 103 ± 0.92 × 103 cells per grass grub larva was defined for AGR96X, and death occurred within 5 to 12 days following the ingestion of a high bacterial dose. During the infection period, the bacterium rapidly multiplied within the insect host and invaded the hemocoel, leading to a mean bacterial load of 8.2 × 109 cells per larva at 6 days postingestion. Genome sequencing of strain AGR96X revealed the presence of a variant of the Serratia entomophila antifeeding prophage (Afp), a tailocin designated AfpX. Unlike Afp, AfpX contains two Afp16 tail-length termination protein orthologs and two putative toxin components. A 37-kb DNA fragment encoding the AfpX-associated region was cloned, transformed into Escherichia coli, and fed to C. giveni and Pyronota larvae, causing mortality. In addition, the deletion of the afpX15 putative chaperone component abolished the virulence of AGR96X. Unlike S. entomophila Afp, the AfpX tailocin could be induced by mitomycin C. Transmission electron microscopy analysis revealed the presence of Afp-like particles of various lengths, and when the purified AfpX tailocin was fed to grass grub or manuka beetle larvae, they underwent phenotypic changes similar to those of larvae fed AGR96X.IMPORTANCESerratia proteamaculans strain AGR96X shows dual activity against larvae of endemic New Zealand pasture pests, the grass grub (Costelytra giveni) and the manuka beetle (Pyronota spp.). Unlike Serratia entomophila, the causal agent of amber disease, which takes 3 to 4 months to kill grass grub larvae, AGR96X causes mortality within 5 to 12 days of ingestion and invades the insect hemocoel. AGR96X produces a unique variant of the S. entomophila antifeeding prophage (Afp), a cell-free phage-like entity that is proposed to deliver protein toxins to the grass grub target site, causing a cessation of feeding activity. Unlike other Afp variants, AGR96X Afp, named AfpX, contains two tail-length termination proteins, resulting in greater variability in the AfpX length. AfpX shows dual activity against both grass grub and manuka beetle larvae. AGR96X is a viable alternative to S. entomophila for pest control in New Zealand pasture systems.


Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets.
The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets. Immunocytochemical colocalization studies demonstrated a close association of insulin with both PC1 and PC2 in the adult mouse and rat pancreas. The coexpression of insulin with the prohormone convertases was further examined in rat pancreatic tumors induced by streptozotocin-nicotinamide treatment. These insulin-synthesizing tumors expressed PC1 and PC2, whereas insulin-silent adenomas did not. Colocalization studies demonstrated that only PC2, not PC1, colocalizes with glucagon, pancreatic polypeptide, and somatostatin. The highest levels of PC2-like immunoreactivity were observed in the glucagon-containing alpha-cells. Ontogeny studies carried out by in situ hybridization in mice showed the first detectable expression of the prohormone convertases in the pancreatic primordium at midgestation, starting for PC1 on embryonic day 11 and for PC2 on embryonic day 10. Enzyme expression was further confirmed by immunocytochemistry, which detected the presence of immunoreactive PC1- and PC2-like proteins on embryonic days 14 and 17, respectively. Taken together, our data suggest that both PC1 and PC2 play a role in proinsulin processing in vivo, whereas PC2 is a likely candidate convertase participating in the processing of proglucagon, propancreatic polypeptide, and prosomatostatin in pancreatic islets.


An unusual synaptic response mediated by a serotonin neurone.
Impulse activity in an identified serotonin-containing neurone produces a delayed slow excitatory response in another identified neurone. An axon of the serotonin neurone passes very close to the follower neurone perikaryon. The synaptic response is frequently accompanied by oscillations of the membrane potential. Constant-current pulsing experiments suggest that it could result from a reduction in membrane conductance. The response is markedly voltage-sensitive, being greatly reduced at potentials in excess of about -55 mV. Serotonin, locally applied, produces a very similar effect. The response to serotonin does not involve a change in conductance to either Na+ or Cl-, but Ca2+ appears to be involved, either by virtue of its influence on K+ conductance, or directly in its transfer of charge across the membrane.


Transforming growth factor beta-induced dissociation between vitamin D receptor level and 1,25-dihydroxyvitamin D3 action in osteoblast-like cells.
In the present study the interaction between a locally produced factor in bone, transforming growth factor beta (TGF beta) and a systemic regulator of bone metabolism, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was investigated. In rat (UMR 106, ROS 17/2.8) and human (MG-63) osteoblastic cell lines and in isolated fetal rat osteoblasts TGF beta caused a comparable increase in vitamin D receptor (VDR) level. A maximum was observed after 6 h at 1 ng/ml TGF beta. Scatchard analysis revealed that up-regulation of VDR is due to an increase in receptor number and not to a change in affinity. This was supported by Northern blot analysis which showed a dose- and time-dependent increase in VDR mRNA by TGF beta. To assess the significance of the TGF beta-induced increase in VDR level for 1,25-(OH)2D3 effects cells were preincubated with TGF for 4 h (causing a 2-3-fold increase of the VDR level) and subsequently incubated with 1,25-(OH)2D3 for 4 h and 24 h. TGF beta preincubation potently inhibited subsequent 1,25-(OH)2D3 stimulation of osteocalcin production in both ROS 17/2.8 and MG-63 cells on protein as well as mRNA level. A similar inhibition by TGF beta was observed on the 1,25-(OH)2D3-induced increase in osteopontin mRNA. The current study demonstrates dissociation between regulation of VDR level and modulation of two 1,25-(OH)2D3 biological responses by TGF beta in osteoblast-like cell lines of different origin. This dissociation shows that, besides interaction at VDR level also at other levels in the cell interaction(s) exist between TGF beta and 1,25-(OH)2D3. Besides, these data emphasize the potential importance of the interplay of locally produced factors and systemic calciotrophic hormones in the regulation of bone metabolism.


Clinical and pharmacokinetic study of oral etoposide in patients with AIDS-related Kaposi's sarcoma with no prior exposure to cytotoxic therapy.
In this phase II and pharmacokinetic study, chronic, low-dose, oral etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's sarcoma who were not previously exposed to cytotoxic therapy. Of 28 patients accrued for the study, 25 were assessable for toxicity and response. Twenty-four patients were male (homosexual or bisexual cases) and one patient was female (partner of a bisexual male). All patients were human immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease. Median age was 33 years (range, 21 to 50), and median World Health Organization (WHO) performance status was 2 (range, 0 to 3). The patients received a mean number of six treatment courses (range, four to 27). Prior therapy included local/regional irradiation, immunotherapy (interferon-alpha), local resection, and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2 weeks. Plasma concentrations of the drug were measured in six patients by a high-performance liquid chromatography (HPLC) method, after chloroform extraction using teniposide as internal standard. The overall response rate was 32% (two complete and six partial responses), and the median progression-free survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease, while 12 cases (48%) did not respond. Patients without a history of opportunistic infections seemed to respond better. The regimen was well tolerated. The main toxic effects consisted of mild to moderate nausea and vomiting in approximately half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two patients had to discontinue treatment because of prolonged and severe neutropenia. No toxic deaths were documented. The pharmacokinetic analyses revealed the achievement of potentially therapeutic and lowly myelosuppressive plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a significant period of time, ie, for approximately 4.6 hours postdosing. At the schedule applied, etoposide shows significant objective antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces acceptable clinical toxicity. This apparent efficacy of the regimen could be a result of the prolonged maintenance of cytotoxic plasma concentrations of etoposide during each treatment course, and the absence of toxic peak levels of the drug. These results, together with the appreciable bioavailability of oral etoposide, make the regimen feasible for outpatient treatment of patients with advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned approach are warranted.


Chemical proteomics reveals interactors of the alarmone diadenosine triphosphate in the cancer cell line H1299.
Intracellular dinucleoside polyphosphates (Npn Ns) have been known for decades but the functional role remains enigmatic. Diadenosine triphosphate (Ap3 A) is one of the most prominent examples, and its intercellular concentration was shown to increase upon cellular stress. By employment of previously reported Ap3 A-based photoaffinity-labeling probes (PALPs) in chemical proteomics, we investigated the Ap3 A interactome in the human lung carcinoma cell line H1299. The cell line is deficient of the fragile histidine triade (Fhit) protein, a hydrolase of Ap3 A and tumor suppressor. Overall, the number of identified potential interaction partners was significantly lower than in the previously investigated HEK293T cell line. Gene ontology term analysis revealed that the identified proteins participate in similar pathways as for HEK293T, but the percentage of proteins involved in RNA-related processes is higher for H1299. The obtained results highlight similarities and differences of the Ap3 A interaction network in different cell lines and give further indications regarding the importance of the presence of Fhit.


[Effectiveness of clinical treatment of survivors of torture].
To research the clinical efficiency in the treatment of the torture survivors in Bosnia and Herzegovina after the therapeutic treatment. There are 51 clients with the experience of the war torture included in the multidisciplinary treatment. All the clients were questioned with SCL 90-R questionnaire at the beginning of the treatment. At the end of the treatment, 6 months later, all were retested with SCL 90-R. All clients received general medical treatment, psychological-psychiatric help included individual and group psychotherapy and pharmacotherapy. According to the results of t-test reduction of the psychopathological response after six months of the therapy is significant for the subscales of somatization p = 0.005, obsessive-compulsive symptoms p = 0.041, depression p = 0, anxiety p = 0, hostility p = 0.041. According to the results of the research therapy of torture survivors must include multidisciplinary approach and combined treatment: medical, psychological and social; Results show high significance in reduction of psychopathological response after six months of combined treatment.


Computer-based smoking cessation interventions in adolescents: description, feasibility, and six-month follow-up findings.
The impact of adolescent smoking cessation clinics has been disappointing due to low participation rates, high attrition, and low quit rates. This paper describes two computerized self-help adolescent smoking cessation intervention programs: 1) a program utilizing the expert system which is based on the transtheoretical model of change and 2) a popular action-oriented smoking cessation clinic program for teens which was modified for computer presentation. High participation rates in the program among 132 smokers demonstrate the high feasibility and acceptability of the programs. Quit rates of up to 20% were observed during the intervention, and an additional 30% made unsuccessful quit attempt(s). The 6-month follow-up findings indicated that adolescents were poorly prepared to maintain abstinence.


NSAIDs counteract H. pylori VacA toxin-induced cell vacuolation in MKN 28 gastric mucosal cells.
The relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori-induced gastric mucosal injury is still under debate. VacA toxin is an important H. pylori virulence factor that causes cytoplasmic vacuolation in cultured cells. Whether and how NSAIDs affect VacA-induced cytotoxicity is unclear. This study was designed to evaluate the effect of NSAIDs on H. pylori VacA toxin-induced cell vacuolation in human gastric mucosal cells in culture (MKN 28 cell line). Our data show that 1) NSAIDs (indomethacin, aspirin, and NS-398) inhibit VacA-induced cell vacuolation independently of inhibition of cell proliferation and prostaglandin synthesis; 2) NSAIDs impair vacuole development/maintenance without affecting cell binding and internalization of VacA; and 3) NSAIDs, as well as the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid, also inhibit cell vacuolation induced by ammonia. We thus hypothesize that NSAIDs might protect MKN 28 cells against VacA-induced cytotoxicity by inhibiting VacA channel activity required for vacuole genesis.


[Heparin-induced thrombocytopenia: implictions for cardiologist].
Heparin-induced thrombocytopenia (HIT) is one of the most life-threatening adverse effects of heparin administration. It is characterized by thrombocytopenia and may also be associated with venous or arterial thrombosis. HIT type 2 is caused by the binding of antibodies, most likely IgG, to a complex of heparin and platelet factor-4, these complexes IgG/PF4/heparin activate platelets causing the release of pro-thrombotic particles that promote thrombin generation. HIT and HIT-thrombosis are associated with high morbidity and mortality. Thrombotic events are most frequently venous and may manifest as pulmonary embolism or cerebral venous thrombosis. Arterial thrombosis leading to limb damage and amputation and to myocardial infarction or stroke may also occur. HIT is a clinical syndrome that requires clinical and laboratory findings to confirm the diagnosis. All forms of heparin treatment should be stopped once HIT is suspected and patients should be treated with an alternative anticoagulant to treat and prevent thrombotic complications. Available alternative anticoagulants include argatroban and lepirudin, a recombinant form of hirudin.


Subwavelength focusing of terahertz waves in silicon hyperbolic metamaterials.
We theoretically demonstrate the subwavelength focusing of terahertz (THz) waves in a hyperbolic metamaterial (HMM) based on a two-dimensional subwavelength silicon pillar array microstructure. The silicon microstructure with a doping concentration of at least 1017 cm-3 offers a hyperbolic dispersion at terahertz frequency range and promises the focusing of terahertz Gaussian beams. The results agree with the simulation based on effective medium theory. The focusing effect can be controlled by the doping concentration, which determines the real part of the out-of-plane permittivity and, therefore, the refraction angles in HMM. The focusing property in the HMM structure allows the propagation of terahertz wave through a subwavelength aperture. The silicon-based HMM structure can be realized using microfabrication technologies and has the potential to advance terahertz imaging with subwavelength resolution.


Effect of maternal dietary starch-to-fat ratio and daily energy intake during late pregnancy on the performance and lipid metabolism of primiparous sows and newborn piglets.
The present study evaluated the effects of maternal dietary energy intake and starch-to-fat ratio during late gestation on the performance and lipid metabolism of sows and their offspring. On day 84 of gestation, 80 Landrace × Yorkshire primiparous sows were assigned to 2 × 2 factorial arrangements according to body weight following a randomized complete block design. The factors were daily energy intake (8,375 kcal ME/d [CE] vs. 9,600 kcal ME/d [HE]) and dietary starch-to-fat ratio (10:1 [CR] vs. 15:1 [HR]). All sows were fed one of four diets from day 85 of gestation until farrowing. Data were analyzed using the GLM procedure in SPSS. High energy intake increased the body weight of sows on day 110 of gestation (P = 0.031) as well as the weight of piglets at birth (P = 0.018). Increased energy intake elevated the plasma triglyceride concentrations in sows (P = 0.027) and piglets (P = 0.044). Maternal high energy intake altered the liver metabolome of newborn piglets in terms of metabolites related to carbohydrate and linoleic acid metabolism. Moreover, maternal high energy intake increased hepatic total cholesterol (P = 0.023) and triglyceride (P = 0.026) concentration in newborn piglets. Furthermore, maternal high energy intake significantly increased the transcript abundance of fatty acid synthase (FAS; P = 0.001) and protein abundance of phosphorylated protein kinase B (P =0.001) in the liver of newborn piglets. A high starch-to-fat ratio reduced low-density lipoprotein cholesterol (LDL-C) concentration in the plasma of sows (P = 0.044) and newborn piglets (P = 0.048) as well as in the liver of newborn piglets (P = 0.015). Furthermore, maternal high starch-to-fat ratio increased the transcript abundances of FAS (P = 0.004) in newborn piglets. In conclusion, high daily energy intake of sows increased the birth weight of newborn piglets. Moreover, maternal high daily energy intake and high dietary starch-to-fat ratio improved the lipid metabolism of newborn piglets.


A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity.
Advances in infectious disease control strategies through genetic manipulation of insect microbiomes have heightened interest in microbially produced small molecules within mosquitoes. Herein, 33 mosquito-associated bacterial genomes were mined and over 700 putative biosynthetic gene clusters (BGCs) were identified, 135 of which belong to known classes of BGCs. After an in-depth analysis of the 135 BGCs, iron-binding siderophores were chosen for further investigation due to their high abundance and well-characterized bioactivities. Through various metabolomic strategies, eight siderophore scaffolds were identified in six strains of mosquito-associated bacteria. Among these, serratiochelin A and pyochelin were found to reduce female Anopheles gambiae overall fecundity likely by lowering their blood-feeding rate. Serratiochelin A and pyochelin were further found to inhibit the Plasmodium parasite asexual blood and liver stages in vitro. Our work supplies a bioinformatic resource for future mosquito-microbiome studies and highlights an understudied source of bioactive small molecules.


Exploring remnants of invariants buried in a deep potential well in chemical reactions.
We revisit the concept of "remnant of invariant manifolds" originally discussed by Shirts and Reinhardt in a two degrees of freedom Henon-Heiles system [J. Chem. Phys. 77, 5204 (1982)]. This is regarded as the remnants of a destroyed invariant manifold that can dominate the transport in phase space even at high energy regions where most of all tori vanish. We present a novel technique to extract such remnants of invariants from a sea of chaos in highly nonlinear coupled molecular systems in terms of the canonical perturbation theory based on Lie transforms. As an illustrative example we demonstrate in HCN isomerization reaction that the conventional procedure based on a finite order truncation of the coordinate transformation prevent us from detecting remnants of invariants. However, our technique correctly captures the underlying remnants of invariants that shed light on the energetics of chemical reaction, that is, how the reactive mode acquires (releases) energy from (to) the other vibrational mode in order to overcome the potential barrier (to be trapped in the potential well). We also found the qualitative difference between the two potential wells, HCN and CNH, which coincides with the nearest neighbor level spacing distribution of the vibrational quantum states within the wells.