A pilot study examining the safety and tolerability of valacyclovir in veterans with hepatitis C virus/herpes simplex virus type 2 coinfection.
We performed a pilot study examining the safety and tolerability of valacyclovir in veterans with herpes simplex virus type 2 and hepatitis C virus (HCV) coinfection. We performed a randomized double-blind, placebo-controlled, crossover clinical trial in U.S. veterans with genotype 1 HCV/herpes simplex virus type 2 coinfection. Patients were randomized 1:1 in blocks of 10 to receive either 1 g twice-daily valacyclovir or matching placebo for 8 weeks followed by a 2-week washout phase with daily placebo. The alternate therapy (valacyclovir or placebo) was given for an additional 8-week period. Safety assessments were performed every 2 weeks. Changes in HCV RNA and alanine aminotransferase (ALT) were estimated using linear mixed models (SAS Proc Mixed). Thirty patients were enrolled. Valacyclovir was not associated with toxicity or adverse events. ALT levels declined 6% to 10%; mean HCV RNA levels were reduced 24% (1.3 million IU/mL [0.21 log10 IU/mL]) during the valacyclovir phase (P = 0.08) with no carryover effect observed (P = 0.21). Valacyclovir 1 g twice daily showed no evidence of hepatotoxicity in U.S. veterans with hepatitis C. A modest reduction in serum levels of ALT and plasma levels of HCV RNA was observed.


Evidence theoretic protein fold classification based on the concept of hyperfold.
In current computational biology, assigning a protein domain to a fold class is a complicated and controversial task. It can be more challenging in the much harder task of correct identification of protein domain fold pattern solely through using extracted information from protein sequence. To deal with such a challenging problem, the concepts of hyperfold and interlaced folds are introduced for the first time. Each hyperfold is a set of interlaced folds with a centroid fold. These concepts are used to construct a framework for handling the uncertainty involved with the fold classification problem. In this approach, an unknown query protein is assigned to a hyperfold rather than a single fold. Ten different sequence based features are used to predicting the correct hyperfold. This architecture is featured by the Dempster-Shafer theory of evidence through the bodies of evidence and Dempster's rule of combination to combine the hyperfolds. The classification architecture thus developed was applied for identifying protein folds among the 27 famous SCOP fold patterns from a stringent well-known dataset. Compared with the existing predictors tested by the same benchmark dataset, our approach might achieve the better results.


A Localized surface plasmon resonance (LSPR) sensor integrated automated microfluidic system for multiplex inflammatory biomarker detection.
Inflammation is a complex biological response of the human body to external or internal stimuli, such as invading pathogens, defective cells, or irritating substances. One important indicator of inflammatory conditions or the progress of various diseases, such as cancer, cardiovascular diseases, neurological diseases, connective tissue diseases, sepsis, or Alzheimer's disease, is the concentration level of inflammatory biomarkers, including immunoglobulins, cytokines, and C-reactive protein (CRP). Since inflammatory biomarkers are highly correlated with each other, it is important to measure them simultaneously. To enable continuous and dynamic inflammatory biomarker detection, we utilized localized surface plasmon resonance (LSPR) to perform label-free molecule sensing. Since the LSPR sensing mechanism requires only a small sensing area with simplified optical setup, it can be easily integrated with a microfluidic device. To simplify reagent operation complexity, we developed an automated microfluidic control system to control reagent guiding and switching in the immunoassay with less manual processes and potential operation errors. Our results successfully demonstrated multiplex IgG, TNF-α, and CRP measurement with only 60 μL assay volume and 3.5 h assay time. In each test, 20 sensing spot measurements under four different reagent conditions can be performed. Overall, we envision that the LSPR sensor integrated automated microfluidic control system could perform rapid, multiplex, and multiparallel continuous inflammatory biomarker detection, which would be beneficial for various applications, such as immune status monitoring, diagnosis and prognosis of inflammatory diseases.


Cucumber mosaic virus 2b protein compensates for restricted systemic spread of Potato virus Y in doubly infected tobacco.
Tobacco plants (Nicotiana tabacum cv. Xanthi-nc) inoculated with a necrotic strain of Potato virus Y (PVY, T01 isolate) developed necrotic symptoms in some systemically infected leaves, but not in younger leaves. However, PVY expressed distinct symptoms not only in the older leaves, but also in the younger leaves, of plants that had been doubly inoculated with PVY and with Cucumber mosaic virus (CMV, strain Pepo). A tissue blot immunoassay of tissues from various positions of the stem detected PVY weakly in each stem, but not in the shoot apex, of singly infected plants, whereas PVY was detected at high levels in almost all sections of doubly infected plants. CMV was also detected at high levels in sections of singly and doubly infected plants. Immunohistochemistry of stem tissues showed that in singly infected plants, PVY was confined to external phloem cells and was not detected in internal phloem cells. However, in doubly infected plants, PVY was distributed uniformly throughout whole tissues, including the external phloem, xylem parenchyma and internal phloem cells. In plants that were doubly infected with PVY and Pepo Delta 2b, a modified CMV that cannot translate the 2b protein, the spread of PVY was restricted as in singly infected plants. These results suggested that the plant host has a counterdefence mechanism that restricts systemic spread of PVY T01, and that the 2b protein of CMV strain Pepo negates this restriction.


Description of suicide ideation among older adults and a psychological profile: a cross-sectional study in Turkey.
This study investigates the suicidal ideation and the possible causes for suicidal behaviour in the elderly. Subjects were 150 patients aged 65 and older who were evaluated using the sociodemographic data collection forms, Geriatric Depression Scale (GDS), Suicidal Ideation Scale (SIS), Reasons for Living Inventory (RLI), and Beck Hopelessness Scale (BHS). Of 150 patients, 72.7% were women and 27.3% were men, ages ranged from 65 to 88 years. Suicidal ideation was noted in 30.7% of patients. When the mean of BHS total score between patients with and without suicidal ideation and the mean of BHS subscale's feelings and expectations regarding the future and loss of motivation and hope in terms of subscales were evaluated between the groups with and without suicidal ideation, the scores had a significant difference. When RLI was evaluated in terms of total scores, the suicidal ideation mean score was 243.74 ± 32.28, while the non-suicidal ideation mean score was 267.27 ± 24.36. There was a significant relationship between the two groups. We found low level of education, low level of reasons for living and higher psychiatric morbidity (generalized anxiety disorder and comorbid depressive disorder) in with suicidal ideation in the elderly.


Validation of a radiotelemetry system for continuous blood pressure and heart rate monitoring in dogs.
A blood pressure telemetry system with catheter placement in the femoral artery was evaluated over a 119-day period in eight mongrel dogs. Every 3 weeks, the pressures recorded by telemetry were compared with direct, simultaneously recorded blood pressures measured from a femoral artery catheter implanted on the contralateral side. One telemetry device failed within 1 week of implant and was replaced before the beginning of data collection. Continuous blood pressure measures were accurate for a minimum of 17 weeks in all eight dogs. Acute changes in blood pressure and heart rate were not evaluated. Validation by simultaneous recording with a physiological monitor indicated that there was no drift in the telemetry blood pressure or heart rate during the 17-week period. Heart rates recorded by telemetry and a physiological monitor were identical, as were mean arterial pressures. The systolic pressure measured by the physiological monitor was consistently higher than that measured by telemetry. This may have been due to differences in the compliance of the catheter material in the two systems. Two devices failed within approximately 6 months of implant, apparently because of exhaustion of the battery. These findings indicate that this telemetry device can be used for periods of up to 17 weeks without appreciable drift or attenuation of the blood pressure signal. The results also describe a validation procedure for monitoring the accuracy of the telemetry system over extended periods of use. We conclude that this telemetry device can be used for the long-term assessment of blood pressure and heart rate in the dog.


Promise of radiosensitizers and radioprotectors in the treatment of human cancer.
Over the past 30 years, as an understanding of radiation chemistry has developed, it has been possible to develop compounds which modify the initial radiochemical event. In addition, certain physiologic means such as hyperbaric oxygen or blood flow restriction have also been developed as methods to modify radiation response through the radiochemical processes. Following the success of certain hyperbaric trials, a great effort was made to develop chemical agents which would mimic oxygen in their sensitization of hypoxic cells. A large series of compounds have now been identified with such properties and several of these have entered clinical trial. The first compound to receive widespread testing, misonidazole, has proven too toxic to be used in adequate doses for clinically relevant sensitization. Two new nitroimidazole analogs, which are excluded from the central nervous system, promise to allow much higher degrees of sensitization in planned clinical trials and new non-nitro drugs are under development. Radioprotection can be achieved through various methods, including restriction in blood flow and the use of sulfhydryl-containing compounds which again modify the initial radiochemical events. To be successful in tumor therapy, such agents must be selective in protecting the normal tissues. One class of compounds, the thiophosphates, show differential protection of normal tissue vis-à-vis tumor through several mechanisms. After extensive animal testing, one of these compounds, WR 2721, is now in phase I clinical testing, with phase II evaluation planned for the near future. Other potential sensitizers with varying degrees of differential activity in tumor versus normal tissue are also discussed.


Quantitative evaluation of frequency domain measurements in high density diffuse optical tomography.
High density diffuse optical tomography (HD-DOT) as applied in functional near-infrared spectroscopy (fNIRS) is largely limited to continuous wave (CW) data. Using a single modulation frequency, frequency domain (FD) HD-DOT has recently demonstrated better localization of focal activation as compared to CW data. We show that combining CW and FD measurements and multiple modulation frequencies increases imaging performance in fNIRS. We evaluate the benefits of multiple modulation frequencies, combining different frequencies as well as CW data in fNIRS HD-DOT. A layered model was used, with activation occurring within a cortex layer. CW and FD measurements were simulated at 78, 141, and 203 MHz with and without noise. The localization error, full width half maximum, and effective resolution were evaluated. Across the average of the three metrics, at 141 MHz, FD performed 8.4% better than CW, and the combination of CW and FD was 21.7% better than CW. FD measurements at 203 MHz performed 5% better than 78 MHz. Moreover, the three combined modulation frequencies of FD and CW performed up to 3.92% better than 141 MHz alone. We show that combining CW and FD measurements offers better performance than FD alone, with higher modulation frequencies increasing accuracy. Combining CW and FD measurements at multiple modulation frequencies yields the best overall performance.


Palliative care needs in Parkinson's disease: focus on anticipatory grief in family carers.
A diagnosis of Parkinson's disease (PD) has a significant psychological impact on both the person diagnosed and their loved ones, and can have a negative effect on family relationships. Caring for someone with a long-term progressing illness may cause anticipatory grief, i.e., experienced before a bereavement. This has been widely studied in illnesses such as dementia and cancer, but less so in relation to PD. The study aims were: (I) to demonstrate the occurrence of anticipatory grief experienced by carers of people with PD; (II) to explore how this grief relates to caregiver burden and caregiver depression and demographic variables. Family carers of people with moderate to advanced PD (Hoehn & Yahr stages 3-5) were invited to complete a survey, including demographic questions and three questionnaires: Zarit Burden Interview (ZBI); 16-item Geriatric Depression Scale (GDS); and Anticipatory Grief Scale (AGS). Anticipatory grief was common among carers of people with PD [mean AGS score =70.41; standard deviation (SD) =16.93; sample range, 38-102]. Though distinct concepts, carers with higher burden and depression scores also experienced more anticipatory grief symptoms. Carers experiencing higher anticipatory grief tended to be caring for someone of a younger age, displaying more non-motor symptoms, at a more advanced disease stage, and who considered either themselves and/or their loved one as depressed. Carers of people with advanced PD experienced anticipatory grief, as well as depression and a high caregiver burden. To improve carer outcomes, our focus should include the period both before and after the death of a loved one, and carers should receive regular psychological assessment and support.


Competition and stoichiometry: coexistence of two predators on one prey.
The competitive exclusion principle (CEP) states that no equilibrium is possible if n species exploit fewer than n resources. This principle does not appear to hold in nature, where high biodiversity is commonly observed, even in seemingly homogenous habitats. Although various mechanisms, such as spatial heterogeneity or chaotic fluctuations, have been proposed to explain this coexistence, none of them invalidates this principle. Here we evaluate whether principles of ecological stoichiometry can contribute to the stable maintenance of biodiverse communities. Stoichiometric analysis recognizes that each organism is a mixture of multiple chemical elements such as carbon (C), nitrogen (N), and phosphorus (P) that are present in various proportions in organisms. We incorporate these principles into a standard predator-prey model to analyze competition between two predators on one autotrophic prey. The model tracks two essential elements, C and P, in each species. We show that a stable equilibrium is possible with two predators on this single prey. At this equilibrium both predators can be limited by the P content of the prey. The analysis suggests that chemical heterogeneity within and among species provides new mechanisms that can support species coexistence and that may be important in maintaining biodiversity.


The role of adipokines in periodontal infection and healing.
Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity-related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases.


A systematic review of the clinical profile of patients with bubonic plague and the outcome measures used in research settings.
Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone-no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease-how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment. This systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints-the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days. This systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial's results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.


New electrode layout for internal selectivity of nerves.
A nerve is an enclosed, cable-like bundle of peripheral axons. Each axon or set of axons carries neural afferent or efferent information. Many applications need to detect or record these specific nervous data inside the nerve but it is a big challenge. The main issue is to achieve a good selectivity inside the nerve without being invasive. In this context, we propose a new layout of multipolar electrode allowing a very high level of spatial selectivity. This electrode has a flat-interface electrode with an array of poles. The idea is to find the best value for the inter-pole distance and the most suitable post processing in order to both improve selectivity in the nerve and reject external parasitic signals. In this preliminary work, we put emphasis on the simulation of the action potential as a method to help the electrode specification.


Uptake of health care services and health status of HIV-infected women diagnosed through antenatal HIV screening in Barbados, 1996-2004.
To study utilization of HIV-related health care services and to describe the health status of HIV-infected women diagnosed through antenatal voluntary counseling and testing (VCT) for HIV infection in Barbados. This is a descriptive study. The study population includes all HIV-infected women in Barbados diagnosed as HIV-infected through VCT for HIV infection during 1996-2004. The median duration of HIV infection from time of diagnosis to the time of this report for the 163 women diagnosed during the study period was 72 months (low range, 9 months; high range, 117 months). Of the 163 women, 102 (62.6%) had attended the centralized HIV/AIDS clinic for follow-up (care, treatment, and monitoring), whereas 61 (37.4%) had never attended the clinic. The median time lag between diagnosis of HIV infection and first presentation to the HIV/AIDS clinic was 36 months (low range, 1 month; high range, 114 months). Of the HIV-infected women who attended the HIV/AIDS clinic, more than one-fourth had severe immunodeficiency at the time of their first follow-up visit. Of the 53 women undergoing highly active anti-retroviral therapy (HAART) at the time of the study, 23 (43.4%) began the therapy within three months of their first follow-up visit. Early HIV diagnosis through antenatal VCT is not enough to ensure that women with HIV will get adequate and timely HIV-related health care. These women suffer significant premature mortality, largely related to inadequate follow-up.


Markers of monocyte activation revealed by lipidomic profiling of arachidonic acid-containing phospholipids.
Stimulated human monocytes undergo an intense trafficking of arachidonic acid (AA) among glycerophospholipidclasses. Using HPLC coupled to electrospray ionization mass spectrometry, we have characterized changes in the levels of AA-containing phospholipid species in human monocytes. In resting cells, AA was found esterified into various molecular species of phosphatidylinositol (PI), choline glycerophospholipids (PCs), and ethanolamine glycerophospholipids (PEs). All major AA-containing PC and PI molecular species decreased in zymosan-stimulated cells; however, no PE molecular species was found to decrease. In contrast, the levels of three AA-containing species increased in zymosan-activated cells compared with resting cells: 1,2-diarachidonyl-glycero-3-phosphoinositol [PI(20:4/20:4)]; 1,2-diarachidonyl-glycero-3-phosphocholine [PC(20:4/20:4)]; and 1-palmitoleoyl-2-arachidonyl-glycero-3-phosphoethanolamine [PE(16:1/20:4)]. PI(20:4/20:4) and PC(20:4/20:4), but not PE(16:1/20:4), also significantly increased when platelet-activating factor or PMA were used instead of zymosan to stimulate the monocytes. Analysis of the pathways involved in the synthesis of these three lipids suggest that PI(20:4/20:4) and PC(20:4/20:4) were produced in a deacylation/reacylation pathway via acyl-CoA synthetase-dependent reactions, whereas PE(16:1/20:4) was generated via a CoA-independent transacylation reaction. Collectively, our results define the increases in PI(20:4/20:4) and PC(20:4/20:4) as lipid metabolic markers of human monocyte activation and establish lipidomics as a powerful tool for cell typing under various experimental conditions.


Fragment length influences affinity for Cu2+ and Ni2+ binding to His96 or His111 of the prion protein and spectroscopic evidence for a multiple histidine binding only at low pH.
The prion protein (PrP) is a Cu2+-binding cell-surface glycoprotein. Using various PrP fragments and spectroscopic techniques, we show that two Cu2+ ions bind to a region between residues 90 and 126. This region incorporates the neurotoxic portion of PrP, vital for prion propagation in transmissible spongiform encephalopathies. Pentapeptides PrP-(92-96) and PrP-(107-111) represent the minimum motif for Cu2+ binding to the PrP-(90-126) fragment. Consequently, we were surprised that the appearance of the visible CD spectra for two fragments of PrP, residues 90-126 and 91-115, are very different. We have shown that these differences do not arise from a change in the co-ordination geometry within the two fragments; rather, there is a change in the relative preference for the two binding sites centred at His111 and His96. These preferences are metal-, pH- and chain-length dependent. CD indicates that Cu2+ initially fills the site at His111 within the PrP-(90-126) fragment. The pH-dependence of the Cu2+ co-ordination is studied using EPR, visible CD and absorption spectroscopy. We present evidence that, at low pH (5.5) and sub-stoichiometric amounts of Cu2+, a multiple histidine complex forms, but, at neutral pH, Cu2+ binds to individual histidine residues. We have shown that changes in pH and levels of extracellular Cu2+ will affect the co-ordination mode, which has implications for the affinity, folding and redox properties of Cu-PrP.


Social determinants of health in patients with arthritis: a cross-sectional analysis of the 2017 Behavioral Risk Factor Surveillance System.
Social determinants of health (SDOH) are economic, social, and political conditions that affect a person's overall health or the health of a group of people. Researchers have investigated the effects of SDOH on various diseases, such as asthma, obesity, and chronic stress, but few publications have been made regarding its effects on arthritis. Our primary objective was to analyze the implications of SDOH on disease severity relating to pain levels and limitations experienced among people with diagnosed arthritis. We performed a cross-sectional analysis of the 2017 Behavioral Risk Factor Surveillance System (BRFSS). We included individuals who reported having arthritis, were over the age of 45, and who also completed the SDOH module. Pain scores from the four-question Arthritis Burden Module were correlated to question responses pertaining to SDOH to determine their associations. For the analysis, our sample size was 25,682, with response rates varying slightly among the SDOH questions. Individuals diagnosed with arthritis were more likely to report functional limitations if they experienced food insecurity (χ2=234.0, p<0.001), financial instability (χ2=149.7, p<0.001), or frequent stress (χ2=297.6, p<0.001). Further, we found that individuals with arthritis experiencing any domain of SDOH reported higher mean pain scores than those not experiencing that domain, with the highest pain score difference among those reporting frequent stress (Coefficient: 1.93, CI=1.74-2.13, t=19.43, p<0.001). Our results show that SDOH profoundly impact pain levels and limitations experienced by patients with arthritis. Although work has already begun to help alleviate burdens associated with SDOH, more research and actions are required to create equitable health throughout the population.


Origin and Migration of Oil: Oil may consist of hydrocarbons that collected from waters containing natural solubilizers.
A relationship exists between the composition of crude oil and the solubility of the component hydrocarbons in dilute colloidal electrolyte solutions, suggesting that crude oil consists of hydrocarbons that were once solubilized in formation waters. It is not solubility in ordinary water or solubility in complete soap solution that correlates with the composition of oil but, rather, solubility in soap micelles. Because it implies a possible unloading mechanism, this concept is attractive, for it follows that when a soap solution is diluted with water, the soap micelles disperse and the hydrocarbons solubilized therein appear as discrete, filterable oil droplets. Thus, it would seem that crude oil originates during the compaction of a sedimentary basin by virtue of the fact that sediment hydrocarbons dissolve in waters containing natural solubilizers and then come out of solution as oil droplets. The composition of crude oil as now understood is consistent with this hypothesis. And-most important-it is now possible to formulate meaningful questions, the answers to which, upon investigation in both field and laboratory, will go far toward enabling us to assess the validity of the mechanism presented here. In addition to the implications regarding the composition of crude oil that are inherent in the hypothesis that crude oil collects from aqueous colloidal electrolyte solutions, there are several interesting implications from the geological viewpoint. To mention one, such a mechanism would lend credence to the suggestion that the source beds of petroleum are not necessarily unique accumulations of hydrocarbons in a limited area but, rather, may generally be coincident with the area from which water is expressed into the porous strata that eventually form the reservoirs.


Quantitative evaluation of China's private universities provincial public funding policies based on the PMC-Index model.
The special public funding policies, formulated and implemented by provincial governments, plays an important role in the development of private universities in China. However, there is a lack of scientific evaluation on the rationality and completeness of the provincial special public funding policy of China's private colleges and universities. Therefore, this paper uses PMC-index model and text mining technology to establish an evaluation index system for the provincial special public funding policy of private universities in China. Based on PMC-Index and PMC-Surface, 13 policy texts issued since 2010 were evaluated scientifically. The results show that the average PMC-Index of the 13 policies is 6.97, and the PMC-Surface map is smooth, which indicates that the overall structure of these policies is reasonable and the policy content has certain completeness. Only one policy is unacceptable. Through further analysis, we found that there is still much room for improvement in the content design of the sample policy, and its rationality and completeness are related to the publication time. This study is helpful to fully understand the advantages and disadvantages of the provincial special public funding policy of private universities in China.


Occam paradox? A variation of tapia syndrome and an unreported complication of guidewire-assisted pedicle screw insertion.
Study Design Case report. Clinical Question The clinical aim is to report on a previously unknown association between guidewire-assisted pedicle screw insertion and neuropraxia of the recurrent laryngeal nerve (RLN), and how this may overlap with the signs of Tapia syndrome; we also report our approach to the clinical management of this patient. Methods A 17-year-old male patient with idiopathic scoliosis experienced Tapia syndrome after posterior instrumentation and arthrodesis at the level of T1-L1. After extubation, the patient had a hoarse voice and difficulty in swallowing. Imaging showed a breach in the cortex of the anterior body of T1 corresponding to the RLN on the right. Results Otolaryngological examination noted right vocal fold immobility, decreased sensation of the endolarynx, and pooling of secretions on flexible laryngoscopy that indicated right-sided cranial nerve X injury and left-sided tongue deviation. Aspiration during a modified barium swallow prompted insertion of a percutaneous endoscopic gastrostomy tube before the patient was sent home. On postoperative day 20, a barium swallow demonstrated reduced aspiration, and the patient reported complete resolution of symptoms. The feeding tube was removed, and the patient resumed a normal diet 1 month later. Tapia syndrome, or persistent unilateral laryngeal and hypoglossal paralysis, is an uncommon neuropraxia, which has previously not been observed in association with a breached vertebral body at T1 along the course of the RLN. Conclusion Tapia syndrome should be a differential diagnostic consideration whenever these symptoms persist postoperatively and spine surgeons should be aware of this as a potential complication of guidewires in spinal instrumentation.


Using spatial equity analysis in the process evaluation of environmental interventions to tackle obesity: the healthy towns programme in England.
Process evaluations of environmental public health interventions tend not to consider issues of spatial equity in programme delivery. However, an intervention is unlikely to be effective if it is not accessible to those in need. Methods are required to enable these considerations to be integrated into evaluations. Using the Healthy Towns programme in England, we demonstrate the potential of spatial equity analysis in the evaluation of environmental interventions for diet and physical activity, examining whether the programme was delivered to those in greatest need. Locations of new physical infrastructure, such as cycle lanes, gyms and allotments, were mapped using a geographic information system. A targeting ratio was computed to indicate how well-located the infrastructure was in relation to those at whom it was specifically aimed, as detailed in the relevant project documentation, as well as to generally disadvantaged populations defined in terms of U.K. Census data on deprivation, age and ethnicity. Differences in targeting were examined using Kruskal-Wallis and t-tests. The 183 separate intervention components identified were generally well located, with estimated targeting ratios above unity for all population groups of need, except for black and ethnic minorities and children aged 5-19 years. There was no evidence that clustering of population groups influenced targeting, or that trade-offs existed when components were specifically targeted at more than one group. The analysis of spatial equity is a valuable initial stage in assessing the provision of environmental interventions. The Healthy Towns programme can be described as well targeted in that interventions were for the most part located near populations of need.


The Maimonides Portrait: An Appraisal of One of the World's Most Famous Pictures.
Surprisingly, an utterly imaginative "portrait" has become synonymous with Maimonides forever. How and when did this particular portrait become associated with Maimonides? This and many other intriguing questions regarding this portrait are systematically addressed, and its origins, possible inspiration, and hidden objectives are revealed.


Implementation of antimicrobial peptides for sample preparation prior to nucleic acid amplification in point-of-care settings.
A variety of sample preparation techniques are used prior to nucleic acid amplification. However, their efficiency is not always sufficient and nucleic acid purification remains the preferred method for template preparation. Purification is difficult and costly to apply in point-of-care (POC) settings and there is a strong need for more robust, rapid, and efficient biological sample preparation techniques in molecular diagnostics. Here, the authors applied antimicrobial peptides (AMPs) for urine sample preparation prior to isothermal loop-mediated amplification (LAMP). AMPs bind to many microorganisms such as bacteria, fungi, protozoa and viruses causing disruption of their membrane integrity and facilitate nucleic acid release. The authors show that incubation of E. coli with antimicrobial peptide cecropin P1 for 5 min had a significant effect on the availability of template DNA compared with untreated or even heat treated samples resulting in up to six times increase of the amplification efficiency. These results show that AMPs treatment is a very efficient sample preparation technique that is suitable for application prior to nucleic acid amplification directly within biological samples. Furthermore, the entire process of AMPs treatment was performed at room temperature for 5 min thereby making it a good candidate for use in POC applications.


Sectioned Images and Surface Models of a Cadaver for Understanding the Dorsalis Pedis Flap.
The aim of this study was to represent the dorsalis pedis (DP) flap on sectioned images and surface models using Visible Korean for medical education and clinical training in the field of maxillofacial reconstructive surgery. Serially sectioned images of the foot were obtained from a cadaver. The important structures in the sectioned images were outlined and stacked to create a surface model. The PDF file (53 MB) of the assembled models is accessible for free download on the Department of Anatomy at Ajou University School of Medicine Web site (http://anatomy.co.kr). In this file, the significant anatomic structures of the DP flap can be inspected in the sectioned images. All surface models and stereoscopic structures of the DP flap are described in real time. We hope that these state-of-the-art sectioned images, outlined images, and surface models will help students and trainees gain a better understanding of the DP flap anatomy.


InsP3 Signaling in Apicomplexan Parasites.
Phosphoinositides (PIs) and their derivatives are essential cellular components that form the building blocks for cell membranes and regulate numerous cell functions. Specifically, the ability to generate myo-inositol 1,4,5-trisphosphate (InsP3) via phospholipase C (PLC) dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to InsP3 and diacylglycerol (DAG) initiates intracellular calcium signaling events representing a fundamental signaling mechanism dependent on PIs. InsP3 produced by PI turnover as a second messenger causes intracellular calcium release, especially from endoplasmic reticulum, by binding to the InsP3 receptor (InsP3R). Various PIs and the enzymes, such as phosphatidylinositol synthase and phosphatidylinositol 4-kinase, necessary for their turnover have been characterized in Apicomplexa, a large phylum of mostly commensal organisms that also includes several clinically relevant parasites. However, InsP3Rs have not been identified in genomes of apicomplexans, despite evidence that these parasites produce InsP3 that mediates intracellular Ca2+ signaling. Evidence to supporting IP3-dependent signaling cascades in apicomplexans suggests that they may harbor a primitive or non-canonical InsP3R. Understanding these pathways may be informative about early branching eukaryotes, where such signaling pathways also diverge from animal systems, thus identifying potential novel and essential targets for therapeutic intervention.


Seroprevalence and genomic divergence of circulating strains of feline immunodeficiency virus among Felidae and Hyaenidae species.
Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today.


[The role of a spasm of the coronary arteries in the pathogenesis of acute myocardial infarct and in the development of sudden coronary death].
Based on the clinical experience and clinicoanatomic correlations, the authors suggest the role of hemorrhage and rupture of atherosclerotic patches in the pathogenesis of sudden coronary death. Proceeding from long-term follow-up studies of patients suffering from CHD, the necessity is substantiated of the regular use of beta-adrenoblockers which significantly reduce the rate of sudden death both in the acute and chronic phases of CHD, particularly in patients with a history of myocardial infarction. Taking into consideration the multifactorial nature of the pathogenesis of acute occlusion of coronary arteries, it is suggested that in addition to the preventive administration of beta-adrenoblockers, thrombolytic agents in combination with antiaggregation remedies and calcium antagonists should be prescribed, especially in cases of arterial pressure rises.


Cannabinoid receptor expression in estrogen-dependent and estrogen-independent endometrial cancer.
The lack of good diagnostic/prognostic biomarkers and the often late presentation of endometrial cancer (EC) hinders the amelioration of the morbidity and mortality rates associated with this primarily estrogen-driven disease, a disease that is becoming more prevalent in the population. Previous studies on the expression of the classical cannabinoid receptors, CB1 and CB2, suggest these could provide good diagnostic/prognostic biomarkers for EC but those observations have been contradictory. In this study, we sought to resolve the inconsistency of CB1 and CB2 expression levels in different EC studies. To that end, we used qRT-PCR and immunohistochemistry (IHC) for CB1 and CB2 in endometrial biopsies from women with or without EC and found that transcript levels for both CB1 and CB2 were significantly decreased by 90 and 80%, respectively in EC. These observations were supported by histomorphometric studies where CB1 and CB2 staining intensity was decreased in all types of EC. These data suggest that the loss of both types of CB receptors is potentially involved in the development of or progression of EC and that CB1 and CB2 receptor expression could serve as useful histological markers and therapeutic targets in the treatment of or prevention of EC.


Autoantibodies against matrix metalloproteinase-1 in patients with localized scleroderma.
Localized scleroderma (LSc) is characterized by cutaneous fibrosis and various autoantibodies. To determine the presence or levels of antibodies (Abs) against matrix metalloproteinase (MMP)-1 and their clinical relevance in LSc. Anti-MMP-1 Ab was examined by ELISA (Enzyme-Linked ImmunoSorbent Assay) and immunoblotting using human recombinant MMP-1. MMP-1 collagenase activity was determined using biotinylated collagen as substrate and the amount of cleaved biotinylated fragments of collagen by MMP-1 was measured by ELISA. LSc patients exhibited significantly elevated IgG anti-MMP-1 Ab levels relative to normal controls at similar level of patients with systemic sclerosis (SSc). However, IgG anti-MMP-1 Ab levels were comparable among the 3 LSc subgroups: morphea, linear scleroderma, and generalized morphea. When absorbance values higher than the mean+2S.D. of normal controls were considered positive, IgG or IgM anti-MMP-1 Ab was found in 46% and 49% of total LSc patients and SSc patients, respectively. Anti-MMP-1 Ab was detected most frequently in morphea patients (60%), followed by linear scleroderma patients (47%) and then generalized morphea patients (25%). LSc patients positive for IgG anti-MMP-1 Ab had elevated levels of IgG anti-single-stranded DNA Ab, IgG anti-nucleosome Ab, and shorter disease duration relative to those negative. The presence of anti-MMP-1 Ab in LSc patients was confirmed by immunoblotting. IgG isolated from LSc patients' sera positive for IgG anti-MMP-1 Ab by ELISA inhibited MMP-1 collagenase activity. These results suggest that anti-MMP-1 autoantibody is a novel autoantibody in LSc.


Use of phage lambda CI857AprTcrN derivative for isolation of prophage-free cells.
A method for obtaining nonlysogenic bacteria from wild-type phage lysogenized strains using phage lambda with AprTcr markers and double amber-mutation in N gene is proposed. When the lysogenic culture is infected with antibiotic-resistant phage, the nonlysogenic cells present in the population are lysogenized and isolated on selective medium with Ap and Tc. Subsequent culturing of lysogenized cells on media without antibiotics leads to phage elimination due to its instability.


Association and linkage analysis of COL1A1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families.
To simultaneously investigate the contribution of the alpha 1 chain of collagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the variation of bone geometric parameters in both Caucasians and Chinese. Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chinese subjects from 400 nuclear families were genotyped at the AHSG-SacI, COL1A1- PCOL2 and Sp1 polymorphisms using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). 5 FN bone geometric parameters were calculated based on bone mineral density and bone area of femoral neck (FN) measured by dual energy X-ray absorptiometry. Population stratification, total family association, within-family association, and linkage tests were performed by the quantitative transmission disequilibrium test program. The t-test showed the significant differences of all bone geometric phenotypes (except ED) between Caucasians and Chinese in the offspring using both unadjusted and adjusted (by age, height, weight, and gender) data. In Caucasians, we found significant within-family association results between the COL1A1-Sp1 polymorphism (rs1800012) and cross sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR) (P=0.018, 0.002, 0.023, and 0.001, respectively); the COL1A1-Sp1 polymorphism also detected significant linkage with BR (P=0.039). In the population of China, the within-family associations between the COL1A1-PCOL2 polymorphism (rs1107946) and CT, BR were significant (P=0.012 and 0.008, respectively). Furthermore, evidence of linkage were observed between the AHSG-SacI polymorphism (rs4918) and CT, BR (P=0.042 and 0.014, respectively) in Caucasians, but not in Chinese. Our results suggest that the COL1A1 gene may have significantly association with bone geometry in both Caucasians and Chinese, and the AHSG gene may be linked to bone geometry in Caucasians, but not in Chinese. This study represents our first efforts on investigating the importance of the COL1A1 and AHSG genes on bone geometry in both Caucasians and Chinese.


Molecular and cellular pathways as treatment targets for biologic therapies in systemic sclerosis.
Recent advances have shed light on the complex pathogenic processes that underlie the development and progression of Systemic Sclerosis (SSc) but management of the disease remains problematic and curative treatment is not available. Better understanding of the underlying pathology has enabled novel therapeutic approaches to be investigated, as therapies in rheumatology are becoming increasingly disease/ organ-specific, targeting unique biological networks and signalling pathways. The pathophysiologic and clinical pleiomorphism of SSc however, represents a major barrier to conducting large well-controlled studies for the evaluation of non-selective immunosuppressive and novel highly selective agents. Therapeutic biologic strategies targeting inflammatory or profibrotic cytokines and lymphocyte activation proved to be efficacious in other systemic rheumatic diseases but have demonstrated contradictory results in SSc. Blocking of tumour necrosis factor alpha and interleukin-6 may improve SSc-associated arthritis, while depletion of B-cells may have benefits for skin and lung fibrosis, but randomized studies are needed. In this review we critically appraise available data for the treatment of SSc focusing on immunologic and antifibrotic strategies. Attenuation of the fibrotic process remains an unmet goal but the potential to prevent damage by promoting tissue repair has been shown in preclinical studies. Translation of these findings into clinical practice will hopefully establish new therapeutic options and improve prognosis of these patients, for which our therapeutic armamentarium remains poor.


Evaluation of a technique for simulation of gamma camera images.
Simulation of the gamma camera imaging process has applications in radionuclide imaging in image formation, interpretation and evaluation. Current algorithms are hindered by the length of time taken to perform accurate simulation. In this study an algorithm is developed which uses a number of simplifying approximations to improve speed of operation: restriction of the extent of the primary and scatter point spread functions, coarse sampling of the PSFs in the direction perpendicular to the camera face and use of a circularly symmetric scatter function. The effect of these approximations is assessed qualitatively and quantitatively by comparing simulations with corresponding real measurements. The application of the technique to clinical images using magnetic resonance data is demonstrated. The results show that improvements in speed of about a factor of ten may be achieved at the expense of minimal loss of accuracy. The algorithm should prove useful in speeding up applications of simulation.


[Higher microsomal monooxygenase activity in chloroquine-resistant strains of malarial plasmodium as a possible cause of drug stability].
Ability to hydroxylate benz(alpha)pyrene--a substrate of arylhydrocarbone hydroxylase (AHH) was distinctly increased in lysates of erythrocytes containing malarial plasmodium. Hydroxylation of benz(alpha)pyrene was inhibited by methyrapone--an inhibitor of microsomal monooxygenases. Activity of AHH was increased from 2- to 3-fold in chloroquine-resistant plasmodium strains as compared with the drug-sensitive strains. Resistance of Plasmodium berghei to chloroquine appears to involve an activation of the monooxygenases system in the parasite.


Serological study of pigs for antibody against African swine fever virus in two areas of southern Malawi.
A serological survey was conducted in July 1991 on domestic pigs in two areas of southern Malawi which were severely affected by the African swine fever (ASF) epizootic in 1989-1991. Sixty-six of the 216 owners questioned reported having witnessed ASF in their pigs. Forty-seven owners had pigs with antibodies against ASF virus, and the overall prevalence of pigs with anti-ASF virus antibodies was found to be 12.4%, in 445 pigs sampled in 35 villages. Spread of ASF was thought to occur principally through the slaughter and sale of infected animals, and due to the free-ranging of pigs. Permanent penning of pigs significantly reduced the attack rate (chi 2 = 7.59, P < 0.01, 1df) in pig pens in Thyolo, an area where permanent penning of pigs was widely practised. Feeding of kitchen scraps did not appear to have been an important means of virus spread. Ornithodoros ticks were found in only 1 of the 35 villages. Although virus was not isolated from 203 pooled sera from pigs in the Mulanje district or from collected ticks, the seroconversion of a small proportion of pigs born after the last reported date of ASF occurrence suggests that the virus had continued to circulate to a limited extent in this area.


Financial literacy among Turkish college students: the role of formal education, learning approaches, and parental teaching.
This study assessed financial literacy and its correlates among Turkish college students, with special emphasis on the role of formal education, learning approaches, and parental influences. Financial literacy was measured by the College Student Financial Literacy Survey, which assesses knowledge in four areas: general financial management, saving and borrowing, insurance, and investing. 853 Turkish university students were administered the survey (416 men, 437 women; M age = 20.3 yr., SD = 0.6). The mean percentage of correct responses was 45% (SD = 12.8%). Regression results showed that formal finance education in college, a deep approach to learning, and direct financial teaching by parents were significantly associated with higher financial literacy scores.


Glycocalyx transduces membrane leak in brain tumor cells exposed to sharp magnetic pulsing.
Mechanisms by which electric (E) or magnetic (B) fields might be harnessed to affect tumor cell behavior remain poorly defined, presenting a barrier to translation. We hypothesized in early studies that the glycocalyx of lung cancer cells might play a role in mediating plasma membrane leak by low-frequency pulsed magnetic fields (Lf-PMF) generated on a low-energy solenoid platform. In testing glioblastoma and neuroblastoma cells known to overexpress glycoproteins rich in modifications by the anionic glycan sialic acid (Sia), exposure of brain tumor cells on the same platform to a pulse train that included a 5 min 50Hz Lf-PMF (dB/dt ∼ 2 T/s at 10 ms pulse widths) induced a very modest but significant protease leak above that of control nonexposed cells (with modest but significant reductions in long-term tumor cell viability after the 5 min exposure). Using a markedly higher dB/dt system (80 T/s pulses, 70 μs pulse-width at 5.9 cm from a MagVenture coil source) induced markedly greater leak by the same cells, and eliminating Sia by treating cells with AUS sialidase immediately preexposure abrogated the effect entirely in SH-SY5Y neuroblastoma cells, and partially in T98G glioblastoma cells. The system demonstrated significant leak (including inward leak of propidium iodide), with reduced leak at lower dB/dt in a variety of tumor cells. The ability to abrogate Lf-PMF protease leak by pretreatment with sialidase in SH-SY5Y brain tumor cells or with heparin lyase in A549 lung tumor cells indicated the importance of heavy Sia or heparan sulfate glycosaminoglycan glycocalyx modifications as dominant glycan species mediating Lf-PMF membrane leak in respective tumor cells. This "first-physical" Lf-PMF tumor glycocalyx event, with downstream cell stress, may represent a critical and "tunable" transduction mechanism that depends on characteristic anionic glycans overexpressed by distinct malignant tumors.


Limitations of electronic compensation for measuring plethysmographic airway resistance in infants.
Electronic compensation to overcome thermal artifacts during plethysmographic estimations of airway resistance is now used routinely in adults and school-age children, and was shown to be a valuable means of discriminating airway function between preschool children with and without lung disease. A similar system is now commercially available for infants, which could increase the applicability of this technique. However, we noted marked discrepancies in electronically calculated values of airway resistance in this age group, both with respect to absolute values displayed and marked within-subject variability on a single test occasion. The aim of this technical report is to summarize our recent findings in order to alert other users to potential problems. Airway resistance (R(aw)) was measured in 62 infants (28 with cystic fibrosis (CF); 34 healthy). Three to five epochs of quiet regular tidal breathing were collected in each infant. Marked within-subject, within-test variability was observed, with the median coefficient of variation (CV) being 9.1% (range, 1.2-52.6%) within and 8.5% (0.1-112%) between epochs. Among healthy infants, R(aw) varied from 0.1-6.4 (kPa x liter(-1) x sec), with no relationship to either body or lung size and complete overlap of results with those from infants with CF, despite abnormal lung function in the latter when assessed by other means. The marked within- and between-subject variability in healthy infants, and lack of discriminative power of R(aw) when derived from electronically compensated values, currently preclude application in either clinical or research studies.


Peripheral blood stem cell collection in pediatric patients: feasibility of leukapheresis under anesthesia in uncompliant small children with solid tumors.
Leukapheresis demands patient's compliance and adequate vascular accesses, which can require invasive methods in very small children whose treatment protocol includes hemopoietic stem cell collection for myeloablative chemotherapy and stem cell rescue. Since 1998, at the Istituto Nazionale Tumori of Milan, in selected uncompliant small children, the placement of peripheral vascular accesses and leukapheresis have been performed at the same time under general anesthesia. Peripheral venous cannulas were positioned for blood collection, while blood was returned through either peripheral cannulas or mono-lumen central catheters previously installed for chemotherapy. A continuous-flow cell separator was used for leukapheresis. Between 1998 and 2003, 47 children with solid tumors underwent anesthesia for a total of 54 leukaphereses. The patients' age ranged from 12.7 to 93 months (median 30.3) and their weight ranged from 7 to 20 kg (median 14.1). Neither metabolic nor anesthesiological complications were recorded. In 89% of cases, the CD 34(+) cell target was achieved at a single harvest; the median number of CD 34(+) cells was 10.8 x 10(6)/kg/leukapheresis (range 1-117) and the median collection efficiency was 63.4% (range 25-100.6). Leukapheresis under anesthesia is feasible and safe in very low-weight children whose compliance is lacking due to age and disease.


The efficacy of radiation therapy in adrenocortical carcinoma: A propensity score analysis of a population-based study.
Adrenocortical carcinoma (ACC) is a rare and malignant tumor. The main treatment is primary surgical resection with or without mitotane therapy. The role of radiation therapy is still controversial. We aim to investigate the survival efficacy of radiotherapy in a large population-based cohort.We queried the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013) to identify cases with ACC. Traditional multivariate Cox regression and propensity score analysis were used to evaluate the effect of radiotherapy on cancer survival. The survival outcomes included overall survival and cancer-specific survival. The treatment effect was evaluated using a hazard ratio (HR) and its 95% confidence interval (95% CI).Five hundred thirty patients diagnosed with ACC were identified. Among them, 74 patients received radiotherapy. In the multivariate Cox regression, radiotherapy did not increase the overall survival (HR 0.794, 95% CI 0.550-1.146, P = .218) or cancer-specific survival (HR 0.842, 95% CI 0.574-1.236, P = .388). In the propensity score analysis, the results consistently showed no survival benefit of radiotherapy regardless of the different propensity score analysis methods.Radiotherapy did not improve overall or cancer-specific survival in ACC patients. Further confirmation is needed from multi-institutional prospective studies in the future.


[A proposal to combine Roy's conceptual framework with crisis theory].
It is reported the crisis theory framework's and is proposed its linkage with the Callista Roy conceptual Model. The aim is to provide the nurse with an instrumental and theoretical framework of the knowledge of the person in crisis intervention. In this proposition is still suggested, a guide to nursing care. It is derived of both theories and exemplified by the author trough practice application.


TLR4, TLR9, and NLRP3 in biliary epithelial cells of primary sclerosing cholangitis: relationship with clinical characteristics.
Inappropriate innate immune responses have been suggested to contribute to the pathogenesis of primary sclerosing cholangitis (PSC). We evaluated the associations of expressions of toll-like receptor (TLR) 4, TLR9, and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in the biliary epithelial cells (BECs) with clinical features of PSC patients. We retrospectively evaluated the expressions of TLR4, TLR9, and NLRP3 in the intrahepatic BECs by immunohistochemical staining in 21 PSC patients and 10 normal controls. In PSC, 17 patients underwent liver biopsy, and, in the other four patients, liver specimens were obtained at the time of liver transplantation. TLR9 expressions in BECs were higher in PSC patients than in normal controls. TLR9 expressions were correlated with Ludwig fibrosis scores in PSC patients. TLR4 and NLRP3 expressions were similar between PSC patients and normal controls. Seventeen PSC patients undergoing liver biopsy were followed up during a median period of 55.7 months. Four reached to liver transplantation and four developed cholangiocarcinoma. Patients developing cholangiocarcinoma showed lower NLRP3 expressions than the others. Patients reaching to liver transplantation showed higher TLR9 expressions. Expression levels of TLR9 and NLRP3 were not correlated with liver biochemical tests and Mayo risk scores. In PSC, excessive immune responses through TLR9 signaling may be associated with the disease progression. Insufficient immune response through NLRP3 signaling may be associated with the development of cholangiocarcinoma. Evaluation of TLR9 and NLRP3 expressions in BECs may be useful for predicting the prognosis as an auxiliary marker.


Turkish Thoracic Society asthma management and prevention guideline: key points.
Asthma still has high morbidity and cost despite all advances in pathogenesis, diagnosis and treatment. Although asthma can be controlled with proper diagnosis and treatment, the low rates of control in our country and in the world can not be attributed to the variable course of the disease and patients' psycho-social behaviours for chronic disease. In this context, Turkish Thoracic Society (TTS) has decided to update Asthma Diagnosis and Management Guide latest published in 2000. National data were collected, compiled and prepared by authors, and final form given by the TTS Asthma and Allergy Study Group, after presenting to consultant individuals and institutions. In June 2009, the National Asthma Management and Prevention Guideline were published in Turkish. In this paper, we aimed to present the national guide in English with its basics and individual differences.


Defining the limits: Protein aggregation and toxicity in vivo.
Abstract others complementary, to resolve mis-folded proteins when they arise, ranging from refolding through the action of molecular chaperones to elimination through regulated proteolytic mechanisms. These protein quality control pathways are sufficient, under normal conditions, to maintain a functioning proteome, but in response to diverse environmental, genetic and/or stochastic events, protein mis-folding exceeds the corrective capacity of these pathways, leading to the accumulation of aggregates and ultimately toxicity. Particularly devastating examples of these effects include certain neurodegenerative diseases, such as Huntington's Disease, which are associated with the expansion of polyglutamine tracks in proteins. In these cases, protein mis-folding and aggregation are clear contributors to pathogenesis, but uncovering the precise mechanistic links between the two events remains an area of active research. Studies in the yeast Saccharomyces cerevisiae and other model systems have uncovered previously unanticipated complexity in aggregation pathways, the contributions of protein quality control processes to them and the cellular perturbations that result from them. Together these studies suggest that aggregate interactions and localization, rather than their size, are the crucial considerations in understanding the molecular basis of toxicity.


Comparisons of the separations of some neutral analytes by LC, MEKC, and CEC.
The relative utility of high-performance liquid chromatography, micellar electrokinetic chromatography (MEKC), and capillary electrochromatography (CEC) is examined for the separation of essentially uncharged solute mixtures. Three model systems are used for which separations by reversed-phase liquid chromatography had been established. These consisted of a set of three substituted hydroxybenzoates; a mixture of six structurally closely related steroids; and the multicomponent aminoglycoside antibiotic, teicoplanin. These sets represented a range of difficulty in achieving separations by reversed-phase LC. It was found that equivalent or better separations for all systems could be established by MEKC and CEC. Both electrophoretic techniques offer much higher peak efficiencies than LC, and MEKC is found to be superior to CEC in terms of peak efficiencies and ruggedness of operation.


The leuO gene product has a latent ability to relieve bgl silencing in Escherichia coli.
The Escherichia coli bgl operon is of interest, since its expression is silent (phenotypically Bgl-), at least under standard laboratory conditions. Here we attempted to identify a trans-acting factor(s) that is presumably relevant to the regulation of bgl by a random insertion mutagenesis with mini-Tn10. These collected mutations, conferring the phenotype of Bgl+, were localized in three loci on the genetic map, two of which appeared to be hns and bglJ, which were previously implicated as the factors affecting the Bgl phenotype. The other locus at 1 to 2 min on the genetic map appeared to be a new one. In this case, the insertion mutation was found to be just in front of the leuO gene encoding a putative LysR-like DNA-binding protein. Genetic analyses revealed that overproduction of LeuO in the wild-type cells causes the phenotype of Bgl+. A leuO deletion mutant was also characterized in terms of expression of bgl. From these results, the possible function of LeuO in bgl expression will be discussed from an evolutionary and/or ecological point of view.


[Parasitological and morphological characteristics of Brazilian strains of Schistosoma mansoni in Mus musculus].
Aiming to determine parasitological and morphological differences between Brazilian strains (CMO, CM and BE) of Schistosoma mansoni the following parameters were studied: prepatent period, kinetics of egg releasing in feces, intestinal oogram, infectivity and the morphology of adult worms. No statistical difference (p>0.05) was found regarding the mean prepatent period (44 and 46 days) and infectivity (26% and 29%). All strains showed a higher concentration of trapped eggs in the small intestine than large intestine (p<0.05). All characteristics of the reproductive system and suckers of male worms presented significant differences (p<0.05). CMO strain was smaller in all measurements. Females showed significant differences (p<0.05) in the larger diameter of the eggs, in the area and perimeter of the spine egg and in the oral sucker area. We conclude that differences in strains can be expressed even when the strains have been cycled for several generations under laboratory conditions.


Diagnostic laparoscopy.
The value of surgical laparoscopy for various therapeutic interventions has been well established. In recent years, the interest of gastroenterologists in this method has revived, since laparoscopy can provide additional information for the staging of oncological and liver diseases. The introduction of miniature lenses may have contributed to this process, and an increasing number of physicians are using minilaparoscopy due to its safety and easy handling. Surgical studies have mainly focused on the evaluation of laparoscopic ultrasound for the detection of liver and lymph-node metastases. In specialized centers, laparoscopic ultrasound is also used for the estimation of locoregional pancreatic tumor spread, but the diagnostic impact of the method, particularly in colorectal carcinoma, still remains to be determined. Remarkably, the number of publications from gastroenterology departments has tended to increase in comparison with last year's review.


Voxel-based morphometry of brain SPECT can detect the presence of active central nervous system involvement in systemic lupus erythematosus.
To determine the value of voxel-based morphometry (VBM) of brain SPECT (single-photon emission computed tomography) images (BSI) in discriminating active central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) patients. Forty SLE patients (mean age 33 yrs) and 33 normal volunteers were submitted to BSI. SLE patients were screened for the presence of CNS involvement following the American College of Rheumatology (ACR) case definition. Patients with CNS infections, uraemia, diabetes and previous ischaemic or haemorrhagic stroke were excluded. Magnetic resonance imaging (MRI) scans were obtained in a 2T scanner (Elscint Prestige) with T1- and T2-weighted images. BSI were performed after injection of 1110 MBq (30 mCi) of (99m)Tc-ECD (ethyl-cysteinate-dimer). BSI were analysed using the statistical parametric mapping. After normalization, segmentation and smoothing the groups of SLE patients with active and inactive CNS manifestations and healthy volunteers were compared using VBM. Post-processed images were compared voxel-by-voxel using t-test in order to determine differences of intensity between groups. This analysis included grand mean scaling, proportional threshold masking (set to 0.4) and implicit masking. A P-value of 0.001 and cluster size of 32 were taken into consideration. VBM analyses of BSI did not show any differences between SLE patients with inactive CNS involvement and normal controls. However, the group of SLE patients with active CNS involvement had a global hypoperfusion, more intense in the frontal, dorsolateral and medial temporal lobe when compared with SLE patients without CNS involvement (P = 0.001) and healthy volunteers (P = 0.001). VBM of BSI is a useful and objective method for detecting perfusion abnormalities in SLE patients, which is indicative of active CNS involvement. However, it is not helpful in differentiating the clinical sub-types of CNS involvement according to the ACR classification.


Eating in the absence of hunger: Stability over time and associations with eating behaviours and body composition in children.
Eating in the absence of hunger (EAH) has been linked to obesity in adults and children. This study examined the stability of EAH in children between 4.5 and 6 years old, and associations with energy intake and portion selection, as well as cross-sectional and prospective associations with body composition. The participants were 158 boys and girls from the Growing Up in Singapore Towards healthy Outcomes cohort. At ages 4.5 and 6 years old children were provided lunch ad libitum, and immediately afterwards were exposed to palatable snacks to measure energy intake in the absence of hunger. At age 6 children completed an additional computer-based task to measure ideal portion size, where they selected pictures of the portions they would like to eat across eight foods. Measures of anthropometry (height/weight/skinfolds) were collected at both ages. Children who consumed energy during the EAH task at age 4.5 years were 3 times more likely to also do so at age 6 years. Children with high EAH intakes at age 4.5 years had high EAH intakes at age 6, highlighting stability of this behaviour over time. Energy consumed at lunch was unrelated to energy consumed during the EAH task, but children who ate in the absence of hunger cumulatively consumed more energy over lunch and the EAH task. Children who showed EAH tended to select larger ideal portions of foods during the computer task. EAH was not associated with measures of body composition. EAH is a stable behavioural risk factor for increased energy intake, but was not associated with body composition in this cohort. The majority of children ate in the absence of hunger, suggesting that interventions aimed at reducing responsiveness to external food cues could help to reduce energy intakes. Trial Registry Number: NCT01174875; https://clinicaltrials.gov/.


[Hemoglobins, XXXVI: The primary structure of a dimeric insect hemoglobin (Erythrocruorin), component IX from Chironomus thummi thummi. Studies on the quarternary structure of the dimeric CTT-hemoglobins (author's transl)].
The primary structure of a dimeric insect hemoglobin (erythrocruorin), component CTT IX (Chironomus thummi thummi) was established by automatic sequence analysis. The alignment of the peptides was facilitated by producing only a few large fragments. The primary structure of CTT IX is compared with the human beta-chains and with CTT III. It is discussed, why for the dimeric CTT-hemoglobins only dimerisation can be observed but no tetramerisation. Experiments were done to locate the binding areas between the subunits in the dimeric molecule. Even after blocking of the alpha-NH2-group by cyanate, the stability of the dimeric molecule is not altered. Therefore the binding regions of the CTT-hemoglobins must be different from those of the tetrameric hemoglobins of vertebrates. Our results lead to a quarternary structure different from that of the hemoglobins of mammalians. This structure explains the possibility of dimerisation, but excludes tetramerisation.


Molecularly clean ionic liquid/rubrene single-crystal interfaces revealed by frequency modulation atomic force microscopy.
The structural properties of ionic liquid/rubrene single-crystal interfaces were investigated using frequency modulation atomic force microscopy. The spontaneous dissolution of rubrene molecules into the ionic liquid was triggered by surface defects such as rubrene oxide defects, and the dissolution rate strongly depended on the initial conditions of the rubrene surface. Dissolution of the second rubrene layer was slower due to the lower defect density, leading to the formation of a clean interface irrespective of the initial conditions. Molecular-resolution images were easily obtained at the interface, and their corrugation patterns changed with the applied force. Force curve measurements revealed that a few solvation layers of ionic liquid molecules formed at the interface, and the force needed to penetrate the solvation layers was an order of magnitude smaller than typical ionic liquid/inorganic solid interfaces. These specific properties are discussed with respect to electric double-layer transistors based on the ionic liquid/rubrene single-crystal interface.


Barriers in systemic delivery and preclinical testing of synthetic microRNAs in animal models: an experimental study on miR-215-5p mimic.
Mus musculus is the most commonly used animal model in microRNA research; however, little is known about the endogenous miRNome of the animals used in the miRNA-targeting preclinical studies with the human xenografts. In the presented study, we evaluated the NOD/SCID gamma mouse model for the preclinical study of systemic miR-215-5p substitution with a semitelechelic poly[N-(2-hydroxypropyl)-methacrylamide]-based carrier conjugated with miR-215-5p-mimic via a reductively degradable disulfide bond. Murine mmu-miR-215-5p and human hsa-miR-215-5p have a high homology of mature sequences with only one nucleotide substitution. Due to the high homology of hsa-miR-215-5p and mmu-hsa-miR-215-5p, a similar expression in human and NOD/SCID gamma mice was expected. Expression of mmu-miR-215 in murine organs did not indicate tissue-specific expression and was highly expressed in all examined tissues. All animals included in the study showed a significantly higher concentration of miR-215-5p in the blood plasma compared to human blood plasma, where miR-215-5p is on the verge of a reliable detection limit. However, circulating mmu-miR-215-5p did not enter the human xenograft tumors generated with colorectal cancer cell lines since the levels of miR-215-5p in control tumors remained notably lower compared to those originally transfected with miR-215-5p. Finally, the systemic administration of polymer-miR-215-5p-mimic conjugate to the tail vein did not increase miR-215-5p in NOD/SCID gamma mouse blood plasma, organs, and subcutaneous tumors. It was impossible to distinguish hsa-miR-215-5p and mmu-miR-215-5p in the murine blood and organs due to the high expression of endogenous mmu-miR-215-5p. In conclusion, the examination of endogenous tissue and circulating miRNome of an experimental animal model of choice might be necessary for future miRNA studies focused on the systemic delivery of miRNA-based drugs conducted in the animal models.


Comparative pharmacokinetics of parenteral and oral gold compounds.
The pharmacokinetics of intramuscular and oral gold compounds differ widely. Aurothioglucose and gold sodium thiomalate absorption is complete; 25% of auranofin (AF) is absorbed. Blood gold concentrations with conventional parenteral treatment generally peak between 600-800 microgram/dl the day of injection and decline gradually to about 300 micrograms/dl 7 days later. Levels range between 30 and 100 micrograms/dl, using 2-9 mg/d AF, and show little variation. A smaller percentage of gold is found in the cellular fraction of blood with I.M. than with oral gold. The blood half-life is approximately 6 days with gold sodium thiomalate, and 21 days with AF. Forty percent of the administered dose of injectable gold is excreted; depending upon dosage, 75-100% of oral gold is recovered in excreta, which is a combination of unabsorbed and excreted gold. Nearly 70% of parenteral gold is excreted in the urine and 30% in feces, while only 5% of AF is in urine and 95% in feces. The amount of gold retained following intravenous 195Au-labelled gold sodium thiomalate is 43% at 60 days and 25% at 250 days, but only 15% with oral radiolabeled AF 10 days after ingestion. Synovial fluid gold levels are much higher with parenteral than with oral gold but the blood-to-synovial fluid ratio is similar. Skin gold concentrations rise steadily with injectable but not oral treatment, but hair and nail accumulation is insignificant. Corneal, lens, and skin chrysiasis may develop with parenteral therapy, but has not been recognized with AF.


National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years--United States, 2013.
The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, 2 doses of meningococcal conjugate (MenACWY) vaccine, and 3 doses of human papillomavirus (HPV) vaccine.* ACIP also recommends administration of "catch-up"† vaccinations, such as measles, mumps, and rubella (MMR), hepatitis B, and varicella, and, for all persons aged ≥6 months, an annual influenza vaccination. ACIP recommends administration of all age-appropriate vaccines during a single visit. To assess vaccination coverage among adolescents aged 13-17 years, CDC analyzed data from the 2013 National Immunization Survey-Teen (NIS-Teen).§ This report summarizes the results of that analysis, which show that from 2012 to 2013, coverage increased for each of the vaccines routinely recommended for adolescents: from 84.6% to 86.0% for ≥1 Tdap dose; from 74.0% to 77.8% for ≥1 MenACWY dose; from 53.8% to 57.3% for ≥1 HPV dose among females, and from 20.8% to 34.6% for ≥1 HPV dose among males. Coverage varied by state and local jurisdictions and by U.S. Department of Health and Human Services (HHS) region. Healthy People 2020 vaccination targets for adolescents aged 13-15 years were reached in 42 states for ≥1 Tdap dose, 18 for ≥1 MenACWY dose, and 11 for ≥2 varicella doses. No state met the target for ≥3 HPV doses.¶ Use of patient reminder and recall systems, immunization information systems, coverage assessment and feedback to clinicians, clinician reminders, standing orders, and other interventions can help make use of every health care visit to ensure that adolescents are fully protected from vaccine-preventable infections and cancers (5), especially when such interventions are coupled with clinicians' vaccination recommendations.


Phase measurement of a segmented wave front using PISton and TILt interferometry (PISTIL).
New architectures for telescopes or powerful lasers require segmented wave front metrology. This paper deals with a new interferometric wave front sensing technique called PISTIL (PISton and TILt), able to recover both piston and tilts of segment beams. The main advantages of the PISTIL technique are the absence of a reference arm and an access to the tilt information. An explanation of the principle, as well as an experimental implementation and the use of a segmented active mirror, are presented. Measurement errors of λ/200 for piston and 40 µrad for tilts have been achieved, well beyond performances requested for the above mentioned applications.


Longitudinal construct validity of the Health Utilities Indices Mark 2 and Mark 3 in hip fracture.
The objective of this study is to evaluate the longitudinal construct validity of the Health Utilities Index Mark 2 (HUI2) and Health Utilities Index Mark 3 (HUI3) using a convergent/divergent validity approach in patients recovering from hip fracture, with the Functional Independence Measure (FIM) as the comparator. A total of 278 patients with a primary diagnosis of hip fracture were interviewed 3-5 days after surgery and then at 1 and 6 months using the HUI2, HUI3 and the FIM and a Likert-type rating of hip pain. A priori hypotheses were formulated. Convergent and divergent correlations between HUI2, HUI3 and FIM change scores for the baseline to 1-month and baseline to 6-month intervals were examined. Overall HUI2 detected continued gain in health-related quality of life between 1 and 6 months after fracture, as the change increased from 0.20 to 0.29 units. The correlation between change in the overall HUI2 score and total FIM score was moderate (r = 0.50) over the 6-month interval, but larger than the observed correlation over the 1-month interval (r = 0.36). The correlation between change in overall HUI3 score and total FIM over the 1-month interval was small (r = 0.32), and the correlation between change in overall HUI3 score and total FIM was moderate (r = 0.37) over the 6-month interval. All hypotheses for the divergent correlations were supported. Weaker correlations were reported for change over 1 month as compared to change over the 6 months after fracture. Findings supported the longitudinal construct validity of the overall HUI2 and HUI3 for the assessment of recovery following hip fracture, particularly for change over the 6 months following fracture.


Synthesis, characterization, DNA binding, cleavage activity, cytotoxicity and molecular docking of new nano water-soluble [M(5-CH₂PPh₃-3,4-salpyr)](ClO₄)₂ (M = Ni, Zn) complexes.
Some new water soluble complexes [N,N'-bis{5-[(triphenyl phosphonium chloride)-methyl]salicylidine}-3,4-diaminopyridine] M(ii), which are formulated as nano-[Zn(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), [Zn(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), nano-[Ni(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), [Ni(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), and [N,N'-bis{5-[(triphenyl phosphonium chloride)-methyl]salicylidine}-2,3-diaminopyridine]Ni(ii) [Ni(5-CH2PPh3-2,3-salpyr)](ClO4)2 () have been isolated and characterized by elemental analysis, FT-IR, (1)H NMR, (13)C NMR, (31)P NMR, and UV-vis spectroscopy. The morphology and size of the nano complexes were determined using FE-SEM and TEM. In vitro DNA binding studies were investigated by UV-vis absorption spectroscopy, viscosity measurements, CD spectroscopy, cyclic voltammetry, emission spectra and gel electrophoresis, which suggest that the metal complexes act as efficient DNA binders. The absorption spectroscopy of the compounds with DNA reveals that the DNA binding affinity (Kb) has this order: > > > > > Ligand. The metal complexes show DNA binding stronger than the ligand, which is expected due to the nature of the metal. The nano complexes display DNA binding stronger than the other complexes which is related to the effect of size on binding affinity and the Ni(ii) complexes reveal DNA binding stronger than the corresponding Zn(ii) analogues, which is expected due to their z* effect and geometry. The prominent double strand DNA cleavage abilities of compound are observed in the absence of H2O2 with efficiencies of more than 50% even at 70 μM complex concentration. Surprisingly, Zn(ii) complexes (compounds & ) exhibit a higher cytotoxicity (IC50: 7.3 & 10.9 μM at 24 h; IC50: 4.6 & 8.7 μM at 48 h) against human hepatoma (HepG2) and HeLa cell lines than the Ni(ii) complexes (compounds , & ) and 5-fluorouracil as control in spite of their inability to cleave DNA. Finally, DNA binding interactions were performed by docking studies. Density functional theory (DFT) studies were performed using the GAUSSIAN 03 program. The DFT method with B3LYP functional, LANL2DZ basis set for metal centers and 6-311g* for other atoms was used. The synthesized compounds and DNA were simulated by molecular docking to explore more details of the ligands conformation and their orientations in the active site of the receptor.


Student-school bonding and adolescent problem behavior.
Adolescent problem behavior, including substance use, school misconduct and delinquency, is a national concern. Implicit in the concept of middle school is the recognition that students who develop positive social bonds with their school are more likely to perform well academically, and refrain from misconduct and other antisocial behavior. However, little scientific attention has been given to the complex interactions between middle school students and the school environment. Prior to implementing a middle school problem behavior prevention program we conducted a survey in the seven middle schools in one US school district. Out of 4668 grade 6-8 students enrolled, 4263 (91.3%) completed the survey. Student-school bonding was positively correlated with school adjustment (r = 0.49) and perceived school climate (r = 0.77), but inversely correlated with problem behavior (r = -0.39 to -0.43). Problem behavior was significantly higher (P < 0.001) among males than females and among students in higher grades. Conversely, school bonding, climate and adjustment were significantly higher (P < 0.001) among females than males, but declined significantly from one grade to the next. The data support the conclusion that school bonding is associated with problem behavior. We describe the development of a multiple-component intervention in middle schools designed to increase student-school bonding and prevent problem behavior.


The Centre for Psychiatric Nursing Research and Practice: an innovative approach to enhancing clinical nursing research in the psychiatric/mental health field.
The available nursing literature suggests that nurses engaged in clinical practice hold a somewhat ambivalent attitude towards nursing research. On the one hand, its value is acknowledged, but on the other, its relevance to clinical practice is questioned. This situation poses a significant barrier to the involvement of clinicians in research and the utilisation of findings in practice. This paper describes the implementation of a model to facilitate the development of a systematic research approach at the Centre for Psychiatric Nursing Research and Practice in Victoria, Australia. The development of strong relationships between the Centre and the clinical field was considered crucial in determining the success of this initiative. The introduction of a number of programs to foster the conduct and utilisation of clinical research are described, including: The Nursing Clinical Development Unit Program, the Clinical Research Fellowship Program, clinical research projects, the Collaborative Psychiatric Nursing Conference and strategies to encourage the dissemination of research information. In combination, these initiatives are expected to contribute to a systematic approach to engendering a research culture within psychiatric nursing in Victoria, Australia.


Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma.
Medulloblastoma is the most common malignant brain tumor in children. It is thought to result from the transformation of granule cell precursors (GCPs) in the developing cerebellum, but little is known about the early stages of the disease. Here, we identify a pre-neoplastic stage of medulloblastoma in patched heterozygous mice, a model of the human disease. We show that pre-neoplastic cells are present in the majority of patched mutants, although only 16% of these mice develop tumors. Pre-neoplastic cells, like tumor cells, exhibit activation of the Sonic hedgehog pathway and constitutive proliferation. Importantly, they also lack expression of the wild-type patched allele, suggesting that loss of patched is an early event in tumorigenesis. Although pre-neoplastic cells resemble GCPs and tumor cells in many respects, they have a distinct molecular signature. Genes that mark the pre-neoplastic stage include regulators of migration, apoptosis and differentiation, processes crucial for normal development but previously unrecognized for their role in medulloblastoma. The identification and molecular characterization of pre-neoplastic cells provides insight into the early steps in medulloblastoma formation, and may yield important markers for early detection and therapy of this disease.


Laboratory measurement of the interface pressures applied by active therapy support surfaces: a consensus document.
A key element in pressure ulcer prevention and management is the selection of appropriate pressure redistributing (PR) patient support surfaces for use while seated and in bed. However little explicit guidance exists allowing standardised quantitative comparison of different PR surfaces based upon their ability to redistribute pressure from anatomical landmarks such as the heels and sacrum. In 2008 a working group was established in Europe through the US National Pressure Ulcer Advisory Panel (NPUAP) support surface standardisation initiative (S3I) and under the aegis of the European Pressure Ulcer Advisory Panel with the specific remit of developing test methods for the evaluation of active therapy support surfaces (alternating pressure air mattresses). This report describes a consensus development process to agree test methods appropriate to compare active therapy surfaces based upon their ability to redistribute pressure from the sacrum and the heels.


Intravenous immunoglobulin therapy for severe Clostridium difficile colitis.
Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis. To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy. Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200-300 mg/kg). Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay. Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4-1.6 mg/ml. Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations and C difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration.


A Review of Extraction and Purification, Biological Properties, Structure-Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis.
Since ancient times, China has used natural medicine as the primary way to combat diseases and has a rich arsenal of natural medicines. With the progress of the times, the extraction of bioactive molecules from natural drugs has become the new development direction for natural medicines. Among the numerous natural drugs, Schisandrin C (Sch C), derived from Schisandra Chinensis (Turcz.) Baill. It has excellent potential for development and has been shown to possess various pharmacological properties, including hepatoprotective, antitumor and anti-inflammatory activities. Based on the biological properties of hepatoprotection, scholars have explored Sch C and its synthetic products in depth; some studies have shown that pentosidine has the effect of improving the symptoms of liver fibrosis and reducing the concentration of alanine transaminase (ALT) and aspartate aminotransferase (AST) in the serum of rats, which is an essential inspiration for the development of anti-liver fibrosis drugs. But more in vivo and ex vivo studies still need to be included. This paper focuses on Sch C's extraction and synthesis, biological activities and drug development progress. The future application prospects of Sch C are discussed to perfect its development work further.


Templating photodimerization of trans-cinnamic acids with cucurbit[8]uril and gamma-cyclodextrin.
Cucurbit[8]uril and gamma-cyclodextrin are able to align two olefin molecules in a head-head fashion within their large cavities. Excitation of such templated olefins results in syn head-head cyclobutanes in nearly quantitative yields. The methodology revealed here works with trans-cinnamic acids that do not dimerize either in solution or in the solid state and with the ones that yield only anti head-tail dimer in the solid state. [reaction: see text]


Calcium and contractions of isolated smooth muscle cells from rat myometrium.
Smooth muscle cells were isolated from estrogenized rat myometrium by collagenase digestion. Electron microscopic examination and measurement of cell lengths by image-splitting micrometry were carried out after fixation with acrolein. Mean lengths of cells before and after isolation were 81.7 and 66.9 micron, respectively. Responses of cells were compared with contractions of isolated strips recorded isometrically. Effects of carbachol and KCl were examined in 2 mM Ca, 2 mM Ca + 4 mM EGTA, and 2 mM Ca + 10(-8) M nitrendipine solution. Carbachol and KCl produced concentration-dependent shortening of isolated cells maximal at 30 s after addition. The concentrations of carbachol required to produce shortenings were about 100-fold less than those required to produce isometric contractions; but no major difference was observed in the concentration dependence of cell shortening and isometric contraction produced by potassium-induced depolarization. In 2 mM Ca solution, there was a phasic response, followed by a tonic response such that more than 50% of maximum cell shortening was maintained for 10 min. However, in 2 mM Ca + 4 mM EGTA or 10(-8) M nitrendipine, the tonic contraction was abolished and cells rapidly relaxed after 30 s. If carbachol was added to cells after varying times in the EGTA-containing solution, the ability to initiate a contraction declined exponentially with a half-time of 160 s. Effects of depolarization by KCl were examined in 2 mM Ca plus nitrendipine and 2 mM Ca + 4 mM EGTA solution. Shortening occurred in 2 mM Ca solution by depolarization but not if nitrendipine was added. Though shortening was not observed in 2 mM Ca + 4 mM EGTA solution by KCl, subsequent addition of carbachol induced shortening. These results suggested that there was an intracellular Ca store site from which Ca was released by carbachol and which was not affected by depolarization in the absence of external Ca. No evidence was obtained that the contraction persists in Ca2+-free medium in isolated cells, which is in agreement with previous findings in small muscle strips in which only a similar transient response was obtained.


Automated cerebrum segmentation from three-dimensional sagittal brain MR images.
We present a fully automated cerebrum segmentation algorithm for full three-dimensional sagittal brain MR images. First, cerebrum segmentation from a midsagittal brain MR image is performed utilizing landmarks, anatomical information, and a connectivity-based threshold segmentation algorithm as previously reported. Recognizing that cerebrum in laterally adjacent slices tends to have similar size and shape, we use the cerebrum segmentation result from the midsagittal brain MR image as a mask to guide cerebrum segmentation in adjacent lateral slices in an iterative fashion. This masking operation yields a masked image (preliminary cerebrum segmentation) for the next lateral slice, which may truncate brain region(s). Truncated regions are restored by first finding end points of their boundaries, by comparing the mask image and masked image boundaries, and then applying a connectivity-based algorithm. The resulting final extracted cerebrum image for this slice is then used as a mask for the next lateral slice. The algorithm yielded satisfactory fully automated cerebrum segmentations in three-dimensional sagittal brain MR images, and had performance superior to conventional edge detection algorithms for segmentation of cerebrum from 3D sagittal brain MR images.


Swing beds: a strategy in rural hospitals' fight to survive.
More rural hospitals now have the opportunity to offer long-term care services under the expanded Federal swing-bed program. The ability to use inpatient beds for acute care or skilled nursing care can, in many cases, help rural hospitals improve their occupancy levels and increase revenues. However, hospitals must be aware of the need to closely monitor costs.