Extraction of diethylhexylphthalate by home total parenteral nutrition from polyvinyl chloride infusion lines commonly used in the home.
Recently, our group detected that polyvinyl chloride (PVC) perfusion lines leach large amounts of the toxic plasticizer diethylhexylphthalate (DEHP) under conditions typical of intensive care units. In the present study, we investigated the extraction of DEHP from PVC connecting tubes that are commonly used for total parenteral nutrition (TPN) solutions. The aim of the study was to estimate the amount of DEHP to which children receiving home TPN are exposed for months and years. 1000 mL of TPN, identical in constitution and amount to the home TPN of 1 of our patients, were perfused through 5 different connecting tube systems and collected in hexane-rinsed glass bottles. The concentration of DEHP in the TPN was analyzed before and after perfusion. Before perfusion of the lines, the solution had a DEHP concentration of 0.05 to 0.69 microg/mL (baseline value). After perfusion of the lines, the load of DEHP in the solution varied between 1.41 and 2.07 microg/mL. This TPN was established for children weighing 20 kg. The daily dosage is between 71 and 104 microg x kg(-1) x day(-1). TPN is administered at home for many months and years. The monthly charge of DEHP is between 42.3 and 62.1 mg. Children weighing 20 kg therefore receive a dosage between 2.1 and 3.1 mg x kg(-1) x month(-1). Diethylhexylphthalate and its metabolite monoethylhexylphthalate have been demonstrated to be carcinogenic, embryotoxic, hepatotoxic, pneumotoxic, and cardiotoxic and are known to disrupt endocrine pathways and liver detoxifying capacity in animals. They are suspected of having multiple effects in humans as well. The doses presented above should therefore be avoided in children receiving home TPN by the use of tubing systems that are completely free of DEHP. Such systems are available.


Prevalence of decubitus ulcer and associated risk factors in an institutionalized Spanish elderly population.
We investigated the prevalence and associated risk factors of decubitus ulcer in an institutionalized Spanish elderly population. A 1 d cross-sectional study in 50 Spanish geriatric facilities was carried out. Data collection included age, sex, body mass index, presence of decubitus ulcer, duration of ulcer, days of hospitalization, risk according to the Norton scale, associated risk factors, and nutrition status evaluation including assessment according to the Nutrition Screening Initiative. Logistic regression analysis calculated prevalence and association with risk factors. Data from 827 elderly people (71.3% female) were collected. Mean age (+/- standard deviation) was 82.4 (+/-8.0) y. Decubitus ulcer prevalence was 35.7%, with no sex differences (34.1% males and 37.2% females). Body mass index was inversely associated with ulcer prevalence in a statistically significant way (odds ratio = 0.94, 95% confidence interval = 0.92-0.97), but the following were risk factors: age (1.03, 1.01-1.06), previous ulcer (3.09, 2.16-4.04), diabetes (1.54, 1.02-2.51), functionality (2.91, 2.05-4.12), immobility (8.30, 5.09-11.51), erythema (12.12, 7.46-16.78), dehydration (2.09, 1.31-2.87), and edema (2.35, 1.64-3.06). Subjective evaluation of nutrition status and nutrition status as assessed by the Nutrition Screening Initiative Determine scale (modified) showed a significant linear association with ulcer (P < 0.001), and a score above 14 points in the modified Norton scale was associated with a lower ulcer rate (P < 0.001). Prevalence of decubitus ulcer in the Spanish elderly population increased with age, poor nutrition status, immobilization, and impaired functionality.


Large transverse Hall-like signal in topological Dirac semimetal Cd3As2.
Cadmium arsenide (Cd3As2) is known for its inverted band structure and ultra-high electron mobility. It has been theoretically predicted and also confirmed by ARPES experiments to exhibit a 3D Dirac semimetal phase containing degenerate Weyl nodes. From magneto-transport measurements in high quality single crystals of Cd3As2, a small effective mass m(*) ≈ 0.05 me is determined from the Shubnikov-de Haas (SdH) oscillations. In certain field orientations, we find a splitting of the SdH oscillation frequency in the FFT spectrum suggesting a possible lifting of the double degeneracy in accord with the helical spin texture at outer and inner Fermi surfaces with opposite chirality predicted by our ab initio calculations. Strikingly, a large antisymmetric magnetoresistance with respect to the applied magnetic fields is uncovered over a wide temperature range in needle crystal of Cd3As2 with its long axis along [112] crystal direction. It reveals a possible contribution of intrinsic anomalous velocity term in the transport equation resulting from a unique 3D Rashba-like spin splitted bands that can be obtained from band calculations with the inclusion of Cd antisite defects.


In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes.
To evaluate the in vitro effects of diacerhein, a new drug for the treatment of osteoarthritis (OA), and its active metabolite, rhein, on interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) synthesis and expression in human OA synovial membrane, and on the IL-1beta and TNF-alpha receptors on human OA chondrocytes. Levels of IL-1beta and TNF-alpha were determined using specific ELISA in culture medium of human synovial membrane explants incubated in the presence of 1 microg/ml of lipopolysaccharide with or without therapeutic concentrations of diacerhein (1.4, 2.7, 5.4 x 10(-5) M) and rhein (1.7, 3.5, 7.0 x 10(-5) M). IL-1beta mRNA level was quantitated by Northern blotting. Using radioligand binding experiments, we determined the effects of these agents on the density and affinity of chondrocyte IL-1 and TNF receptors. IL-1beta synthesis was significantly inhibited by diacerhein and rhein, with maximum inhibition at 5.4 x 10(-5) M for diacerhein (p < 0.02) and 3.5 x 10(-5) M for rhein (p < 0.05). The effect of both agents on IL-1beta was found to be translational and/or post-translational, judging by the absence of effect on gene expression level. Both agents produced dose and time dependent decreases in the number of IL-1 receptors (IL-1R) on OA chondrocytes. This effect was mediated through a reduction in the level of the type I IL-1R as shown by experiments using a blocking monoclonal antibody against this receptor type. Both agents also markedly reduced the IL-1 induced synthesis and expression of stromelysin 1. Neither diacerhein nor rhein significantly affected the level of synthesis of TNF-alpha or the level of TNF-R. Diacerhein and rhein can effectively inhibit the synthesis of IL-1beta on human OA synovium, as well as the action of this cytokine at the cartilage level, by reducing the number of chondrocyte IL-1R. The effects of these agents seemed "selective" to the IL-1 system.


Multimodality image guidance with Dyna-CT for transcatheter treatment of paravalvular leak of a stentless valve.
The transcatheter treatment of paravalvular leaks (PVL) are technically challenging procedures; they pose increasing difficulty in cases where there is a stentless valve, without the usual fluoroscopic landmarks. Hence, there is limited experience in treating this defect percutaneously. We present a case of a patient with an aortic PVL of a stentless valve and how the integrated use of multi-imaging modalities (transesophageal echocardiography, computed tomography and rotational angiography) allowed the demarcation of landmarks onto live fluoroscopy and guided the transcatheter occlusion of the PVL.


Social and economic costs and health-related quality of life in non-institutionalised patients with cystic fibrosis in the United Kingdom.
This study aimed to determine the societal economic burden and health-related quality of life (HRQOL) of cystic fibrosis (CF) patients in the UK. A bottom-up cost-of-illness, cross-sectional, retrospective analysis of 74 patients was conducted aiming to estimate the economic impact of CF. Data on demographic characteristics, health resource utilisation, informal care, productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) instrument. Using unit costs for 2012 we found that the average annual cost for a CF patient was €48,603, with direct health care costs amounting to €20,854 (42.9 % of total costs), direct non-health care costs being €21,528 (44.3 %) and indirect costs attributable to productivity losses being €6,222 (12.8 %). On average, the largest expenditures by far were accounted for by informal care (44.1 %), followed by medications (14.5 %), acute hospitalisations (13.9 %), early retirement (9.1 %) and outpatient and primary health care visits (7.9 %). Sharp differences existed depending on whether CF patients were in need of caregiver help (€76,271 versus €26,335). In adult CF patients, mean EQ-5D index scores were 0.64 (0.93 in the general population) and mean EQ-5D visual analogue scale scores were 62.23 (86.84 in the general population); among caregivers, these scores were 0.836 and 80.85, respectively. Our analysis highlights the importance of the economic and quality of life consequences of CF from a societal perspective. The results highlight that beyond conventional costs such as acute hospitalisations, medication and outpatient and primary care visits, indirect costs related to informal care and early retirement, have significant societal implications. Similarly, our analysis showed that the average EQ-5D index score of adult CF patients was significantly lower than in the general population, an indication that a methodological bias may exist in using the latter in economic analyses. CF poses a significant cost burden on UK society, with non-health care and indirect costs representing 57 % of total average costs, and HRQOL being considerably lower than in the general population.


Poly[dinitrato[μ(3)-2,4,6-tris-(4-pyrid-yl)-1,3,5-triazine]cobalt(II)].
The solvothermal reaction of Co(NO(3))(2) and 2,4,6-tris(4-pyridyl)-1,3,5-triazine in dimethyl-formamide/ethanol mixed solvent afforded the title coordination polymer, [Co(NO(3))(2)(C(18)H(12)N(6))](n), in which the Co(II) atom is seven-coordinated by pyridyl groups of three different ligands and two chelating nitrate anions. The complex displays a nano-sized porous metal-organic framework that belongs to a (10,3) topological network.


Harmonics as an alternative method for measuring I0 during x-ray absorption spectroscopy experiments at laboratory scale.
In the recent years, the advent of an efficient and compact laboratory-scale spectrometer for x-ray absorption spectroscopy experiments has been extensively reported in the literature. Such modern instruments offer the advantage to routinely use x-ray absorption spectroscopy on systematic studies, which is usually unconceivable at synchrotron radiation source facilities due to often limited time access. However, one limiting factor is the fact that due to laboratory x-ray source brightness compared to a synchrotron, two separate measures of the incoming and transmitted x-ray intensities, i.e., the so-called I0 and I1, respectively, are usually required. Herein, we introduce and discuss an alternative approach for measuring I0 and I1 simultaneously. Based on the usage of harmonics arising naturally from the use of monochromator crystals, the reliability and robustness of our proposed approach is demonstrated through experiments at the Co K-edge measured using Co metal foil and at the Nd L3-edge measured in Nd2O3.


A meta-analysis of percutaneous compression plate versus sliding hip screw for the management of intertrochanteric fractures of the hip.
Intertrochanteric hip fractures are associated with high morbidity and mortality rates. Percutaneous compression plating (PCCP) is a minimally invasive technique for fracture fixation that has been advocated to reduce blood loss, relieve pain, and lead to faster rehabilitation. The present systematic review and meta-analysis was performed to evaluate PCCP in patients with intertrochanteric hip fractures compared with patients with sliding hip screw (SHS). A comprehensive review of related literature was conducted to identify all articles in PubMed, EMBASE, Springer, Ovid, China National Knowledge Infrastructure (CNKI), and the Cochrane Central Register of Controlled Trials published on or before July 26th, 2011. Only prospective or retrospective comparative studies reporting clinical and radiographic outcomes of PCCP for intertrochanteric hip fractures were included. The methodological qualities of the included studies were assessed using the Coleman methodology score, and the reported data of individual studies were extracted. Meta-analytic pooling of group outcomes across studies was performed for both the PCCP and SHS techniques. Fourteen studies met the inclusion criteria. Minimally invasive PCCP was associated with a decrease in surgical time, blood loss, transfusion rate, and systematic complications. No significant differences between PCCP and SHS were observed in other parameters, including hospital stay, mortality, reoperation, implant-related complications. Based on these finding, PCCP appeared similar to SHS in terms of mechanical stability in the clinical setting, but had obvious advantages in terms of blood loss, transfusion need, and systematic complications, which may be attributed to reduced soft tissue and bone damage. Although orthopedic surgeons are advised to consider PCCP fixation as an additional alternative treatment for intertrochanteric fractures, high-quality randomized trials are still needed to assess the benefits of this minimally invasive technique. III, systematic review.


Narcotics: the latest chapter in a long story. A review.
Extraordinary significant discoveries have been made in the pharmacology of opioid drugs in the last fifteen years. One has to go back to the beginning of the eighteenth century to find a comparably significant period. The advances in our understandings and uses of opioids have taken place in four different areas: postulating the existence of several types of receptors and the discovery of receptors sites, the isolation of endogenous opioids, the development of new opioid substances, and the use of new routes and modes of administration of narcotics.


Candida albicans biotypes in human immunodeficiency virus type 1-infected patients with oral candidiasis before and after antifungal therapy.
A prospective 19-month study of 26 human immunodeficiency virus type 1-infected patients with episodes of erythematous or pseudomembranous oral candidiasis was done to evaluate the significance of Candida albicans biotypes in patients treated with antifungal therapy. Changes in the biotype of C. albicans were frequently noted in recurrent oral candidiasis. However, no correlation was found between the various biotypes and the clinical features of oral candidiasis, the clinical stage of human immunodeficiency virus type 1 infection, or the number of CD4+ lymphocytes. On the contrary, a significant correlation appeared among clinical lesion features, CD4+ cell numbers, and time of clinical disappearance of the oral lesions. Changes in the biotype of C. albicans were observed at the end of the antifungal therapy in 17 of 26 patients who had a second appearance of oral candidiasis as well as in 10 of 14 subjects who experienced a third reappearance of oral candidiasis.


Gene delivery by functional inorganic nanocarriers.
Gene delivery into cells to elicit cellular response has received a great attention recently. Viruses, lipids, peptides, cationic polymers and certain inorganic nanomaterials have been reported as gene delivery vectors. In this review, we focus on the recent literature on gene delivery using inorganic nanoparticles. This emerging field of study is concisely summarized and illustrated by selected examples and recent patents. New approaches and directions towards the practical use of multifunctional nanocarriers are highlighted.


Effects of age and estrogen status on serum parathyroid hormone levels and biochemical markers of bone turnover in women: a population-based study.
Although estrogen deficiency is responsible for the increase in bone turnover in early postmenopausal women, age-related factors, such as the progressive increase in serum PTH levels, are believed to be responsible for the increase in bone turnover in elderly women. Whether estrogen deficiency continues to play a role, either directly or indirectly, in the pathogenesis of the increased bone turnover in elderly women remains unclear. Thus, we measured serum PTH, markers of bone turnover, and serum sex steroid levels in a population-based sample of 351 women (age range, 21-94 yr), which included 47 postmenopausal women who were receiving long term estrogen replacement therapy. Serum PTH increased as a function of age when the premenopausal women and the estrogen-deficient postmenopausal women were analyzed together (r = 0.35; P < 0.001). By contrast, this age-related increase in serum PTH was eliminated in the postmenopausal women receiving long term estrogen therapy, which also resulted in a similar suppression of markers of bone formation and resorption in both the early (< or = 20 yr) and late (> 20 yr) postmenopausal women. By multivariate analysis, serum 25-hydroxyvitamin D levels were highly predictive of serum PTH levels regardless of menopausal status, whereas serum estrone levels were predictive of markers of bone resorption in the postmenopausal women. We conclude that estrogen deficiency may be responsible not only for the increase in bone turnover in early postmenopausal women, but also indirectly for the secondary hyperparathyroidism and increase in bone turnover found in late postmenopausal women. Residual serum estrogen levels are important determinants of bone resorption in postmenopausal women.


Demonstration that a case of human alveolar echinococcosis in Minnesota in 1977 was caused by the N2 strain.
Alveolar echinococcosis is the most serious helminthic zoonosis of the northern hemisphere affecting humans. The causative agent, Echinococcus multilocularis, occurs in geographically distinct strains that can be distinguished based on sequence variations of mitochondrial genes and nuclear microsatellite targets. This report finds that the human case of Alveolar echinococcosis occurring in Minnesota in 1977 was caused by the N2 haplotype described previously; the N2 haplotype is distinct from European and Asian isolates of the parasite and is restricted to the central region of North America.


Recruiting and retaining participants in a combined behavioral and pharmacological clinical trial.
This article focuses on the practical and methodological considerations that went into recruiting and retaining participants in a complex clinical trial. It describes multiple recruitment strategies that were employed to meet stringent eligibility criteria and manage efficiently the flow of participants to fulfill recruitment goals. Both study-wide and site-specific methods that were employed to maximize retention rates are discussed. Also discussed is how the coordinating center worked together with study investigators to improve recruitment and retention. A multidimensional perspective on recruitment and retention is discussed. Details are provided on how barriers to recruitment and retention were addressed. Intervention strategies designed by the coordinating center to meet performance goals are described. Data are presented to support the utility of recruitment and retention methods. The COMBINE Study served as a case illustration for various issues addressed in the article. As a result of the combined efforts of the coordinating center and study sites, there was steady improvement in recruitment and retention rates over the course of the trial. The recruitment goal of 1,375 participants was surpassed by September 2003. Also, improvement in data completeness rates improved by 18-27 percentage points over a 3-year period, culminating in follow-up rates meeting or exceeding performance goals by 2004. Various strategies and procedures designed to address recruitment and retention problems in large, complex combination pharmacotherapy and behavioral trials were effective in meeting recruitment and retention goals. The lessons learned may be of value to investigators not only involved in multisite, combination trials but in monotherapy and/or single-site studies as well.


Gestational-age-specific stillbirth risk among Australian Aborigines.
Previous studies have found that, for preterm babies, the risk of stillbirth among Australian Aborigines is similar to the risk for whites. In contrast, at full term, the risk for Aborigines is more than twice the risk for whites. However, these studies (like most other analyses of stillbirths) used the number of births at each gestational age to calculate the risk. For stillbirths, the risk is more appropriately estimated using the number of babies in utero. This paper presents the first comparison of stillbirth risk for Australian Aborigines and whites using the more appropriate denominator. I used 6 years of data (1987-1992) from the routinely-maintained Queensland Perinatal Data Collection. Contingency-table analyses were used to compare the gestational-age-specific risk of stillbirth in Aborigines and whites. Multiple births were excluded; male and female babies were analysed separately. When the number of babies in utero was used as the denominator, preterm Aborigines had a statistically significant three- to fourfold increase in the risk of stillbirth compared with whites. At full term, the risks for Aborigines and whites were not statistically significantly different. A different pattern of gestational-age-specific stillbirth risk was obtained when the appropriate denominator was used. Specifically, the high risk of stillbirth for preterm Aborigines was revealed. Research is needed to identify the causes of the Aboriginal-white difference in stillbirth risk for preterm babies.


Distributed Optimization Design of Continuous-Time Multiagent Systems With Unknown-Frequency Disturbances.
In this paper, a distributed optimization problem is studied for continuous-time multiagent systems with unknown-frequency disturbances. A distributed gradient-based control is proposed for the agents to achieve the optimal consensus with estimating unknown frequencies and rejecting the bounded disturbance in the semi-global sense. Based on convex optimization analysis and adaptive internal model approach, the exact optimization solution can be obtained for the multiagent system disturbed by exogenous disturbances with uncertain parameters.


Health care in high school athletics in West Virginia.
The purpose of this study was to determine the level of implementation of emergency preparedness procedures and administrative procedures to provide appropriate medical coverage to high school athletics in the predominantly rural US state of West Virginia. Particular attention was given to determine the extent to which the schools provided the recommendations for best practice in the National Athletic Trainers Association consensus statement outlining appropriate medical coverage for high school athletics. A listing of all public schools participating in the state high school athletic association with at least one team participating in interscholastic competition was obtained from the state Department of Education office. An electronic survey was sent to the principal at each high school with instructions that an administrator or sports medicine professional complete the survey. A total of 62 respondents completed the survey (49.6% response rate). Most respondents were principals (92%), followed by athletic administrators (8%). The majority of schools reported a rural zip code at the school level based on the Rural Urban Community Area Codes. Measures assessed the school demographics, including size and rurality. Additional measures assessed the development and implementation of a comprehensive athletic healthcare administrative system, and the development and implementation of a comprehensive emergency action plan. The majority of respondents reported that there was a consent form on file for student athletes (91%) and comprehensive insurance was required for participation (80%). A third of the respondents (33%) reported that all members of the coaching staff were certified in first aid and cardiac pulmonary resuscitation (CPR) and 31% reported 'never' when asked if all coaches were required to be certified in CPR and first aid. When asked if there was a written emergency action plan (EAP) that outlines procedures to follow in emergency situations during athletic participation, 36% responded 'never' and 38% responded 'always'. When asked about specific limitations for health care to athletes the three main themes identified in qualitative analysis were lack of funding, lack of certified medical personnel, and the inability to locate certified medical personnel in a rural area. This study confirmed expected barriers to health care for high school athletes in West Virginia, specifically the lack of funding and resources available to rural schools. In order to prevent a life threatening emergency or possibly sudden cardiac death, preparing and planning for emergencies should be an essential part of high school athletic programs. Rural areas face significant challenges in regards to funding and qualified personnel. Requiring first aid and CPR certification for coaches and requiring an EAP are two steps that could improve the health care provided to athletes. These are inexpensive and achievable steps that could be taken to improve the safety for athletes at high schools in both rural and non-rural areas.


New contribution to the genetics of the Basques: heterogeneity in the esterase D subtype distribution.
A random sample of 1,491 individuals from three Basque provinces was studied for the red-cell esterase D (ESD) polymorphism by means of isoelectric focusing. The following allele frequencies were observed: Vizcaya, ESD*1 = 0.933, ESD*2 = 0.058, ESD*5 = 0.009; Guipuzcoa, ESD*1 = 0.938, ESD*2 = 0.053, ESD*5 = 0.009; and Alava, ESD*1 = 0.894, ESD*2 = 0.088, ESD*5 = 0.018. The Basques from Vizcaya and Guipuzcoa display the lowest values for allele ESD*5 of any European population studied to date. The value obtained for this allele in the Basque population of Alava is significantly higher than those found in the other two Basque samples. This, together with the fact that Basques from Alava display the lowest ESD*1 frequency of any Basque series, suggests that there are genetic differences between Basque provinces.


Pulsatile release of LH and secretion of ovarian steroids in sheep during the luteal phase of the estrous cycle.
The concentration of LH and progesterone in jugular venous plasma and the secretion of steroids by the ovary were measured every 10 minutes for 2 hours on days 12, 14, and 16 of the estrous cycle in 5 ewes with utero-ovarian autotransplants. A pulse of LH occurred about once every 2 hours, when the concentration rose from a basal level of 0.57 +/- 0.08 ng/ml to a peak of 2.97 +/- 0.57 ng/ml. Within 5 minutes of the pulse of LH, the secretion of estradiol (an exclusive product of the follicle) rose rapidly from a basal level of 0.75 +/- 0.12 ng/min to reach a peak value of 2.16 +/- 0.33 ng/min in about 30 minutes. In contrast, the secretion of progesterone from the corpus luteum, and the concentration of progesterone in the peripheral plasma changed very little following the pulse of LH. The secretion of androstenedione, which arises from the follicle and corpus luteum, increased from 3.03 +/-0.75 ng/min to 7.85 +/- 1.78 ng/min by 30 minutes after the pulse of LH. These findings indicate that the follicle, and possibly the stroma, respond rapidly to episodic fluctuations in the concentration of LH and are probably involved in the negative feedback loop between the ovary and the hypothalamic pituitary system. The fluctuations in the secretion of progesterone from the corpus luteum, on the other hand, are unrelated to pulses of LH.


Effect of sorbitol on interaction of phenolic preservatives with polysorbate 80.
The effect of sorbital on the binding of several commonly used phenolic preservatives (i.e., p-hydroxybenzoic acid, methylparaben, ethylparaben, and propylparaben) with the nonionic surfactant polysorbate 80 was investigated using an equilibrium dialysis technique. The binding data were expressed in the form of Scatchard plots utilizing a modified form of the Scatchard equation. The data analysis indicated that all four phenolic preservatives were bound to two distinct loci within the polysorbate micelle; one exhibited a high affinity and a low capacity for the preservative molecules, while the other appeared to have a near-zero affinity but an almost infinite binding capacity. The high affinity site was assumed to be located near the junction of the hydrocarbon core with the polyoxyethylene region of the micelle. The interaction of the preservatives with the second class of sites apparently involved a non-specific and nonsaturable partitioning of the preservative molecules into the polyoxyethylene region of the micelle. Sorbitol was ineffective in displacing significant amounts of bound preservative from either binding site, presumably because it was too polar to partition into the micelle sufficiently to displace bound preservative.


Overexpression of the mitochondrial anti-viral signaling protein, MAVS, in cancers is associated with cell survival and inflammation.
Mitochondrial anti-viral signaling protein (MAVS) plays an important role in host defense against viral infection via coordinating the activation of NF-κB and interferon regulatory factors. The mitochondrial-bound form of MAVS is essential for its anti-viral innate immunity. Recently, tumor cells were proposed to mimic a viral infection by activating RNA-sensing pattern recognition receptors. Here, we demonstrate that MAVS is overexpressed in a panel of viral non-infected cancer cell lines and patient-derived tumors, including lung, liver, bladder, and cervical cancers, and we studied its role in cancer. Silencing MAVS expression reduced cell proliferation and the expression and nuclear translocation of proteins associated with transcriptional regulation, inflammation, and immunity. MAVS depletion reduced expression of the inflammasome components and inhibited its activation/assembly. Moreover, MAVS directly interacts with the mitochondrial protein VDAC1, decreasing its conductance, and we identified the VDAC1 binding site in MAVS. Our findings suggest that MAVS depletion, by reducing cancer cell proliferation and inflammation, represents a new target for cancer therapy.


An Exploratory Study on University Students' Perceptions of Posthumous Organ Donation Base on the Theory of Reasoned Action.
In view of the general support for organ donation but low registration rate in Hong Kong, the present research attempted to understand the attitude-behavior inconsistency by identifying the underlying beliefs for organ donation through employing the theory of reasoned action. A qualitative approach using semi-structured focus groups was adopted and 19 students from three universities in Hong Kong participated; 10 constructs were identified: attitude, subjective norm, helping, continuation, contribution, body intact, distrust to the medical system, indifference to organ donation, negative affect, and family burden. Findings suggested that their attitudes toward organ donation were of both the cognitive and affective nature; subjective norm of family, friends, and people they respect were identified as influential to students' views on organ donation. The study provided insight in promoting organ donation, that the cognitive concerns about keeping the body intact, and the negative affects introduced should also be addressed.


Upper gastrointestinal bleeding due to peptic ulcer disease is not associated with air pollution: a case-crossover study.
Recent studies have demonstrated an association between short-term elevations in air pollution and an increased risk of exacerbating gastrointestinal disease. The objective of the study was to evaluate if day-to-day increases in air pollution concentrations were positively associated with upper gastrointestinal bleeding (UGIB) secondary to peptic ulcer disease (PUD). A time-stratified case-crossover study design was used. Adults presenting to hospitals with their first UGIB secondary to PUD from 2004-2010 were identified using administrative databases from Calgary (n = 1374; discovery cohort) and Edmonton (n = 1159; replication cohort). Daily concentrations of ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and particulate matter (PM10 and PM2.5) were estimated in these two cities. Conditional logistic regression models were employed, adjusting for temperature and humidity. Odds ratios (OR) with 95 % confidence intervals (CI) were expressed relative to an interquartile range increase in the concentration of each pollutant. No statistically significant associations were observed for any of the individual pollutants based on same-day, or 1-day lag effects within the Calgary discovery cohort. When the air pollution exposures were assessed as 3-, 5-, and 7-day averages, some pollutants were inversely associated with UGIB in the discovery cohort; for example, 5-day averages of nitrogen dioxide (OR = 0.68; 95 % CI: 0.53-0.88), and particulate matter <2.5 μm (OR = 0.75; 95 % CI: 0.61-0.90). However, these findings could not be reproduced in the replication cohort. Our findings suggest that short-term elevations in the level of ambient air pollutants does not increase the incidence of UGIB secondary to PUD.


Hip arthroscopy versus total hip arthroplasty in patients above 40 differences: outcome and residual complain.
This study aimed to compare patient outcomes and residual complains after hip arthroscopy (HAS) and total hip arthroplasty (THA) to improve patient counseling. It includes 140 hips/129 HAS-patients and 77 hips/62 THA-patients aged 40 to 55 years with a BMI under 30. All patients underwent primary HAS or primary THA in our hospital from 2007 until 2014. Exclusion criteria were a history of prior hip surgery or suffering sequels of childhood's hip disease, systemic inflammatory disease or avascular hip osteonecrosis. Outcome measures were WOMAC, subjective hip value, residual complains, the need of infiltrations and the complication and conversion rate. Patient data and scores were collected pre-operative, after one year and at the last follow-up. Scores indicated significant patient benefits in both groups (p < 0.0001). Variability of outcome was significantly higher and less predictable in the HAS group (HAS: 1.9 vs. THA: 0.9). While THA showed significant improvement mainly after one year, HAS showed significant improvements after one year and the latest follow-up. Residual complains were more frequent after HAS (p = 0.026). Groin pain was the main complain after HAS, limping and disturbing leg length discrepancy after THA. THA more predictably improves patient's outcome with shorter recovery time. Limping and leg length discrepancy are predominant after THA.


32P-pyrophosphate in the treatment of persistent metastatic bone pain.
Eight patients with persistent pain due to disseminated bone metastases from mammary carcinoma were given about 370 MBq (10 mCi) of 32P-pyrophosphate on 10 occasions. All but one of the patients experienced alleviation of pain lasting 1 to 4 months. The side effects, which derived mainly from haematopoetic tissue, prevent the routine use of this compound.


Basal insulin requirement of youth with type 1 diabetes differs according to age.
We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2-h postprandial C-peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.


HER2 reduces breast cancer radiosensitivity by activating focal adhesion kinase in vitro and in vivo.
Growing evidence has demonstrated that human epidermal growth factor receptor 2 (HER2) is involved in the radiation response to breast cancer. However, the underlying mechanism remains elusive. Therefore, we investigated if HER2 overexpression is associated with radiosensitivity of breast cancer. We constructed breast cancer cell lines differing in HER2 expression by transducing HER2 cDNA or short hairpin RNA against HER2. We then assessed the radiosensitivity and investigated the potential mechanism by using cell proliferation assay, cell adhesion assays, anoikis assays, colony formation assays, and western blotting analyses. We found that HER2 introduction in breast cancer cell lines MCF-7 (low HER2 expression) and MDA-MB-231 (HER2 is not expressed) promoted cell proliferation and invasion and enhanced cell adhesion and resistance to anoikis. Moreover, HER2 reduced radiosensitivity in these two cells compared with the corresponding control. The opposite results were observed when HER2 was silenced in breast cancer cell lines ZR-7530 and SK-BR-3 (both cells with high expression of HER2) using HER2 shRNA. In addition, animal experiment results showed HER2 could enhance the radioresistance of xenograft tumors. Further studies showed HER2 promoted the phosphorylation of focal adhesion kinase (Fak) and thereby up-regulated the expression of proteins associated with the epithelial-to-mesenchymal transition such as Claudin-1, ZO-1, and ZEB-1. The inhibition of Fak activity using the Fak inhibitor (PF-562281) restored the radiosensitivity in HER2-overexpressing cells. In conclusion, HER2 reduces the radiosensitivity of breast cancer by activating Fak in vitro and in vivo. Fak might be a potential target for the radiosensitization of HER2-overexpressed breast cancer.


Molecular mechanisms of the microsomal mixed function oxidases and biological and pathological implications.
The cytochrome P450 mixed function oxidase enzymes play a major role in the metabolism of important endogenous substrates as well as in the biotransformation of xenobiotics. The liver P450 system is the most active in metabolism of exogenous substrates. This review briefly describes the liver P450 (CYP) mixed function oxidase system with respect to its enzymatic components and functions. Electron transfer by the NADPH-P450 oxidoreductase is required for reduction of the heme of P450, necessary for binding of molecular oxygen. Binding of substrates to P450 produce substrate binding spectra. The P450 catalytic cycle is complex and rate-limiting steps are not clear. Many types of chemical reactions can be catalyzed by P450 enzymes, making this family among the most diverse catalysts known. There are multiple forms of P450s arranged into families based on structural homology. The major drug metabolizing CYPs are discussed with respect to typical substrates, inducers and inhibitors and their polymorphic forms. The composition of CYPs in humans varies considerably among individuals because of sex and age differences, the influence of diet, liver disease, presence of potential inducers and/or inhibitors. Because of such factors and CYP polymorphisms, and overlapping drug specificity, there is a large variability in the content and composition of P450 enzymes among individuals. This can result in large variations in drug metabolism by humans and often can contribute to drug-drug interactions and adverse drug reactions. Because of many of the above factors, especially CYP polymorphisms, there has been much interest in personalized medicine especially with respect to which CYPs and which of their polymorphic forms are present in order to attempt to determine what drug therapy and what dosage would reflect the best therapeutic strategy in treating individual patients.


Tumor-derived aberrant methylation in plasma of invasive ductal breast cancer patients: clinical implications.
Progressive p16 methylation has been associated with metastasis and invasive phenotypes in many cancers. Loss of E-cadherin (CDH1) function contributes to breast cancer progression by promoting cell proliferation, invasion and metastasis. Using methylation-specific PCR, aberrant hypermethylation of p16 and CDH1 in tumor and plasma was analyzed and correlated with levels of serum protein markers, carcinoembryonic antigen (CEA) and carcinoma antigen 15-3 (CA15.3), in 36 patients with invasive ductal breast cancer. Aberrant p16 methylation was found in 11% (4/36) of primary tumors and 8% (3/36) of plasma samples. Aberrant CDH1 methylation was detected in 25% (9/36) of primary tumors and 20% (7/36) of plasma samples. p16 and/or CDH1 hypermethylation was found in 31% (11/36) of primary breast carcinomas and 82% (9/11) of breast cancer patients with tumoral methylation showing identical epigenetic changes in plasma. The 25 patients without tumoral methylation did not show epigenetic changes in the plasma. Tumoral p16 methylation was significantly associated with advanced tumor stage (p=0.028; Fisher's exact test), tumor size (p=0.017) and nodal metastasis (p=0.002). However, p16 methylation in plasma was only associated with nodal metastasis (p=0.012). Altogether, aberrant p16 methylation in plasma and elevated serum CEA level were associated with advanced tumor stage (p=0.033), tumor size (p=0.022) and extensive nodal metastasis (p=0.003). With clinical implications, p16 hypermethylation in plasma and/or raised serum CEA levels may prove useful as diagnostic and prognostic markers for breast cancer.


Identification of monoclonal immunoglobulins and quantitative immunoglobulin abnormalities in hairy cell leukemia and chronic lymphocytic leukemia.
Serum and urine samples from 161 cases of hairy cell leukemia (HCL) and 50 cases of chronic lymphocytic leukemia (CLL) were analyzed for monoclonal immunoglobulin (MIg) by using a combination of high-resolution protein electrophoresis, immunoelectrophoresis, and immunofixation. Quantitative immunoglobulin analysis also was performed on all serum samples. Monoclonal immunoglobulin, usually of low intensity, was identified in serum or urine in 26 (16.1%) cases of HCL compared with 27 (54%) cases of CLL. Forty-eight (29.8%) cases of HCL had an increase in one or more immunoglobulins; increases in IgG were the most frequent. In CLL, 48 (96.0%) cases had a decrease in one or more immunoglobulins, with decreases in IgG, IgA, and IgM in 76%, 68%, and 56% of the cases, respectively. The correlation between serum or urine monoclonal immunoglobulin light chain and the surface membrane light chain was 88% in CLL compared with 47.4% in HCL. These findings confirm previous observations of frequent polyclonal hyper-gamma-globulinemia in HCL, hypo-gamma-globulinemia in CLL, and weak monoclonal immunoglobulins in both disorders. The contrasting immunoglobulin abnormalities in HCL and CLL indicate distinctive biologic differences in these chronic B-cell leukemias.


Enhanced bone formation by strontium modified calcium sulfate hemihydrate in ovariectomized rat critical-size calvarial defects.
The development of a new generation of biomaterials with high osteogenic ability for treatment of osteoporotic fractures is being intensively investigated. The objective of this paper was to investigate new bone formation in an ovariectomized rat (OVX rat) calvarial model of critical size bone defects filled with Sr-containing α-calcium sulfate hemihydrate (SrCSH) cement compared to an α-calcium sulfate hemihydrate (α-CSH) cement and empty defect. X-ray diffraction analysis verified the partial substitution of Sr2+ for Ca2+ did not change the phase composition of α-CSH. Scanning electron microscopy showed that Sr-substituted α-CSH significantly increased the surface roughness. The effects of Sr substitution on the biological properties of SrCSH cement were evaluated by adhesion, proliferation, alkaline phosphatase (ALP) activity of osteoblast-like cells MC3T3-E1. The results showed that SrCSHs enhanced MC3T3-E1 cell proliferation, differentiation, and ALP activity. Furthermore, SrCSH cement was used to repair critical-sized OVX rat calvarial defects. The in vivo results revealed that SrCSH had good osteogenic capability and stimulated new blood vessel formation in a critical sized OVX calvarial defect within 12 weeks, suggesting that SrCSH cement has more potential for application in bone tissue regeneration.


The taxonomy of some new isolates of dissimilatory sulfate-reducing bacteria.
The interrelationships between 92 isolates of sporing and non-sporing sulfate-reducing bacteria were determined. Of the 116 biochemical and physiological characteristics examined, only 25 were useful for discrimination of groups. Responses to most of the test were negative. A similarity coefficient and a principal component factor analysis of these data were made. The deoxyribonucleic acids buoyant densities (DNA) from all strains and the electrophoretic properties of adenylylsulfotransferase (ATP-sulfurylase), adenylphosphosulfate (APS)-reductase, and sulfite reductase of selected isolated were determined. On the basis of these various data eight groups were recognized. Isolated of seven of these groups appeared to be similar to one or more named strains. Isolates of group E(DNA buoyant density, 1.708) were different from previously named strains. Sporins strains were not isolated from the Papua New Guinea location. Halophilic and non-halotolerant strains were isolated from highly saline locations in Australia. Results pertinent to the taxonomy and ecology of the sulfate-reducing bacteria are discussed.


[Patient injuries in response to anaesthetic procedures: cases evaluated by the Danish Patient Insurance Association--secondary publication].
We investigated the Danish Patient Insurance Association files of patients, who were given financial compensation, because of an injury caused by an anaesthetic procedure. In the six-year-period 1996-2002, 374 patients were compensated in total 8.0 million euros for an injury caused by an anaesthetic procedure. Some anaesthetic complications may result in severe disability, whereby the financial compensation to the suffering patients is high. We estimate that approximately 0.2 per 1,000 of all patients receiving anaesthesia may develop complications that entitle them to financial compensation.


Whole-genome resequencing of honeybee drones to detect genomic selection in a population managed for royal jelly.
Four main evolutionary lineages of A. mellifera have been described including eastern Europe (C) and western and northern Europe (M). Many apiculturists prefer bees from the C lineage due to their docility and high productivity. In France, the routine importation of bees from the C lineage has resulted in the widespread admixture of bees from the M lineage. The haplodiploid nature of the honeybee Apis mellifera, and its small genome size, permits affordable and extensive genomics studies. As a pilot study of a larger project to characterise French honeybee populations, we sequenced 60 drones sampled from two commercial populations managed for the production of honey and royal jelly. Results indicate a C lineage origin, whilst mitochondrial analysis suggests two drones originated from the O lineage. Analysis of heterozygous SNPs identified potential copy number variants near to genes encoding odorant binding proteins and several cytochrome P450 genes. Signatures of selection were detected using the hapFLK haplotype-based method, revealing several regions under putative selection for royal jelly production. The framework developed during this study will be applied to a broader sampling regime, allowing the genetic diversity of French honeybees to be characterised in detail.


Congenital malformation syndromes associated with peripheral neuroblastic tumors: A systematic review.
Malformation syndromes with predisposition to peripheral neuroblastic tumors (pNT), including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, may provide clues to critical mutations influencing pNT development. Our objective was to identify and characterize features of pNT associated with specific malformation syndromes. A systematic review of the literature was performed using MEDLINE, Scopus, and Web of Science. We identified 154 of 1014 papers that met eligibility, comprising 207 cases. The patient's age, tumor histology, and frequency of multiple primary tumors varied by malformation syndrome. Genomic studies and systematized reporting are necessary to elucidate cancer risk and the distinct clinical and biological pNT patterns within syndromes.


Regulation of bone marrow lymphocyte production: IV. Altered kinetic steady state of lymphocyte production after chronic changes in exogenous stimuli.
A transient increase in B lymphocyte production in mouse bone marrow has previously been shown to follow a single administration of various exogenous agents. The effect of sustained changes in exogenous stimuli on the level of bone marrow B lymphocyte production has now been studied. In mice given multiple injections of sheep red blood cells (SRBC) for four weeks the production of bone marrow lymphocytes was augmented, as indicated by increased numbers of cytoplasmic mu-chain-bearing pre-B cells and of surface mu-chain-bearing B lymphocytes, as well as increased rates of pre-B cell proliferation and small lymphocyte turnover. In an attempt to reduce potential external stimuli, mice were raised on an elemental diet. When compared to conventionally reared mice, however, they showed little difference in bone marrow small lymphocyte production and an identical pre-B cell proliferation rate. In addition, the small lymphocyte production rate in the thymus was not consistently altered either in SRBC-treated mice or elemental diet-fed mice, whereas small lymphocyte renewal in the spleen showed changes reflecting those in the bone marrow. The results demonstrate that a chronic increase in exposure to extrinsic agents can produce a long-term elevation of the population size and production rate of bone marrow B lineage cells. This suggests that the level of the kinetic steady state of primary B lymphocyte production normally observed in the bone marrow may reflect the level of exposure to potential stimulants in the external environment.


Using non-invasive ventilation in acute wards: Part 1.
Non-invasive ventilation (NIV) is increasingly being used in domestic and acute health settings. Part one of this article identifies the benefits of NIV and describes the use of continuous positive airway pressure (CPAP). Part two, published in next week's Nursing Standard, discusses bilevel NIV, which has fewer complications and so is largely replacing CPAP. Part two also examines how to monitor and assess patients receiving NIV.


Readmission Outcomes of Sliding Scale Insulin Compared to Basal-Bolus Insulin Prescribed at Discharge in an Insulin-Naive Patient Population.
Limited data are available that examine hospital readmission outcomes of sliding scale compared to basal-bolus insulin in indigent and insulin-naive patients. To evaluate hospital readmission outcomes in patients who are insulin naive with type 2 diabetes mellitus who are initiated on either sliding scale or basal-bolus insulin upon hospital discharge. A retrospective chart review was conducted of adult patients with a history of type 2 diabetes mellitus, who were insulin naive, had a hemoglobin A1c (HbA1c) 10% or greater, and were discharged with a prescription for sliding scale or basal-bolus insulin from January 2015 to July 2018. The primary objective measured all-cause 30-day hospital readmissions. The secondary objectives measured diabetes-related 30-day hospital readmissions and HbA1c change after 3 months of initial hospital admission. Data were analyzed using descriptive statistics, χ2 test, paired sample t test, and logistic regression. Forty-one patients were prescribed sliding scale insulin and 105 patients were prescribed basal-bolus insulin. The majority were male (60%), spoke English (84%), were self-pay (39%), and had a mean age of 51 ± 10.2 years, initial HbA1c of 13% ± 1.9%, and LACE+ score of 51 ± 15.6 upon discharge. All-cause 30-day hospital readmissions occurred in 14.6% of sliding scale and 6.7% of basal-bolus insulin groups (odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.75-7.63). Hyperglycemia occurred in 7.3% of sliding scale and 0.9% of basal-bolus insulin groups. Mean HbA1c difference for basal-bolus and sliding scale insulin was 3.3 ± 3.1 and 2.9 ± 2.7, respectively (P = 0.459). There was no significant difference in all-cause 30-day hospital readmissions comparing sliding scale to basal-bolus insulin.


Detection of Pathogens Associated with Psyllids and Leafhoppers in Capsicum annuum L. in the Mexican States of Durango, Zacatecas, and Michoacán.
In fall 2014, 5 to 75% percent of chili and bell pepper (Capsicum annuum L.) in commercial fields located in the Mexican states of Durango, Zacatecas, and Michoacán had symptoms of deformed, small, mosaic, curled, and chlorotic leaves; shortened internodes; plant dwarfing; or phyllody and rosetting leaf tips. At the same time, leafhoppers and psyllids were observed in the fields, and more than 50 beet leafhoppers (Circulifer tenellus) and nearly 300 potato psyllids (Bactericera cockerelli) were collected from the pepper plants and adjacent weeds. Based on the insect pressure and observed symptoms, nearly 400 pepper samples were collected across this region of Mexico and tested for the presence of leafhopper- and psyllid-associated pathogens. In all, 76% of the pepper samples were found to be infected with 'Candidatus Liberibacter solanacearum', beet leafhopper-transmitted virescence agent (BLTVA) phytoplasma, a strain of a curtovirus, or a combination of any two or three of these pathogens. Additionally, 77% of the collected leafhoppers and 40% of the psyllids were infected with one or more of these pathogens, in addition to Spiroplasma citri. Specifically, the leafhoppers were infected with BLTVA phytoplasma, S. citri, or a strain of curtovirus. Of particular interest, potato psyllids were not only infected with 'Ca. L. solanacearum' but also with phytoplasmas that belong to the groups 16SrVI subgroup A and 16SrI subgroup A. The presence of mixed infections in pepper plants and the insect vectors highlights the need for growers to effectively control both leafhoppers and potato psyllids from solanaceous crops in this region of Mexico in order to prevent the spread of these bacterial and viral pathogens.


Iridium complexes containing mesoionic C donors: selective C(sp3)-H versus C(sp2)-H bond activation, reactivity towards acids and bases, and catalytic oxidation of silanes and water.
Metalation of a C2-methylated pyridylimidazolium salt with [IrCp*Cl2]2 affords either an ylidic complex, resulting from C(sp(3))-H bond activation of the C2-bound CH3 group if the metalation is performed in the presence of a base, such as AgO2 or Na2CO3, or a mesoionic complex via cyclometalation and thermally induced heterocyclic C(sp(2))-H bond activation, if the reaction is performed in the absence of a base. Similar cyclometalation and complex formation via C(sp(2))-H bond activation is observed when the heterocyclic ligand precursor consists of the analogous pyridyltriazolium salt, that is, when the metal bonding at the C2 position is blocked by a nitrogen rather than a methyl substituent. Despite the strongly mesoionic character of both the imidazolylidene and the triazolylidene, the former reacts rapidly with D(+) and undergoes isotope exchange at the heterocyclic C5 position, whereas the triazolylidene ligand is stable and only undergoes H/D exchange under basic conditions, where the imidazolylidene is essentially unreactive. The high stability of the Ir-C bond in aqueous solution over a broad pH range was exploited in catalytic water oxidation and silane oxidation. The catalytic hydrosilylation of ketones proceeds with turnover frequencies as high as 6,000 h(-1) with both the imidazolylidene and the triazolylidene system, whereas water oxidation is enhanced by the stronger donor properties of the imidazol-4-ylidene ligands and is more than three times faster than with the triazolylidene analogue.


Souakine mouth rinse solution protects deciduous enamel from simulated erosion in vitro.
To determine whether a souakine mouth rinse solution can provide protection of deciduous teeth against simulated erosion in vitro. Thirty deciduous anterior teeth were used. Half of each tooth was covered with a varnish and teeth were randomly divided into a treated (S) and a control group (C). Each group was immersed in cola drink for 5 minutes and treated with an aqueous solution of Souakine (S) or water (C) for 2 minutes. The treatment was renewed 5 times a day for 8 days. Teeth were then embedded, sectioned and observed under polarised light microscope. Observed data were quantitatively analysed by SPSS software. In group (C), the unvarnished part of the enamel showed a deep green layer of erosion, compared to the varnished part. The difference in depth of this layer was significant (p<0.05). In group (S), the green layer of erosion was highly located in the unvarnished part as compared to the unvarnished part of the control group (C) (p<0.05). This layer of erosion was comparable to that in the varnished part, either in control or treated groups. The beneficial results of Souakine against erosion are validated either by a protective or a remineralisation effect.


Diagnostic Value of Serum SMP30 and Anti-SMP30 Antibody in Hepatocellular Carcinoma.
To evaluate the clinical value of senescence marker protein 30 (SMP30) and anti-SMP30 antibody in serum. We used enzyme-linked immunosorbent assay (ELISA) to analytically validate serum levels of SMP30 and anti-SMP30 antibody in 143 patients with hepatocellular carcinoma (HCC), compared with those levels in serum from 137 patients with chronic hepatitis (CH), 51 with liver cirrhosis (LC), and 165 healthy control individuals. The positivity rate of SMP30 in the HCC group (8.39%) was significantly higher than that rate in the CH group (.73%) and in the healthy control group (1.21%). The positivity rate for anti-SMP30 antibody in patients with HCC was 25.87%, that in the CH group was 4.38%, and that in the LC group was 3.92%. Anti-SMP30 antibody levels can be used as a biomarker for diagnosing HCC; marked results have been observed for patients with alpha-fetoprotein (AFP) negativity, in particular.


[Minimally invasive direct coronary artery bypass grafting (MIDCAB) for right and circumflex coronary artery systems].
Single-vessel coronary bypass grafting of the left internal thoracic artery (LITA) to the left anterior descending coronary artery (LAD) with mini-thoracotomy has been shown to produce excellent results with almost no mortality. However this procedure cannot be used in patients with double or triple vessel disease. Between Aug. 96 and Dec. 97, 17 pts underwent minimally invasive direct coronary artery bypass (MIDCAB) to right (RCA) and circumflex coronary artery (CX). LITA and RITA were thoracicscopically harvested and the right gastroepiploic artery (RGEA), inferior epigastric artery, and radial artery were then harvested. A limited left thoracotomy in combination with limited anterior right thoracotomy (n = 3) or right lower parasternal incision extending to below the xiphoid process (n = 6) were made. The double MIDCAB as performed in 16 pts and triple in 1 pt. There was no operative death. At follow up, all pts are alive and well. The postoperative angiographic studies showed 30/31 grafts were patent. The utility of multi-vessel MIDCAB for the LAD, CX and RCA with in-site arterial grafts has been demonstrated in the present study. This less invasive surgical technique may become a viable option for the management of multi-vessel coronary artery disease.


Anticancer antifolates: current status and future directions.
Antifolates are the oldest of the antimetabolite class of anticancer agents and were one of the first modern anticancer drugs. The first clinically useful antifolate, described in 1947, was 2,4-diamino-pteroylglutamate (4-amino-folic acid; aminopterin; AMT) which yielded the first-ever remissions in childhood leukemia. AMT was soon superseded by its 10-methyl congener, methotrexate (MTX), based on toxicity considerations; MTX remains, with one limited exception, the only antifolate anticancer agent in clinical use to this date. Because of the safety and utility of MTX, considerable effort has been invested in attempting to design more therapeutically selective antifolates or antifolates with a wider tumor spectrum. Initially, the design was based on the burgeoning knowledge of folate-dependent pathways and the determinants of the mechanism of action of MTX. These determinants include transport, the tight-binding inhibition of its target (the folate-dependent enzyme dihydrofolate reductase (DHFR)), and metabolism of MTX to poly-gamma-glutamate (Glu(n)) metabolites. These early studies led to the development of other antifolate DHFR inhibitors of two types: (1). "classical" analogs that use the same cellular transport systems as MTX and are also metabolized to Glu(n); and (2). "nonclassical" (i.e., lipophilic) analogs that do not require transport systems and that are not metabolized to Glu(n). Although several of these analogs have undergone clinical trial, none is proved superior to MTX. Detailed examination of the mechanisms of cytotoxicity and selectivity of MTX showed that inhibition of both dTMP synthesis and de novo purine synthesis, secondary to DHFR inhibition, led to DNA synthesis inhibition and subsequent cell death; inhibition of other folate-dependent pathways did not appear necessary for cell death. Further studies showed that the contribution of inhibition of dTMP or purine synthesis to cell death varied in different cell types. These data suggested that inhibition of one of these pathways individually might (at least in some cases) be therapeutically superior to the dual inhibition induced by MTX. Thus in rational design and in structure-based design studies, two new classes of antifolate enzyme inhibitors were elaborated-direct inhibitors of thymidylate synthase (TMPS) and direct inhibitors of one or both of the two folate-dependent enzymes of de novo purine synthesis. Members of each class included both classical and nonclassical types. After preclinical evaluation, several of these have moved into clinical trials. To date only one new TMPS inhibitor has successfully completed clinical trials and been approved for routine use; this drug, Tomudex (D1694, raltitrexed) is currently approved only in Europe and only for the treatment of colon cancer. This still represents a step forward for antifolates, however, since MTX is well-known to be ineffective in colon cancer; thus Tomudex extends the tumor range of antifolates. Antifolate development continues. Based on the immense body of knowledge now extant on antifolates, specific aspects of the mechanism of action have been the focus. Newer antifolates have been described that inhibit more than one pathway in folate metabolism, that have improved delivery, or that inhibit other targets in folate metabolism. These new analogs are in various stages of preclinical and clinical development.


Proofreading by DNA polymerase III of Escherichia coli depends on cooperative interaction of the polymerase and exonuclease subunits.
The polymerase subunit (alpha) of Escherichia coli DNA polymerase III holoenzyme and the 3'----5' exonuclease subunit (epsilon) are each less active separately than together in the holoenzyme core (an assembly of alpha, epsilon, and theta subunits). In a complex formed from purified alpha and epsilon subunits, polymerase activity increased 2-fold, and that of the 3'----5' exonuclease increased 10- to 80-fold. The alpha-epsilon complex contains one each of the subunits as does the core. Stimulation of 3'----5' exonuclease activity is due mainly to a greatly increased affinity of the epsilon subunit for the 3'-hydroxyl terminus, resulting from DNA binding by the alpha subunit. Proofreading in the course of DNA synthesis by the alpha-epsilon complex was indistinguishable from that of the core. These findings identify the participation of the alpha subunit in proofreading by polymerase III holoenzyme and suggest that the fidelity of DNA replication may be influenced by the relative levels of the alpha and epsilon subunits in the cell.


Mutational analysis of driver genes with tumor suppressive and oncogenic roles in gastric cancer.
Gastric cancer (GC) is a complex disease with heterogeneous genetic mechanisms. Genomic mutational profiling of gastric cancer not only expands our knowledge about cancer progression at a fundamental genetic level, but also could provide guidance on new treatment decisions, currently based on tumor histology. The fact that precise medicine-based treatment is successful in a subset of tumors indicates the need for better identification of clinically related molecular tumor phenotypes, especially with regard to those driver mutations on tumor suppressor genes (TSGs) and oncogenes (ONGs). We surveyed 313 TSGs and 160 ONGs associated with 48 protein coding and 19 miRNA genes with both TSG and ONG roles. Using public cancer mutational profiles, we confirmed the dual roles of CDKN1A and CDKN1B. In addition to the widely recognized alterations, we identified another 82 frequently mutated genes in public gastric cancer cohort. In summary, these driver mutation profiles of individual GC will form the basis of personalized treatment of gastric cancer, leading to substantial therapeutic improvements.


Behavioral and respiratory dysfunction in the freshwater fish, Labeo rohita (Hamilton) under malathion intoxication.
A short term definitive test by static renewal bioassay method was conducted to determine the acute toxicity (LC50) of the commercial grade organophosphate insecticide malathion (50% EC) in the freshwater edible fish, Labeo rohita. Carp fingerlings were exposed for 96 h to different concentrations (6.0 to 10.1 microL/L) of malathion. The acute toxicity value was found to be 9.0 microL/L and one tenth of LC50 (0.9 microL/L) was selected for sub acute studies. Behavioral patterns and oxygen consumption were studied in lethal (1, 2, 3, and 4 d) and sublethal concentrations (1, 5, 10, and 15 d). Carp in toxic media exhibited irregular, erratic, and darting swimming movements, hyperexcitability, and loss of equilibrium and sinking to the bottom, which might be due to the inactivation of acetylcholine esterase activity, resulting in excess accumulation of acetylcholine in cholinergic synapses leading to hyperstimulation. Variation in oxygen consumption (70.39% to 80.50%/4.45% to 21.35%) was observed in both lethal and sublethal concentrations of malathion, respectively. Such alterations in oxygen consumption may be due to respiratory distress because of impairment in oxidative metabolism. Fish at sub lethal concentrations were found under stress, but that was not fatal.


Simultaneous balancing of geometric transformation and linear polarizations using six-fold-mirror geometry over the visible region.
The presence of optical rotation due to the Berry phase and coating-induced linear polarizations across a set of rays deteriorate the form of a point spread function. In this Letter, we model an optical system with six aluminum coated fold mirrors, and we show how to balance geometric transformation, linear retardance, and linear diattenuation simultaneously. We minimize the linear polarizations by arranging the six fold mirrors in three pairs of crossed-fold-mirror geometry. In the same optical model, we also show that geometric transformation induced by the first set of three mirrors is canceled out by the second set of three mirrors by rotating the eigen-polarizations in opposite direction with the same amount. We perform experimental verification using a spectroscopic Mueller matrix polarimeter over the visible spectral range.


Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review.
Fragility fractures are a strong indicator of underlying osteoporosis (OP). With the risk of future fracture being increased 1.5- to 9.5-fold following a fragility fracture, the diagnosis and treatment of OP in men and women with fragility fractures provides the opportunity to prevent future fragility fractures. This review describes the current status of practice in investigation and diagnosis of OP in men and women with fragility fractures, the rates and types of postfracture treatment in patients with fragility fractures and OP, interventions undertaken in this population, and the barriers to OP identification and treatment. A literature search performed in Medline, Healthstar, CINAHL, EMBASE, PreMedline, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 37 studies on OP diagnosis, treatment, and interventions. The studies varied in design methodology, study facilities, types of fractures, and pharmacological treatments. Some studies revealed that no patients with fragility fractures received investigation or treatment for underlying OP. Investigation of OP by bone mineral density was low: 14 of 16 studies reported investigation of less than 32% of patients. Investigation by bone mineral density resulted in high rates of OP diagnosis (35-100%), but only moderate use of calcium and vitamin D (8-62%, median 18%) and bisphosphates (0.5-38%) in patients investigated postfracture. Studies on barriers to OP identification and treatment focused on various groups of health practitioners. Barriers included the cost of therapies, time and cost of resources for diagnosis, concerns about medications, and the lack of clarity regarding the responsibility to undertake this care.


Mental practice with interactive 3D visual aids enhances surgical performance.
Evidence suggests that Mental Practice (MP) could be used to finesse surgical skills. However, MP is cognitively demanding and may be dependent on the ability of individuals to produce mental images. In this study, we hypothesised that the provision of interactive 3D visual aids during MP could facilitate surgical skill performance. 20 surgical trainees were case-matched to one of three different preparation methods prior to performing a simulated Laparoscopic Cholecystectomy (LC). Two intervention groups underwent a 25-minute MP session; one with interactive 3D visual aids depicting the relevant surgical anatomy (3D-MP group, n = 5) and one without (MP-Only, n = 5). A control group (n = 10) watched a didactic video of a real LC. Scores relating to technical performance and safety were recorded by a surgical simulator. The Control group took longer to complete the procedure relative to the 3D&MP condition (p = .002). The number of movements was also statistically different across groups (p = .001), with the 3D&MP group making fewer movements relative to controls (p = .001). Likewise, the control group moved further in comparison to the 3D&MP condition and the MP-Only condition (p = .004). No reliable differences were observed for safety metrics. These data provide evidence for the potential value of MP in improving performance. Furthermore, they suggest that 3D interactive visual aids during MP could potentially enhance performance, beyond the benefits of MP alone. These findings pave the way for future RCTs on surgical preparation and performance.


Mutations in rotavirus nonstructural glycoprotein NSP4 are associated with altered virus virulence.
Rotaviruses are major pathogens causing life-threatening dehydrating gastroenteritis in children and animals. One of the nonstructural proteins, NSP4 (encoded by gene 10), is a transmembrane, endoplasmic reticulum-specific glycoprotein. Recently, our laboratory has shown that NSP4 causes diarrhea in 6- to 10-day-old mice by functioning as an enterotoxin. To confirm the role of NSP4 in rotavirus pathogenesis, we sequenced gene 10 from two pairs of virulent and attenuated porcine rotaviruses, the OSU and Gottfried strains. Comparisons of the NSP4 sequences from these two pairs of rotaviruses suggested that structural changes between amino acids (aa) 131 and 140 are important in pathogenesis. We next expressed the cloned gene 10 from the OSU virulent (OSU-v) and OSU attenuated (OSU-a) viruses by using the baculovirus expression system and compared the biological activities of the purified proteins. NSP4 from OSU-v virus increased intracellular calcium levels over 10-fold in intestinal cells when added exogenously and 6-fold in insect cells when expressed endogenously, whereas NSP4 from OSU-a virus had little effect. NSP4 from OSU-v caused diarrhea in 13 of 23 neonatal mice, while NSP4 from OSU-a caused disease in only 4 of 25 mice (P < 0.01). These results suggest that avirulence is associated with mutations in NSP4. Results from site-directed mutational analyses showed that mutated OSU-v NSP4 with deletion or substitutions in the region of aa 131 to 140 lost its ability to increase intracellular calcium levels and to induce diarrhea in neonatal mice, confirming the importance of amino acid changes from OSU-v NSP4 to OSU-a NSP4 in the alteration of virus virulence.


Micro-optical coherence tomography tracking of magnetic gene transfection via Au-Fe3O4 dumbbell nanoparticles.
Heterogeneous Au-Fe3O4 dumbbell nanoparticles (NPs) are composed of Au NPs and Fe3O4 NPs that bring in optical and magnetic properties respectively. This article reports the engineering of Au-Fe3O4 NPs as gene carriers for magnetic gene transfection as well as contrast agents for micro-optical coherence tomography (μOCT). As a proof-of-concept, Au-Fe3O4 NPs are used to deliver the green fluorescent protein to HEK 293T cells and their entrance into the cells is monitored through μOCT.


L-Rhamnose and Phenolic Esters-Based Monocatenar and Bolaform Amphiphiles: Eco-Compatible Synthesis and Determination of Their Antioxidant, Eliciting and Cytotoxic Properties.
Symmetrical and dissymmetrical bolaforms were prepared with good to high yields from unsaturated L-rhamnosides and phenolic esters (ferulic, phloretic, coumaric, sinapic and caffeic) using two eco-compatible synthetic strategies involving glycosylation, enzymatic synthesis and cross-metathesis under microwave activation. The plant-eliciting activity of these new compounds was investigated in Arabidopsis model plants. We found that the monocatenar rhamnosides and bolaforms activate the plant immune system with a response depending on the carbon chain length and the nature of the hydrophilic heads. Their respective antioxidant activities were also evaluated, as well as their cytotoxic properties on dermal cells for cosmetic uses. We showed that phenolic ester-based compounds present good antioxidant activities and that their cytotoxicity is low. These properties are also dependent on the carbon chains used.


Catalysis of zinc transfer by D-penicillamine to secondary chelators.
The antiarthritis drug D-penicillamine (D-PEN) catalyzes zinc(II) transfer from carboxypeptidase A to chelators such as thionein and EDTA at a rate constant up to 400-fold faster than the uncatalyzed release. Once D-PEN releases zinc(II) from enzyme stronger chelators can tightly bind zinc(II) leading to complete and essentially irreversible inhibition. D-PEN is the first drug to inhibit a zinc protease by catalyzing metal removal, and the name "catalytic chelation" is proposed for this mechanism.


Mechanisms mediating the vasoactive effects of the B1 receptors of bradykinin.
Bradykinin normally exerts its vasodilatory effect via the B2 receptor (B2R), but in this receptor's absence, the B1 receptor becomes expressed and activated. To explore the mechanism of B1R-mediated vasodilation, 8 groups of B2R gene-knockout mice received a 2-week infusion of a B1R antagonist (300 microg x kg(-1) x d(-1)) or vehicle (groups 1 and 2), B1R antagonist or vehicle plus NO inhibition with Nomega-nitro-L-arginine methyl ester (groups 3 and 4), B1R antagonist or vehicle plus cyclooxygenase inhibition with indomethacin (groups 5 and 6), or B1R antagonist or vehicle plus blockade of vasoconstricting prostaglandin (PG) H2 and thromboxane A2 (TxA2) with SQ29548 (groups 7 and 8). The B1R antagonist produced significant (P<0.05) blood pressure increases of 17.7+/-3.1 mm Hg in group 1 and 10.4+/-3 mm Hg in group 3, whereas their vehicle-treated respective control groups 2 and 4 had no significant blood pressure changes. Indomethacin abolished the capacity of the B1R antagonist to raise blood pressure, as did blockade of the receptors of PGH2 and TxA2. Injection with the B1R agonist produced a hypotensive response (12+/-1.3 mm Hg), which was further accentuated by TxA2 blockade (21.7+/-4.1 mm Hg). Analysis of B1R gene expression by reverse transcription-polymerase chain reaction (PCR) in cardiac and renal tissues revealed marked expression at baseline, with further upregulation by 1.5- to 2-fold after various manipulations. Expression of the TxA2 receptor gene in renal tissue by quantitative real-time PCR was significantly lower in mice treated with the B1R antagonist, consistent with increased levels of agonist for this receptor. The data confirm that the B1R becomes markedly expressed in the absence of B2R and suggest that it contributes to vasodilation by inhibiting a vasoconstricting product of the arachidonic acid cascade acting via the PGH2/TxA2 receptor.


Relaxant actions of nonprostanoid prostacyclin mimetics on human pulmonary artery.
The specific prostacyclin (IP) receptor agonist cicaprost relaxed human pulmonary artery preparations precontracted with phenylephrine [50% inhibitory concentration (IC50) approximately 0.6 nM], U-46619 (IC50 approximately 0.9 nM), and K+ (approximately 40% maximal relaxation); endothelium removal had little effect on relaxant activity. Ranking of relaxant potencies for prostacyclin and five of its analogs was 17 alpha, 20-dimethyl-delta 6,6a-6a-carba PGI1 (TEI-9063) > or = cicaprost > iloprost > prostacyclin > taprostene > benzodioxane prostacyclin > 15-deoxy-16 alpha-hydroxy-16 beta,20-dimethyl-delta 6,6a-6a-carba PGI1 (TEI-3356). The potency of the isocarbacyclin TEI-3356 may have been under-estimated because of its contractile (EP3 receptor agonist) activity. The potency ranking of four nonprostanoid prostacyclin mimetics was 3-[4-(4,5-diphenyl-2-oxazolyl)-5-oxazolyl]phenoxy] acetic acid (BMY 45778; IC50 approximately 2.5 nM) > > 2-[3-[2-(4, 5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid (BMY 42393) > octimibate > CU 23 (a novel diphenylindole). From IP receptor binding affinities obtained on human platelet membranes, it is suggested that the slightly shallower log concentration-response curves for BMY 45778, BMY 42393, and CU 23 may reflect the near-maximal receptor occupancy required for complete relaxation. A fifth nonprostanoid, CU 602, had much shallower log concentration-response curves than cicaprost against phenylephrine tone but not against U-46619 tone; this may indicate IP receptor partial agonism coupled with TP receptor antagonism. The relaxant actions of the nonprostanoid mimetics were more persistent than those of the prostacyclin analogs on washout of the organ bath; by the inhalation route, this type of compound may be retained within pulmonary tissue and thus afford greater pulmonary/systemic selectivity than currently used pulmonary vasodilators.


Purpose: To examine the temporal stability and relative validity of the adapted French version of an English self-reported questionnaire measuring the beverage intake (BEVQ) of adolescents.Methods: The French adaptation of the BEVQ (AF-BEVQ) included conversion from the imperial to the metric system and the adjustment of some formats to those available in Canada. Next, 60 adolescents from two regions in Quebec completed the AF-BEVQ and two web-based 24-hour dietary recalls (R24W) (one for a weekday and one for a weekend day) on two occasions, two weeks apart.Results: The AF-BEVQ had moderate intraclass correlation coefficients (ICC) for amounts of sugar-sweetened beverages (ICC: 0.68; 95% confidence interval [CI]: 0.46-0.81), fruit juice (ICC: 0.54; 95% CI: 0.23-0.72) and water (ICC: 0.66; 95% CI: 0.38-0.81) consumed. The amounts of sugar-sweetened beverages (rs = 0.49; p < 0.0001), fruit juice (rs = 0.38; p = 0.0024) and water (rs = 0.65; p < 0.0001) reported in the AF-BEVQ were significantly correlated with those of both R24Ws.Conclusions: For the most part, the AF-BEVQ had adequate metrological properties. It is an interesting tool to quickly measure the sugar-sweetened beverage, fruit juice and water intake of French-speaking adolescents.


An analysis of poor risk assignment in patients with germ cell tumours.
Four methods for assigning patients with germ cell tumours to poor risk programmes were compared using 118 consecutive patients treated on 'good' and 'poor' risk studies. The median survival of patients deemed poor risk by Memorial Sloan-Kettering Cancer Center was 11 months, by Indiana University 15 months, by the National Cancer Institute 15 months, and by the European Organization for Research on the Treatment of Cancer 23.5 months. The major differences between these criteria were in the use of pretreatment tumour marker values, and the use of specific sites of metastases as independent prognostic variables. These data imply that a variable number of good prognosis patients enter some poor risk trials, the number being dependent upon the criteria used. Poor risk criteria should be as restrictive as possible in order to avoid over treating good risk patients, and to avoid artificially inflated response rates resulting from the successful treatment of such poor risk patients.


Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.
Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immunosuppressive microenvironments, and leukemic stem cell populations elusive to immune recognition and destruction. While there are promising T cell-based therapies including chimeric antigen receptor (CAR)-T designs under development, other cytotoxic lymphocyte cell subsets have unique phenotypes and capabilities that might be of additional benefit in AML treatment. Of particular interest are the natural killer (NK) and unconventional T cells known as invariant natural killer T (iNKT) and gamma delta (γδ) T cells. NK, iNKT, and γδT cells exhibit intrinsic anti-malignant properties, potential for alloreactivity, and human leukocyte-antigen (HLA)-independent function. Here we review the biology of each of these unconventional cytotoxic lymphocyte cell types and compare and contrast their strengths and limitations as the basis for adoptive cell therapies for AML.


Transbilayer organization of the chlorophyll-proteins of spinach thylakoids.
To investigate the transverse bilayer organization of the chlorophyll-proteins of the three intrinsic chlorophyll-protein complexes, the effects of proteolytic enzymes, and an antibody against the light-harvesting complex were compared using right-side-out and inside-out thylakoid vesicles. The vesicles were isolated by aqueous polymer phase partitioning following the fragmentation of spinach thylakoids by passage through a Yeda press. Both vesicle types were agglutinated by an antiserum specific for the light-harvesting complex, although proteolytic degradation of the complex occurred only in right-side-out vesicles. In addition, there are different antigenic sites for the light-harvesting complex on the inner and outer thylakoid surfaces. Polypeptides of the chlorophyll-alpha-protein complex of photosystem II were degraded by proteases at both membrane surfaces. We concluded that both these chlorophyll-protein complexes are membrane spanning and transversely asymmetric, but that the light-harvesting complex polypeptides accessible at the inner thylakoid surface are more resistant to proteolytic attack. In contrast, the main chlorophyll-containing polypeptide (Mr = 64 500) of photosystem I complex was resistant to proteolytic attack at both the outer and inner thylakoid surfaces.


The 43-kDa neuronal growth-associated protein (GAP-43) is present in plasma membranes of rat astrocytes.
One of the neuronal growth-associated proteins, GAP-43 (molecular mass, approximately 43 kDa; pI 4.3), is abundant in growth-cone membranes and corresponds to a major protein kinase C substrate, the 46-kDa phosphoprotein (pp46), of a growth-cone-enriched subcellular fraction. This protein has the following additional designations (depending on context): B-50 (phospholipid metabolism), F1 (synaptic plasticity), and p57 (calmodulin binding). We show that a protein with the same molecular mass and isoelectric point as GAP-43, which interacts with anti-GAP-43 antibodies on immunoblots, is present in the plasma membranes of cultured neonatal rat cortical astrocytes. Double-immunofluorescence labeling of cells with a serum against glial fibrillary acidic protein and anti-GAP-43 antibody was observed. Furthermore, astrocytic protein was phosphorylated in vitro by protein kinase C and comigrated in two-dimensional PAGE with GAP-43. The data indicate that GAP-43, heretofore believed to be neuron-specific, is present in at least one class of glial cells.


Analysis of intrafractional organ motion by megavoltage computed tomography in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy.
To analyze intrafractional organ motion in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy (SBRT-HT). Data from 25 patients with lung cancer who received 50 Gy/5 fractions of SBRT-HT were analyzed. Slow-scan megavoltage computed tomography (MVCT) images were acquired before (pre-MVCT) and after (post-MVCT) each fraction. We analyzed the imaging quality of the 124 post-MVCT images to identify tumor contours using low-density settings. Next we examined tumor contour deviations from the planning target volume (PTV) in post-MVCT images for intrafractional tumor displacement. Image quality was determined as good in 111/124 images from 22 patients (92%). None of the upper lung tumor images were of poor quality (74 images in 15 patients), whereas lower lung tumors yielded 14 poor-quality images out of the 50 images (3/10 patients). The difference in image quality between upper and lower lung tumors was statistically significant (p<0.01), especially when accompanied by interstitial lung shadows. Deviations in tumor position in post-MVCT images were analyzed in 110 images from 23 patients and revealed 99 images (90%) with tumor contours confined to PTV. In upper lung tumors, 4/74 images in 15 patients (5.4%) showed tumor contour deviations outside PTV. Lower lung tumors showed a higher rate of deviation with 7/36 images in 8 patients (19.4%) showing tumor contour deviations outside PTV (p<0.05). The maximum deviation was 1 mm for upper lung tumors and 2 mm for lower lung tumors. Upper lung tumors are good candidates for MVCT image-guided SBRT-HT. However, lower lung tumors, especially those adjacent to the diaphragm or pleura, can be difficult to assess, warranting precise dose delivery by MVCT image-guided SBRT-HT.


Nanoindentation of the pristine and irradiated forms of a sodium borosilicate glass: Insights from molecular dynamics simulations.
We have carried out classical molecular dynamics simulations in order to get insight into the atomistic mechanisms of the deformation during nanoindentation of the pristine and irradiated forms of a sodium borosilicate glass. In terms of the glass hardness, we have found that the primary factor affecting the decrease of hardness after irradiation is depolymerization rather than free volume, and we argue that this is a general trend applicable to other borosilicate glasses with similar compositions. We have analyzed the changes of the short- and medium-range structures under deformation and found that the creation of oxygen triclusters is an important mechanism in order to describe the deformation of highly polymerized borosilicate glasses and is essential in the understanding of the folding of large rings under stress. We have equally found that the less polymerized glasses present a higher amount of relative densification, while the analysis of bond-breaking during the nanoindentation has showed that shear flow is more likely to appear around sodium atoms. The results provided in this study can be proven to be useful in the interpretation of experimental results.


Whiplash Syndrome Reloaded: Digital Echoes of Whiplash Syndrome in the European Internet Search Engine Context.
In many Western countries, after a motor vehicle collision, those involved seek health care for the assessment of injuries and for insurance documentation purposes. In contrast, in many less wealthy countries, there may be limited access to care and no insurance or compensation system. The purpose of this infodemiology study was to investigate the global pattern of evolving Internet usage in countries with and without insurance and the corresponding compensation systems for whiplash injury. We used the Internet search engine analytics via Google Trends to study the health information-seeking behavior concerning whiplash injury at national population levels in Europe. We found that the search for "whiplash" is strikingly and consistently often associated with the search for "compensation" in countries or cultures with a tort system. Frequent or traumatic painful injuries; diseases or disorders such as arthritis, headache, radius, and hip fracture; depressive disorders; and fibromyalgia were not associated similarly with searches on "compensation." In this study, we present evidence from the evolving viewpoint of naturalistic Internet search engine analytics that the expectations for receiving compensation may influence Internet search behavior in relation to whiplash injury.


Natriuretic peptides after pulmonary resection.
Little is known about alterations in the levels and influence of natriuretic peptide (NP) on cardiopulmonary function after pulmonary resection for lung cancer. This study was designed to investigate the patterns and activity of NP after pulmonary resection. We investigated changes in plasma A-type (atrial) NP and B-type (brain) NP (BNP) using radioimmunoassay, in lung cancer patients before and after lobectomy (n = 15) or pneumonectomy (n = 10). Patient characteristics, respiratory function, operative time, blood loss, intraoperative fluid administration, and intraoperative urine output in both groups were also compared. Pulmonary hemodynamic variables were monitored continuously. Plasma concentrations of A-type NP and BNP did not differ between the two groups preoperatively. However, the group undergoing pneumonectomy exhibited higher concentrations of A-type NP and BNP than the group undergoing lobectomy on postoperative days 3 and 7. Alterations in A-type NP and BNP after pulmonary resection therefore differed according to the volume of lung tissue resected. Both mean pulmonary artery pressure and total pulmonary vascular resistance increased significantly in the pneumonectomy group. The total pulmonary vascular resistance on postoperative day 3 correlated with the plasma BNP concentration in the pneumonectomy group. A-type NP and BNP effectively compensate for the right ventricular dysfunction noted after pulmonary resection, and this is more evident after pneumonectomy than after lobectomy. Changes in ventricular activity associated with changes in plasma BNP and total pulmonary vascular resistance are indicative of cardiopulmonary adjustments after pneumonectomy.


Conformal Fabrication of an Electrospun Nanofiber Mat on a 3D Ear Cartilage-Shaped Hydrogel Collector Based on Hydrogel-Assisted Electrospinning.
Electrospinning is a common and versatile process to produce nanofibers and deposit them on a collector as a two-dimensional nanofiber mat or a three-dimensional (3D) macroscopic arrangement. However, 3D electroconductive collectors with complex geometries, including protruded, curved, and recessed regions, generally caused hampering of a conformal deposition and incomplete covering of electrospun nanofibers. In this study, we suggested a conformal fabrication of an electrospun nanofiber mat on a 3D ear cartilage-shaped hydrogel collector based on hydrogel-assisted electrospinning. To relieve the influence of the complex geometries, we flattened the protruded parts of the 3D ear cartilage-shaped hydrogel collector by exploiting the flexibility of the hydrogel. We found that the suggested fabrication technique could significantly decrease an unevenly focused electric field, caused by the complex geometries of the 3D collector, by alleviating the standard deviation by more than 70% through numerical simulation. Furthermore, it was experimentally confirmed that an electrospun nanofiber mat conformally covered the flattened hydrogel collector with a uniform thickness, which was not achieved with the original hydrogel collector. Given that this study established the conformal electrospinning technique on 3D electroconductive collectors, it will contribute to various studies related to electrospinning, including tissue engineering, drug/cell delivery, environmental filter, and clothing.


The spatiotemporal substrates of autobiographical recollection: Using event-related ICA to study cognitive networks in action.
Higher cognitive functions depend upon dynamically unfolding brain network interactions. Autobiographical recollection - the autonoetic re-experiencing of context rich, emotionally laden, personally experienced episodes - is an excellent example of such a process. Autobiographical recollection unfolds over time, with different cognitive processes engaged at different times throughout. In this paper we apply a recently developed analysis technique - event related independent components analysis (eICA) - to study the spatiotemporal dynamics of neural activity supporting autobiographical recollection. Participants completed an in-scanner autobiographical recollection paradigm in which the recalled episodes varied in chronological age and emotional content. By combining eICA with these cognitive manipulations we show that the brain-wide response to autobiographical recollection comprises brain networks with (i) different sensitivities to psychological aspects of the to-be-recollected material and (ii) distinct temporal profiles of activity during recollection. We identified networks with transient activations (in language and cognitive control related regions) and deactivations (in auditory and sensorimotor regions) to each autobiographical probe question, as well as networks with responses that are sustained over the course of the recollection period. These latter networks together overlapped spatially with the broader default mode network (DMN), indicating subspecialisation within the DMN. The vividness of participants' recollection was associated with the magnitude of activation in left dorsolateral prefrontal cortex and deactivation in visual association cortices. We interpret our results in the context of current theories of the spatial and temporal organisation of the human autobiographical memory system. Our findings demonstrate the utility of eICA as a tool for studying higher cognitive functions. The application of eICA to high spatial and temporal resolution datasets identifies in a single experimental protocol spatially specific networks that are recruited during cognitive activity, as well as the temporal order of activation of these networks.