Increased Levels of Cardiac Troponin I in Subjects with Extremely Low B-type Natriuretic Peptide Levels.
Because of the lack of studies focused on the biological implications of extremely low B-type natriuretic peptide (BNP) levels, we investigated whether extremely low BNP levels could be harmful to the cardiovascular system due to compromised cardio-protection. By using cardiac troponin I (cTnI) as an indicator of cardiovascular disorder, we assessed whether cTnI was inversely associated with BNP in populations with low BNP levels. A total of 2,001 apparently healthy subjects older than 38 years were included in this study. We defined subgroups from this population by limiting the maximum BNP level with cut-off values ranging from 1 through 20 pg/mL and performed covariance structure analyses by comparing log(BNP) with log(cTnI) in each subgroup. The beta values between log(BNP) and log(cTnI) sharply decreased as the BNP cut-off was reduced from 20 pg/mL (beta = 0.04) to 1 pg/mL (beta = -0.29) and became significant when the BNP cut-off levels were lower than 4 pg/mL (p < 0.005). In subgroups with BNP levels lower than 4 pg/mL, elevation in cTnI level was inversely associated with BNP (p < 0.005), which suggests that insufficient BNP may play a pathogenic role in the occurrence of cardiovascular abnormalities.


Multifunctional Polymer-Based Graphene Foams with Buckled Structure and Negative Poisson's Ratio.
In this study, we report the polymer-based graphene foams through combination of bottom-up assembly and simple triaxially buckled structure design. The resulting polymer-based graphene foams not only effectively transfer the functional properties of graphene, but also exhibit novel negative Poisson's ratio (NPR) behaviors due to the presence of buckled structure. Our results show that after the introduction of buckled structure, improvement in stretchability, toughness, flexibility, energy absorbing ability, hydrophobicity, conductivity, piezoresistive sensitivity and crack resistance could be achieved simultaneously. The combination of mechanical properties, multifunctional performance and unusual deformation behavior would lead to the use of our polymer-based graphene foams for a variety of novel applications in future such as stretchable capacitors or conductors, sensors and oil/water separators and so on.


[Hyperbaric oxygen therapy and inert gases in cerebral ischemia and traumatic brain injury].
Cerebral ischemia is a common thread of acute cerebral lesions, whether vascular or traumatic origin. Hyperbaric oxygen (HBO) improves tissue oxygenation and may prevent impairment of reversible lesions. In experimental models of cerebral ischemia or traumatic brain injury, HBO has neuroprotective effects which are related to various mechanisms such as modulation of oxidative stress, neuro-inflammation or cerebral and mitochondrial metabolism. However, results of clinical trials failed to prove any neuroprotective effects for cerebral ischemia and remained to be confirmed for traumatic brain injury despite preliminary encouraging results. The addition of inert gases to HBO sessions, especially argon or xenon which show neuroprotective experimental effects, may provide an additional improvement of cerebral lesions. Further multicentric studies with a strict methodology and a better targeted definition are required before drawing definitive conclusions about the efficiency of combined therapy with HBO and inert gases in acute cerebral lesions.


Improved DNA content histograms from formalin-fixed, paraffin-embedded liver tissue by proteinase K digestion.
An improved method for the enzymatic digestion of formalin-fixed, paraffin-embedded liver tissue for DNA content analysis by flow cytometry is presented. Forty samples of histologically normal liver were alternately digested by the traditional pepsin method or a new method utilizing proteinase K and heat. Sixteen (40%) of the pepsin-digested samples had apparent DNA aneuploid peaks by flow cytometry. False DNA aneuploid peaks were not present in any of the histograms obtained after proteinase K digestion. Microscopy showed that the pepsin-digested samples had residual cytoplasmic remnants which contained fluorescent material. Samples digested with proteinase K had few cytoplasmic remnants. The average G0/G1 coefficient of variation after proteinase K treatment was lower (41%) and the fluorescent intensity higher (128%) than the pepsin-treated samples. The apparent mean S-phase (a combination of S-phase cells and underlying debris) after proteinase K digestion was 35% of the pepsin-treated samples. Primary and secondary tumors of the liver that were DNA aneuploid after pepsin treatment were also DNA aneuploid after proteinase K treatment. A modified digestion protocol utilizing proteinase K and heat can provide superior results for DNA content analysis of formalin-fixed, paraffin-embedded liver tissue.


A relationship between acute respiratory illnesses and weather.
Weekly data from 7 years (2004-2010) of primary-care counts of acute respiratory illnesses (ARIs) and local weather readings were used to adjust a multivariate time-series vector error correction model with covariates (VECMX). Weather variables were included through a partial least squares index that consisted of weekly minimum temperature (coefficient = - 0·26), weekly median of relative humidity (coefficient = 0·22) and weekly accumulated rainfall (coefficient = 0·5). The VECMX long-term test reported significance for trend (0·01, P = 0·00) and weather index (1·69, P = 0·00). Short-term relationship was influenced by seasonality. The model accounted for 76% of the variability in the series (adj. R 2 = 0·76), and the co-integration diagnostics confirmed its appropriateness. The procedure is easily reproducible by researchers in all climates, can be used to identify relevant weather fluctuations affecting the incidence of ARIs, and could help clarify the influence of contact rates on the spread of these diseases.


The value of leucocyte stix results in predicting bacteriuria and urinary tract infection after gynaecological surgery.
This prospective study was carried out on 454 women to determine the value of a leucocyte dipstick test in predicting significant bacteriuria and symptomatic postoperative urinary tract infection after routine gynaecological surgery. Urine was cultured and tested for leucocytes with a dipstick test (Nephur test, Boehringer) at catheter removal and 2 days later. Among the 454 patients, 16.3% developed urinary tract infection and 53.3% had significant bacteriuria at least once. Among 898 urine specimens, taken from asymptomatic patients, 41.6% were stix-positive and 58.4% stix-negative. The predictive value of a positive stix result was 59.6% for a positive culture and 27.5% for urinary tract infection. It is concluded that, the predictive value of a positive stix for postoperative significant bacteriuria or urinary tract infection is too low to be of practical use. However, the predictive value of a negative test was high, and few patients developed symptomatic urinary tract infection when the leucostix was negative.


Cysteine cathepsins in the immune response.
Antigen (Ag) processing by major histocompatibility complex class II (MHC) class II molecules is tightly linked with the proteases of the endosomal/lysosomal system. Cysteine (Cys) cathepsins, which constitute a major portion of this proteolytic system, have been found to have essential roles in both Ag processing and maturation of the MHC class II molecules. In this review, we will cover some specific functions of individual Cys cathepsins and particularly those most relevant to the immune system.


Spatial and temporal evaluation of locally induced skin trauma recorded with laser Doppler techniques.
The single-fiber laser Doppler flowmetry (SF-LDF) technique has been used to study perfusion within tissues. The insertion of the SF-LDF probe into human skin locally alters microcirculation for more than 70 min after positioning. In this study the SF-LDF and a newly developed laser Doppler imager (LDI) were used to describe the spatial distribution, the intensity, and the temporal course of the trauma following intracutaneous insertion of the probe. The LDI scanned a human skin area of 6 x 6 cm (36 x 36 pixels). A flexible SF-LDF probe was inserted intradermally in the same measuring region. Recordings were performed for 120 min with the two techniques simultaneously. With the SF-LDF probe maximal hyperemia was recorded after 5-30 min. After a gradual and slow decrease most of the subjects reached a steady-state level within 80-100 min. A 3-min tourniquet occlusion test was performed 120 min after SF probe positioning. A significant hyperemic response was recorded, indicating that almost no posttraumatic activity was present at this time. The area of increased perfusion recorded with the LDI had an oval to circular configuration with a maximal extension after 5-10 min (radius 1.5-2 cm, area 8.9 cm2). The zone of maximal hyperemia was distributed adjacent to the intradermal probe, gradually decreasing toward the periphery. No significant hyperemia was shown with LDI after 100 min. There was a concordance between the time courses of the hyperemic response obtained with the two techniques.


Is working later in life good or bad for health? An investigation of multiple health outcomes.
To examine the mutual influences between changes in work status and multiple dimensions of health outcomes (immediate memory, physical disability, and depressive symptoms) over later years. We used a subsample of 8,524 older adults who participated in the Health and Retirement Study from 1998 to 2008 and were 62 years or older in 1998 to examine work status and health outcomes after controlling for age and background characteristics. We present results of cross-lagged auto-regressive models. Work status (level of work) predicted subsequent residual changes in immediate memory over time, whereas immediate memory predicted subsequent residual changes in work status over time, even after controlling for physical disability and depressive symptoms. Similar results were indicated for the associations between work status and physical disability and depressive symptoms over time. Consistent with social causation and social selection traditions, the findings support bi-directional associations among changes in work status (the level of work), immediate memory, physical disability, and depressive symptoms in later years. Practical implications are discussed.


Conversion factors estimating indicative chronic no-observed-adverse-effect levels from short-term toxicity data.
Data on chronic toxicity are generally required to derive a health-based acceptable exposure limit, such as the acceptable daily intake. However, only acute and/or subacute toxicity data are available for many compounds. In this study, we assessed conversion factors (CFs) to estimate a chronic no-observed-adverse-effect-level (NOAELchronic) from these short-term toxicity data. We evaluated distributions of ratios between (sub)acute and chronic toxicity data for 332 compounds. By defining the CF as the upper 95% confidence limit of the 95th percentile for the relevant ratio distribution, both the variation between compounds (95th percentile) and the estimation error (upper 95% confidence limit) could be taken into account. Dividing a NOAELsubacute or LD50 by the corresponding CF results in a conservative estimate of the chronic NOAEL. We assessed a CF of 87 for a NOAELsubacute and a CF of 1.7 x 10(4) for an LD50. We found the NOAELsubacute to be a better predictor of the NOAELchronic than the LD50. Moreover, the added value of an LD50 in estimating a NOAELchronic appeared to be limited when a NOAELsubacute was available.


ETA: An Efficient Training Accelerator for DNNs Based on Hardware-Algorithm Co-Optimization.
Recently, the efficient training of deep neural networks (DNNs) on resource-constrained platforms has attracted increasing attention for protecting user privacy. However, it is still a severe challenge since the DNN training involves intensive computations and a large amount of data access. To deal with these issues, in this work, we implement an efficient training accelerator (ETA) on field-programmable gate array (FPGA) by adopting a hardware-algorithm co-optimization approach. A novel training scheme is proposed to effectively train DNNs using 8-bit precision with arbitrary batch sizes, in which a compact but powerful data format and a hardware-oriented normalization layer are introduced. Thus the computational complexity and memory accesses are significantly reduced. In the ETA, a reconfigurable processing element (PE) is designed to support various computational patterns during training while avoiding redundant calculations from nonunit-stride convolutional layers. With a flexible network-on-chip (NoC) and a hierarchical PE array, computational parallelism and data reuse can be fully exploited, and memory accesses are further reduced. In addition, a unified computing core is developed to execute auxiliary layers such as normalization and weight update (WU), which works in a time-multiplexed manner and consumes only a small amount of hardware resources. The experiments show that our training scheme achieves the state-of-the-art accuracy across multiple models, including CIFAR-VGG16, CIFAR-ResNet20, CIFAR-InceptionV3, ResNet18, and ResNet50. Evaluated on three networks (CIFAR-VGG16, CIFAR-ResNet20, and ResNet18), our ETA on Xilinx VC709 FPGA achieves 610.98, 658.64, and 811.24 GOPS in terms of throughput, respectively. Compared with the prior art, our design demonstrates a speedup of 3.65× and an energy efficiency improvement of 8.54× on CIFAR-ResNet20.


Measurements of CO(2) concentration and temperature at high pressures using 1f-normalized wavelength modulation spectroscopy with second harmonic detection near 2.7 microm.
Tunable diode lasers (TDL) near 2.7 mum are used to measure high-resolution direct absorption and wavelength modulation with second harmonic (WMS-2f) spectra at high pressures for two CO(2) transitions near 3633.08 and 3645.20 cm(-1), belonging to the nu(1)+ nu(3) vibrational band. Important factors influencing the design of a high-pressure TDL sensor and the variation of WMS-2f line shape with changes in pressure and laser parameters are discussed. Measurements of line strength and line broadening parameters are carried out for the 3645.20 cm(-1) transition in an atmospheric-pressure, high-temperature cell. A room-temperature high-pressure cell is then used to measure the pressure shift for both CO(2) transitions. Deviation of the direct absorption and wavelength modulation spectroscopy (WMS) spectra from the Lorentzian profile is studied in a high-density (9.2 amagats) CO(2)-Ar mixture. The WMS spectra are shown to be negligibly affected by non-Lorentzian effects up to 10 atm and room temperature, in contrast with direct absorption. Measurements of CO(2) concentration and temperature are carried out in nonreactive shock-tube experiments (P approximately 8-12 atm, T~800-1200 K) to validate the accuracy and precision of wavelength-modulation-spectroscopy-based sensing. CO(2) time histories are then measured in heptane ignition experiments and compared with reaction kinetics mechanisms to demonstrate the use of this sensor in high-pressure combustion systems.


Replacement of estrogens and progestins to prevent morbidity and mortality in preterm infants.
A potential therapeutic effect of sex steroids on premature infants has been proposed from animal data and observational studies in humans. Purported benefits include reduction in chronic lung disease, improved bone density and improved neurodevelopmental outcome. To determine if estrogens or progestins, either alone or in combination, when compared to placebo or no treatment, reduce morbidity and/or mortality in preterm infants. The standard search strategy of the Cochrane Neonatal Review Group as outlined in the Cochrane Library (Issue 2, 2004) was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE 1966 to July 2004 inclusive, previous reviews including cross references, abstracts, conferences and symposia proceedings (Perinatal Society of Australia and New Zealand 1998-2004 and Pediatric Academic Societies meetings 1998-2004). Randomised controlled trials comparing the use of estrogens and/or progestins with placebo or no treatment in preterm infants born less than 30 weeks gestation were included in this review. The primary outcome measures were neonatal mortality and medium-term neurodevelopmental outcome. Other outcomes included length of hospital stay, incidence of chronic lung disease, osteopaenia causing fractures and adverse effects of sex steroid administration. Two reviewers independently selected, assessed the quality of and extracted data from the included studies. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Two randomised controlled trials were identified by the search strategy and one was included in this review, comprising 30 preterm infants. There was no significant effect of replacement of estradiol and progesterone on the outcomes of mortality or neurodevelopmental disability in survivors followed. No adverse effects of sex steroid replacement on short or longer term outcomes were detected. The one small randomised controlled trial demonstrated neither evidence of benefit or harm related to the replacement of estradiol and progesterone in preterm infants less than 30 weeks gestation. A properly powered randomised controlled trial is required to determine whether or not administration of estradiol or progesterone, either alone or in combination, and at varying doses, confers any clinically significant benefits, or poses any risk, to the preterm infant.


Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides.
Sorting nexins (SNXs) are phox homology (PX) domain-containing proteins thought to regulate endosomal sorting of internalized receptors. The prototypical SNX is sorting nexin-1 (SNX1), a protein that through its PX domain binds phosphatidylinositol 3-monophosphate [PtdIns(3)P] and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)]. SNX1 is associated with early endosomes, from where it has been proposed to regulate the degradation of internalized epidermal growth factor (EGF) receptors through modulating endosomal-to-lysosomal sorting. We show here that SNX1 contains a BAR (Bin/Amphiphysin/Rvs) domain, a membrane binding domain that endows SNX1 with the ability to form dimers and to sense membrane curvature. We present evidence that through coincidence detection, the BAR and PX domains efficiently target SNX1 to a microdomain of the early endosome defined by high curvature and the presence of 3-phosphoinositides. In addition, we show that the BAR domain endows SNX1 with an ability to tubulate membranes in-vitro and drive the tubulation of the endosomal compartment in-vivo. Using RNA interference (RNAi), we establish that SNX1 does not play a role in EGF or transferrin receptor sorting; rather it specifically perturbs endosome-to-trans Golgi network (TGN) transport of the cation-independent mannose-6-phosphate receptor (CI-MPR). Our data support an evolutionarily conserved function for SNX1 from yeast to mammals and provide functional insight into the molecular mechanisms underlying lipid-mediated protein targeting and tubular-based protein sorting. We conclude that through coincidence detection SNX1 associates with a microdomain of the early endosome-characterized by high membrane curvature and the presence of 3-phosphoinositides-from where it regulates tubular-based endosome-to-TGN retrieval of the CI-MPR.


Current insights into ocular graft-versus-host disease.
To update our knowledge on hematopoietic stem cell transplantation (SCT) and graft-versus-host disease (GVHD) and summarize the current treatment options for ocular GVHD. Allogeneic (allo)-SCT represents a treatment option for a number of hematological malignancies and bone marrow disorders; the indications for this procedure are still increasing. Ocular GVHD develops in 40-60% of patients after allo-SCT, can cause severe ocular surface disease and has a negative impact on quality of life. There are no widely accepted guidelines for the treatment of ocular GVHD. In addition to the usual treatment with artificial tears, topical steroids, punctal occlusion and contact lenses, recent treatment options include anti-inflammatory medications including topical cyclosporine A and tacrolimus. Unfortunately, none of the treatment regimens are completely satisfactory and systematic data on the efficacy of these agents are lacking. The preventive treatment possibilities for ocular GVHD have not been defined. This review summarizes current data on ocular GVHD and focuses on novel treatment options for this severe ocular disorder. More data on the impact of ocular GVHD and the development of therapeutic and preventive measures are needed.


Implications of the foliar phytochemical diversity of the avocado crop Persea americana cv. Hass in its susceptibility to pests and pathogens.
Phytochemical diversity (PD) can be considered as a defensive trait; it can operate through single plant secondary metabolites or usually as complex mixtures of them. We tested the more diversity-better defense hypothesis correlating the leaf plant secondary metabolites (PSMs) with the incidence of plant enemies on Hass avocado trees. We expected a negative correlation between the occurrence of plant enemies and PD metrics. Also, as intraspecific PSMs polymorphisms in plant populations are common, we studied the incidence of plant enemies on Hass avocado trees representing chemical variants (chemotypes). We expected a differential incidence of plant enemies among trees grouped by their mono and sesquiterpene + phenylpropanoid chemotypes. We analyzed foliar hexane extracts from 236 trees in 17 orchards by gas chromatography and for the incidence of red mite, thrips, whitefly, avocado branch borer, fruit rot, scab, and peduncle collar blight. The predicted negative correlation between the plant enemies' incidence and the phytochemical metrics did not occur. To determine the relationship between enemy incidence and chemotypes we grouped the trees by cluster analysis using a matrix of PSMs in each tree. Most trees were grouped under four out of 23 chemotypes. Branch borers attacked trees of low-frequency chemotypes more frequently than trees with common chemotypes. The incidence of five plant enemies was different among the predominant chemotypes. The hypothesis of more diversity-better defense was not supported by the correlations between the phytochemical diversity and the incidence of pests and pathogens in Hass avocado orchards. Based on our results, we hypothesize that phytochemical diversity function as a defensive trait relies more on differentiation among individuals in a population than on the sole increase of chemical diversity. Also, the differential incidence of pests and pathogens on trees classified by their foliar chemotypes implies that these susceptibility or resistance markers represent potential useful tools for Hass avocado orchard pest management.


Semiautomation of preparation of fixed paraffin-embedded tissue for DNA analysis.
The usual manual preparation of single-cell suspensions from fixed paraffin-embedded tissue sections for flow cytometric (FCM) DNA ploidy analysis is a time-consuming, labor-intensive technique that requires 70 minutes to deparaffinize and rehydrate 50 microns sections as the initial step. Manual deparaffinization was compared with two semiautomated methods using an automatic slide stainer with either a 70-minute or 35-minute schedule. Samples from 6 normal tissues and 21 tumors (13 diploid and 8 aneuploid) were prepared using all three methods and analyzed by FCM. The mean cell counts in all samples were over 10(6). The DNA indices for the three samples prepared from a given tissue showed no significant differences. Using the 70-minute automation schedule, no aneuploid peaks were lost, and the ratio of G0G1 normal cells to aneuploid tumor cells was maintained. The automation of deparaffinization can thus provide a significant reduction in the labor need to produce single-cell suspensions for FCM; it can be especially helpful when handling large numbers of tumors. At the same time, the automated procedure decreases the exposure to hazardous chemicals and lowers the chance of losing tissue.


Ethical issues raised by managed care.
Health care costs have risen steadily for many years as a result of an inflationary reimbursement system, technologic advances, an aging population, and increasing patient expectations. The growth of managed care organizations (MCOs) has accelerated rapidly in recent years as an attempt to control costs. Because MCOs are involved with medicine, a moral enterprise, they enter the ethical arena. In this report several of the ethical issues raised by the attempted union of potentially conflicting systems are explored. The discussion focuses on four sets of relationships: physician-patient, physician-physician, patient-MCO and medicine-MCO as systems. Some remedies for dealing with the conflicts raised are offered.


Overview of Maternal, Neonatal and Child Deaths in South Africa: Challenges, Opportunities, Progress and Future Prospects.
The fact that most sub-Saharan Africa countries including South Africa (SA) are not on track to meet the 2015 target of improving maternal, neonate and child health (MNCH) is a major public health concern. The aim of this paper to give an overview of the current state of MNC deaths in SA, their relative causes, highlight challenges, existing opportunities, progress made and future prospects. The overview involved a synthesis and review of recent data and information from key national representative peer reviewed articles and grey literature from the National Department of Health and related stakeholder reports. Since 1990 the situation in SA aroused a lot of research interest in tracing the historical context of the problem, evaluating progress made and actions for improving MNCH. In 2009 the SA government established three national committees for confidential enquiry on MNC deaths. Multifactorial systems' related challenges were identified. Subsequently, the new National Strategic Plan for MNC and Women's Health and Nutrition has, in addition to provision of comprehensive interventions, been linked and aligned with efforts to strengthen the health systems particularly through the re-engineering of the Primary Health Care (PHC) services and district health systems. The overview gives an insight of the process that has influenced MNCH policy and programs in the country. The SA experience and current MNCH situation may be different compared to other African countries, however, the political commitment and government stewardship coupled with critical and yet complimentary research is exemplary, especially, given several global and regional plans and commitments to improve MNCH in the continent.


Splenic abscess caused by Klebsiella pneumoniae and non-Klebsiella pneumoniae in Taiwan: emphasizing risk factors for acquisition of Klebsiella pneumoniae splenic abscess.
Klebsiella pneumoniae was recently reported to be the major pathogen causing pyogenic splenic abscess in Taiwan. To better understand the characteristics of K. pneumoniae splenic abscess, which may be helpful in alerting clinicians to this infection entity when dealing with a suspicious patient, patients hospitalized between January 1981 and December 2002 with the diagnosis of splenic abscess were included in a retrospective study. Among the 38 enrolled patients, 9 (23.7%) suffered from K. pneumoniae splenic abscess. Compared to those with non-K. pneumoniae splenic abscess, patients suffering from splenic abscess caused by K. pneumoniae had a higher prevalence of underlying diabetes mellitus (88.9% vs 37.9%; p = 0.006) and higher incidence of concomitant liver abscess (44.4% vs 0%; p < 0.001) caused by the same pathogen. When dealing with patients suffering from K. pneumoniae splenic abscess, clinicians should work up to exclude a concomitant liver abscess caused by the same pathogen.


[Internal jugular vein cannulation guided by pulsation].
We are accustomed to right internal jugular vein (IJV) cannulation guided by pulsation for 20 years or more. This study was conducted to evaluate whether this method is a safe and certain method. After obtaining informed consent, 100 elective surgical patients requiring central venous catheterization during perioperative period were randomly assigned to either the pulsation group in which IJV pulsation was used for a landmark of puncture or the US group in which IJV was recognized with ultrasonography before puncture. Pulsation was observed in 98 patients. Successful rate of first attempt with a 23 G seeking needle was 85.7% in the pulsation group and 86% in the US group. IJV was successfully cannulated at 1 pass in the entire pulsation group and 92% in the US group. The frequency of puncture with cannula was significantly lower in the pulsation group than that of the US group. Arterial puncture with the seeking needle was recorded in 3 patients in the US group. Successful rate of first attempt in this study was comparable to other studies using ultrasonographic guidance. Internal jugular vein cannulation by pulsation method is a safe and certain method.


[Analysis of quality of life of 115 parents with cleft lip and/or palate children].
To investigate the quality of life of cleft lip and/or palate children's parents and discuss the factors to provide the oretical basis for improving the quality of life of these parents and promoting the healthy growth of children with cleft lip and/or palate. A total of 115 parents whose children had cleft lip and/or palate surgery treatment were selected as the experiment group, and another 198 parents (with healthy children having a similar age with those in the experiment group) as the control group. The experiment group was divided into three subgroups according to different types of cleft lip and/or palate: cleft Lip (CL), cleft palate (CP), cleft lip and palate (CLP). The experiment group and the control group were both divided into four subgroups according to age: 0-1, 1-3, 3-6 years old, and more than 6 years old. The experiment group and the control group were both divided into three subgroups according to education: junior middle school and the following, high school and technical secondary school, junior college degree or above. The GQOLI-74 scale was selected to assess the experiment group and the control group. SPSS 16.0 software was used to analyze data. 1) The experiment group had no significant difference with the control group in terms of the overall score and the scores of various children ages. 2) The scores of every item had no significant difference in CL, CP, CLP subgroup (P > 0.05). 3) The quality of life scores and scores of psychological function dimension and social function dimension of parents with 3-6 years old patients were obviously lower than those of parents with more than 6 years old patients (P<0.05). The scores of social function dimension of parents with 0-1, 1-3, 3-6 years old patients were obviously lower than those of parents with more than 6 years old patients (P < 0.05). The other items had no significant difference. 4) The scores of material life dimension and social function dimension of parents with junior college degree or above were higher than those of parents with junior middle school degree and the following (P < 0.05). The scores of social function dimension of parents with high school and technical secondary school degree were higher than those of parents with junior middle school degree and the following (P < 0.05). No difference was observed in the quality of life between cleft lip and/or palate children's parents and normal group. The parents with the low age children with cleft lip and/or palate and low-levels of education need more help and support to improve quality of life.


Depression and cerebral stroke.
Behavioral and psychological changes following cerebrovascular pathology have long been known. Depression, often severe and long-lasting, is a common and often unrecognized component of stroke. Although many of the clinical characteristics of poststroke depression have been reported in the literature for years, systematic studies of the frequency, course, relationship to lesion location, and response to treatment have only recently been undertaken. In this review, the authors briefly examine these various aspects of poststroke depression.


Diabetes service management training and the need for a patient perspective: a 10-year evolution of training strategies and goals.
In 1977, the Swedish National Board of Health and Welfare published guidelines for comprehensive care of patients with diabetes. The Stockholm County (1.6 million inhabitants) responded and opened a Diabetes Education and Training Centre, LUCD, in 1979. The goal was to reduce the impact of long-term complications. The centre should translate available knowledge about diabetes care into clinical practice, promoting a shift of patients and resources to the primary health care sector. Follow-up studies and new knowledge have changed the short-term training strategies; the long-term goal has remained unchanged. Current work is concentrated on training of staff, improving methods to support better patient learning, aiding organisational changes, and supporting large-scale interventions aimed at both patients, staff and the public. The patient can realize the goals. Knowledge and demands expressed by persons with diabetes are necessary for improvements of diabetes care. The skilled patient is also a guarantee for continuity of care. Regular follow-up of diabetes services was an important impetus for progressive change of short-term training strategies.


Aggressive pregnancy tumor mimicking a malignant neoplasm: a case report.
The aim of this report is to present the management of an aggressive, highly proliferative pregnancy tumor with clinical and radiographic characteristics highly suggestive of a malignant neoplasm. Pregnancy tumor is a benign hyperplastic gingival lesion occurring during pregnancy that is indistinguishable from a pyogenic granuloma arising in nonpregnant females, or in males. The lesion usually grows over a few months and tends to bleed. A 28-year-old woman at four months of gestation was referred for a massive gingival swelling (5.5 cm in greatest diameter) on the mandibular left side. The lesion was painful and continued to grow very rapidly over a three-week period, with spontaneous bleeding, and it interfered with speech and mastication. Advanced alveolar bone loss also was found beneath the lesion. A malignant process was suspected, and an incisional biopsy revealed a pregnancy tumor. The lesion was excised under general anesthesia during the pregnancy with no untoward reactions. Pregnancy tumor represents an important differential diagnosis of oral masses and can behave in a very aggressive fashion, mimicking a malignant tumor. This lesion should always be included in the differential diagnosis of soft tissue masses in a pregnant woman even if the lesion is clinically very aggressive. It is acceptable practice to excise aggressive variants of this lesion during pregnancy to avoid distressing side effects.


Morphological and histopathological changes in tongues of experimentally developed acromegaly-like rats.
An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I) was used to investigate morphological and histopathological tongue changes and clarify whether the changes were reversible. Human recombinant IGF-I (640 microg/day) was continuously subcutaneously infused into ten-week-old male rats for four weeks (IGF-I group; n = 6). Control sham-operated animals were injected saline alone (control group; n = 6). Rats were sacrificed immediately on ending administration at the age of fourteen weeks. Another 12 rats (6 from each group) were housed for an additional four weeks after administration ended. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. Tongue weights significantly increased with histopathological changes present (increases in the muscle-bundle width, spaces between muscle-bundles and epithelium thickness) in the IGF-I group compared to control rats. Tongue size returned to control levels after discontinuation of IGF-I administration. These findings suggest that the characteristic tongue enlargement was developed experimentally in our acromegaly-like rat model, and that such morphological and histopathological tongue changes are reversible on normalization of circulating IGF-I levels.


Risk factors for sporadic shigellosis, FoodNet 2005.
An estimated 450,000 cases of shigellosis occur annually in the United States. Outbreaks have been associated with food, water, child daycare centers, and men who have sex with men. However, for sporadic infections, which account for the majority of cases, risk exposures are poorly characterized. Foodborne Diseases Active Surveillance Network (FoodNet) conducts active, laboratory-based shigellosis surveillance in 10 US sites. We interviewed cases with illness onset during 2005 about exposures during the week before symptom onset using a standardized questionnaire. The proportion of patients who denied nonfood risks was used to estimate the burden attributable to foodborne transmission. Overall, 1494 cases were identified. The approximate incidence was 3.9/100,000, with the highest rates among children aged 1-4 years (16.4) and Hispanics (8.4). Of the 929 cases interviewed, 223 (24%) reported international travel in the week before symptom onset. Of the 626 nontraveling cases with complete risk factor information, 298 (48%) reported exposure to daycare or a household member with diarrhea; 99 (16%) reported drinking untreated water or recreational exposure to water; and 16 (3%) reported sexual contact with a person with diarrhea. Two hundred and fifty-nine (41%) denied all nonfood exposures examined. Sporadic shigellosis is most common among young children and Hispanics. Common exposures include international travel and contact with ill persons or daycare. However, more than one-third of US shigellosis cases annually might be due to food consumed in the United States.


[Conservative medicine: an attitude that can be learned?].
The rising costs and potential harms of medical care are matters of growing concern. In a recent article from the USA, Sirovich et al. examined the association between the intensity of the training environment and clinical-management decisions made by recent graduates. They found that, regardless of overall medical knowledge, internists trained at programmes in hospital referral regions with lower-intensity medical practice are more likely to recognise situations in which conservative management is appropriate. These internists remain capable of choosing a more active approach when indicated. This study suggests that residents adopt the practice style experienced in their training environment. Sometimes less healthcare can actually result in better health. In contrast, an aggressive practice style may waste resources and harm patients through inappropriate intervention. The training environment appears to have a considerable impact on the wisdom of medical decision making.


Adolescents' attitude towards carrier testing for cystic fibrosis and its relative stability over time.
Attitudes towards cystic fibrosis (CF) carrier testing, benefits of and barriers to having such a test were assessed within a randomly selected group of high school students in Flanders, after they had received sufficient basic information about the nature and the mode of inheritance of CF. Attitudes towards carrier testing for CF were not negative, but the majority preferred to wait to have a test. This result changed little after 6 months. A hypothetical testing offer from the Medical School Health Service elicited positive answers from nearly two thirds, suggesting that such an offer may function as a cue to action. Nevertheless, the appropriateness of such an offer may be questioned, considering the disadvantages of testing adolescents. Concern about a negative impact of the carrier status on self-image was reported by 10% of the students. These findings suggest that education about genetics is not only a prerequisite for allowing more informed decisions about CF carrier testing, but also for avoiding negative psychosocial effects of such a test.


Hydrogen Sulfide Plays an Important Role by Influencing NLRP3 inflammasome.
Inflammasome is a complex composed of several proteins and an important part of the natural immune system. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. It plays an important role in many diseases. Hydrogen sulfide (H2S) is an important signaling molecule that regulates many physiological and pathological processes. Recent studies indicated that H2S played anti-inflammatory and pro-inflammatory roles in many diseases through influencing NLRP3 inflammasome, but its mechanism was not fully understood. This article reviewed the progress about the effects of H2S on NLRP3 inflammasome and its mechanisms involved in recent years to provide theoretical basis for in-depth study.


Affinity for class II MHC determines the extent to which soluble peptides tolerize autoreactive T cells in naive and primed adult mice--implications for autoimmunity.
The N-terminal peptide (Ac1-9) of myelin basic protein (MBP) is the immunodominant encephalitogenic epitope in H-2u mice. Previous studies have defined the role of amino acid residue 4 in binding to I-Au. Accordingly, substitutions at this residue have generated peptides spanning a wide range of affinities for the MHC. In the present study, we have tested the tolerogenicity of three of these peptides. Ac1-9, Ac1-9[4A] and Ac1-9[4Y], by administering these to mice i.p. in the absence of adjuvant. Significantly, mice treated with the high affinity analogues Ac1-9[4A] and Ac1-9[4Y] prior to immunization became less susceptible to Ac1-9-induced experimental autoimmune encephalomyelitis (EAE), whereas those given the low affinity peptide Ac1-9 were only moderately protected. T cell priming, as assessed by in vitro proliferative and lymphokine assays, demonstrated a direct correlation between the level of disease inhibition and T cell unresponsiveness. In treatment studies, Ac1-9 and Ac1-9[4Y] were also shown to be effective when given on the first day of disease onset. Priming of T cells, when measured by proliferation in vitro, however, became more resistant to inactivation when soluble peptides were administered close to the day of assay. Kinetic studies revealed that tolerance could be achieved in primed mice but that this takes time to develop.(ABSTRACT TRUNCATED AT 250 WORDS)


Minimally invasive saphenous vein harvesting: is there an improvement of the results with the endoscopic approach?
In the postoperative course after conventional open removal of the greater saphenous vein, wound healing disturbances are common and often painful. Therefore the primary goal of this investigation was to prove the safety and practicability of this new less invasive technique for saphenous vein harvesting and the effect on complications and morbidity. The study comprised 103 coronary artery bypass grafting (CABG) patients with an endoscopic approach to harvest the saphenous vein (MIVH). We used the VasoView II system developed by Origin, and compared the intraoperative procedure time and the clinical results with 105 equivalent patients in which a conventional open technique was used. In 101 patients endoscopic vein harvesting was successful; a conversion into open technique was necessary in two patients. On average 2.6 vein segments could be harvested in the endogroup versus 2.9 segments in the opengroup. The mean procedure time was 13.2 min per segment in the endogroup compared to 12.2 min per segment in the opengroup. Relevant hematoma were found in 29 patients (27.6%) of the opengroup, whereas only nine patients (8.7%) of the endogroup revealed severe hematoma. Infection was apparent in nine patients (8.5%) after conventional vein harvesting. Two infections were found after endoscopic intervention. Endoscopic saphenous vein harvesting as part of a less invasive concept in cardiac surgery is a safe and after the learning curve, fast alternative to harvest the saphenous graft. The cosmetic result is excellent and the complication rate seems to be lower. It must be noted however, that the cost effectiveness of the method has to be proved and that further histological and functional studies are needed in order to check the intimal structure of the vein.


Visual lateralisation in quails (Coturnix coturnix).
Two-week-old quails (Coturnix coturnix) were trained to discriminate food grains scattered randomly on a background of small pebbles of similar size adhering to the floor and differing from the grains in texture and hue ("pebble floor task"). Quails tested binocularly or with only their right eye in use showed less pecking to the pebbles and more pecking to the grains than quails tested with only their left eye in use. Adult quails in contrast did not show lateralisation. These findings add to previous evidence for visual lateralisation in birds in the pebble floor task suggesting that neural structures fed by the right eye, mainly located to the left hemisphere, are better suited to rapid visual categorisation of food objects. Like other galliformes species such as the domestic chick (Gallus gallus), but unlike non-galliformes species such as the pigeon, behavioural lateralisation in the pebble floor task may be associated with transitory anatomical asymmetries in the thalamofugal visual pathway.


Diagnosis of Raynaud's phenomenon in quarrymen's traumatic vasospastic disease.
An epidemiologic and clinical study of traumatic vasospastic disease (TVD) was carried out involving 18 workers in a granite quarry. The prevalence of TVD was found to be 72% (95% confidence limits 47-90%) estimated from the combined information from a questionnaire and a clinical interview. The fingers of the hand contralateral to the preferred working hand were the most frequently affected. A newly developed cold provocation test measuring reduction in finger systolic blood pressure during combined body and finger cooling was applied to the quarrymen and to 20 age-matched men in a reference group. Raynaud's phenomenon with digital arterial closure was verified by the measurement of zero pressure in the test finger at 15 or 6 degrees C in 12 of 13 quarrymen with anamnestic and clinical evidence of TVD. The test showed an abnormal response as compared to that of the reference group in all the workers having used vibrating hand tools for more than five years. The precision, estimated as 95% confidence limits from double determinations, was 18.7%. The cold provocation test can be employed diagnostically, and it can also be used to observe the effects of prophylactic measures.


CD11c(+) CD103(+) cells of Mycobacterium tuberculosis-infected C57BL/6 but not of BALB/c mice induce a high frequency of interferon-γ- or interleukin-17-producing CD4(+) cells.
The magnitude of the cellular adaptive immune response is critical for the control of Mycobacterium tuberculosis infection in the chronic phase. In addition, the genetic background is equally important for resistance or susceptibility to tuberculosis. In this study, we addressed whether lung populations of dendritic cells, obtained from genetically different hosts, would play a role in the magnitude and function of CD4(+) populations generated after M. tuberculosis infection. Thirty days post-infection, C57BL/6 mice, which generate a stronger interferon-γ (IFN-γ)-mediated immune response than BALB/c mice, exhibited a higher number and frequency of lung CD11c(+) CD11b(-) CD103(+) cells compared with BALB/c mice, which exhibited a high frequency of lung CD11c(+) CD11b(+) CD103(-) cells. CD11c(+) CD11b(-) CD103(+) cells, purified from lungs of infected C57BL/6 mice, but not from infected BALB/c mice, induced a higher frequency of IFN-γ-producing or interleukin-17 (IL-17)-producing CD4(+) cells. Moreover, CD4(+) cells also arrive at the lung of C57BL/6 mice faster than in BALB/c mice. This pattern of immune response seems to be associated with higher gene expression for CCL4, CCL19, CCL20 and CCR5 in the lungs of infected C57BL/6 mice compared with infected BALB/c mice. The results described here show that the magnitude of IFN-γ-producing or IL-17-producing CD4(+) cells is dependent on CD11c(+) CD11b(-) CD103(+) cells, and this pattern of immune response is directly associated with the host genetic background. Therefore, differences in the genetic background contribute to the identification of immunological biomarkers that can be used to design human assays to predict progression of M. tuberculosis infection.


Diagnosis of Rhinocerebral Mucormycosis by Treatment of Cavernous Right Internal Carotid Artery Occlusion With Mechanical Thrombectomy: Special Case Presentation and Literature Review.
Background: Mucormycosis is a rapidly progressive, angioinvasive fungal infection that has a predilection for the paranasal sinuses and adjacent mucosa. Rhinocerebral mucormycosis (RCM) is the most common form and is known to invade the skull base and its associated blood vessels-leading to mycotic aneurysms, ischemic infarcts, and intracerebral hemorrhage. There are documented cases of mechanical thrombectomy in ischemic stroke due to RCM, however, there are no known cases that were diagnosed primarily by histological and pathological analysis of the embolus. We present a case of treatment of large vessel occlusion that led to the diagnosis and treatment of RCM. Case Presentation: A 21 year-old male inmate with history of type 1 diabetes presented with generalized weakness, abdominal pain, right eye blindness, and ophthalmoplegia after an assault in prison. He underwent treatment for diabetic ketoacidosis, but subsequently developed left hemiplegia and was found to have complete occlusion of his right internal carotid artery. He underwent successful mechanical thrombectomy and pathological analysis of the embolus revealed a diagnosis of mucormycosis. He completed a course of amphotericin B, micafungin, and posaconazole. With the aid of acute rehabilitation he achieved a modified Rankin score of 2. Discussion: We review the pathogenesis, diagnosis, and treatment of RCM. A comprehensive multidisciplinary approach is critical in the management of this often-fatal disease. Early diagnosis and treatment are essential in RCM as delaying treatment by more than 6 days significantly increases mortality. Treatment includes surgical debridement and intravenous antifungal therapy (amphotericin B + micafungin or caspofungin) for a minimum of 6-8 weeks.


Multidisciplinary management of locally advanced SCCHN: optimizing treatment outcomes.
The management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is highly complex. Data from recent clinical trials have altered the treatment landscape by refining the use of existing therapies, such as radiation therapy and chemotherapy, and providing new treatment options, such as cetuximab. Selecting the most appropriate treatment for an individual patient requires a multidisciplinary approach and careful assessment of the relative advantages and disadvantages of each treatment approach. Surgery is highly effective but can have debilitating long-term consequences. Chemoradiation and altered fractionation radiation therapy are more effective than conventional radiation therapy, but also more toxic; as a consequence of toxicity, suboptimal delivery of radiation may diminish, in practice, the efficacy observed in clinical trials of these strategies. Cetuximab plus radiation therapy is more effective than radiation alone and does not substantially increase radiation-related toxicity, or affect the delivery of planned radiotherapy. However, whether cetuximab plus radiation therapy is similar in efficacy to chemoradiation is unknown at this time. Ideally, multidisciplinary teams weigh all these factors when making individual treatment decisions. Data from current trials will help further optimize multimodality treatment for LA-SCCHN.


Liraglutide Increases the Catabolism of Apolipoprotein B100-Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression.
Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins. We performed an in vivo kinetic study with stable isotopes (L-[1-13C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-containing lipoprotein clearance. In patients with T2D, liraglutide treatment significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 ± 0.11 g/L, P = 0.011) and fasting triglycerides (1.76 ± 0.37 vs. 2.48 ± 0.69 mmol/L, P = 0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL1-apoB100 (4.11 ± 1.91 vs. 2.96 ± 1.61 pools/day, P = 0.005), VLDL2-apoB100 (5.17 ± 2.53 vs. 2.84 ± 1.65 pools/day, P = 0.008), and IDL-apoB100 (5.27 ± 2.77 vs. 3.74 ± 1.85 pools/day, P = 0.017) and in catabolism of LDL-apoB100 (0.72 ± 0.22 vs. 0.56 ± 0.22 pools/day, P = 0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced proprotein convertase subtilisin/kexin type 9 (PCSK9), retinol-binding protein 4 (RBP4), and tumor necrosis factor-α (TNF-α) gene expression in adipose tissue and decreased PCSK9 mRNA and increased LDL receptor protein expression in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver. Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL1, VLDL2, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100-containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2D.


Benchmarking implementation of a computerized system for long-term care.
The purpose of this study was to apply a benchmarking methodology to identify the most effective approaches used by long-term care facilities in implementing new computerized resident assessment instrument/minimum data set (RAI/MDS) systems and to develop implementation protocols based on these "best practices." Site visits were conducted with 3 long-term care facilities, selected on the basis of a national search. Facility directors, directors of nursing, information system managers, and frontline staff at each facility were targeted, and questionnaires were developed for each to assess factors viewed as important to successful implementation. A convergence was found in recommended action steps reported across sites to facilitate introduction and implementation of new RAI/MDS software. An example of how benchmarking results were used to develop an implementation plan is provided. Benchmarking provided a useful methodology for identifying best practices to guide implementation planing for adoption of a new computerized RAI/MDS system in the current trial. The benchmarking steps described are replicable and can be used to guide implementation of other new systems in the nursing home setting.


The phospholipid/arachidonic acid second messenger system: its possible role in physiology and pathophysiology of metabolism.
The phospholipid/arachidonic acid second messenger system is a signaling system by which systemic regulators (hormones) and local mediators (tissue factors) control certain aspects of tissue metabolism. In vivo and in vitro evidence indicates that these effectors activate phospholipolytic enzymes in cellular membranes. The products of these enzymatic reactions (such as inositol phosphates or arachidonic acid metabolites) can serve as second messengers that can potentially influence glucose, lipid and protein metabolism at the cellular level. Alterations in this second messenger system could be involved in metabolic changes associated with some pathologic conditions as well as certain drug treatments, and thus, a better understanding of the system could reveal new possibilities for therapeutic interventions.


Therapeutic Nanoreactors as In Vivo Nanoplatforms for Cancer Therapy.
Therapeutic nanoreactors have been proposed as nanoplatforms to treat diseases through in situ production of therapeutic agents. When this treatment strategy is applied in cancer therapy, it can efficiently produce highly toxic anticancer drugs in situ from low-toxic prodrugs or some biomolecules in tumor tissues, which can maximize the therapeutic efficacy with a significantly low systemic toxicity. An ideal therapeutic nanoreactor can provide the reaction space, protect the loaded fragile catalysts, target the desired pathological site, and be selectively activated. In this minireview, we highlight the recent advances concerning the applications of therapeutic nanoreactors as in vivo nanoplatforms particularly in cancer therapy. Herein, the therapeutic nanoreactors are discussed on the basis of treatment strategies and various nanoparticles. Specifically, the treatment strategies of nanoreactors including single enzyme, single enzyme with chemodrugs, and multienzymes, as well as varying types of engineered nanoparticle-loaded active catalysts, primarily including liposomes, polymersomes, polymeric micelles, inorganic nanoparticles, and metal-organic framework (MOF) architectures, are documented and briefly discussed. Finally, we elucidate the current challenges to be addressed toward further development and translation into clinical applications of these therapeutic nanoreactors in cancer therapy.


Crizotinib reduces the rate of dark adaptation in the rat retina independent of ALK inhibition.
Crizotinib (Xalkori) is a tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (c-Met). Though not predicted from standard nonclinical toxicological evaluation, visual disturbance became a frequently observed adverse event in humans. To understand the possible mechanism of this vision effect, an in vivo electroretinogram (ERG) study was conducted to assess retinal functional changes following oral administration of crizotinib. Immunohistochemical (IHC) staining of ALK and c-Met in the neural retinas of human, non-human primate, dog, rat, and mouse was used to aid in the animal model selection. ALK IHC staining was identified predominantly in the ganglion cell and inner nuclear layers of most species evaluated, in the inner plexiform layer in human and rodent, and in the nerve fiber layer in human and rat only. There was no apparent staining of any layer of the neural retina for c-Met in any of the species evaluated. ERG measurements identified a significant reduction in b-wave amplitude during the initial phase of dark adaptation in the crizotinib-treated rats. ERGs were also taken following oral administration of PF-06463922 (an ALK-selective inhibitor), for an understanding of potential kinase involvement. ERG effects were not observed in PF-06463922-treated animals when comparable exposures in the vitreous humor were achieved. Collectively, our results suggest that the ERG b-wave amplitude decreases during dark adaption following crizotinib administration may be related to signaling changes within the retina in rats, likely independent of ALK inhibition.


First report of Fusarium lacertarum causing Fusarium Head Blight on sorghum in North Carolina.
In August 2018, sorghum plants (Sorghum bicolor (L.) Moench) from research field plots in Wake County, North Carolina were observed with head blight symptoms including panicles with red lesions, visible mycelium, and necrosis. At the time of collection, all plants in research plots displayed symptoms of Fusarium head blight and panicles averaged 33% area affected by symptoms and signs. From these affected plants, samples (n = 5) were collected for further identification. Symptomatic grains were surface sterilized for one minute in 0.825% sodium hypochlorite solution and rinsed for one minute in sterile, deionized water. After drying on sterile paper towels, grains were plated onto water agar. Resulting fungal hyphal tips were then transferred to antibiotic-amended potato dextrose agar (PDA) and incubated at 25oC. Cultures were incubated for 3 to 5 days. Isolates had abundant white hyphae accompanied with peach-colored pigment production. Macroconidia with 5-6 septations were 23.47 ± 7.74 µm long and 3.47 ± 0.66 µm wide with foot-shaped basal cells, tapering to hooked apical cells. Chlamydospores were present in chains but microconidia were not present. Morphological species recognition (MSR) criteria tentatively identified the isolate as Fusarium lacertarum Subrahm., in the Fusarium incarnatum-equiseti species complex (FIESC) using characteristics described by Leslie and Summerell 2006. Molecular characterization using translation elongation factor 1α (TEF-1 α, primers EF1 and EF2 from O'Donnell et al. 1998), β tubulin (TUB2, primers T1 and T22 from O'Donnell and Cigelnik 1997), and ribosomal protein subunit II (RPB2, primers 5F2 and 11AR from Cerón-Bustamante et al. 2018) was conducted to confirm morphological identification. DNA from the hyphae of pure cultures was extracted using the DNeasy PowerSoil DNA extraction kit according to manufacturer's guidelines. DNA amplification conditions followed the protocols for each primer set (O'Donnell et al. 1998; O'Donnell and Cigelnik 1997; Cerón-Bustamante et al. 2018). BLASTn analysis of TEF-1α (Isolate Accession MT149915, 573bp) alignment had 99.8% identity to F. lacertarum (NCBI accession: JF740828), TUB2 (Isolate Accession MT149914, 1,183bp) alignment had 99.3% identity to F. equiseti (NCBI accession: KJ396338), and RPB2 (Isolate Accession MT184173, 1,538bp) concatenated sequences had 95.3% identity to F. lacertarum (NCBI accession: MH582185). The TUB2 region most closely aligns to F. equiseti, which is likely due to an absence of TUB2 sequences labeled for F. lacertarum in the NCBI database. Pathogenicity was confirmed by spray-inoculating Southern Harvest 80G4 sorghum panicles (n = 9) at anthesis with four ml of conidial suspension (3.3×104 conidia/ml). Control plants (n = 9) were sprayed with sterile water. Plastic bags were placed around panicles for 24 hours to ensure moist conditions during the infection period. Plants were maintained in a greenhouse under a 12-hour light cycle and fertilized bi-weekly with 20-20-20 fertilizer. Symptoms were observed on inoculated panicles after 14 days, and the F. lacertarum isolate was recovered from inoculated plants and confirmed using methods described above. Fusarium spp. were not re-isolated from non-inoculated control plants. Members of FIESC are known to contribute to the Fusarium Head Blight disease complex and may be capable of producing mycotoxins associated with infections (Lincy et al. 2011; Marin et al. 2012; Moretti 2017); however, mycotoxin characterization in F. lacertarum has not been characterized. To our knowledge, this is the first report of F. lacertarum causing disease to sorghum in North Carolina and the United States. Fusarium lacertarum may cause impactful losses to sorghum producers due to direct yield and quality losses by the pathogen as well as the potential for mycotoxins to impact trade.


Screening for cognitive impairment in a Chinese ALS population.
Despite growing interest in cognitive impairment of ALS patients, there are only limited studies available that characterize cognitive deficits in the Chinese ALS population through highly sensitive and specific screening tools. The Chinese version of the Addenbrooke's Cognitive Examination-revised (ACE-R) and mini-mental state examination (MMSE) were applied to evaluate cognitive function in 145 sporadic ALS patients and 50 healthy controls. The mean onset age was 50.72 ± 12.38 years. Results showed that the prevalence of cognitive deficits was 14.48% and 30.34% based on the MMSE and ACE-R, respectively. Patients had a broad range of cognitive impairment domains, including language (26.21%), orientation/attention (24.13%), visuospatial ability (24.13%), memory (23.45%) and verbal fluency (22.76%). Logistic regression indicated that older age of onset, female gender and lower educational levels were potential determinants of cognitive deficits in ALS. Multiple regression analyses showed that the cognitive deficit during the baseline visit was not associated with the progression rate of ALS. In conclusion, cognitive impairment is common in Chinese ALS patients, but does not necessarily worsen the progression of ALS. ACE-R is superior to MMSE in detecting deficits in patients. Cognitive impairment in ALS patients may relate to age of onset, female gender and lower education level.


Pathophysiological Role of Hepatocyte Nuclear Factor 6 in Negative Regulation of Hepatic Apoptosis: A Novel Hypothesis.
Apoptosis is a prominent characteristic in the pathogenesis of liver disease. The molecular mechanism of hepatic apoptosis is not well understood. Liver injury induces a downregulation of hepatocyte nuclear factor 6 (HNF6) that is negatively correlated with the degree of apoptosis. However, an enhancement of HNF6 can relieve hepatic apoptosis and impede the progression of liver disease. HNF6 has distinct mechanisms to modulate hepatic apoptosis. Pathophysiological role of HNF6 may be apoptosis-resistant and liver-protective during different types of liver injury. The enhancing modality of HNF6 is a novel therapeutic intervention for liver disease.


Pooled resequencing of larvae and adults reveals genomic variations associated with Ostreid herpesvirus 1 resistance in the Pacific oyster Crassostrea gigas.
The Ostreid herpesvirus 1 (OsHV-1) is a lethal pathogen of the Pacific oyster (Crassostrea gigas), an important aquaculture species. To understand the genetic architecture of the defense against the pathogen, we studied genomic variations associated with herpesvirus-caused mortalities by pooled whole-genome resequencing of before and after-mortality larval samples as well as dead and surviving adults from a viral challenge. Analysis of the resequencing data identified 5,271 SNPs and 1,883 genomic regions covering 3,111 genes in larvae, and 18,692 SNPs and 28,314 regions covering 4,863 genes in adults that were significantly associated with herpesvirus-caused mortalities. Only 1,653 of the implicated genes were shared by larvae and adults, suggesting that the antiviral response or resistance in larvae and adults involves different sets of genes or differentiated members of expanded gene families. Combined analyses with previous transcriptomic data from challenge experiments revealed that transcription of many mortality-associated genes was also significantly upregulated by herpesvirus infection confirming their importance in antiviral response. Key immune response genes especially those encoding antiviral receptors such as TLRs and RLRs displayed strong association between variation in regulatory region and herpesvirus-caused mortality, suggesting they may confer resistance through transcriptional modulation. These results point to previously undescribed genetic mechanisms for disease resistance at different developmental stages and provide candidate polymorphisms and genes that are valuable for understanding antiviral immune responses and breeding for herpesvirus resistance.


swDMR: A Sliding Window Approach to Identify Differentially Methylated Regions Based on Whole Genome Bisulfite Sequencing.
DNA methylation is a widespread epigenetic modification that plays an essential role in gene expression through transcriptional regulation and chromatin remodeling. The emergence of whole genome bisulfite sequencing (WGBS) represents an important milestone in the detection of DNA methylation. Characterization of differential methylated regions (DMRs) is fundamental as well for further functional analysis. In this study, we present swDMR (http://sourceforge.net/projects/swDMR/) for the comprehensive analysis of DMRs from whole genome methylation profiles by a sliding window approach. It is an integrated tool designed for WGBS data, which not only implements accessible statistical methods to perform hypothesis test adapted to two or more samples without replicates, but false discovery rate was also controlled by multiple test correction. Downstream analysis tools were also provided, including cluster, annotation and visualization modules. In summary, based on WGBS data, swDMR can produce abundant information of differential methylated regions. As a convenient and flexible tool, we believe swDMR will bring us closer to unveil the potential functional regions involved in epigenetic regulation.


Two cases of vaginal bleeding in pet rats.
Two unrelated rats were presented to the Western College of Veterinary Medicine emergency service for vaginal bleeding. Each was taken to surgery due to marked blood loss and suspicion of uterine pathology. Despite similar clinical presentation, gross and histopathologic examination revealed 2 different underlying disease processes, uterine dilatation with mild endometritis and vaginal polyp.


Cardiac troponin I concentrations, electrocardiographic and echocardiographic variables remained unchanged in dogs experimentally infected with Ehrlichia canis.
Canine monocytic ehrlichiosis (CME, Ehrlichia canis) has occasionally been associated with myocardial injury. The aim of the present study was to serially measure and evaluate cardiac troponin I (cTnI) concentrations in dogs with experimentally induced acute and subclinical CME and to evaluate potential associations between cTnI concentration and an array of echocardiographic and electrocardiographic parameters. Serum cTnI concentration and simultaneous echocardiographic and electrocardiographic recordings were evaluated in 12 healthy Beagle dogs prior to experimental infection and on days 20 and 90 post-inoculation with E. canis. Almost all serum cTnI concentrations were below the limit of detection and selected electrocardiographic and echocardiographic parameters remained unchanged throughout the study.


Losing sleep over work: A self-determination theory view on need frustration, sleep disturbance, and mental ill health.
Given the centrality of sleep and work in most individuals' lives, it is interesting to note that an empirical understanding of the association between what happens in the workplace and how well people sleep is in an early stage of development, at least relative to other topics that are of interest in the literature on stress and health. Using self-determination theory, the current study examined how maladaptive motivational processes at work relate to sleep disturbance and mental ill health. In line with hypotheses, the results of a cross-sectional analysis and analyses using data from two time points over 15 months revealed that employees are more likely to report sleep disturbance, anxiety, and depressive symptoms when they experience frustration of the basic psychological needs for autonomy, competence, and relatedness in the workplace. Additional results revealed an indirect effect of change in basic psychological need frustration on change in anxiety-but not on change in depressive symptoms-through change in sleep disturbance. Taken together, these findings add to the burgeoning literature on the maladaptive motivational origins of ill health and dysfunction in the workplace.


Standing and Responding in Solidarity with Disenfranchised Immigrant Families in the United States: An Ongoing Call for Action.
The status of immigrant families resettled to the United States in the past decade has been fraught with upsurges of governmental policies that have systematically increasing the levels of oppression, violence, and abuses of human rights. The socio-political-economic toll of xenophobic practices on specifically targeted immigrant populations is magnified by the psychological and relational impact they have on individuals, families, and communities. This manuscript is conceptualized as an ongoing call for social action and specific mobilization by mental health professionals in response to the increasing threats to civility and dignity faced by various immigrant communities. The paper is organized in three sections: (a) an overview of the effects of immigration policy on immigrant family experiences; (b) the impact of mental and relational health on immigrant populations; and (c) elaborations of three exemplar community projects designed to support immigrant families. The manuscript concludes with a discussion exploring avenues for promoting a stronger base for solidarity and social action.


Identification of an essential gene, l(3)73Ai, with a dominant temperature-sensitive lethal allele, encoding a Drosophila proteasome subunit.
Proteasomes are multicatalytic proteinase complexes that function as a major nonlysosomal proteolytic system in all eukaryotes. These particles are made up of 13-15 nonidentical subunits, and they exhibit multiple endopeptidase activities that promote the intracellular turnover of abnormal polypeptides and short-lived regulatory proteins. Although the biochemical characterization of proteasomes has been quite extensive, and although a number of the genes encoding proteasome subunits have been cloned from various organisms, there is still much to be learned about their function in vivo and what role(s) they might play during development. Here, we report the identification of the l(3)73Ai1 allele of Drosophila melanogaster as a dominant temperature-sensitive lethal mutation in a gene encoding a component of the proteasome, thus opening the way for future genetic and developmental studies on this important proteolytic system in a higher eukaryote.


Effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women.
Visfatin is a highly expressed protein with insulin-like functions located predominantly in visceral adipose tissue and has been linked to obesity and increased health risks. The purpose of this study was to examine the effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women. Subjects were randomly assigned to either a training (n = 10) or control (n = 10) group. The training group exercised for 1 hour, 3 days per week during the 12 week supervised training program. The training program included 3 sets of 10 repetition maximum (10RM) resistance exercise as well as aerobic exercise at an intensity of 60-70% of their heart rate reserve (HRR). The control group was asked to maintain their normal daily activities. Two-way (group X time) repeated measured analysis of variance revealed no significant main effects, but there was a significant group X time interaction for the following variables: body weight (p < 0.01), percent body fat (% fat) (p < 0.01), waist hip ratio (WHR) (p < 0.01), diastolic blood pressure (DBP) (p < 0.05), fasting glucose level (p < 0.01), triglyceride levels (TG) (p < 0.01), high density lipoprotein cholesterol levels (HDL-C) (p < 0.05), and visfatin (p < 0.01). In conclusion, the 12 week combined resistance and aerobic training program used in this study was very effective for producing significant benefits to body composition and metabolic syndrome factors, as well as lowering visfatin levels in these obese middle-aged women. Key pointsRecent studies have linked visfatin to obesity and increased health risks.The study was done to investigate the effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women.The exercise program used in this study was found to be very effective for lowering visfatin levels in obese middle-aged women.


Congenital goitre and juvenile hypothyroidism in a Nigerian child.
A 7-year-old girl from an area where endemic goitre is not known presented with a collar-like goitre which on palpation was diffusely nodular. Investigations showed high TSH and 'low' thyroxine serum levels. She was neither mentally retarded nor spastic. The goitre was reduced in size with supplementary l-thyroxine sodium but on withdrawal of therapy the gland size increased. An inborn error of thyroxine synthesis is the most likely cause of the condition. In our environment, the first line of treatment should not be surgery but rather a thoughtful approach to the causes of hypothyroidism.


Transition from Laparotomy to Laparoscopic Repair of Congenital Duodenal Obstruction in Neonates: Our Early Experience.
The aim of this report was to review our early experience of the last 7 years with repairs of congenital duodenal obstruction (CDO) to determine the efficacy and outcomes of laparoscopic repairs compared to laparotomy. A retrospective review was conducted on all neonate (<30 days) with CDO between 2009 and 2015. Patients with duodenal atresia, stenosis, web, and annular pancreas were included. Patients with only malrotation or delayed presentation were excluded. Twenty-six neonates underwent laparoscopy and 30 underwent traditional laparotomy. The operative time was longer in the laparoscopic group (P = 0.001), but time to initiation of feeds and time to full feeds were similar for the laparoscopic and open groups. There was no mortality, anastomosis leakage, or stenosis in the laparoscopic group. Six laparoscopic cases required conversion to an open procedure (23%). In the earlier cases, the open conversion rate was high, but it decreased over time (P = 0.003). Laparoscopic repair is safe and effective for repair of CDO in neonates. Despite operative time was slightly longer in the laparoscopic group, clinical outcomes remained similar to the open group. For pediatric surgeon with experience in laparoscopic techniques, laparoscopic duodenoduodenostomy is a sufficient available procedure.


Common pain syndromes in stroke patients: review of two cases.
Due to multiple neurological and musculoskeletal factors, stroke patients are at significant risk for the development of disabling pain syndromes. This article provides examples of two commonly encountered clinical situations, poststroke shoulder and poststroke hip pain. Appropriate use of imaging, medications, modalities, and injections are discussed for the purpose of enhancing management strategies that decrease pain and increase overall function.


[The mechanism of the development of drug dependence].
Drug dependence, the physical and psychological one after chronic drug administration, is a serious clinical and social problem. The mechanism of development of drug dependence is mainly related to the modification of dopaminergic system. In addition, recent reports demonstrate that the other neuronal systems including noradorenergic, glutamatergic, serotonergic, histaminergic and orexinergic neurons could regulate the activity of dopaminergic neurons that results in the development of drug addiction after chronic drug administration. In the cellular and molecular levels, the up-regulation of some key signaling molecules such as cAMP and PKA or peptides such as NPY and dynorphin may be involved in the mechanisms. In this review, we outline the recent knowledge about the mechanism of development of drug addiction.


Phase II trial of response-based radiation therapy for patients with localized germinoma: a Children's Oncology Group study.
The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.


Dysplastic lesions in ulcerative colitis: changing paradigms.
Crohn and Rosenberg first highlighted the increased risk of colorectal cancer in ulcerative colitis in 1925. Cancer rates as high as 34 percent after 30 yrs of disease have been reported in several population-based studies, although the reported risk varies substantially. Lower rates have been reported in: population-versus specialist centre-cohorts, local practices with a high colectomy rate and high 5-aminosalicylate usage, and more recent as opposed to older reports. Despite this variation in reported risk, and lack of controlled evidence for cancer reduction, colonoscopic surveillance programmes are a routine part of care in many centres. Cancer is believed to arise most commonly in dysplastic epithelium, and the detection of either dysplasia or early cancer forms the basis of such programmes. Further confusion stems from the variety of terms used to describe dysplastic change.


Some properties of the rhodanese system of Thiobacillus denitrificans.
1. Rhodanese has been extracted from Thiobacillus denitrificans by ultrasonic disintegration of the cells. 2. Studies with Sephadex columns have shown that the enzyme aggregates, forming a tetramer. 3. The molecular weights of the monomer and of an enzymically active sub-unit one-quarter this size have been determined by gel filtration. 4. Higher-molecular-weight forms of rhodanese are broken down by mercaptoethanol to enzymically active fragments of mol.wt. 7000 and 2000 respectively. 5. It is suggested that these fragments are linked in vivo via disulphide bridges to form the monomer, which can then aggregate via further disulphide links. 6. The fragment of mol.wt. 7000 has been obtained in a substantially pure state. 7. Both disulphide and thiol groups are necessary for enzyme activity. 8. Similarities and differences existing between bacterial rhodanese, mammalian rhodanese and beta-mercaptopyruvate sulphurtransferase are discussed.


Factors affecting the healing response of intrabony defects following guided tissue regeneration and access flap surgery.
Identification and control of significant factors determining clinical outcomes is of paramount importance to improve expected results of a variety of therapeutic procedures. The aim of this investigation was to identify, with a multivariate approach, factors associated with healing outcomes of 3 periodontal surgical procedures in deep intrabony defects. 45 patients with evidence of deep intrabony defects were randomly assigned to 3 treatment groups: access flap (group C), conventional guided tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethilene (ePTFE) membranes (group B), and GTR with self supporting membranes combined with the modified papilla preservation technique (group A). In both GTR procedures, membranes were positioned coronal to the interproxymal alveolar crest. Primary outcome variables (i.e., probing attachment level gains at 1 year and the amount of newly formed tissue present at membrane removal) were explained in terms of a series of patient, defect morphology and surgical factors, using a multivariate approach. Highly significant treatment effects were observed, indicating that the 3 tested therapeutic modalities resulted in significant differences in primary outcome variables. Detailed analysis assessing the significance of the tested factors in determining the healing outcomes following each procedure was performed with a stepwise elimination approach of non-significant factors. The results indicated that: (i) the need to create and maintain space should be a key objective of regenerative approaches based upon the principles of guided tissue regeneration; (ii) control of patient's oral hygiene and residual periodontal infection in the oral cavity are strongly associated with clinical outcomes of both regenerative and conventional surgical procedures and should receive proper attention.


[Concomitant radiochemotherapy in rectal tumors].
Requirements for improved cancer control led to the testing of the combined-modality therapy for many types of cancer. This review attempts to analyse possibilities of the simultaneous application of both strategies in the treatment of rectal cancer. Postoperative radiochemotherapy has been shown to be effective in rectum carcinomas. Preoperative combined-modality therapy can ensure downstaging (T3, T4). Operation was carried out 4 to 6 weeks after the end of preoperative therapy.


[Poorly cohesive gastric carcinoma. Validity of using the term; translation variants].
Gastric cancer is one of the leading causes of cancer morbidity and mortality worldwide. It is common practice to use two classification systems: the Lauren classification system and the WHO classification of tumors in the morphological study of gastric carcinomas. Since 2010, the WHO classifications have included the term "poorly cohesive carcinoma", which refers to all diffuse forms of gastric cancer, including signet ring cell carcinoma and other subtypes. Despite this, the term has not been widely used in the world community, and it is almost not found in Russian literature. Only recently, after the publication of the 5th edition of the WHO classification (2019), there have been review articles where the term is used, but its name can be translated into Russian in different ways: poor-, weak -, low-adhesive, discogesive. The paper analyzes the Pubmed and Elibrary databases in order to find out the frequency of using various designations for diffuse gastric carcinoma, justifies the use of the term «poorly cohesive carcinoma», and proposes a variant of the term interpretation in Russian.


Assessment of global atrial fibrillation organization to optimize timing of atrial defibrillation.
We hypothesized that frequency domain analysis of a wide bipolar interatrial electrogram describes the global organization of atrial fibrillation (AF) and should vary over time. By timing shocks to periods of high organization of AF, cardioversion efficacy should improve. A total of 15 dogs (weight, 28.2+/-3.4 kg) were rapidly paced for 48 to 72 hours to induce AF. Coil electrodes with a surface area of 1.80 cm(2) were then placed in the left and right atria to form a wide bipole. Wide bipolar electrograms were digitally filtered, and a fast Fourier transform was performed over a sliding 2-s window every 0.5 s. The organization index (OI) was calculated as the ratio of the area of the dominant peak and its harmonics to the total area of the magnitude spectrum. The atrial defibrillation threshold (ADFT(50)) was determined using a 3-ms/3-ms biphasic shock and an up-down-up protocol. Additional shocks with higher and lower energies were delivered in a random sequence to develop a distribution curve. The OI varied over time, with a mean of 0.42+/-0.03, a maximum of 0.65+/-0.07, and a minimum of 0.20+/-0.06. The OI changed rapidly, with durations of high organization (OI>0.5) ranging from 1 to 5 s. The ADFT(50) for QRS complex-synchronized shocks was 183+/-56 V, versus 142+/-49 V for shocks synchronized to an OI>0.5 (P<0.001). The distribution curve shifted leftward when shocks were synchronized to an OI>0.5. AF signals show a high degree of variability. Shock efficacy is increased when shocks are delivered during periods of high AF organization as determined by the OI method.


The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC. Serum protein profiles of 45 hepatitis C virus infection (HCV)-related HCC patients (HCV-HCC) were compared to 42 HCV-related chronic liver disease patients without HCC (HCV-CLD) and 21 healthy volunteers using the ProteinChip SELDI system. One of the identified proteins was evaluated as a diagnostic marker for HCC in patients with HCV. Five protein peaks (4067, 4470, 7564, 7929, and 8130 m/z) had p-values less than 1 x 10(-7) and were significantly increased in the sera of HCV-HCC patients compared to HCV-CLD patients and healthy volunteers. Among these proteins, an 8130 m/z peak was the most differentially expressed and identified as the complement component 3a (C3a) fragment. For HCV-HCC and HCV-CLD, the relative intensity of this C3a fragment had the best area under the ROC curve [0.70], followed by des-gamma-carboxy prothrombin (DCP) [0.68], lectin-bound alpha fetoprotein (AFP-L3) [0.58] and AFP [0.53] for HCC. A combined analysis of the C3a fragment, AFP and DCP led to a 98% positive identification rate. In addition, the measurable C3a fragment in some HCC patients was not only significantly higher in the year of HCC onset compared to the pre-onset year, but also decreased after treatment. The 8130 m/z C3a fragment is a potential marker for the early detection of HCV-related HCC.


Issues in community care services.
In the first part of this series on issues in ward management facing charge nurses, Helen Evers addresses the problem of communication between hospital and community on patient discharges. Recent years have seen the development of liaison and co-ordinator posts whose incumbents aim to facilitate planned and organised discharge procedures, but the appointment of such personnel may not provide a complete answer to the problem. The ultimate arbiter of effective transition from hospital to home is more likely to be the quality of communication between charge and district nurse.


Embarras de richesses - It is not good to be too anomalous: Accurate structure of selenourea, a chiral crystal of planar molecules.
Selenourea, SeC(NH2)2, recently found an application as a derivatization reagent providing a significant anomalous diffraction signal used for phasing macromolecular crystal structures. The crystal structure of selenourea itself was solved about 50 years ago, from data recorded on films and evaluated by eye and refined to R = 0.15 with errors of bond lengths and angles about 0.1 Å and 6°. In the current work this structure is re-evaluated on the basis of synchrotron data and refined to R1 = 0.021 with bond and angle errors about 0.007 Å and 0.5°. The nine planar molecules of selenourea pack either in the P31 or in the P32 unit cell. All unique molecules are connected by a complex network of Se•••H-N hydrogen bonds and Se•••Se contacts. The packing of selenourea molecules is highly pseudosymmetric, approximating either of the P31(2)12, R3, and R32 space groups. Because the overwhelming majority of diffracted X-ray intensity originates form the anomalously scattering selenium atoms, the measurable anomalous Bijvoet differences are diminished and it was not possible to solve this crystal structure based on the anomalous signal alone.


Dosimetric feasibility of intensity modulated proton therapy in a transverse magnetic field of 1.5 T.
Proton therapy promises higher dose conformality in comparison with regular radiotherapy techniques. Also, image guidance has an increasing role in radiotherapy and MRI is a prime candidate for this imaging. Therefore, in this paper the dosimetric feasibility of Intensity Modulated Proton Therapy (IMPT) in a magnetic field of 1.5 T and the effect on the generated dose distributions compared to those at 0 T is evaluated, using the Monte Carlo software TOol for PArticle Simulation (TOPAS). For three different anatomic sites IMPT plans are generated. It is shown that the generation of an IMPT plan in a magnetic field is feasible, the impact of the magnetic field is small, and the resulting dose distributions are equivalent for 0 T and 1.5 T. Also, the framework of Monte Carlo simulation combined with an inverse optimization method can be used to generate IMPT plans. These plans can be used in future dosimetric comparisons with e.g. IMRT and conventional IMPT. Finally, this study shows that IMPT in a 1.5 T magnetic field is dosimetrically feasible.


Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation.
Protein aggregation is involved in the pathogenesis of neurodegenerative diseases and hence is considered an attractive target for therapeutic intervention. However, protein-protein interactions are exceedingly difficult to inhibit. Small molecules lack sufficient steric bulk to prevent interactions between large peptide surfaces. To yield potent inhibitors of beta-amyloid (Abeta) aggregation, we synthesized small molecules that increase their steric bulk by binding to chaperones but also have a moiety available for interaction with Abeta. This strategy yields potent inhibitors of Abeta aggregation and could lead to therapeutics for Alzheimer's disease and other forms of neurodegeneration.


The effect of branched-chain amino acid-enriched parenteral nutrition on gut permeability.
In situations of catabolic stress, the gut becomes atrophic and has a diminished barrier function as evidenced by an increased permeability to a variety of molecules. It is known that the parenteral administration of branched-chain amino acids (BCAA) reduce gut atrophy. The aim of this study was to examine the effect of BCAA-enriched solutions of parenteral nutrients on gut permeability. A secondary aim was to observe the association between gut permeability and variables that have been used to assess jejunal atrophy. Central venous lines were inserted into 30 rats before randomization to receive nutritional support with: (1) a conventional parenteral solution (CPN), (2) A 2.0% BCAA-enriched solution (BCAA), or (3) rat food ad lib (Rat Food). The rats were assessed after 7 d for nutritional status, gut morphology, and gut permeability ratio (ratio of the permeability to 14C raffinose and 3H mannitol). We found that rats in the Rat Food Group lost the least amount of weight, had the least amount of jejunal atrophy, and had better preservation of barrier function as determined by gut permeability. When compared with the CPN Group, the BCAA Group had better preservation of jejunal morphology and protein content (p < 0.05), but a similar gut permeability. A cross-correlation matrix demonstrated a significant negative correlation between permeability to mannitol and mucosal weight, mucosal protein content and mucosal DNA content. Branched-chain amino acid-enriched parenteral nutrition reduced gut atrophy but not the gut permeability associated with parenteral nutrition. In the parenterally nourished rat model, atrophy of the jejunum is associated with increased permeability to small molecules.


Inhibition of mechanosensitive cation channels inhibits myogenic differentiation by suppressing the expression of myogenic regulatory factors and caspase-3 activity.
Mechanosensitive cation channels (MSC) are ubiquitous in eukaryotic cell types. However, the physiological functions of MSC in several tissues remain in question. In this study we have investigated the role of MSC in skeletal myogenesis. Treatment of C2C12 myoblasts with gadolinium ions (MSC blocker) inhibited myotube formation and the myogenic index in differentiation medium (DM). The enzymatic activity of creatine kinase (CK) and the expression of myosin heavy chain-fast twitch (MyHCf) in C2C12 cultures were also blocked in response to gadolinium. Treatment of C2C12 myoblasts with gadolinium ions did not affect the expression of either cyclin A or cyclin D1 in DM. Other inhibitors of MSC such as streptomycin and GsTMx-4 also suppressed the expression of CK and MyHCf in C2C12 cultures. The inhibitory effect of gadolinium ions on myogenic differentiation was reversible and independent of myogenic cell type. Real-time-polymerase chain reaction analysis revealed that inhibition of MSC decreases the expression of myogenic transcription factors MyoD, myogenin, and Myf-5. Furthermore, the activity of skeletal alpha-actin promoter was suppressed on MSC blockade. Treatment of C2C12 myoblasts with gadolinium ions prevented differentiation-associated cell death and inhibited the cleavage of poly (ADP-ribose) polymerase and activation of caspase-3. On the other hand, delivery of active caspase-3 protein to C2C12 myoblasts reversed the inhibitory effect of gadolinium ions on myogenesis. Our data suggest that inhibition of MSC suppresses myogenic differentiation by inhibiting the caspase-3 activity and the expression of myogenic regulatory factors.