The World Congress of Paediatric Cardiology and Cardiac Surgery: "The Olympics of our profession".
The first World Congress of Paediatric Cardiology was held in London, United Kingdom, in 1980, organised by Dr. Jane Somerville and Prof. Fergus Macartney. The idea was that of Jane Somerville, who worked with enormous energy and enthusiasm to bring together paediatric cardiologists and surgeons from around the world. The 2nd World Congress of Paediatric Cardiology took place in New York in 1985, organised by Bill Rashkind, Mary Ellen Engle, and Eugene Doyle. The 3rd World Congress of Paediatric Cardiology was held in Bangkok, Thailand, in 1989, organised by Chompol Vongraprateep. Although cardiac surgeons were heavily involved in these early meetings, a separate World Congress of Paediatric Cardiac Surgery was held in Bergamo, Italy, in 1988, organised by Lucio Parenzan. Thereafter, it was recognised that surgeons and cardiologists working on the same problems and driven by a desire to help children should really rather meet together. A momentous decision was taken to initiate a Joint World Congress of Paediatric Cardiology and Cardiac Surgery. A steering committee was established with membership comprising the main organisers of the four separate previous Congresses, and additional members were recruited in an effort to achieve numerical equality of cardiologists and surgeons and a broad geographical representation. The historic 1st "World Congress of Paediatric Cardiology and Cardiac Surgery" took place in Paris in June, 1993, organised by Jean Kachaner. The next was to be held in Japan, but the catastrophic Kobe earthquake in 1995 forced relocation to Hawaii in 1997. Then followed Toronto, Canada (2001, organised by Bill Williams and Lee Benson), Buenos Aires, Argentina (2005, organised by Horatio Capelli and Guillermo Kreutzer), and most recently Cairns, Australia (2009, organised by Jim Wilkinson). Having visited Europe (1993), Asia-Pacific (1997), North America (2001), South America (2005), and Australia (2009), and reflecting the "African Renaissance", the World Congress is coming to Africa. The 6th World Congress of Paediatric Cardiology and Cardiac Surgery will be held in Cape Town, South Africa, from 17 to 22 February, 2013. Cape Town is a sublime and compelling African destination with irresistible appeal. The South African Heart Association is the host. Information about The 6th World Congress of Paediatric Cardiology and Cardiac Surgery can be found at http://www.pccs2013.co.za.


Neurocognitive differential diagnosis of dementing diseases: Alzheimer's Dementia, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder.
Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder, pose differential diagnosis challenges. The current study identifies specific neuropsychological patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological domains directly assessed in the study included: immediate memory, delayed memory, confrontational naming, verbal fluency, attention, concentration, and executive functioning. The results reveal specific neuropsychological comparative profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. The identification of these profiles will assist in the differential diagnosis of these disorders and aid in patient treatment.


Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter.
This Letter presents a novel approach to study electron transport in warm dense matter. It also includes the first x-ray Thomson scattering (XRTS) measurement from low-density CH foams compressed by a strong laser-driven shock at the OMEGA laser facility. The XRTS measurement is combined with velocity interferometry (VISAR) and optical pyrometry (SOP) providing a robust measurement of thermodynamic conditions in the shock. Evidence of significant preheat contributing to elevated temperatures reaching 17.5-35 eV in shocked CH foam is measured by XRTS. These measurements are complemented by abnormally high shock velocities observed by VISAR and early emission seen by SOP. These results are compared to radiation hydrodynamics simulations that include first-principles treatment of nonlocal electron transport in warm dense matter with excellent agreement. Additional simulations confirm that the x-ray contribution to this preheat is negligible.


Self-supported MOF/cellulose-nanocrystals materials designed from ultrafiltration.
Metal-organic-frameworks (MOFs) are promising materials for addressing critical issues such as petrochemical separation, water purification, energy storage and drug delivery. Their large-scale deployment, however, is hampered by a limited processability due to their powdery nature. Recently, the hybridization of MOFs with biopolymers has emerged as a greener, biocompatible strategy to shape MOFs composites into more processable membranes, films, and porous materials. In this work, cellulose nanocrystals (CNCs) were used in combination with ZIF-8 (a widely used synthetic zeolite) to produce hybrid composites through ultrafiltration. Results showed that small quantities of CNCs (1 to 20 CNC:ZIF-8 volume ratio) were sufficient to form a self-supported, dense deposit with high ZIF-8 loadings. Compared to classical MOF in situ growth strategies, this approach allowed the tuning of the composition of the final nanocomposite by controlling the nature and quantities of particles in the suspension. The fabrication of the deposit was strongly dependent on the physiochemical properties of the suspension, which were fully characterized with a set of complementary techniques, including in situ SAXS. This technique was employed to investigate the filtration process, which exhibited a homogeneous deposition of ZIF-8 particles mediated by CNC self-assembly. Finally, the available pore volume and integrity of the internal porosity of ZIF-8 were characterized by water porosimetry, demonstrating that the presence of CNCs did not alter the properties of the supported ZIF-8.


The development and validation of the mini-surgical theatre educational environment measure.
The operating theatre educational environment during medical school may influence student's perceptions of a surgical career. Interest in a surgical career is declining both in the USA and the UK. This study sought to develop and validate a practical questionnaire for distribution to medical undergraduates to assess their operating theatre educational environment. A previously published questionnaire--the Surgical Theatre Educational Environment Measure (STEEM) (validated on postgraduates) was distributed to 83 final year medical students. The STEEM was found to be a reliable and valid tool for use on undergraduates (Cronbach's alpha = 0.86). From this preliminary study, factor analysis identified 13 factors covering 73% of the variance, which enabled the development of a shorter 14-item questionnaire (mini-STEEM). The mini-STEEM was distributed to 99 medical students following their final year surgical placement at a UK medical school, with a 100% response rate. The mini-STEEM was shown to be a valid, reliable (Cronbach's alpha = 0.80) and practical tool, which was easy to complete, code and analyse. The results showed that the overall climate within the operating theatre for medical undergraduates in one UK Medical School was good with no gender differences in the overall scores.


The chloroplast genome hidden in plain sight, open access publishing and anti-fragile distributed data sources.
We sequenced several cannabis genomes in 2011 of June and the first and the longest contigs to emerge were the chloroplast and mitochondrial genomes. Having been a contributor to the Human Genome Project and an eye-witness to the real benefits of immediate data release, I have first hand experience with the potential mal-investment of millions of dollars of tax payer money narrowly averted due to the adopted global rapid data release policy. The policy was vital in reducing duplication of effort and economic waste. As a result, we felt obligated to publish the Cannabis genome data in a similar spirit and placed them immediately on a cloud based Amazon server in August of 2011. While these rapid data release practices were heralded by many in the media, we still find some authors fail to find or reference said work and hope to compel the readership that this omission has more pervasive repercussions than bruised egos and is a regression for our community.


Colorimetric assay for heterogeneous-catalyzed lipase activity: enzyme-regulated gold nanoparticle aggregation.
Lipase is a neglected enzyme in the field of gold nanoparticle-based enzyme assays. This paper reports a novel colorimetric probe to rapidly visualize lipase activities by using Tween 20 functioned GNPs (Tween 20-GNPs) as a reporter. The present strategy hence could overcome the limitations caused by the heterogeneous interface in lipase assay. Catalytic hydrolytic cleavage of the ester bond in Tween 20-GNPs by lipase will trigger the rapid aggregation of GNPs at a high salt solution. The color change from red to purple could be used to sense the activity of lipase. The detection limit (3σ) is as low as 2.8 × 10-2 mg/mL. A preliminary enzyme activity screening was carried out for seven commercially purchased lipase samples. It also has been successfully applied to detecting lipase in fermentation broth of Bacillus subtilis without any pretreatment.


Expression of the gene coding for human prostate-specific antigen and related hGK-1 in benign and malignant tumors of the human prostate.
Human glandular kallikrein-1 gene (hGK-1) is closely related to the gene of human prostate-specific antigen (PSA) and both genes are expressed in the human prostate. We have studied PSA and hGK-1 mRNAs in human prostatic tissue samples from patients with benign prostatic hyperplasia (BPH) or adenocarcinoma (CA), using Northern and slot-blot analysis in order to gain insight into the expression of these highly similar genes. Multiple mRNAs were found to originate from both genes. The major mRNA species of 1.6 kb accounted for 57% to 76% of the total coding capacity for PSA in different tissue specimens, but a variant mRNA species of 1.9 kb was also abundant. Most of the BPH samples contained marked amounts of an aberrant 0.9 kb mRNA, and long PSA mRNAs of 6.1 kb, 4.5 kb and 3.1 kb were found in elevated amounts in some of the CA samples. The amount of PSA mRNAs that would produce aberrant PSA proteins if translated into protein varied from 18% to 38% in these tissue samples. The major mRNA species originating from hGK-1 was of 1.6 kb, but other less abundant mRNA species could also be observed. The amount of PSA and hGK-1 mRNAs was determined from slot blots hybridized with specific oligonucleotide probes. No significant differences could be found in the PSA gene expression between BPH and CA samples. The total amount of the PSA mRNAs in all the different BPH specimens was fairly similar, but there was a 3-fold difference between the highest and lowest PSA mRNA levels in the CA samples. The hGK-1 mRNA levels in the BPH specimens studied demonstrated greater variance than the PSA mRNA levels in the same samples. The correlation between PSA gene and hGK-1 expression in the BPH samples was good, suggesting that there are similarities in the regulation of these genes. However, the lack of correlation between the amounts of PSA and hGK-1 mRNAs in the CA samples except in sample C1 indicates that there are also differences in the gene regulation. The observed 3.7- to 6.5-fold excess of PSA mRNAs as compared with the amount of hGK-1 mRNAs present in the same tissue specimen also indicated differences in the cis- or trans-acting regulatory elements of these genes.


Musculoskeletal Problems Affect the Quality of Life of Patients with Parkinson's Disease.
Musculoskeletal problems are more common in patients with Parkinson's disease (PD) than in normal elderly, but the impact of musculoskeletal problems on health-related quality of life (HRQoL) in patients with PD is unknown. Four hundred consecutive patients with PD were enrolled for the evaluation of musculoskeletal problems and HRQoL. HRQoL was assessed by the 36-Item Short Form Health Survey, which comprised physical health and mental health. Of the total patients, 265 patients had musculoskeletal problems, and 135 patients did not have musculoskeletal problems. Patients with musculoskeletal problems reported lower levels of HRQoL in terms of physical health than did patients without musculoskeletal problems (p < 0.05). In women, all components of physical health were lower in patients with musculoskeletal problems than in patients without musculoskeletal problems (p < 0.05). Meanwhile, in men, only the bodily pain score of physical health was lower in patients with musculoskeletal problems than in patients without musculoskeletal problems. Mental health and physical health were negatively correlated with depression, Unified Parkinson's Disease Rating Scale I & II scores, and pain severity from musculoskeletal problems, in that order (p < 0.01 for all). These results suggest that musculoskeletal problems in patients with PD affect HRQoL significantly, mainly in terms of physical health rather than mental health and especially in women rather than men. Musculoskeletal problems should not be overlooked in the care of patients with PD.


Rating scale analysis of the Berg Balance Scale.
To examine, using Rasch analysis, the rating scale performance of the Berg Balance Scale (BBS) and to describe the 45/56 cutoff score in functional terms. Retrospective chart review of BBS scores. Rasch rating scale analysis was performed on these data. Outpatient Veterans Affairs medical center. One hundred (99 men, 1 woman) community-dwelling veterans referred for balance deficits (age range, 64-88y). Not applicable. The BBS. Condensing item-rating categories allowed the elimination of underutilized categories and constructed categories that better separated people of differing abilities. Rating pivot points were developed for each item to represent a transition between passing and failing. Following pivot-point development and rating scale rescoring, person and item measures became more evenly distributed across the BBS and resulted in changes in item difficulty order. In our sample, functional indicators of a score of at least 45/56 were a rating of passing the item "tandem stance," as well as passing 2 of the following 3 items: "alternating foot," "standing on one leg," and "look behind." Our findings provide direction for improving the rating scale structure for each of the items and establish a connection between the BBS cutoff score of 45/56 and functional ability.


Osseous choristoma of the choroid. A familial disease.
Two patients in the same family (daughter and mother) had osseous choristoma of the choroid in four otherwise normal eyes. The clinical diagnosis of the choroidal lesion was confirmed by B-scan ultrasonography. Both patients were followed up for five years and neither showed any essential change of the fundus. The high prevalence of this choroidal tumor in girls and women (20 of 22 reported cases) and the present report on two patients in the same family suggest that a hereditary factor should be considered in the etiology of this unusual choroidal lesion.


The in vitro isolation and characterization of monosomic sublines derived from a Colcemid-treated Chinese hamster cell population.
A series of 18 sublines deficient for one or two chromosomes was isolated in vitro from a pseudodiploid Chinese hamster cell population treated appropriately with Colcemid to obtain maximal induction of aneuploidy. Chromosomes 10 and 11 were the most frequently involved and, to a lesser extent, chromosome 9 and the partially deleted 6. Since analysis of chromosome banding patterns did not reveal any evidence of chromosome rearrangement, it was concluded that entire chromosomes were absent, and thus the sublines are presumed to be monosomic. The monosomic state was quickly lost during serial culture, and the 15th passage after isolation, the monosomic cell type accounted for less than 50% of the cell population in over half the sublines. This was due to a shift in chromosome number back to 22, apparently by reacquistion of the absent chromosome, or to the appearance of tetraploidy.


Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor-T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1).
CARTIFAN-1 aimed to evaluate the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeting chimeric antigen receptor T-cell therapy, in Chinese patients with relapsed/refractory multiple myeloma (RRMM). This pivotal phase II, open-label study (ClinicalTrials.gov identifier: NCT03758417), conducted across eight sites in China, enrolled adult patients with RRMM who had received ≥ 3 lines of prior therapy, including a proteasome inhibitor and immunomodulatory drug. Patients received a single infusion of cilta-cel (target dose 0.75 × 106 chimeric antigen receptor-positive viable T cells/kg). The primary end point was overall response rate. Secondary end points included progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs). As of the clinical cutoff of July 19, 2021, 48 patients received a cilta-cel infusion. At an 18-month median follow-up, the overall response rate was 89.6% (95% CI, 77.3 to 96.5), with a median time to first response of approximately 1 month; 77.1% of patients (95% CI, 62.7 to 88.0) achieved complete response or better. Medians for duration of response, PFS, and OS were not reached. The 18-month PFS and OS rates were 66.8% (95% CI, 49.4 to 79.4) and 78.7% (95% CI, 64.0 to 88.0), respectively. Hematologic AEs were common, including anemia (100%), neutropenia (97.9%), lymphopenia (95.8%), and thrombocytopenia (87.5%). Cytokine release syndrome occurred in 97.9% of patients (35.4% grade 3/4); the median time to onset was 7 days, and the median duration was 5 days. Infections occurred in 85.4% of patients (37.5% grade 3/4). Ten deaths occurred after cilta-cel infusion, eight of which were due to treatment-related AEs. These data demonstrate a favorable risk-benefit profile for a single infusion of cilta-cel, resulting in early, deep, and durable responses in heavily pretreated patients with RRMM in China.


[Role of long noncoding RNA SNHG3 in regulating proliferation, migration and invasion of cervical cancer SiHa cells].
To investigate the regulatory role of the long non-coding RNA (lncRNA) small nucleolar host gene 3 (SNHG3) in proliferation, migration and invasion of human cervical cancer cell line SiHa. Array data were retrieved from GEO database to analyze the expression levels of SNHG3 in cervical cancer and adjacent normal tissues. SiHa cells were transfected with a small interfering RNA (siRNA) targeting SNHG3, and the changes in the transcriptional levels of lncRNA SNHG3 and the epithelial-mesenchymal transition (EMT) markers N-cadherin, Snail, vimentin and E-cadherin were detected using real-time quantitative PCR; the protein expressions of N-cadherin, Snail, vimentin and E-cadherin were determined using Western blotting. Cell counting kit-8 (CCK8) assay was utilized to assess the proliferation capacity of the transfected cells. Wound healing assay and Transwell assay were performed to evaluate the transversal and longitudinal migration and invasion abilities of the cells. SNHG3 was over-expressed in cervical cancer tissues and SiHa cells. In SiHa cells, knocking down SNHG3 significantly inhibited the proliferation (P < 0.001), migration (P < 0.01) and invasion abilities (P < 0.001) of the cells, down-regulated the expression levels of N-cadherin, Snail and vimentin (P < 0.001) and up-regulated the expression of E-cadherin (P < 0.001). SNHG3 may promote the proliferation, migration and invasion of SiHa cells by activating the EMT signaling pathway.


Perioperative Risk Factors for Mortality in Patients Undergoing Surgery for Ebstein's Anomaly at a Single Institution: A Retrospective Analysis.
Mortality after cardiac surgery for Ebstein's anomaly ranges from 2.5% to 31%. Independent predictors for mortality and morbidity remain poorly defined because of the low incidence of this congenital anomaly. To identify potentially modifiable factors, this retrospective study investigates the prognostic value of perioperative variables for mortality and morbidity. We reviewed the charts of 171 patients with Ebstein's anomaly who were at one point in follow-up at our center. Only patients who underwent cardiac surgery for this anomaly were included. The primary endpoint was a composite of mortality or rehospitalization for cardiac reasons within 1 year of surgery. Logistic regression and Cox regression models were used to study the predictive value of various variables. We identified 32 patients (median age 12 years; range 7 days to 70 years) who underwent a total of 49 surgical procedures for Ebstein's anomaly at our institution between November 1987 and March 2015. The following variables were significantly associated with the primary outcome: increased severity of tricuspid valve stenosis (odds ratio 2.089; 95% confidence interval 1.175 to 3.713) and right ventricular dysfunction (1.826; 1.109 to 3.006), partial corrective surgery (versus corrective surgery) (6.709; 1.436 to 31.344), occurrence of major postoperative complications (5.460; 1.419 to 21.008), and increased length of stay in the intensive care unit (1.051; 1.010 to 1.093). A better outcome was observed with the use of intraoperative cardioplegic arrest (0.185; 0.063 to 0.550), atrial septal defect closure during surgery, and longer duration of surgery (0.991; 0.984 to 0.998). Several patient-specific characteristics and perioperative characteristics were associated with a poorer outcome after cardiac surgery for Ebstein's anomaly. The outcome seems to be primarily determined by the severity of the valve dysfunction and right ventricular performance, with only a minor role for perioperative surgical or anesthetic technical determinants.


Protein synthesis dependent and independent apoptosis of murine splenic T cells.
To elucidate the mechanism of apoptosis in matured T cells, we examined the effect of phorbol esters capable of activating protein kinase C, cAMP agonists, calcium ionophores, and dexamethasone on apoptosis in mouse splenic T cells. All of these agents induced apoptosis in thymocytes. Neither phorbol esters nor calcium ionophores induced apoptosis in the splenic T cells. Dibutyrylcyclic AMP induced apoptosis in splenic T cells but to a lesser extent than that in thymocytes. The results suggest that matured T cells are more resistant to various apoptogenic stimuli than thymocytes. Dexamethasone induced apoptotic cell death in splenic T cells as well as in thymocytes. Cycloheximide, an inhibitor of protein synthesis which completely inhibited thymocyte apoptosis, induced slight apoptosis in splenic T cells, but it inhibited the dexamethasone-induced apoptosis to a level at which cycloheximide induced apoptosis, indicating that at least two pathways of apoptosis exist in peripheral T cells; one protein synthesis dependent and the other independent. Taken together, the results suggest that the apoptosis of peripheral T cells is regulated by a mechanism different from that of thymocytes.


Treatment Patterns, Outcomes, and Costs for Bowel Obstruction in Ovarian Cancer.
The aim of this study was to assess treatment patterns, outcomes, and costs for bowel obstruction in ovarian cancer. All patients with stage II to IV ovarian cancer who were admitted for bowel obstruction greater than or equal to 6 months after cancer diagnosis from 2000 to 2011 were identified from the Surveillance, Epidemiology, and End Results registry-Medicare database. Management strategies and outcomes of bowel obstruction were compared. Among 1397 women with bowel obstruction, 562 (40%) underwent surgery, and 154 (11%) had a gastrostomy or jejunostomy (G/J) tube placed. Thirty-four percent of patients who underwent surgery subsequently received chemotherapy, compared with 8% of those managed with a G/J tube (odds ratio, 4.8; 95% confidence interval [CI], 2.7-8.8). Thirty-day complications were higher for patients in the surgery group compared with those in the tube group (69% vs 46%; odds ratio, 2.5; 95% CI, 1.8-3.7), as were mean adjusted 30-day total costs ($28,872 vs $18,528, P < 0.001). Median survival was greater for women who underwent surgery compared with those who had a G/J tube (5.3 vs 1.2 months; adjusted hazard ratio, 0.31; 95% CI, 0.25-0.38). The median survival of patients in whom surgical correction failed and required G/J tube placement during the same inpatient admission was 2.6 months. Women who received postintervention chemotherapy had improved survival compared with those who did not in both the surgery (17.0 vs 2.8 months, P < 0.001) and G/J tube (5.7 vs 1.0 months, P < 0.001) groups. In women with ovarian cancer who develop bowel obstruction, surgery may benefit a subset of patients, likely related to the ability to receive subsequent chemotherapy. Efforts to identify those who derive no benefit may reduce unnecessary laparotomy, along with its associated complications and costs. Given this population's limited survival, patient preferences should be evaluated in future studies assessing the management of bowel obstruction.


Long-term follow up of surgical repair of late bleb leaks after glaucoma filtering surgery.
To study the long-term outcomes of surgical revision of leaking blebs after trabeculectomy and identify possible risk factors for failure. A retrospective, nonrandomized, noncomparative interventional study of 34 eyes with late bleb leaks after trabeculectomy that underwent bleb excision with conjunctival advancement. The primary outcome measure was successful repair and control of intraocular pressure (IOP). The other measures evaluated included change in visual acuity from baseline and complications such as recurrence of bleb leak, endophthalmitis or the need for additional antiglaucoma medication to control IOP. After a mean follow up of 36.2+/-23 months, the mean IOP at the last visit was 14.5+/-7.6 mm Hg. IOP in 58.8% of eyes was controlled without medication. Complications included early leaks (7/34), late recurrent or persistent leaks (1/34), and endophthalmitis (1/34). In all, 41.2% patients required additional medication at the last visit. Survival analysis at 22 months the probability of total and qualified success was 52% and 72%, respectively. However, this dropped to 10% and 15%, respectively, at 5 years. The probability of total and qualified success further dropped to 2.5% and 5% at 5 years when the IOP cut-off was lowered from 21 to 15 mm Hg. Cox regression analysis failed to identify risk factors for bleb failure. Surgical bleb revision seems to be effective in treating late bleb leaks with few postoperative complications. However, patients should be followed carefully as late failure of bleb function beyond 2 years is a significant possibility.


Neurobiological findings in first admission patients with schizophrenia or schizophreniform disorder.
Fifty patients with a DSM-III-R diagnose of schizophrenia or schizophreniform disorder were compared to 25 healthy volunteers on structural and functional brain measurements. The patients were studied during their first admission to psychiatric hospital. In the patient group correlations between structural and functional brain measurements and clinical symptoms were performed. Brain structure was studied by CT scans. The schizophrenic patients had significantly smaller brain volume and brain length and more sulcal, but not ventricular, CSF than the controls. These findings were not an effect of sex, abuse, educational status or neuroleptic treatment. Brain function was studied by rCBF measurement (at baseline conditions and during mental activation), neuropsychological tests and neurological examination. The patients had significantly lower rCBF in the prefrontal regions during baseline condition and this was more pronounced during mental activation when compared with the controls. In the striatal region the patients had higher rCBF than the controls during activation. In no other region did rCBF differ between the patients and the controls. This points to a dysfunction in schizophrenic patients somewhere in th fronto-striatal-thalamic circuit. The patients performed poorer than the controls on practically all the psychological tests. Especially poor performance was seen in the more complicated tests depending on ability of abstraction, planning and sequential organisation and on semantic memory. The patients had more neurological abnormalities than the controls. Correlations between brain structure and rCBF were few. The neurological impaired patient group had more signs of structural brain deficits than the neurological normal patient group. Poor performance on a variety of psychological tests was correlated to signs of structural cerebral deficits. The significant correlations between the neurobiological measurements and clinical symptoms in the patients were sparse. However there was a trend that more symptoms both positive, negative and thought disorder were correlated to higher rCBF values in frontal, temporal and striatal regions, and that absence of positive symptoms correlated to structural brain deficits. Thus both structural and functional brain deficits can be detected early in the disease of schizophrenia. The findings point to primary cortical deficits probably located in the frontal and temporo-limbic areas.


Long-term effects of a community-based intervention: 5-year follow-up of 'Clubs against Drugs'.
To evaluate long-term effects of a multi-component community-based club drug prevention programme. A pre- (2003) and post-intervention study (2004 and 2008) design. High-risk licensed premises in central Stockholm, Sweden. The intervention programme, 'Clubs against Drugs', included community mobilization, drug-training for doormen and other staff, policy work, increased enforcement, environmental changes and media advocacy and public relations work. The indicator chosen for this study was the frequency of doormen intervention towards obviously drug-intoxicated guests at licensed premises. Professional male actors (i.e. pseudopatrons) were trained to act impaired by cocaine/amphetamines while trying to enter licensed premises with doormen. An expert panel standardized the scene of drug intoxication. Each attempt was monitored by two male observers. At the follow-up study in 2008 the doormen intervened in 65.5% of the attempts (n=55), a significant improvement compared to 27.0% (n=48) at the first follow-up in 2004 and to 7.5% (n=40) at baseline in 2003. The 'Clubs against Drugs' community-based intervention programme, a systems approach to prevention, appears to increase the frequency and effectiveness of club doormen's interventions regarding obviously drug-intoxicated guests.


Magnaporthiopsis, a new genus in Magnaporthaceae (Ascomycota).
The phylogenetic relationships among taxa in the Magnaporthaceae are investigated based on DNA sequences of multiple genes including SSU, ITS, LSU, MCM7, RPB1 and TEF1. The genera Magnaporthe and Gaeumannomyces are shown to be polyphyletic and their members are divided into four major groups based on the phylogenetic analyses. Considering morphological, biological and molecular data, we establish a new genus, Magnaporthiopsis. It is characterized by black and globose perithecia with a cylindrical neck, two-layered perithecial wall, clavate asci with a refractive apical ring, fusiform to fusoid and septate ascospores, simple hyphopodia, and Phialophora-like anamorph. Species in this genus are necrotrophic parasites infecting roots of grasses. Three new combinations, Magnaporthiopsis poae, M. rhizophila and M. incrustans, are proposed accordingly. Pyricularia is suggested as the generic name for the rice blast fungus over Magnaporthe, following Article 59.1 of the International Code of Nomenclature for algae, fungi and plants. A new combination, Nakataea oryzae, is proposed for the rice stem rot fungus.


[Primary non-Hodgkin's lymphoma of the prostate].
A patient with a rare primary lymphoma of the prostate is presented. Clinical symptoms may be a reason of mistake, that are highly suggestive of benign prostatic hyperplasia or prostatic adenocarcinoma. Before treatment all patients should have to determined the histopathological diagnosis (made by prostatic biopsy or by prostatectomy) because treatment of patients with primary non-Hodgkin's lymphoma of the prostate is quite different then treatment of patients with prostatic adenocarcinoma. After treatment with combination chemotherapy appropriate for the clinical stage and the specific histological subtype our patient achieved a complete remission and remained free of disease after twelve months.


Improving competencies in evidence-based dementia care: Results from a pilot study on a novel inter-professional training course (the KOMPIDEM project).
In order to address well-known challenges in dementia care, an inter-professional course was developed to improve medical students' and nursing students' competencies in the provision of evidence-based care for people with dementia. The course comprises lectures, problem-based learning (PbL) tutorials and visitations to care facilities. A pilot study was conducted to evaluate the acceptance and feasibility of the inter-professional course. Alongside preliminary implementation of the newly developed course, a pre-post survey was carried out involving all participating students. The questionnaire contained standardized and open-ended questions on participants' views regarding the quality and relevance of several course components and characteristics. The data were analyzed by means of descriptive statistics. When the course was offered the first time, multiple barriers became evident, leading to premature course termination and subsequent revision of the curriculum. When the revised course was offered, 10 medical students and 8 nursing students participated. The course proved feasible, and the median overall quality was rated as "2" (IQR 2-3) at a rating scale ranging from 1 (very good) to 6 (inadequate). Following aspects were most frequently judged positively: the course's inter-professional scope, the visitations to care facilities and the PbL tutorials. Potential for improvement was particularly noted with regard to a more distinct focus on well-defined, mainly practical learning outcomes. There were no indications of systematic between-group differences in the medical and nursing students' perceptions of the course program. The results confirmed the feasibility of the inter-professional course on dementia care and the relevance of its inter-professional scope. However, to ensure sustainable course implementation in the long term, further program adaptations based on current findings and further evaluation studies focusing on objective parameters of the process and outcome quality are required.


Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN.
Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologous and heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN.


Is Intraoperative Use of QuikClot Combat Gauze Effective for Hemostasis after Total Knee Arthroplasty?
To assess the hemostatic effect of QuikClot Combat Gauze (QCG) compared to that of standard gauze during cruciate-retaining total knee arthroplasty (TKA). Sixty knees underwent TKA using a pneumatic tourniquet in this prospective randomized study. After implantation of the femoral and tibial components and hardening of the bone cement, the tourniquet was deflated and QCG (group 1) or standard gauze (group 2) was packed into the joint cavity for 5 minutes for hemostasis. Perioperative bleeding volume and blood transfusion volume were compared between two groups. The mean intraoperative bleeding volume was 64.7 ± 12.7 mL in group 1 and 63.9 ± 9.2 mL in group 2 (p = 0.808). The mean postoperative blood drainage was 349.0 ± 170.6 mL in group 1 and 270.1 ± 136.3 mL in group 2 (p = 0.057). The average postoperative blood transfusion volume was 323.7 ± 325.9 mL in group 1 and 403.6 ± 274.8 mL in group 2 (p = 0.314). QCG was not significantly effective for reducing perioperative bleeding volume or the blood transfusion rate compared with standard gauze during TKA.


Current methods for evaluating people's exposure to green space: A scoping review.
People's exposure to green space is a critical link between urban green space and urban residents' health. Since green space may affect human health through multiple pathways regarding diverse human health outcomes, the measurement of people's exposure to green space must be tailored to concrete study contexts and research questions. In this scoping review, we systematically categorized the available green space representations and metrics in the last two decades that can be used to derive people's exposure to green space regarding different research topics. A three-phase systematic review was conducted after a generalized search of relevant research articles from the three most-used publication databases, namely Scopus, the Web of Science, and PubMed. We identified 260 research articles that particularly discuss green space representations and metrics. We further developed a multi-pathway framework to articulate the complicated context issues in green space studies. We categorized the most relevant green space representations and metrics into five groups, including green space indices, the delineation, inventory, and usage of green space, the spatiotemporal evolution of green space, the attributes and components of green space, and the green space landscape and fragmentation. Finally, we discussed the inter-conversion between different green space representations and metrics, the "mobility-turn" in green space studies and how it may affect the derivation of people's exposure to green space, and other potential methodological issues in measuring people's exposure to green space. Our scoping review provides the most comprehensive framework and categories for deriving people's exposure to green space to date, which may strongly support a broad range of studies that concern green space's health effects.


Crystal structure, Hirshfeld surface analysis and density functional theory study of benzyl 2-oxo-1-(prop-2-yn-1-yl)-1,2-di-hydro-quinoline-4-carboxyl-ate.
The title mol-ecule, C20H15NO3, adopts a Z-shaped conformation with the carboxyl group nearly coplanar with the di-hydro-quinoline unit. In the crystal, corrugated layers are formed by C-H⋯O hydrogen bonds and are stacked by C-H⋯π(ring) inter-actions. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (43.3%), H⋯C/C⋯H (26.6%) and H⋯O/O⋯H (16.3%) inter-actions. The optimized structure calculated using density functional theory at the B3LYP/ 6-311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated HOMO-LUMO energy gap is 4.0319 eV.


Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.
COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts.


Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia.
To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). We analyzed the outcome of patients who underwent SCT according to their VH mutational status. Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.


Considerations and preparations for making managed care part of your practice.
The decision to integrate managed care into the traditional FFS practice is one that requires careful consideration. Should you decide that it offers your practice an attractive opportunity to fill empty chairtime while positioning the practice for positive growth, now may be an opportune time for involvement. Furthermore, embracing a new mind-set could prove to be an invaluable business move-change is essential, no matter which path is taken. Most consultants believe that dentists who expand their horizons now will maintain a competitive edge over those who stick with more traditional methods of operation. As with any industry, it is important to aim for where things are going, not for where they have been; the positive focus should be on the dental practice of the future. According to Reengineering the Corporation (HarperBusiness, 1993) by Hammer and Champy, businesses today must not forget the three Cs: customers, competition, and change. The book points out that the customers are in charge, the competition has intensified, and change is a constant. The decisions made now regarding the direction of dental practices will determine how dentists deal with the forces in this uncharted future.


Cytosolic and Mitochondrial Hsp90 in Cytokinesis, Mitochondrial DNA Replication, and Drug Action in Trypanosoma brucei.
Trypanosoma brucei subspecies cause African sleeping sickness in humans, an infection that is commonly fatal if not treated, and available therapies are limited. Previous studies have shown that heat shock protein 90 (Hsp90) inhibitors have potent and vivid activity against bloodstream-form trypanosomes. Hsp90s are phylogenetically conserved and essential catalysts that function at the crux of cell biology, where they ensure the proper folding of proteins and their assembly into multicomponent complexes. To assess the specificity of Hsp90 inhibitors and further define the role of Hsp90s in African trypanosomes, we used RNA interference (RNAi) to knock down cytosolic and mitochondrial Hsp90s (HSP83 and HSP84, respectively). Loss of either protein led to cell death, but the phenotypes were distinctly different. Depletion of cytosolic HSP83 closely mimicked the consequences of chemically depleting Hsp90 activity with inhibitor 17-AAG. In these cells, cytokinesis was severely disrupted, and segregation of the kinetoplast (the massive mitochondrial DNA structure unique to this family of eukaryotic pathogens) was impaired, leading to cells with abnormal kinetoplast DNA (kDNA) structures. Quite differently, knockdown of mitochondrial HSP84 did not impair cytokinesis but halted the initiation of new kDNA synthesis, generating cells without kDNA. These findings highlight the central role of Hsp90s in chaperoning cell cycle regulators in trypanosomes, reveal their unique function in kinetoplast replication, and reinforce their specificity and value as drug targets.


Employment status, psychological needs, and mental health: Meta-analytic findings concerning the latent deprivation model.
Marie Jahoda's latent deprivation model proposes that unemployed people have a worse mental health compared to employed people. This is because they suffer not only from a lack of the manifest function of employment (earning money), but also from a lack of five so-called latent functions of employment: Time structure, social contact, collective purpose (i.e., the sense of being useful to other people), status, and activity. In order to test the basic assumptions of this theory, a study based on meta-analytic methods was conducted. Results showed that employed people reported higher levels on all five latent functions, as well as on the manifest function, compared to unemployed people. They also report more latent functions than people who are out of the labor force (OLF). Moreover, OLF-people reported more manifest and latent functions than unemployed people. Specific analyses for three OLF-subgroups found retired people to be almost as deprived of the latent functions (but not the manifest function) as unemployed people, while students were more similar to employed people but still experienced some manifest and latent deprivation. For homemakers, the effect sizes pointed in the expected direction, but they were not significant. Thus, the proposition that employment is the best provider of the latent functions was generally endorsed, although homemakers need further scrutiny in future studies. All latent functions, as well as the manifest function, emerged as significant independent predictors of mental health, when the influence of the other manifest and latent functions was controlled. Together, the dimensions in the model explained 19% of variation in mental health.


[Data mining-based analysis of formulation rules for prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix].
By the in-depth excavation of prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix in the Dictionary of Traditional Chinese Medicine Prescriptions, this study analyzed their formulation rules, so as to provide reference for their clinical application and new drug development. First, the prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were collected from the Dictionary of Traditional Chinese Medicine Prescriptions, and their indications, herbal compatibility, and dosage forms were analyzed statistically using the Traditional Chinese Medicine Inheritance Support System(TCMISS). Meanwhile, the formulation rules and common dosage forms for the top four indications(amnesia, palpitation, mania, and epilepsy) sorted by frequency were analyzed with Apriori algorithm. A total of 507 prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were screened out, involving 15 indications(frequency>10) like amnesia, palpitation, mania, and epilepsy. There were 30 commonly used Chinese herbs(frequency≥60), with the Qi-tonifying herbs(Ginseng Radix et Rhizoma and Glycyrrhizae Radix et Rhizome), mind-tranquilizing herbs(Poria and Poria cum Radix Pini), and Yin-nourishing herbs(Angelicae Sinensis Radix and Ophiopogonis Radix) being the core ones. The commonly used dosage forms were honey pill, paste pill, decoction, and powder. These have indicated that the herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix is often combined with Qi-tonifying, Yin-nourishing, and mind-tranquilizing herbs for the treatment of "heart or brain diseases" caused by phlegm production due to spleen deficiency, Qi and blood deficiency, and phlegm-turbidity blocking orifice. In the treatment of amnesia, supplementing essence and replenishing marrow are considered on the basis of tonifying Qi, nourishing Yin, and tranquilizing mind. In the treatment of palpitation and mania, tranquilizing mind is emphasized. In the treatment of epilepsy, the emphasis is placed on resolving phlegm, extinguishing wind, and stopping convulsion.


Infant discrimination of humanoid robots.
Recently, extremely humanlike robots called "androids" have been developed, some of which are already being used in the field of entertainment. In the context of psychological studies, androids are expected to be used in the future as fully controllable human stimuli to investigate human nature. In this study, we used an android to examine infant discrimination ability between human beings and non-human agents. Participants (N = 42 infants) were assigned to three groups based on their age, i.e., 6- to 8-month-olds, 9- to 11-month-olds, and 12- to 14-month-olds, and took part in a preferential looking paradigm. Of three types of agents involved in the paradigm-a human, an android modeled on the human, and a mechanical-looking robot made from the android-two at a time were presented side-by-side as they performed a grasping action. Infants' looking behavior was measured using an eye tracking system, and the amount of time spent focusing on each of three areas of interest (face, goal, and body) was analyzed. Results showed that all age groups predominantly looked at the robot and at the face area, and that infants aged over 9 months watched the goal area for longer than the body area. There was no difference in looking times and areas focused on between the human and the android. These findings suggest that 6- to 14-month-olds are unable to discriminate between the human and the android, although they can distinguish the mechanical robot from the human.


Dual function of the pectoral girdle for feeding and locomotion in white-spotted bamboo sharks.
Positioned at the intersection of the head, body and forelimb, the pectoral girdle has the potential to function in both feeding and locomotor behaviours-although the latter has been studied far more. In ray-finned fishes, the pectoral girdle attaches directly to the skull and is retracted during suction feeding, enabling the ventral body muscles to power rapid mouth expansion. However, in sharks, the pectoral girdle is displaced caudally and entirely separate from the skull (as in tetrapods), raising the question of whether it is mobile during suction feeding and contributing to suction expansion. We measured three-dimensional kinematics of the pectoral girdle in white-spotted bamboo sharks during suction feeding with X-ray reconstruction of moving morphology, and found the pectoral girdle consistently retracted about 11° by rotating caudoventrally about the dorsal scapular processes. This motion occurred mostly after peak gape, so it likely contributed more to accelerating captured prey through the oral cavity and pharynx, than to prey capture as in ray-finned fishes. Our results emphasize the multiple roles of the pectoral girdle in feeding and locomotion, both of which should be considered in studying the functional and evolutionary morphology of this structure.


Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study.
Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. Cross-sectional study at six teaching and research institutions. To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.


[Ventricular late potentials in acute myocardial infarct].
Ventricular late potentials are regarded as an expression of delayed impulse conduction in an area of myocardial ischemia and, accordingly, indicative of a preformed reentry circuit. Late potentials can be detected in chronic, stable coronary artery disease and their presence correlates closely with impairment of ventricular function and with the probability of future occurrence of tachyarrhythmic events or sudden cardiac death. While repetitive ventricular arrhythmias in the chronic stage of coronary artery disease result almost invariably from circling intraventricular wavefronts, tachyarrhythmias associated with acute myocardial infarction appear attributable to differing pathomechanisms. According to experimental studies, in acute myocardial infarction, three phases of arrhythmogenesis can be differentiated: phase 1 encompasses the first hours after vessel occlusion which generally corresponds with the prehospital phase. Due to the difference in potential of up to 25 mV between ischemic and nonischemic cardiac muscle areas, an injury current is called into existence which leads to depolarization of normal cardiac muscle tissue. The ectopic impulses so precipitated, the conduction of which is supported by the functional inhomogeneity of the infarcted region, are capable of initiating reentry tachycardia. During phase 2, a few hours to days after the ischemic event, only the subendocardial Purkinje fibers in the infarcted region exhibit focal arrhythmogenicity. In contrast to the working myocardial cells, the latter survive due to their immediate proximity to the cardiac chamber and show, ischemia-induced, a propensity to high-frequency impulse formation in terms of abnormal automaticity. Similar to the experimental findings, the cause of the frequently-observed ventricular arrhythmias in the early hospital phase appears predominantly attributable to a focal arrhythmia mechanism. During phase 3, several days to weeks after the acute myocardial ischemic event, reentry mechanisms again are in the foreground in which the electrophysiologic changes in the Purkinje fibers, in terms of increasing desynchronization, together with conduction barriers arising through the infarct scar, pave the way for reentry phenomenon. After abrupt restoration of patency of a previously occluded vessel the very frequent "reperfusion arrhythmias" are also attributable primarily to reentry mechanisms due to inhomogeneous improvement of the conduction properties in the region of the reperfused myocardium. Ventricular late potentials can be registered both invasively by means of epi- or endocardial leads as well as noninvasively from the body surface.(ABSTRACT TRUNCATED AT 400 WORDS)


Vertex operator algebras, the Verlinde conjecture, and modular tensor categories.
Let V be a simple vertex operator algebra satisfying the following conditions: (i) V(n)) = 0 for n < 0, V(0)=C1, and the contragredient module V' is isomorphic to V as a V-module; (ii) every N-gradable weak V-module is completely reducible; (iii) V is C(2)-cofinite. We announce a proof of the Verlinde conjecture for V, that is, of the statement that the matrices formed by the fusion rules among irreducible V-modules are diagonalized by the matrix given by the action of the modular transformation tau |--> -1/tau on the space of characters of irreducible V-modules. We discuss some consequences of the Verlinde conjecture, including the Verlinde formula for the fusion rules, a formula for the matrix given by the action of tau |--> -1/tau, and the symmetry of this matrix. We also announce a proof of the rigidity and nondegeneracy property of the braided tensor category structure on the category of V-modules when V satisfies in addition the condition that irreducible V-modules not equivalent to V have no nonzero elements of weight 0. In particular, the category of V-modules has a natural structure of modular tensor category.


Whole-genome characterization and genotyping of global WU polyomavirus strains.
Exploration of the genetic diversity of WU polyomavirus (WUV) has been limited in terms of the specimen numbers and particularly the sizes of the genomic fragments analyzed. Using whole-genome sequencing of 48 WUV strains collected in four continents over a 5-year period and 16 publicly available whole-genome sequences, we identified three main WUV clades and five subtypes, provisionally termed Ia, Ib, Ic, II, IIIa, and IIIb. Overall nucleotide variation was low (0 to 1.2%). The discriminatory power of the previous VP2 fragment typing method was found to be limited, and a new, larger genotyping region within the VP2/1 interface was proposed.


Age- and gender-related changes in the temporal-spatial characteristics of forwards and backwards gaits.
Backward walking is used increasingly as a rehabilitation technique for individuals with neurological and orthopaedic impairments. The purpose of the present study was to examine changes in the temporal-spatial characteristics of gain resulting from walking backwards as opposed to forwards, and to determine age and gender effects on these changes. Thirty young and 40 aged, independently functioning, subjects were asked to walk forwards and backwards across a computer-based walkway system, providing data on gait velocity, stride length, cadence, swing phase and double support phase. Subjects were divided into groups based on age (young and old) and gender, and each subject was tested under two walking conditions (forwards and backwards). Five temporal-spatial gait parameters were evaluated separately as a function of the three independent variables, with the walking condition repeated for each subject. Backwards ambulation is characterized by a slower velocity, shorter stride length and an increased double support phase in both young and older adults. These changes were significantly greater in the older subjects, among whom the swing phase was also decreased. Cadence, however, was not affected by direction of ambulation in either group. The female subjects had a shorter stride length in both movement directions, associated with reduced speed only in backwards ambulation. Older individuals are capable of walking backwards for short distances. However, changes in gait characteristics typical to the reversal of movement direction are accentuated with age. These effects must be considered when planning to use backwards ambulation as a rehabilitation technique for older individuals.


The thyroxine-binding site of human apolipoprotein-A-I: location in the N-terminal domain.
We tested the ability of nine monoclonal antibodies (MAb) against human apolipoprotein-A-I (apoA-I), the 28.3-kDa major apoprotein of high density lipoproteins (HDL), to inhibit its photoaffinity labeling with [125I]T4. Two forms were evaluated: isolated lipid-free apoA-I (Sigma or Calbiochem) and lipid-complexed apoA-I [HDL2, (density, 1.063-1.125 g/ml) and HDL3 (density, 1.125-1.210 g/ml)]. After labeling with 0.5 nM [125I]T4 in the presence of MAb or normal mouse IgG, the products were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent densitometric quantitation of radioactivity associated with the 28.3-kDa band. Group I MAbs, namely those having epitopes in the N-terminal portion of apoA-I, include MAb 16 (epitopes at residues 1-16), 4 and 14 (residues 1-86), and 18 (residues 98-105); group II includes MAbs 7,10, 15, and 17 (epitopes at residues 87-148); group III includes MAb 9 (residues 149-243). All group I MAbs inhibited [125I]T4 binding to isolated apoA-I with this order of potency: MAb 16 (-50% to -61%) greater than MAb 14 (-37% to -41%) greater than MAb 4 (-27% to -33%) greater than MAb 18 (-19% to -27%). In the case of lipid-associated apoA-I, the pattern of hierarchy was variable, presumably related to the known markedly polydisperse nature of HDL, but a constant feature, in contrast to the case of isolated apoA-I, was that MAb 4 was more potent than MAb 14. Group II MAbs gave less than 3% inhibition in both isolated and lipid-complexed apoA-I. Group III MAb 9 either failed to inhibit or gave 18-27% inhibition (one preparation each of HDL2 and HDL3). We conclude that the T4 site of apoA-I is in the N-terminal domain of apoA-I, closer to the epitope for MAb 16 than to that for MAb 18, and that conformational changes occurring when apoA-I is associated with lipids in the HDL particle alter the spatial relationship between some epitopes and the T4 site. Our definition of the T4 site of apoA-I is consistent with another set of data showing that heparin failed to inhibit [125I]T4 binding to isolated apoA-I. Heparin is known to interact with clusters of basic residues, and these residues are concentrated in the midregion of apoA-I.


Adhesive models to understand the sensitivity of bio-molecules to environmental signals.
Recently, contact mechanics has been widely used to get some understanding of the biological adhesion mechanisms, such as cell-cell adhesion, insects' adhesion and locomotion. JKR theory is usually adopted as a basis, in which the interaction of molecules is considered in contrast to the classical Hertz solution. In this paper, two problems are summarized, which may give some insights to cells or bio-molecules sensitivity to environmental signals: (1) cell reorientation on a stretched substrate; (2) spontaneous detachment between cells or bio-molecules under the variation of environmental signals. The intention here is only to illustrate the possibilities that contact mechanics may explain or predict some bio-phenomena using simple mechanical models. A complete analysis taking into account the full biological complexities is far beyond the scope of this paper. With this objective in mind, the sensitivity of bio-molecules to the environmental signals is described through the variation of adhesive contact area, which is affected by the external forces or deformations. In the first problem, two-dimensional generalized JKR model is used to explain why there exist three stages with two critical values of stretch amplitude controlling cells' reorientation. Three-dimensional adhesive model is used in the second problem, to analyze the spontaneous detachment between two adhering cells or bio-molecules, which may happen at a critical condition.


Towards a general model for protein-substrate stereoselectivity.
Protein-substrate interactions in enzymatic, neurological, and immunological systems are typically characterized by a high degree of stereoselectivity towards complex substrates. We propose a novel stereocenter-recognition (SR) model for stereoselectivity of proteins (or receptors in general) towards substrates that have multiple stereocenters, based on the topology of substrate stereocenters. The model provides the minimum number of substrate locations that need to enter into binding, nonbinding, or repulsive interactions with receptor sites, for stereoselectivity to occur. According to this model, a substrate location may interact with multiple receptor sites, or multiple substrate locations may interact with a single receptor site, but a stereoselective receptor has to offer, in the correct geometry, at least as many interactions as the required minimum number of substrate locations. The SR model predicts that stereoselectivity towards an acyclic substrate with N stereocenters distributed along a single chain requires interactions involving a minimum of N + 2 substrate locations, distributed over all stereocenters in the substrate, such that effectively three locations exist per stereocenter. Thus, enantioselective recognition of molecules with one chiral center requires a protein to interact with a minimum of three substrate locations, while stereoselectivity towards substrates with two or three stereocenters requires interactions with a minimum of four or five substrate locations, respectively, and so on. We demonstrate the general applicability of this model to protein-substrate interactions by interpreting several previous experimental observations.


Ultralarge suspended and perforated graphene membranes for cell culture applications.
With its high mechanical strength and its remarkable thermal and electrical properties, suspended graphene has long been expected to find revolutionary applications in optoelectronics or as a membrane in nano-devices. However, the lack of efficient transfer and patterning processes still limits its potential. In this work, we report an optimized anthracene-based transfer process to suspend few layers of graphene (1-, 2- and 4-layers) in the millimeter range (up to 3 mm) with high reproducibility. We have explored the advantages and limitations for patterning of these membranes with micrometer-resolution by focused ion beam (FIB) and picosecond pulsed laser ablation techniques. The FIB approach offers higher patterning resolution but suffers from the low throughput. We demonstrate that cold laser ablation is a fast and flexible method for micro-structuring of suspended graphene. One promising field of application of ultimately thin, microporous graphene membranes is their use as next-generation cell culture supports as alternative to track-etched polymer membranes, which often exhibit poor permeability and limited cell-to-cell communication across the membranes. To this end, we confirmed good adhesion and high viability of placental trophoblast cells cultivated on suspended porous graphene membranes without rupturing of the membranes. Overall, there is high potential for the further development of ultrathin suspended graphene membranes for many future applications, including their use for biobarrier cell culture models to enable predictive transport and toxicity assessment of drugs, environmental pollutants, and nanoparticles.


Renin-angiotensin system expression and secretory function in cultured human ciliary body non-pigmented epithelium.
Renin-angiotensin system (RAS) components have been identified in human ciliary body and aqueous humour, pointing to a role for the RAS in the regulation of aqueous humour dynamics. Here, the authors examine the functional expression of a RAS and the effects of angiotensin II (AII) on a signal transduction pathway and ion secretion mechanism in cultured human ciliary body non-pigmented epithelium (HNPE). RAS expression was examined in cultured HNPE cells using polymerase chain reaction (PCR) analysis. Secretory function was determined using spectrofluorescence imaging microscopy to measure cell calcium (Ca(2+)(I)) and volume responses. Single channel patch clamp techniques were employed to investigate ion channel activity. PCR analysis demonstrated the expression of angiotensinogen and the AT(1b) receptor in HNPE cells. A large conductance potassium (BK) channel (mean 190 (SEM 5.6) pS, n = 22 cells), was observed in plasma membrane patches. This channel was calcium sensitive with channel open probability (Po) increasing with increasing Ca(2+)(I) (K(0.5) 10.79 (0.44) microM Ca(2+), Hill coefficient of 1.04 (0.04)). AII (100 nM) increased the number (N) of active BK channels in HNPE cells and also the probability of channel opening (Po). N.P(o) increased from 0.008 (0.002) to 1.38 (0.4) following the addition of AII (p=0.0064). AII also induced a rapid rise in Ca(2+)(I) from resting values of 112 (14) nM to a peak of 992 (106) nM (p<10(-4)). A simultaneous cell volume reduction of 24.70% (3.34%) (p<10(-4)) occurred during this calcium signal. Losartan (1 microM) significantly blocked the AII induced BK channel activation (p=0.0131), the Ca(2+)(I) response (p<10(-4)), and the AII induced volume effect (p=0.0046). It was demonstrated that AII activates a Ca(2+)(I) signalling system which subsequently increases potassium ion channel activity. These effects are accompanied simultaneously by cell volume loss, indicating that AII acts as receptor operated secretagogue in HNPE cells. The ability of an AT(1) receptor antagonist to inhibit these processes may thus offer a new family of pharmaceutical agents to the current armamentarium in the treatment of glaucoma.


Correction of metabolic alkalosis by the kidney after isomertric expansion of extracellular fluid.
Metabolic alkalosis was induced in dogs by administering ethacrynic acid and sustained by feeding a chloride-deficient diet. At the height of the alkalosis extracellular fluid was expanded "isometrically," i.e., with an infusion that duplicated plasma sodium, chloride, and bicarbonate concentrations. Correction of metabolic alkalosis promptly followed such expansion and was attributed to the selective retention by the kidneys of chloride from the administered solution. Since plasma chloride concentration was not increased as an immediate consequence of the infusion, it is concluded that the change in renal tubular function that led to the selective retention of chloride must have been mediated by factors independent of filtrate chloride concentration.A decrease in circulating mineralocorticoid level, as a consequence of volume expansion, does not seem to account for this change in tubular function since identical studies in dogs receiving excessive amounts of 11-deoxycorticosterone acetate during the day of infusion yielded similar findings. Moreover, no other consequence of volume expansion appears to be sufficient to cause this change in tubular function in the absence of metabolic alkalosis; when the alkalosis was corrected with hydrochloric acid before infusion, isometric expansion of extracellular volume did not induce selective chloride retention. We suggest that isometric expansion during metabolic alkalosis causes a decrease in proximal sodium reabsorption that relinquishes filtrate to a more distal site in the nephron and that this site may retain chloride preferentially when hypochloremia or chloride deficiency is present.


Nanopore-based direct sequencing of RNA transcripts with 10 different modified nucleotides reveals gaps in existing technology.
RNA undergoes complex posttranscriptional processing including chemical modifications of the nucleotides. The resultant-modified nucleotides are an integral part of RNA sequences that must be considered in studying the biology of RNA and in the design of RNA therapeutics. However, the current "RNA-sequencing" methods primarily sequence complementary DNA rather than RNA itself, which means that the modifications present in RNA are not captured in the sequencing results. Emerging direct RNA-sequencing technologies, such as those offered by Oxford Nanopore, aim to address this limitation. In this study, we synthesized and used Nanopore technology to sequence RNA transcripts consisting of canonical nucleotides and 10 different modifications in various concentrations. The results show that direct RNA sequencing still has a baseline error rate of >10%, and although some modifications can be detected, many remain unidentified. Thus, there is a need to develop sequencing technologies and analysis methods that can comprehensively capture the total complexity of RNA. The RNA sequences obtained through this project are made available for benchmarking analysis methods.


Resistance to epithelial growth factor receptor tyrosine kinase inhibitors in a patient with transformation from lung adenocarcinoma to small cell lung cancer: A case report.
First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer (non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy. Deletion of exon 19 of EGFR was identified by next-generation sequencing technology. The patient improved markedly when treated with gefitinib, but relapsed after 1 year, with markedly increased serum levels of neuron-specific enolase (NSE). Transformation to SCLC was detected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) re-biopsy, which was negative for the deletion of exon 19 of EGFR. The patient was positive for vimentin expression and refractory to etoposide and cisplatin chemotherapy, and succumbed to the disease 18 months after diagnosis. Transformation of the disease from adenocarcinoma to SCLC may have been due to cancer heterogeneity. Re-biopsy is therefore important in EGFR-TKI-resistant patients for genetic and histological re-evaluation. NSE serum levels may also be useful for detecting early SCLC transformation.


Effective Enhancement of Hypoglycemic Effect of Insulin by Liver-Targeted Nanoparticles Containing Cholic Acid-Modified Chitosan Derivative.
Liver is responsible for the balance of blood glucose level. In this study, cholic acid and N-(2-hydroxy)-propyl-3-trimethylammonium chloride modified chitosan (HTCC-CA) was used as a liver-targeted vehicle for insulin delivery. A novel approach was developed to effectively load insulin by mixing insulin and HTCC-CA in 50% ethanol and water mixed solvent at pH 2 and then dialysis against pH 7.4 phosphate buffer subsequently against water. The insulin-loaded HTCC-CA nanoparticles have an average diameter of 86 nm and insulin loading efficiency of 98.7%. Due to random distribution of the hydrophobic cholic acid groups in HTCC-CA, some of the cholic acid groups located on the nanoparticle surface. Compared with free insulin, the nanoparticles increased in vitro cellular uptake of insulin to 466%, and the nanoparticles accumulated in liver for more time after subcutaneous injection into mice. The therapy for diabetic rats displayed that the nanoparticles increased the pharmacological bioavailability of insulin to 475% relative to free insulin, and the nanoparticles could maintain the hypoglycemic effect for more than 24 h. This study demonstrates that the nanoparticles with cholic acid groups on their surface possess liver-targeted property and biocompatible insulin-loaded HTCC-CA nanoparticles can effectively enhance the hypoglycemic effect of insulin.


Dementia: a brief review.
Dementia is an increasingly common diagnosis in our aging population, and the numbers are expected to rise exponentially in coming years. Alzheimer's disease alone now affects 4.5 million people in the US, while millions more are currently affected by vascular dementia, Lewy Body disease and frontotemporal dementia. Each of these is a distinct entity, though overlapping symptoms and comorbidities occur frequently. Within the past two decades research has progressed rapidly on multiple fronts, including epidemiology, etiology, pathology, diagnosis and treatment. It is important for clinicians to recognize early signs and symptoms of dementia, and to note critical differences among them. Dementia research has moved beyond description of symptoms and clinicopathological correlation to the elucidation of risk factors, the pathobiology of the disease process, and most important, to the first generation of dementia treatments. Our purpose here is to review the current state of knowledge and directions of research for the four major dementias noted above. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new disease-specific diagnostic tools and treatment modalities.


[Evaluation of postoperative adhesions in rats submitted to peritoneostomy with polypropylene mesh associated to nitrofurazone].
Peritoneal injuries, common in per and postoperative, lead to the formation of adhesions. The use of polypropylene mesh increases the postoperative adhesions incidence. Based on the fact of nitrofurazone accelerates the healing process, a possible action on peritoneal adhesions was cogitated. To evaluate postoperative adhesions in rats submitted to peritoneostomy with polypropylene mesh fixation associated to nitrofurazone. Thirty-three Wistar rats were separated into three groups of eleven animals each one. In group I was performed the laparotomy with exposition of the abdominal cavity followed by the laparotomy suture; in group II was performed the resection of a abdominal wall fragment followed by polypropylene mesh fixation on the gap and in group III was performed the same done in group II, but the mesh was previously impregnated with nitrofurazone. After 45 days the animals were sacrificed and necropsied. Seven animals of group I had no adhesions (degree 0), two had degree 1 adhesions and two had degree 2. In group II, one animal was classificated as degree 3 and ten as degree 4. In group III, one had degree 0, eight had degree 3 and one had degree 4 (one animal died before 45 days). All adhesions found involved the abdominal wall; ten animals had adhesions involving only omentum (group I = 4; group II = 1 and group III = 5); eleven animals had adhesions involving omentum, small bowel and other abdominal organs (group II = 10; group III = 1); three animals had adhesions involving only small bowel, all belonged to group III. Fourteen animals had adhesions involving small bowel, of these ten belonged to group II (nine with more than one fixation point) and four belonged to group III (three with just one fixation point). The association of nitrofurazone with polypropylene mesh did not reduce significantly the postoperative adhesions incidence in rats, but reduced the intensity and severity of these adhesions.


3D QSAR pharmacophore based lead identification of G9a lysine methyltransferase towards epigenetic therapeutics.
The G9a, Lysine Methyltransferase that methylates the histone 3 lysine 9 (H3K9) of the nucleosome, is an excellent epigenetic target having no clinically passed inhibitor currently owing to adverse in vivo ADMET toxicities. In this work, we have carried out detailed computational investigations to find novel and safer lead against the target using advanced 3 D QSAR pharmacophore screening of databases containing more than 400000 entrees of natural compounds. The screening was conducted at different levels at increasing stringencies by employing pharmacophore mapping, druglikenesses and interaction profiles of the selected to identify potential hit compounds. The potential hits were further screened by advanced flexible docking, ADME and toxicity analysis to eight hit compounds. Based on the comparative analysis of the hits with the reference inhibitor, we identified one lead inhibitor against the G9a, having better binding efficacy and a safer ADMET profile than the reference inhibitor. Finally, the results were further verified using robust molecular dynamics simulation and MM-GBSA binding energy calculation. The natural compounds are generally considered benign due to their long human uses and this is the first attempt of in silico screening of a large natural compound library against G9a to our best knowledge. Therefore, the finding of this study may add value towards the development of epigenetic therapeutics against the G9a.Communicated by Ramaswamy H. Sarma.


Fault Diagnosis from Raw Sensor Data Using Deep Neural Networks Considering Temporal Coherence.
Intelligent condition monitoring and fault diagnosis by analyzing the sensor data can assure the safety of machinery. Conventional fault diagnosis and classification methods usually implement pretreatments to decrease noise and extract some time domain or frequency domain features from raw time series sensor data. Then, some classifiers are utilized to make diagnosis. However, these conventional fault diagnosis approaches suffer from the expertise of feature selection and they do not consider the temporal coherence of time series data. This paper proposes a fault diagnosis model based on Deep Neural Networks (DNN). The model can directly recognize raw time series sensor data without feature selection and signal processing. It also takes advantage of the temporal coherence of the data. Firstly, raw time series training data collected by sensors are used to train the DNN until the cost function of DNN gets the minimal value; Secondly, test data are used to test the classification accuracy of the DNN on local time series data. Finally, fault diagnosis considering temporal coherence with former time series data is implemented. Experimental results show that the classification accuracy of bearing faults can get 100%. The proposed fault diagnosis approach is effective in recognizing the type of bearing faults.


Cleft lip and palate, pili torti, malformed ears, partial syndactyly of fingers and toes, and mental retardation: a new syndrome?
Two sibs with a syndrome including cleft lip and palate, sparse scalp hair, malformed protruding ears, and partial syndactyly of the fingers and toes are reported. The older child also has mental retardation and pili torti. This syndrome is most probably inherited as an autosomal recessive disorder.


[Effects of transforming growth factor beta1 on dendritic cells function].
To investigate the effects of transforming growth factor beta1 (TGF-beta1) on dendritic cells (DC). Murine bone marrow cells were cultured with different cytokine combinations to develop immature DC (imDC, GM-CSF only) and TGFbeta-DC (GM-CSF + TGF-beta1), and their responses to lipopolysaccharide (LPS) stimulation were observed. The cell ultrastructure was observed by transmission electron microscopy and their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was assayed by mixed lymphocyte reaction (MLR) with BrdU incorporation. IL-12p70 protein was detected by ELISA and the expressions of Toll-like receptor 4 (TLR4) on DCs were analyzed with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Compared to imDC, the TGFbeta-DC had no significant alterations in ultrastructure after LPS stimulation. The expressions of CD80, CD86 were lower on TGFbeta-DC than on imDC [(4.14 +/- 0.95)% vs (13.90 +/- 7.22)%; (8.60 +/- 0.75)% vs (20.63 +/- 5.03)%, P < 0.05, both]. The TGFbeta-DC kept their immature morphology after LPS stimulation, but the expressions of I-Ab and CD80 were slightly increased. After 96 h MLR, TGFbeta-DC had weaker stimulating capacity than imDC did, especially when DC/T cells ratios were 1:4 and 1:1 (P < 0.05, both). TGFbeta-DC showed impaired IL-12p70 production and down-regulation of TLR4 expression. TGF-beta1 can inhibit the expression of co-stimulatory molecules on DC. The TGFbeta-DC is resistant to maturation stimulus (LPS) and might be linked with TLR4 down-regulation.


Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon cancer: A cohort study of two cancer centres.
Adjuvant chemotherapy for Stage II colon cancer offers a small (2-3%) overall survival benefit and is not universally recommended. Mismatch repair deficiency (dMMR) confers an improved prognosis identifying patients unlikely to benefit from adjuvant chemotherapy. The aim of this study was to investigate the use of dMMR immunohistochemistry in two major cancer treatment centres. Prospective data were collected on all patients with resected Stage II colon cancer between 2010 and 2015 across two large Australian hospitals. Data collected included patient demographics, tumour histology, dMMR immunohistochemistry, chemotherapy use, and outcomes. All 355 patients (56.1% female, median age 81) with resected Stage 2 Colon cancer entered on to the surgical database were included in this analysis. MMR testing was performed on 167 patient samples (47%), most occurred post-2013 (73.1% vs. 26.9% patients). dMMR rates were 34.1%. 25 (7.3%) received adjuvant chemotherapy, with no patient >80 years receiving treatment. Presence of ≥2 high-risk feature increased the likelihood of adjuvant chemotherapy. Only 3.6% dMMR patients received chemotherapy; both were young with high-risk features. 27/288 (7.6%) patients (with follow up) relapsed, with 7 disease-free post-resection of metastatic disease, 9 are alive with metastatic disease, and 11 deceased. Unlike clinical trial populations, Stage 2 colon cancer patients are often elderly, have high rates of dMMR tumours, are rarely offered chemotherapy, yet still have excellent outcomes. dMMR immunohistochemistry is being increasingly used to identify Stage 2 patients who do not require chemotherapy.


Models of spatial and orientational self-organization of microtubules under the influence of gravitational fields.
Tabony and co-workers [C. Papaseit, N. Pochon, and J. Tabony, Proc. Natl. Acad. Sci. U.S.A. 97, 8364 (2000)] showed that the self-organization of microtubules from purified tubulin solutions is sensitive to gravitational conditions. In this paper, we propose two models of spatial and orientational self-organization of microtubules in a gravitational field. First, the spatial model is based on the dominant chemical kinetics. The pattern formation of microtubule concentration is obtained (1) in terms of a moving kink in the limit when the disassembly rate is negligible, and (2) for the case of no free tubulin and only assembled microtubules present. Second, the orientational pattern of striped microtubule domains is consistent with predictions from a phenomenological Landau-Ginzburg free energy expansion in terms of an orientational order parameter.


Expected and observed proportion of subjects excluded from paternity by blood phenotypes of a child and its mother in a sample of 171 families.
The proportion of exclusion for a given mother-child pair is the proportion of males excluded from the paternity of this child of a known mother and may be calculated given both the child's and mother's phenotypes and the population gene frequencies. Its expected value in the population is equal to the probability of exclusion, which expresses a laboratory's capability to exclude from paternity nonbiological fathers.In a sample of 171 families examined for 20 genetic systems at the National Blood Group Reference Laboratory, 25 exclusions of putative fathers were detected. The ranking by efficiency of the systems used in these exclusions fits the "expectation of their efficiency," and the average proportion of males excluded by the child's and mother's phenotypes is not different from the expected proportion. Additionally, the repetition of exclusions in an incompatible putative father-mother-child trio is not dependent on the overall proportion of males excluded by the mother and the child, but rather on some high values of the proportion of excluded men in some specific systems.Here, formulas and some factors modifying these parameters as well as a more efficient sequence of examinations to exclude paternity than has previously been used are given. Using this sequence, laboratories which carry out several analyses per day can work by levels of five examinations at a time, done in a particular order, to obtain a rather rapid exclusion of certain families.


Variations in the accuracy of obstetric procedures and diagnoses on birth records in Washington State, 1989.
The authors abstracted a sample of 7,536 hospital medical records to validate the accuracy of the coding of obstetric information on 1) birth certificates, 2) a statewide computerized hospital discharge abstract data system, and 3) a linked file merging birth certificates and the hospital abstract data for Washington State deliveries occurring in 1989. Measures of accuracy of coding of delivery method and obstetric procedures varied greatly among the 23 hospitals that participated in the study. Computerized hospital discharge data were generally more complete and accurate than were birth certificate data. The linked file was more likely to identify obstetric procedures than was either source alone. For example, only 84.1% of cesarean deliveries noted in the hospital charts were identified on birth certificates (range among hospitals, 37-100%). Using the linked file, the authors identified 99.8% of cesarean deliveries (range, 97-100%). Linked birth certificate-hospital abstract files may become an excellent source of data for epidemiologic and health care studies; however, further training of medical record personnel and standardization of coding are needed to improve the quality of computerized data on obstetric events.


Killing effects of Huaier Granule combined with DC-CIK on nude mice transplanted with colon carcinoma cell line.
This study aims to compare the efficacy of different treatments for nude mice transplanted with HT-29 colon carcinoma cell line. BalB/C nude mice were transplanted with HT-29 colon carcinoma cell line and randomly divided into four groups, with 5 mice in each group: blank control group, DC-CIK group, Huaier Granule group, and Huaier Granule group combined with DC-CIK group (combined treatment group). For DC-CIK group and combined treatment group, 1×106 DC-CIK cells were injected via the tail vein 4 days after transplantation. The injection was performed twice weekly for a total of 2 weeks. For Huaier Granule group and combined treatment group, Huaier Granule was administered at the dose of 20 g/60 g, by dissolving 20 g of Huaier granules in 600 ml of pure water. Intragastric administration of 0.2 ml of granules was performed once daily for 3 weeks. For the blank control group, equal volume of normal saline was given. Tumor size and body weight of nude mice were measured every 2 days during the 3-week treatment. The mice were sacrificed at the end of treatment to harvest tumors. Key genes of the signaling pathway were detected by RT-PCR. At the end of treatment, mice in combined treatment group, DC-CIK group and Huaier Granule group remained stable emotionally with normal mobility and water and food intake. However, in the blank control group, the mobility was restricted starting from the third week and the mice were on the verge of dying. The expression of PI3KR1, Akt, Wnt1, CTTNB1, Notch1, Notch2 and Notch3 genes were all downregulated significantly in the combined treatment group compared with DC-CIK group and Huaier Granule group (P<0.05). Therefore, the combined treatment of Huaier Granule combined with DC-CIK achieved the best effect in nude mice transplanted with HT-29 colon carcinoma cell line.


Burden of celiac disease in Europe: a review of its childhood and adulthood prevalence and incidence as of September 2014.
Recent epidemiological studies have demonstrated that coeliac disease (CD) prevalence is still underestimated both in Europe and in Mediterranean regions. Here we review the latest data on CD prevalence and incidence in the European Union (EU) as of September 2014. The current epidemiological scenario of CD prevalence and incidence was investigated by searching PubMed for papers in English using the following key words: "celiac disease", "celiac disease plus prevalence" (limits: 1990-2014), "incidence" (limits: 1970-2014), and "frequency", plus "in Europe". Another search was performed with the same key words plus the name of each European country. Only prevalence data obtained by serology using anti-gliadin antibodies (AGA), EMA test, tTG test, and/or duodenal biopsy were included. The study designs considered were retrospective and prospective studies: population-based (PB), cross-sectional, case-control and cohort studies. Extensive research based on serological screening has demonstrated that 0.5-1% of the EU population suffers from undiagnosed CD, whereas the highest estimate reported in PB studies is approximately 1%. Considering data from different periods, incidence seems to range from 0.1 to 3.7/1000 live births in the child population and from 1.3 to 39/100,000/year in the adult population. The present data disclose marked geographical variation in CD incidence and prevalence in different European countries. Here we document rising CD occurrence in recent decades in European countries due partly to the advent of improved serological testing (tTG + EMA) and partly to increased awareness of its clinical presentation.


The effects of childhood cancer on siblings.
When a child is diagnosed with cancer, it is usually devastating for the entire family. Childhood cancer creates an enormous amount of stress that can result in a variety of family problems and negative outcomes for each family member. The family typically faces role changes and financial burdens. For example, parents spend less time at home that subsequently leads to less family time together (Byrne, 1994). Although numerous prior studies have focused on describing the impact of this disease on the affected child and his or her parents (Van Dongen-Melman, De Groot, Hahlen, & Verhulst, 1995), far less research has attempted to identify the effects of childhood cancer on siblings.


Low-contrast visual acuity versus low-luminance visual acuity in choroideremia.
Choroideremia is a progressive X-linked inherited rod-cone dystrophy. Patients present with nyctalopia and progressive visual field loss, but visual acuity remains well preserved early on. This study showed that low-luminance visual acuity may be a useful clinical outcome measure during earlier disease stages. Choroideremia is a progressive X-linked inherited rod-cone dystrophy. Patients present with nyctalopia and progressive visual field loss. However, visual acuity remains well preserved until late in the disease process, limiting its usefulness as a clinical trial endpoint across the disease spectrum. Visual acuity measurements under low-luminance and low-contrast conditions may be affected sooner and have been suggested as early markers in other ocular diseases. This study assesses whether low-luminance visual acuity and low-contrast visual acuity provide useful endpoints in choroideremia clinical trials. Standard high-contrast and low-luminance visual acuity was obtained on 29 choroideremia subjects and 16 healthy controls, using a logMAR chart, set at four metres. Low-luminance visual acuity was tested using a 2.0-log unit neutral density filter, with the same chart set-up, without formal dark adaptation. This was followed by low-contrast visual acuity measured using 1.25 per cent and 2.5 per cent low-contrast logMAR charts placed also at four metres. Data from the right eyes only were analysed using non-parametric statistics. High-contrast visual acuity minus low-luminance and low-contrast visual acuity provided the low-luminance and low-contrast difference scores. A higher number of choroideremia subjects were able to complete the low-luminance test than the low-contrast visual acuity tests. Choroideremia subjects had significantly higher low luminance, 2.5 per cent low-contrast and 1.25 per cent low-contrast difference scores compared with controls (p < 0.01, Mann-Whitney U-test); 1.25 per cent low-contrast visual acuity revealed the poorest performance. A strong positive correlation was found between low-luminance and high-contrast visual acuities (ρ = 0.818, p < 0.001) and 2.5 per cent low-contrast and high-contrast visual acuities (ρ = 0.671, p < 0.001). The low-luminance visual acuity test may be a useful additional clinical trial outcome measure for early-to-moderate disease, when high-contrast visual acuity is preserved.


Construction of C(sp2)-X (X = Br, Cl) Bonds through a Copper-Catalyzed Atom-Transfer Radical Process: Application for the 1,4-Difunctionalization of Isoquinolinium Salts.
A highly efficient Cu-catalyzed 1,4-difunctionalization of isoquinolinium salts was developed with ether and X- (X = Br, Cl) as the halogen source under mild conditions. This transformation involves the combination of oxidative coupling and copper-catalyzed halogen atom-transfer radical processes. This method not only provides an efficient way to prepare various substituted azaarenes but also achieves the selective construction of C(sp2)-X (X = Br, Cl) bonds from a halogen anion and nucleophilic carbon atom via a free-radical process.