Antifibrotic and tumor microenvironment modulating effect of date palm fruit (Phoenix dactylifera L.) extracts in pancreatic cancer.
Date palm fruit (Phoenix dactylifera L.) is an endemic functional food, with great nutritional and economic importance due to its phytochemical compositions. The microenvironment of pancreatic cancer consists of cellular and acellular components, including fibroblasts, myofibroblasts, pancreatic stellate cells (PSCs), immune cells, blood vessels, extracellular matrix (ECM) and soluble proteins, such as cytokines and growth factors. The ECM represents a physical barrier that protects the tumor cell from active therapeutic compounds. In this study, four different solvents; water, ethanol, acetone, and ethyl acetate have been used to extract natural products from date palm fruit using a maceration method. The prepared extracts were investigated for antifibrotic (expression of fibronectin-1 and alpha-smooth muscle actin) and antiproliferative activity in tumor necrosis factor (TNF) stimulated PSCs in vitro. Based on the pharmacological test results, the ethyl acetate extract was subsequently partitioned into nine fractions based on polarity using silica gel column chromatography. These nine collective fractions were further evaluated for their activity. Ethanol, ethyl acetate and acetone, but not water extract significantly reduced PSC proliferation (p < 0.05). Date fruit fractions reduced fibrosis, decreased PSC activity and reversed the PSCs' fibrotic phenotype. The findings suggest a new approach for targeting pancreatic cancer through the modulation of PSC activity, thereby possibly enhancing the effect of known anticancer drugs. Moreover, date palm fruit appears to have chemopreventive activity protecting from pancreatic and probably other types of cancer, and thereby might be useful candidate to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial anticancer product.


Refractory and relapsing multiple myeloma treated by blood stem cell transplantation.
Between June 1989 and June 1992, 12 patients with advanced multiple myeloma underwent peripheral blood stem cell autotransplantation after high-dose chemotherapy and radiotherapy. The conditioning regimen included melphalan (140 mg/m2), high-dose cyclophosphamide (120 mg/kg), methylprednisolone (2 g daily x 7), and total body irradiation (9-12 Gy). Transplant morbidity included severe mucositis (n = 7) and acute renal failure (n = 2) related to infusion of the stem cells. Engraftment was delayed (n = 4) in this heavily pretreated population, and two patients had complete graft failure. Despite the advanced nature and chemotherapy-refractory state of their disease, 11 of 11 evaluable patients achieved an objective response. Six patients survived to leave the hospital, and four remain alive--one died of acute leukemia induced by prior melphalan exposure. Three of the four are relapse-free at a median of 24.9 months (range, 18-28 months). Some patients with advanced refractory multiple myeloma can achieve objective responses from highdose chemoradiotherapy with peripheral blood stem cell rescue. Harvesting peripheral blood stem cells from high-risk patients early in their disease for later use may decrease the risk of graft failure. Peripheral blood stem cell transplantation after high-dose chemotherapy and total body irradiation can produce durable responses in patients with advanced refractory myeloma.


A modified Mediterranean diet score is associated with a lower risk of incident metabolic syndrome over 25 years among young adults: the CARDIA (Coronary Artery Risk Development in Young Adults) study.
The Mediterranean diet has been reported to be inversely associated with incident metabolic syndrome (MetSyn) among older adults; however, this association has not been studied in young African American and white adults. The objective of the present study was to evaluate the association of a modified Mediterranean diet (mMedDiet) score with the 25-year incidence of the MetSyn in 4713 African American and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. A diet history questionnaire was used to assess dietary intake at baseline, year 7 and year 20 and a mMedDiet score was created. Cardiovascular risk factors were measured at multiple examinations over 25 years. The MetSyn was defined according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. Cox proportional-hazards regression analysis was use to evaluate associations for incident MetSyn across the mMedDiet score categories adjusting for demographic characteristics, lifestyle factors and BMI. Higher mMedDiet scores represented adherence to a dietary pattern rich in fruit, vegetables, whole grains, nuts and fish, but poor in red and processed meat and snack foods. The incidence of MetSyn components (abdominal obesity, elevated TAG concentrations and low HDL-cholesterol concentrations) was lower in those with higher mMedDiet scores than in those with lower scores. Furthermore, the incidence of the MetSyn was lower across the five mMedDiet score categories; the hazard ratios and 95 % CI from category 1 to category 5 were 1·0; 0·94 (0·76, 1·15); 0·84 (0·68, 1·04); 0·73 (0·58, 0·92); and 0·72 (0·54, 0·96), respectively (P trend= 0·005). These findings suggest that the risk of developing the MetSyn is lower when consuming a diet rich in fruit, vegetables, whole grains, nuts and fish.


Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid.
Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers. As chronic inflammations are associated with malignancies, it is important to prevent inflammation-mediated neoplastic formation, promotion and/or progression. One possible intervention will be using cancer chemopreventive agents such as curcumin (CUR), a potent anti-inflammatory and anti-oxidative stress compound. Polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) are potent anti-inflammatory agents by decreasing the production of inflammatory eicosanoids, cytokines, and reactive oxygen species (ROS). The present study aims at examining whether CUR with DHA or EPA would have synergistic anti-inflammatory effects in RAW 264.7 cells. Non-toxic concentrations of single and combination of the compounds were investigated at 6, 12 and 24h. The nitric oxide (NO) suppression effects were most prominent at 24h. All the combinations of CUR and DHA or EPA with lower concentrations of CUR 5 microM and 25 microM of DHA or EPA were found to have synergistic effects in suppressing LPS-stimulated NO and endogenous NO levels. Importantly, very low doses of CUR 2.5 microM and DHA or EPA of 0.78 microM could synergistically suppress the LPS-induced prostaglandin E(2) (PGE(2)). The combinations were also found to suppress iNOS, COX-2, 5-lipoxygenase (5-LOX) and cPLA(2) but induce HO-1. Taken together, the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA.


A lung-on-a-chip array with an integrated bio-inspired respiration mechanism.
We report a lung-on-a-chip array that mimics the pulmonary parenchymal environment, including the thin alveolar barrier and the three-dimensional cyclic strain induced by breathing movements. The micro-diaphragm used to stretch the alveolar barrier is inspired by the in vivo diaphragm, the main muscle responsible for inspiration. The design of this device aims not only at best reproducing the in vivo conditions found in the lung parenchyma but also at making the device robust and its handling easy. An innovative concept, based on the reversible bonding of the device, is presented that enables accurate control of the concentration of cells cultured on the membrane by easily accessing both sides of the membranes. The functionality of the alveolar barrier could be restored by co-culturing epithelial and endothelial cells that form tight monolayers on each side of a thin, porous and stretchable membrane. We showed that cyclic stretch significantly affects the permeability properties of epithelial cell layers. Furthermore, we also demonstrated that the strain influences the metabolic activity and the cytokine secretion of primary human pulmonary alveolar epithelial cells obtained from patients. These results demonstrate the potential of this device and confirm the importance of the mechanical strain induced by breathing in pulmonary research.


Non-occupational exposure to heavy metals of the residents of an industrial area and biomonitoring.
In areas at high environmental risk, a major issue is the assessment of the exposure of the general population to industrial pollutants. To date, few studies have investigated exposure to heavy metals in a population residing in a high risk environmental area. The aim of this study is to evaluate the exposure to heavy metals in the industrial area of Taranto, Southern Italy, through biological monitoring techniques. We measured the levels of inorganic arsenic and methylated metabolites, lead, cadmium, chromium, and manganese in the urine samples of 279 subjects residing in Taranto and neighboring areas. After obtaining informed consent from each participant, qualified health staff administered a standardized structured questionnaire investigating lifestyle habits and assessing any confounding factors. The biological monitoring data showed high urinary concentrations of nearly all of the heavy metals investigated. These findings could be related to the presence of industrial plants and is sufficient to warrant the expectation that local and national institutions should be required to adopt preventive measures to reduce the environmental exposure of the general population to heavy metals.


Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015.
Few neoplastic diseases have undergone a transformation in a relatively short period like chronic myeloid leukemia (CML) has in the last few years. In 1960, CML was the first cancer in which a unique chromosomal abnormality was identified and a pathophysiologic correlation suggested. Landmark work followed, recognizing the underlying translocation between chromosomes 9 and 22 that gave rise to this abnormality and, shortly afterward, the specific genes involved and the pathophysiologic implications of this novel rearrangement. Fast forward a few years and this knowledge has given us the most remarkable example of a specific therapy that targets the dysregulated kinase activity represented by this molecular change. The broad use of tyrosine kinase inhibitors has resulted in an improvement in the overall survival to the point where the life expectancy of patients today is nearly equal to that of the general population. Still, there are challenges and unanswered questions that define the reasons why the progress still escapes many patients, and the details that separate patients from ultimate cure. In this article, we review our current understanding of CML in 2015, present recommendations for optimal management, and discuss the unanswered questions and what could be done to answer them in the near future.


High Prevalence and Mortality Associated with Upper Extremity Deep Venous Thrombosis in Hospitalized Patients at a Tertiary Care Center.
Upper extremity deep venous thrombosis (UEDVT) and its associated complications are increasing in incidence, but management strategies are largely derived from experience treating lower extremity deep venous thrombosis (LEDVT). The purpose of this study is to examine our single institution's experience with in-hospital venous thromboembolism (VTE), specifically the characteristics and outcomes of the UEDVT population as it compares to LEDVT. This is a single tertiary care center retrospective cohort study of all consecutive inpatients diagnosed with acute VTE from June 2015 to December 2015. During this period, 4,495 patients underwent venous duplex examination (622 UE and 3,873 LE), identifying 83 inpatient DVTs. Chronic DVT and those diagnosed in the outpatient population were excluded. DVTs were classified as either provoked or unprovoked. Provoked DVT were defined as the presence of any of the following factors within 30 days prior to diagnosis: major surgery, immobilization (greater than 3 days of bedrest), trauma, infection requiring antibiotics, central venous access, pregnancy, and/or hormonal medication use. Inpatient pulmonary embolisms (PE) detected on chest computed tomography (CT) were also evaluated during this time frame. Patient data were collected, including age, gender, race, lifestyle factors, comorbidities, VTE risk factors, symptomatology at presentation, management including anticoagulation choice and filter placement if applicable, as well as discharge disposition. Statistical analysis was performed using GraphPad Prism 8.0 (GraphPad Software, San Diego, California), and a threshold P-value of <0.05 set for significance. During the study period, 83 DVTs (48 LEDVT, 35 UEDVT) and 24 PE were identified in 96 inpatients. Of these DVTs, 77.1% of these were defined as provoked. Eleven patients had simultaneous DVT and PE, and thirteen patients had PE with presumed occult pelvic or LEDVT. UEDVT patients had a higher proportion of comorbidities than LEDVT patients: coronary artery disease (25.7% vs. 13.1%, P = 0.16), congestive heart failure (20% vs. 6.6%, P = 0.09), as well as a trend toward higher incidence of malignancy (60% vs. 42.6%, P = 0.13). Of provoked VTE, UEDVT correlated more significantly with central venous catheters (88.4% vs. 12.5%, P=<0.0001), but was less commonly associated with prolonged bed rest (19.2% vs. 39.5%, P = 0.11). PE was diagnosed in 24/96 (25%) of the study population. Patients with LEDVT were found to have a significantly higher incidence of PE compared to those with UEDVT (34.4% vs. 8.6%, P = 0.006). Same-admission mortality for patients with VTE was 13/96 (13.5%). Of these, patients with UEDVT had significantly higher all-cause mortality than patients with LEDVT (28.5% vs. 4.9%, P = 0.004). When catheter-related UEDVT was excluded, there remained a significant difference in mortality between non-catheter-related UEDVT and LEDVT (33.3% vs. 4.9% P = 0.0119). This study demonstrates a high prevalence of UEDVT in hospitalized patients who experience VTE. Despite a lower incidence of synchronous PE, patients with UEDVT had a higher prevalence of significant medical comorbidities and higher all-cause mortality on the index hospital admission.


Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia.
Invasive cervical carcinomas frequently reveal additional copies of the long arm of chromosome 3. The detection of this genetic aberration in diagnostic samples could therefore complement the morphological interpretation. We have developed a triple-color DNA probe set for the visualization of chromosomal copy number changes directly in thin-layer cervical cytology slides by fluorescence in situ hybridization. The probe set consists of a BAC contig that contains sequences for the RNA component of the human telomerase gene (TERC) on chromosome band 3q26, and repeat sequences specific for the centromeres of chromosomes 3 and 7 as controls. In a blinded study, we analyzed 57 thin-layer slides that had been rigorously screened and classified as normal (n = 13), atypical squamous cells (ASC, n = 5), low-grade squamous intraepithelial lesions (LSIL, n = 14), and high-grade squamous intraepithelial lesions (HSIL) grade 2 (CIN2, n = 8), and grade 3 (CIN3, n = 17). The percentage of tetraploid cells (P(Trend) < 0.0005) and cells with multiple 3q signals increased with the severity of the cytologic interpretation (P(Trend) < 0.0005). While only few normal samples, ASC and LSIL lesions, revealed copy number increases of 3q, 63% of the HSIL (CIN2) lesions and 76% of the HSIL (CIN3) lesions showed extra copies of 3q. We conclude that the visualization of chromosome 3q copy numbers in routinely prepared cytological material using BAC clones specific for TERC serves as an independent screening test for HSIL and may help to determine the progressive potential of individual lesions.


Injury and biomechanical perspectives on the rugby scrum: a review of the literature.
As a collision sport, rugby union has a relatively high overall injury incidence, with most injuries being associated with contact events. Historically, the set scrum has been a focus of the sports medicine community due to the perceived risk of catastrophic spinal injury during scrummaging. The contemporary rugby union scrum is a highly dynamic activity but to this point has not been well characterised mechanically. In this review, we synthesise the available research literature relating to the medical and biomechanical aspects of the rugby union scrum, in order to (1) review the injury epidemiology of rugby scrummaging; (2) consider the evidence for specific injury mechanisms existing to cause serious scrum injuries and (3) synthesise the information available on the biomechanics of scrummaging, primarily with respect to force production. The review highlights that the incidence of acute injury associated with scrummaging is moderate but the risk per event is high. The review also suggests an emerging acknowledgement of the potential for scrummaging to lead to premature chronic degeneration injuries of the cervical spine and summarises the mechanisms by which these chronic injuries are thought to occur. More recent biomechanical studies of rugby scrummaging confirm that scrum engagement forces are high and multiplanar, but can be altered through modifications to the scrum engagement process which control the engagement velocity. As the set scrum is a relatively 'controlled' contact situation within rugby union, it remains an important area for intervention with a long-term goal of injury reduction.


Gloom and doom? The future of marine capture fisheries.
Predicting global fisheries is a high-order challenge but predictions have been made and updates are needed. Past forecasts, present trends and perspectives of key parameters of the fisheries--including potential harvest, state of stocks, supply and demand, trade, fishing technology and governance--are reviewed in detail, as the basis for new forecasts and forecasting performance assessment. The future of marine capture fisheries will be conditioned by the political, social and economic evolution of the world within which they operate. Consequently, recent global scenarios for the future world are reviewed, with the emphasis on fisheries. The main driving forces (e.g. global economic development, demography, environment, public awareness, information technology, energy, ethics) including aquaculture are described. Outlooks are provided for each aspect of the fishery sector. The conclusion puts these elements in perspective and offers the authors' personal interpretation of the possible future pathway of fisheries, the uncertainty about it and the still unanswered questions of direct relevance in shaping that future.


The Association Between Five Factor Model Personality Traits and Verbal and Numeric Reasoning.
Five-factor model (FFM) personality traits are related to basic cognitive functions and risk of cognitive impairment in late life. The present study addresses whether FFM traits are also associated with a more complex cognitive function, reasoning, across adulthood. We used seven samples to examine the relation between personality and verbal (total N= 39,177) and numeric (total N= 76,388) reasoning. A meta-analysis indicated higher Neuroticism was associated modestly with worse performance on verbal and numeric reasoning tasks. Openness was associated with better verbal reasoning and was unrelated to numeric reasoning. Surprisingly, Extraversion was associated modestly with worse performance in both domains, and Conscientiousness was essentially unrelated to reasoning. Agreeableness was unrelated to reasoning. There was significant heterogeneity across the samples but only limited evidence for moderation by age or sex. Consistent with other cognitive domains, the results suggested that Neuroticism is related to worse performance globally, whereas Openness tends to be associated with better verbal abilities. Among the unexpected findings was the better reasoning of introverts. The pattern also suggests that the common positive association between Conscientiousness and cognition does not extend to reasoning and suggests that Conscientiousness may support healthier cognitive aging through basic cognitive functions rather than through complex functions like reasoning.


PTEN: an intercellular peacekeeper?
It is generally assumed that cells synthesize their own intracellular enzymes. Therefore, if expression of a specific gene is silenced in a potential cancer cell, it is expected that loss of protein function will follow. A provocative study indicates an unexpected mechanism of intercellular tumor suppression, showing that PTEN (phosphatase and tensin homolog deleted from chromosome 10), a cytosolic enzyme, can be transferred between cells in exosomes to suppress signaling and proliferation in target cells.


Ecology and molecular targets of hypermutation in the global microbiome.
Changes in the sequence of an organism's genome, i.e., mutations, are the raw material of evolution. The frequency and location of mutations can be constrained by specific molecular mechanisms, such as diversity-generating retroelements (DGRs). DGRs have been characterized from cultivated bacteria and bacteriophages, and perform error-prone reverse transcription leading to mutations being introduced in specific target genes. DGR loci were also identified in several metagenomes, but the ecological roles and evolutionary drivers of these DGRs remain poorly understood. Here, we analyze a dataset of >30,000 DGRs from public metagenomes, establish six major lineages of DGRs including three primarily encoded by phages and seemingly used to diversify host attachment proteins, and demonstrate that DGRs are broadly active and responsible for >10% of all amino acid changes in some organisms. Overall, these results highlight the constraints under which DGRs evolve, and elucidate several distinct roles these elements play in natural communities.


RNA-Seq Assembly - Are We There Yet?
Transcriptomic sequence resources represent invaluable assets for research, in particular for non-model species without a sequenced genome. To date, the Next Generation Sequencing technologies 454/Roche and Illumina have been used to generate transcriptome sequence databases by mRNA-Seq for more than fifty different plant species. While some of the databases were successfully used for downstream applications, such as proteomics, the assembly parameters indicate that the assemblies do not yet accurately reflect the actual plant transcriptomes. Two different assembly strategies have been used, overlap consensus based assemblers for long reads and Eulerian path/de Bruijn graph assembler for short reads. In this review, we discuss the challenges and solutions to the transcriptome assembly problem. A list of quality control parameters and the necessary scripts to produce them are provided.


50W CW visible laser source at 589nm obtained via frequency doubling of three coherently combined narrow-band Raman fibre amplifiers.
We demonstrate the cascaded coherent collinear combination of a seed-split triplet of 1178nm high-power narrow-band (sub-1.5MHz) SBS-suppressed CW Raman fibre amplifiers via nested free-space constructive quasi-Mach-Zehnder interferometry, after analysing the combination of the first two amplifiers in detail. Near-unity combination and cascaded-combination efficiencies are obtained at all power levels up to a maximum P(1178) > 60W. Frequency doubling of this cascaded-combined output in an external resonant cavity yields P(589) > 50W with peak conversion efficiency eta(589) ~85%. We observe no significant differences between the SHG of a single, combined pair or triplet of amplifiers. Although the system represents a successful power scalability demonstrator for fibre-based Na-D(2a)-tuned mesospheric laser-guide-star systems, we emphasise its inherent wavelength versatility and consider its spectroscopic and near-diffraction-limited qualities equally well suited to other applications.


National Institute of Nursing Research Centers of Excellence: a logic model for sustainability, leveraging resources, and collaboration to accelerate cross-disciplinary science.
The National Institute of Nursing Research (NINR) Centers of Excellence program is a catalyst enabling institutions to develop infrastructure and administrative support for creating cross-disciplinary teams that bring multiple strategies and expertise to bear on common areas of science. Centers are increasingly collaborative with campus partners and reflect an integrated team approach to advance science and promote the development of scientists in these areas. The purpose of this paper is to present the NINR Logic Model for Center Sustainability. The components of the logic model were derived from the presentations and robust discussions at the 2013 NINR center directors' meeting focused on best practices for leveraging resources and collaboration as methods to promote center sustainability. Collaboration through development and implementation of cross-disciplinary research teams is critical to accelerate the generation of new knowledge for solving fundamental health problems. Sustainability of centers as a long-term outcome beyond the initial funding can be enhanced by thoughtful planning of inputs, activities, and leveraging resources across multiple levels.


A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development.
The mammalian Y chromosome carries the SRY gene, which determines testis formation. Here we review data on individuals who are XX but exhibit male characteristics: some have SRY; others do not. We have analyzed three families containing more than one such individual and show that these individuals lack SRY. Pedigree analysis leads to the hypothesis that they carry recessive mutations (in a gene termed Z) that allow expression of male characteristics. We propose that wild-type Z product is a negative regulator of male sex determination and is functional in wild-type females. In males, SRY product represses or otherwise negatively regulates Z and thereby allows male sex determination. This hypothesis can also explain other types of sex reversal in mammals, in particular, XY females containing SRY. Some of these individuals may have mutations at the Z locus rendering them insensitive to SRY. Recessive mutations (such as the polled mutation of goats) leading to sex reversal are known in a variety of animals and might be used to map and ultimately clone the human Z gene.


Fermentation characteristics of Dekkera bruxellensis strains.
The influence of pH, temperature and carbon source (glucose and maltose) on growth rate and ethanol yield of Dekkera bruxellensis was investigated using a full-factorial design. Growth rate and ethanol yield were lower on maltose than on glucose. In controlled oxygen-limited batch cultivations, the ethanol yield of the different combinations varied from 0.42 to 0.45 g (g glucose)(-1) and growth rates varied from 0.037 to 0.050 h(-1). The effect of temperature on growth rate and ethanol yield was negligible. It was not possible to model neither growth rate nor ethanol yield from the full-factorial design, as only marginal differences were observed in the conditions tested. When comparing three D. bruxellensis strains and two industrial isolates of Saccharomyces cerevisiae, S. cerevisiae grew five times faster, but the ethanol yields were 0-13% lower. The glycerol yields of S. cerevisiae strains were up to six-fold higher compared to D. bruxellensis, and the biomass yields reached only 72-84% of D. bruxellensis. Our results demonstrate that D. bruxellensis is robust to large changes in pH and temperature and may have a more energy-efficient metabolism under oxygen limitation than S. cerevisiae.


Cat-bite-induced Francisella tularensis infection with a false-positive serological reaction for Bartonella quintana.
Introduction. Tularaemia is caused by infection with Francisella tularensistransmitted via direct contact with an infected hare carcass or indirectly through the bites of vectors, but may be cat-bite-associated as well. Medical history and reliable diagnostic analysis are important in order to differentiate it from other cat-associated infections, e.g. Bartonella spp. Casepresentation. A healthy 56-year-old man was examined because of a cat-bite-associated ulceroglandular wound on his right thumb. Nineteen days after the cat bite occurred, a serology test was positive for anti-Bartonella quintana, but negative for anti-F. tularensis. Since Bartonella infections are rare in Sweden, another serology test was analysed 2 weeks later with a positive result for anti-F. tularensis. The patient was treated with doxycycline for 14 days and recovered. The patient was re-sampled after 18 months to obtain a convalescent sample. The acute and the convalescent samples were both analysed at a reference centre, with negative results for anti-Bartonella spp. this time. Conclusion. This case is enlightening about the importance of extending the medical history and re-sampling the patient for antibody detection when the clinical suspicion of cat-bite-associated tularaemia is high. The false-positive result for anti-B. quintana antibodies may have been due to technical issues with the assay, cross-reactivity or both.


Detection rate of trisomy 21 in fetuses with isolated and non-isolated aberrant right subclavian artery.
The purpose of this study was to determine the frequency of chromosomal anomalies among the fetuses with isolated and non-isolated aberrant right subclavian artery (ARSA), and to evaluate the sonographic findings associated with ARSA. This is a retrospective study conducted during the period between January 2008 and December 2012 at the maternal fetal medicine units of three different referral centers. Among the 148 cases of ARSA, 98 were isolated and 50 were associated with cardiac anomalies, extracardiac malformations or soft markers. Trisomy 21 was the only chromosomal anomaly with a prevalence of 6.8% (10/148). The corresponding rate was 6.1% (6/98) and 8% (4/50) for isolated and non-isolated ARSA, respectively. Cardiac anomalies, extracardiac findings and soft markers were detected in 5.4% (8), 10.8% (16) and 24.3% (36) of cases, respectively. Among the 10 fetuses with trisomy 21, 6 were isolated, 4 were associated with soft markers, 2 were associated with fetal growth restriction and 1 was associated with hydrops fetalis. Cardiac anomalies were not observed in any of these fetuses. The prenatal diagnosis of ARSA should prompt meticulous anatomic survey, and karyotype analysis might be offered even in the absence of associated findings.


Transformation of single MOF nanocrystals into single nanostructured catalysts within mesoporous supports: a platform for pioneer fluidized-nanoreactor hydrogen carriers.
Well-dispersed nanostructured catalysts along mesoporous materials have been systematically prepared via a novel multistep approach involving either the pyrolysis under nitrogen, the calcination under oxygen or the reduction under hydrogen of MOF nanocrystals decorated with transition metal complexes and previously confined within the mesoporous cavities via novel solid state synthesis. The resulting supported nanostructured catalysts can be composed of metals, metal oxides, heteroatom-doped carbons and combinations thereof depending on the transformation conditions. The pioneering concept of Fluidized-Nanoreactor Hydrogen Carriers has been proposed for the first time by using the resulting nanostructured catalysts within fluidized mesoporous silica.


Enhanced bromate formation during chlorination of bromide-containing waters in the presence of CuO: catalytic disproportionation of hypobromous acid.
Bromate (BrO(3)(-)) in drinking water is traditionally seen as an ozonation byproduct from the oxidation of bromide (Br(-)), and its formation during chlorination is usually not significant. This study shows enhanced bromate formation during chlorination of bromide-containing waters in the presence of cupric oxide (CuO). CuO was effective to catalyze hypochlorous acid (HOCl) or hypobromous acid (HOBr) decay (e.g., at least 10(4) times enhancement for HOBr at pH 8.6 by 0.2 g L(-1) CuO). Significant halate concentrations were formed from a CuO-catalyzed hypohalite disproportionation pathway. For example, the chlorate concentration was 2.7 ± 0.2 μM (225.5 ± 16.7 μg L(-1)) after 90 min for HOCl (C(o) = 37 μM, 2.6 mg L(-1) Cl(2)) in the presence of 0.2 g L(-1) CuO at pH 7.6, and the bromate concentration was 6.6 ± 0.5 μM (844.8 ± 64 μg L(-1)) after 180 min for HOBr (C(o) = 35 μM) in the presence of 0.2 g L(-1) CuO at pH 8.6. The maximum halate formation was at pHs 7.6 and 8.6 for HOCl or HOBr, respectively, which are close to their corresponding pK(a) values. In a HOCl-Br(-)-CuO system, BrO(3)(-) formation increases with increasing CuO doses and initial HOCl and Br(-) concentrations. A molar conversion (Br(-) to BrO(3)(-)) of up to (90 ± 1)% could be achieved in the HOCl-Br(-)-CuO system because of recycling of Br(-) to HOBr by HOCl, whereas the maximum BrO(3)(-) yield in HOBr-CuO is only 26%. Bromate formation is initiated by the formation of a complex between CuO and HOBr/OBr(-), which then reacts with HOBr to generate bromite. Bromite is further oxidized to BrO(3)(-) by a second CuO-catalyzed process. These novel findings may have implications for bromate formation during chlorination of bromide-containing drinking waters in copper pipes.


The algorithm of equal acceptance region for detecting copy number alterations: applications to next-generation sequencing data.
The information of copy number alterations (gains and losses) in tumour genomes can be used to discovery cancer-causing genes. The estimate of copy number can be obtained from the estimate copy number ratio. The higher the depth of underlying sequencing data, the more accurate the estimate of copy number ratio. At the same time, the higher depth of a sequencing data used in copy number analysis, the more cost of data analysis. To develop a method for identifying a necessary depth of sequencing data for copy number analysis before test data are produced is of interest. In this paper, we proposed an algorithm of equal acceptance regions for detecting copy number ratios. This algorithm can be used to determine the depth of sequencing data required for copy number analysis.


A repository of assays to quantify 10,000 human proteins by SWATH-MS.
Mass spectrometry is the method of choice for deep and reliable exploration of the (human) proteome. Targeted mass spectrometry reliably detects and quantifies pre-determined sets of proteins in a complex biological matrix and is used in studies that rely on the quantitatively accurate and reproducible measurement of proteins across multiple samples. It requires the one-time, a priori generation of a specific measurement assay for each targeted protein. SWATH-MS is a mass spectrometric method that combines data-independent acquisition (DIA) and targeted data analysis and vastly extends the throughput of proteins that can be targeted in a sample compared to selected reaction monitoring (SRM). Here we present a compendium of highly specific assays covering more than 10,000 human proteins and enabling their targeted analysis in SWATH-MS datasets acquired from research or clinical specimens. This resource supports the confident detection and quantification of 50.9% of all human proteins annotated by UniProtKB/Swiss-Prot and is therefore expected to find wide application in basic and clinical research. Data are available via ProteomeXchange (PXD000953-954) and SWATHAtlas (SAL00016-35).


Abrupt change of Antarctic moisture origin at the end of Termination II.
The deuterium excess of polar ice cores documents past changes in evaporation conditions and moisture origin. New data obtained from the European Project for Ice Coring in Antarctica Dome C East Antarctic ice core provide new insights on the sequence of events involved in Termination II, the transition between the penultimate glacial and interglacial periods. This termination is marked by a north-south seesaw behavior, with first a slow methane concentration rise associated with a strong Antarctic temperature warming and a slow deuterium excess rise. This first step is followed by an abrupt north Atlantic warming, an abrupt resumption of the East Asian summer monsoon, a sharp methane rise, and a CO(2) overshoot, which coincide within dating uncertainties with the end of Antarctic optimum. Here, we show that this second phase is marked by a very sharp Dome C centennial deuterium excess rise, revealing abrupt reorganization of atmospheric circulation in the southern Indian Ocean sector.


What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study.
Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.


The interplay between national and parental unemployment in relation to adolescent life satisfaction in 27 countries: analyses of repeated cross-sectional school surveys.
Previous research shows that parental unemployment is associated with low life satisfaction in adolescents. It is unclear whether this translates to an association between national unemployment and adolescent life satisfaction, and whether such a contextual association is entirely explained by parental unemployment, or if it changes as a function thereof. For adults, associations have been shown between unemployment and mental health, including that national unemployment can affect mental health and life satisfaction of both the employed and the unemployed, but to different degrees. The aim of this paper is to analyse how national unemployment levels are related to adolescent life satisfaction, across countries as well as over time within a country, and to what extent and in what ways such an association depends on whether the individual's own parents are unemployed or not. Repeated cross-sectional data on adolescents' (aged 11, 13 and 15 years, n = 386,402) life satisfaction and parental unemployment were collected in the Health Behaviour in School-aged Children (HBSC) survey, in 27 countries and 74 country-years, across 2001/02, 2005/06 and 2009/10 survey cycles. We linked this data to national harmonised unemployment rates provided by OECD and tested their associations using multilevel linear regression, including interaction terms between national and parental unemployment. Higher national unemployment rates were related to lower adolescent life satisfaction, cross-sectionally between countries but not over time within countries. The verified association was significant for adolescents with and without unemployed parents, but stronger so in adolescents with unemployed fathers or both parents unemployed. Having an unemployed father, mother och both parents was in itself related to lower life satisfaction. Living in a country with higher national unemployment seems to be related to lower adolescent life satisfaction, whether parents are unemployed or not, although stronger among adolescents where the father or both parents are unemployed. However, variation in unemployment over the years did not show an association with adolescent life satisfaction.


Attitudes and practices among pediatric oncologists regarding end-of-life care: results of the 1998 American Society of Clinical Oncology survey.
In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications for care of children dying from cancer. The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which was completed by 228 pediatric oncologists. Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year. Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as a barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control. Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge.


Gynecologic factors in sexual dysfunction of the older woman.
Older women may experience sexual dysfunction due to many different causes. Some problems related to menopausal hormonal change may be easily treated with estrogen supplements. Other problems involve intricate interpersonal relations between the woman and her sexual partner and may require a combination of medical therapy and sexual counseling. Gynecologic cancer and cancer treatments are often accompanied by problems in sexual functioning. These problems may then impair relations and self-image, leading to a vicious circle of deteriorating social function. Some recommendations for the clinician follow. The clinician should maintain an attitude of openness to the possibility of sexual concerns in older women. Such concerns should be taken seriously and should not be dismissed as part of aging. Routine periodic health examinations can include a question such as "Do you have any concerns about your sexual life that you would like to discuss?" In follow-up visits for procedures with a high likelihood of causing sexual dysfunction, questions that would open the door to a discussion of sexuality should be asked. Sexual dysfunction should be recognized as a couple-oriented phenomenon. A woman's anxiety about her appearance, postoperative depression, or dyspareunia may be perceived by her partner as a sexual rejection and may initiate a cycle of decreasing contact or may even lead to erectile dysfunction. Sexual counseling should include both partners. When a surgical procedure that will probably have an impact on sexual function is contemplated, provide the patient and her partner with advance counseling. Descriptions of surgery should not be simply a statement of body parts to be removed but should specifically address the anticipated sexual effects. Counseling should include a description of basic anatomy and function of the genital organs. Illustrations and appropriate demonstration during the physical examination should be used to ensure the patient's understanding. Descriptions should be accurate without being either frightening or falsely reassuring. The patient should be counseled about the benefits of including her partner in discussions. Then, when possible, the sexual partner of the patient should be invited to sessions of advance counseling on contemplated procedures. Clinicians should remain open to the possibility that the sexual partner will be a nontraditional one, e.g., an unmarried male partner or another woman. The clinician should be alert to remediable causes of dysfunction. For example, decreased vaginal lubrication may be managed with use of water-soluble lubricants.(ABSTRACT TRUNCATED AT 400 WORDS)


EGF receptor expression in mineralized tissues: an in situ hybridization and immunocytochemical investigation in rat and human mandibles.
There is extensive evidence that growth factors play a central part in the autocrine/paracrine regulation of cell growth and differentiation in mineralized tissues. In order to investigate involvement of the EGFr receptor (EGFr) in forming mineralized tissues, its expression was studied by in situ hybridization and immunocytochemistry in mandibles of growing rats, as well as in human embryos. In Hertwig's epithelial root sheath of rat molar, EGFr mRNAs appeared strongly expressed, while dental pulp and dental follicle showed weak labeling. The lingual epithelium of rat incisor showed strong labeling, which decreased after epithelial dislocation. Cells of the adjoining lingual dental pulp and dental follicle, as compared to epithelium, contained a low level of EGFr mRNAs. In contrast, a significant signal with antisense RNA probe was observed in bone. Sense RNA probes provided a regular background or no labeling. Undifferentiated cells located in the periosteum and endosteal spaces were labeled. EGFr mRNAs were also present in osteoblasts and in lesser amounts in some osteocytes. In rat and in human bone, both osteoblasts and osteocytes were positive on immunostaining. Similarly in the Hertwig's root sheath, EGFr immunostaining and in situ hybridization labeling were closely related. These data show that different patterns of EGFr expression in forming mineralized tissues are tissue- and stage-specific. However, in all these cells, the present in situ investigation supports the assumption that EGFr is involved in the early stages of cellular proliferation and differentiation. This report also suggests that EGFr may play a role in differentiated and mature cells of mineralized tissues.


Microscopic characterization of FO/PRO membranes--a comparative study of CLSM, TEM and SEM.
Osmotically driven membrane processes (including forward osmosis (FO) and pressure retarded osmosis (PRO)) have received increasing attention in recent decades. The performance of an FO/PRO membrane is significantly limited by internal concentration polarization, which is a strong function of the membrane support layer pore structure. The objective of the current study was to develop microscopic characterization methods for quantitative/semiquantitative analysis of membrane pore structure (both pore diameter and porosity distribution across membrane thickness). The use of confocal laser scanning microscopy (CLSM) for noninvasive characterization of the internal pore structure of FO/PRO membranes is reported for the first time. By performing optical sectioning, information on pore diameter, porosity depth profile and pore connectivity can be obtained. The CLSM porosity results are further compared to those obtained using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and reasonably good agreement was observed. A comparison of these characterization methods reveals their complementary nature, and a combination of these techniques may allow a more comprehensive understanding of membrane structure. The current study also provided a comprehensive insight into the pore structure of commercially available FO/PRO membranes.


An instructional DVD fall-prevention program for patients with cancer and family caregivers.
Determine the efficacy of a fall-prevention skills training program for patients with cancer and family caregivers. Randomized, controlled trial with repeated measures and postintervention measure of fall occurrence. A comprehensive cancer center in the midwestern United States. 132 patient and family caregiver dyads. Dyads were randomly assigned to one of two groups: a control group that received standard fall-prevention education or a treatment group that received standard education and a fall-prevention DVD program to view at home. Participants completed surveys at baseline, one week, one month, and three months. Follow-up phone calls were made at three months. Fall occurrence, perceptions of fall risks, and fall-prevention knowledge. Patients in the treatment group were significantly more likely to report not falling at three months than patients in the control group. The number of falls was lower for the treatment group. The difference was not statistically significant. Dyads in the treatment group showed significantly greater improvement over time in fall risk awareness and fall-prevention knowledge. Mobility skills training is a promising educational intervention for reducing fall occurrences in the home for patients with cancer. Efforts are needed for improving the knowledge and skills of cancer survivors and their family members in recognizing patient fall risks, making home adjustments, and performing mobility skills competently.


Toll-like receptor profiling of seven trophoblast cell lines warrants caution for translation to primary trophoblasts.
Excessive placental inflammation is associated with pregnancy complications. Toll-like receptors (TLRs) are sensors for danger signals from infections and damaged tissue and initiate inflammation. Trophoblasts in the placenta broadly express TLRs. Trophoblast cell lines are used as surrogates for primary trophoblasts for in vitro studies, but the inflammatory translatability of trophoblast cell lines warrants examination. We aimed to assess TLR1-10 gene expression and activation in seven trophoblast cell lines and compare this to primary trophoblasts. The five choriocarcinoma trophoblast cell lines BeWo, JAR, JEG-3, AC1M-32 and ACH-3P, and the two SV40 transfected trophoblast cell lines HTR-8/SVneo and SGHPL-5 were included and compared to primary first trimester trophoblasts (n = 6). TLR1-10 gene expression was analyzed by RT-qPCR. Cells were stimulated by specific TLR1-9 ligands for 24 h and cytokine release was measured by a 10-plex immunoassay. All choriocarcinoma cell lines demonstrated broad TLR gene expression, but lacked functional cytokine response to TLR ligand activation. In contrast, SV40 transfected cell lines showed restricted TLR gene expression, but SGHPL-5 cells displayed significantly increased levels of interleukin (IL)-6, IL-8, IL-12 and vascular endothelial growth factor A after TLR3 and/or TLR4 activation (P < 0.01), while TLR2 activation increased IL-6 and IL-8 levels (P < 0.05). HTR8/SVneo cells responded to TLR3 activation by increased IL-6 and interferon (IFN)-γ (P < 0.05). The SGHPL-5 TLR profile most closely resembled primary trophoblast. The characterized trophoblast cell line TLR profiles serve as a reference and warrant caution when selecting trophoblast cell lines as in vitro models for immune responses in primary trophoblasts.


Microbial contamination of drinking water from risky tubewells situated in different hydrological regions of Bangladesh.
This study, conducted in 40 selected upazilas covering four hydrological regions of Bangladesh, aimed at determining the risk of selected shallow tubewells (depth<30m) used for drinking purpose (n=26,229). This was based on WHO's sanitary inspection guidelines and identifying the association of sanitary inspection indicators and risk scores with microbiological contamination of shallow tubewells. The main objective of the study was to observe the seasonal and regional differences of microbial contamination and finally reaching a conclusion about safe distance between tubewells and latrines by comparing the contamination of two tubewell categories (category-1: distance ≤10m from nearest latrine; n=80 and category 2: distances 11-20m from nearest latrine; n=80) in different geographical contexts. About 62% of sampled tubewells were at medium to high risk according to WHO's sanitary inspection guidelines, while the situation was worst in south-west region. Microbiological contamination was significantly higher in sampled category-1 tubewells compared to category-2 tubewells, while the number of contaminated tubewells and level of contamination was higher during wet season. About 21% (CI95=12%-30%), 54% (CI95=43%-65%) and 58% (CI95=46%-69%) of water samples collected from category-1 tubewells were contaminated by E. coli, FC, and TC respectively during the wet season. The number of category-1 tubewells having E.coli was highest in the north-west (n=8) and north-central (n=4) region during wet season and dry season respectively, while the level of E.coli contamination in tubewell water (number of CFU/100ml of sample) was significantly higher in north-central region. However, the south-west region had the highest number of FC contaminated category-1 tubewells (n=16 & n=17; respectively during wet and dry season) and significantly a higher level of TC and FC in sampled Category-1 tubewells than north-west, north-central and south-east region, mainly during wet season. Multivariate regression analysis could identified some sanitary inspection indicators, such as tubewell within <10m of latrine, platform absent/broken, pollution source (i.e. household's waste dumping point/poultry/dairy farm) within 10m of tubewell and unimproved sanitation facility which were significantly associated with presence of microbial contaminants in tubewell water (p<0.01). A tubewell with high risk level was associated with a higher chance of having FC and TC in tubewell water than a tubewell with a medium risk during wet season, but no such conclusion could be drawn in case of E.coli contamination. Construction of pit latrine in areas with high water table should be highly discouraged. Raised sealed pits or flush/pour flash to septic tank could be installed considering sanitary inspection criteria. Water should be treated before drinking.


Evidence for middle Eocene Arctic sea ice from diatoms and ice-rafted debris.
Oceanic sediments from long cores drilled on the Lomonosov ridge, in the central Arctic, contain ice-rafted debris (IRD) back to the middle Eocene epoch, prompting recent suggestions that ice appeared in the Arctic about 46 million years (Myr) ago. However, because IRD can be transported by icebergs (derived from land-based ice) and also by sea ice, IRD records are restricted to providing a history of general ice-rafting only. It is critical to differentiate sea ice from glacial (land-based) ice as climate feedback mechanisms vary and global impacts differ between these systems: sea ice directly affects ocean-atmosphere exchanges, whereas land-based ice affects sea level and consequently ocean acidity. An earlier report assumed that sea ice was prevalent in the middle Eocene Arctic on the basis of IRD, and although somewhat preliminary supportive evidence exists, these data are neither comprehensive nor quantified. Here we show the presence of middle Eocene Arctic sea ice from an extraordinary abundance of a group of sea-ice-dependent fossil diatoms (Synedropsis spp.). Analysis of quartz grain textural characteristics further supports sea ice as the dominant transporter of IRD at this time. Together with new information on cosmopolitan diatoms and existing IRD records, our data strongly suggest a two-phase establishment of sea ice: initial episodic formation in marginal shelf areas approximately 47.5 Myr ago, followed approximately 0.5 Myr later by the onset of seasonally paced sea-ice formation in offshore areas of the central Arctic. Our data establish a 2-Myr record of sea ice, documenting the transition from a warm, ice-free environment to one dominated by winter sea ice at the start of the middle Eocene climatic cooling phase.


Impaired phagocytosis in caveolin-1 deficient macrophages.
Caveolae are plasma membrane invaginations that function as important regulators of numerous cellular processes, including signal transduction, cholesterol trafficking, and endocytosis. Caveolin-1 (Cav-1) constitutes the main structural protein of caveolae membranes. Here, we report an in vivo increase in the number of apoptotic cells in the thymus and spleen of Cav-1 deficient mice, following whole-body gamma-irradiation. We demonstrate that this increase in apoptotic cells is not due to increased apoptosis in lymphocytes per se, which normally do not express Cav-1, but rather to the decreased phagocytic clearance of apoptotic cells by macrophages, which do express Cav-1. Utilizing in vitro phagocytosis assays of both apoptotic thymocytes and Escherichia coli K-12 BioParticles, we demonstrate that the loss of Cav-1 decreases the phagocytic ability of thioglycollate-elicited peritoneal macrophages. We suggest that impaired macrophage phagocytosis in Cav-1 knockout mice could have implications for altered innate immunity against pathogens, the regulation of inflammatory responses, and the development of autoimmune disease.


Determinants of the reliability of ultrasound tomography sound speed estimates as a surrogate for volumetric breast density.
High breast density, as measured by mammography, is associated with increased breast cancer risk, but standard methods of assessment have limitations including 2D representation of breast tissue, distortion due to breast compression, and use of ionizing radiation. Ultrasound tomography (UST) is a novel imaging method that averts these limitations and uses sound speed measures rather than x-ray imaging to estimate breast density. The authors evaluated the reproducibility of measures of speed of sound and changes in this parameter using UST. One experienced and five newly trained raters measured sound speed in serial UST scans for 22 women (two scans per person) to assess inter-rater reliability. Intrarater reliability was assessed for four raters. A random effects model was used to calculate the percent variation in sound speed and change in sound speed attributable to subject, scan, rater, and repeat reads. The authors estimated the intraclass correlation coefficients (ICCs) for these measures based on data from the authors' experienced rater. Median (range) time between baseline and follow-up UST scans was five (1-13) months. Contributions of factors to sound speed variance were differences between subjects (86.0%), baseline versus follow-up scans (7.5%), inter-rater evaluations (1.1%), and intrarater reproducibility (∼0%). When evaluating change in sound speed between scans, 2.7% and ∼0% of variation were attributed to inter- and intrarater variation, respectively. For the experienced rater's repeat reads, agreement for sound speed was excellent (ICC = 93.4%) and for change in sound speed substantial (ICC = 70.4%), indicating very good reproducibility of these measures. UST provided highly reproducible sound speed measurements, which reflect breast density, suggesting that UST has utility in sensitively assessing change in density.


Helicobacter pylori and gastric cancer: what can be learned by studying the response of gastric epithelial cells to the infection?
The development of gastric adenocarcinoma is closely linked to chronic infection with the bacterial pathogen Helicobacter pylori. One Helicobacter-specific virulence factor in particular, the CagA protein, has emerged as a main effector molecule in the interaction of H. pylori with gastric epithelial cells and has been implicated in gastric carcinogenesis. This review highlights the latest insights that have been gained into the pathogenesis of the disease by transcriptional profiling approaches studying gene expression in normal gastric tissue and gastric cancer tissue from human biopsy material as well as animal models of Helicobacter infection. The potential role of CagA as a bacterial oncoprotein is also discussed.


Bone resorption by macrophage polykaryons of giant cell tumour of tendon sheath.
The antigenic phenotype, ultrastructure and bone resorbing ability of mononuclear and multinucleated giant cells of four giant cell tumour of tendon sheath (GCTTS) lesions was assessed. Both the giant cells and the mononuclear cells exhibited the antigenic phenotype of cells of the monocyte/macrophage lineage. The giant cells, unlike osteoclasts, did not respond morphologically to calcitonin and showed ultrastructural and immunophenotypic features of macrophage polykaryons. However, like osteoclasts, the giant cells showed direct evidence of resorption pit formation on bone slices. This indicates that the GCTTS is composed of cells of histiocytic differentiation with the giant and mononuclear cell components expressing a similar antigenic phenotype. Bone resorption by macrophage polykaryons shows that this is not a unique defining characteristic of osteoclasts. Qualitative differences in the degree and pattern of bone resorption by macrophage polykaryons distinguish it from that of osteoclasts and may underlie the clinical behaviour of osteolytic lesions.


Germ-line chimerism and paternal care in marmosets (Callithrix kuhlii).
The formation of viable genetic chimeras in mammals through the transfer of cells between siblings in utero is rare. Using microsatellite DNA markers, we show here that chimerism in marmoset (Callithrix kuhlii) twins is not limited to blood-derived hematopoietic tissues as was previously described. All somatic tissue types sampled were found to be chimeric. Notably, chimerism was demonstrated to be present in germ-line tissues, an event never before documented as naturally occurring in a primate. In fact, we found that chimeric marmosets often transmit sibling alleles acquired in utero to their own offspring. Thus, an individual that contributes gametes to an offspring is not necessarily the genetic parent of that offspring. The presence of somatic and germ-line chimerism may have influenced the evolution of the extensive paternal and alloparental care system of this taxon. Although the exact mechanisms of sociobiological change associated with chimerism have not been fully explored, we show here that chimerism alters relatedness between twins and may alter the perceived relatedness between family members, thus influencing the allocation of parental care. Consistent with this prediction, we found a significant correlation between paternal care effort and the presence of epithelial chimerism, with males carrying chimeric infants more often than nonchimeric infants. Therefore, we propose that the presence of placental chorionic fusion and the exchange of cell lines between embryos may represent a unique adaptation affecting the evolution of cooperative care in this group of primates.


Imaging the unfolded protein response in primary tumors reveals microenvironments with metabolic variations that predict tumor growth.
Cancer cells exist in harsh microenvironments that are governed by various factors, including hypoxia and nutrient deprivation. These microenvironmental stressors activate signaling pathways that affect cancer cell survival. While others have previously measured microenvironmental stressors in tumors, it remains difficult to detect the real-time activation of these downstream signaling pathways in primary tumors. In this study, we developed transgenic mice expressing an X-box binding protein 1 (XBP1)-luciferase construct that served as a reporter for endoplasmic reticulum (ER) stress and as a downstream response for the tumor microenvironment. Primary mammary tumors arising in these mice exhibited luciferase activity in vivo. Multiple tumors arising in the same mouse had distinct XBP1-luciferase signatures, reflecting either higher or lower levels of ER stress. Furthermore, variations in ER stress reflected metabolic and hypoxic differences between tumors. Finally, XBP1-luciferase activity correlated with tumor growth rates. Visualizing distinct signaling pathways in primary tumors reveals unique tumor microenvironments with distinct metabolic signatures that can predict for tumor growth.


Crystallization and preliminary X-ray diffraction characterisation of both a native and selenomethionyl VLA-4 binding fragment of VCAM-1.
Soluble fragments of the extracellular region of vascular cell adhesion molecule 1 (VCAM-1) expressed in Escherichia coli retain functional adhesive activity. An integrin (VLA-4) binding fragment consisting of the N-terminal two immunoglobulin-like domains (VCAM-d1,2) has been crystallized. The crystals belong to space group P2(1)2(1)2(1) with cell dimensions of a = 52.7 A, b = 66.5 A, c = 113.2 A and contain two molecules in the crystallographic asymmetric unit. A batch of protein produced in the standard E. coli strain (HW1110), but grown in the presence of selenomethionine enriched media, showed 85% incorporation of selenium in place of sulphur at methionine residues. The selenomethionyl VCAM-d1,2 was crystallized by microseeding techniques initially using the native crystals for nucleation. Both native and selenomethionyl crystals diffract X-rays to a minimum Bragg spacing of 1.8 A.


Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion.
An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity.


Droplet Misalignment Limit for Inkjet Printing into Cavities on Textured Surfaces.
The control of droplets deposited onto textured surfaces is of great importance for both engineering and medical applications. This research investigates the dynamics of a single droplet deposited into a confined space and its final equilibrium morphology, with emphasis given to droplet deposition under print head misalignment, the effect of nonuniform wettability, and deposition of droplets with varying sizes. A multiphase pseudopotential lattice Boltzmann methodology is used to simulate the process of deposition. The print quality is characterized in terms of a parameter referred to as the wetted fraction, which describes the proportion of the cavity that is wetted by the droplet. Our results show how single and multiple axis misalignment affect the final equilibrium morphology, and it was found for comparable configurations that multiaxis misalignment resulted in a higher wetted fraction. Investigations into wettabilities of the substrate and cavity wall revealed how larger ratios of the contact angles between the two enhance the ability for the droplet to self-align within the cavity. Additionally, a range of uniform wettabilities between the substrate and cavity were found, which mitigate against misalignment. Investigations into varying droplet sizes relative to the cavity revealed how misalignment can be compensated for with larger droplets, and limits for filling a cavity with a single drop are defined. Finally, we explore the deposition with misalignment into closely positioned cavities where it is found that the spacing between cavities is a key factor in determining the maximum permissible misalignment.


Implicit Racial/Ethnic Bias Among Health Care Professionals and Its Influence on Health Care Outcomes: A Systematic Review.
In the United States, people of color face disparities in access to health care, the quality of care received, and health outcomes. The attitudes and behaviors of health care providers have been identified as one of many factors that contribute to health disparities. Implicit attitudes are thoughts and feelings that often exist outside of conscious awareness, and thus are difficult to consciously acknowledge and control. These attitudes are often automatically activated and can influence human behavior without conscious volition. We investigated the extent to which implicit racial/ethnic bias exists among health care professionals and examined the relationships between health care professionals' implicit attitudes about racial/ethnic groups and health care outcomes. To identify relevant studies, we searched 10 computerized bibliographic databases and used a reference harvesting technique. We assessed eligibility using double independent screening based on a priori inclusion criteria. We included studies if they sampled existing health care providers or those in training to become health care providers, measured and reported results on implicit racial/ethnic bias, and were written in English. We included a total of 15 studies for review and then subjected them to double independent data extraction. Information extracted included the citation, purpose of the study, use of theory, study design, study site and location, sampling strategy, response rate, sample size and characteristics, measurement of relevant variables, analyses performed, and results and findings. We summarized study design characteristics, and categorized and then synthesized substantive findings. Almost all studies used cross-sectional designs, convenience sampling, US participants, and the Implicit Association Test to assess implicit bias. Low to moderate levels of implicit racial/ethnic bias were found among health care professionals in all but 1 study. These implicit bias scores are similar to those in the general population. Levels of implicit bias against Black, Hispanic/Latino/Latina, and dark-skinned people were relatively similar across these groups. Although some associations between implicit bias and health care outcomes were nonsignificant, results also showed that implicit bias was significantly related to patient-provider interactions, treatment decisions, treatment adherence, and patient health outcomes. Implicit attitudes were more often significantly related to patient-provider interactions and health outcomes than treatment processes. Most health care providers appear to have implicit bias in terms of positive attitudes toward Whites and negative attitudes toward people of color. Future studies need to employ more rigorous methods to examine the relationships between implicit bias and health care outcomes. Interventions targeting implicit attitudes among health care professionals are needed because implicit bias may contribute to health disparities for people of color.


Novel use of field-portable-XRF for the direct analysis of trace elements in marine macroalgae.
Samples of dried marine macroalgae (Fucus serratus, Palmaria palmata and Ulva lactuca) have been analysed for trace elements by a novel, non-destructive approach involving a Niton field-portable-X-ray fluorescence (FP-XRF) spectrometer configured in a low density plastics mode with thickness correction. Detection limits for a 200-s counting time ranged from <5 μg g-1 for As and Pb in F. serratus and As in P. palmata to several tens of μg g-1 for Cd, Sb and Sn in all species tested. Arsenic, Cu, Pb and Zn were detected by the XRF in samples collected from a protected beach (n = 18) and in samples therefrom that had been exposed to additional aqueous elements in combination (n = 72) with concentrations returned (in μg g-1) ranging from 3.9 to 39.7 for As, 13.0 to 307 for Cu, 6.1 to 14.7 for Pb and 12.5 to 522 for Zn. Independent measurements of trace elements in the macroalgae by ICP-MS following nitric acid digestion revealed a direct and significant proportionality with concentrations returned by the XRF, with slopes of the XRF-ICP relationships (As = 1.0; Cu = 2.3; Pb = 2.4; Zn = 1.7) that can be used to calibrate the instrument for direct measurements. The approach shows potential for the in situ monitoring of macroalgae in coastal regions that is currently being investigated.


Markers for dopaminergic neurotransmission in the cerebellum in normal individuals and patients with Parkinson's disease examined by RT-PCR.
The presence of neuronal elements that are indicative of dopaminergic neurotransmission in cerebellum suggest that this brain region may contribute to the motor symptoms or dyskinesia seen in Parkinson's disease. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of markers for dopaminergic neurotransmission in the cerebellum from postmortem brain tissue obtained from normal subjects and patients dying with Parkinson's disease who were receiving treatment with dopaminergic drugs. Dopamine D1-3 receptors, tyrosine hydroxylase and dopamine transporter mRNA was detected in the uvula and nodulus (lobules 9 and 10, respectively) of the vermis of cerebellum from normal individuals. In Parkinson's disease, the level of dopamine D1 and D3 receptor mRNA was significantly reduced in lobule 9 and the level of tyrosine hydroxylase mRNA was significantly reduced in lobule 10. No alteration in the level of dopamine D2 receptor or dopamine transporter mRNA was found in either lobule in patients with Parkinson's disease. These results show that mRNA expression for the functional components of dopaminergic neurotransmission is present in human cerebellum. The discrete changes in the levels of dopamine D1 and D3 receptors and tyrosine hydroxylase mRNA in cerebellum from l-DOPA treated Parkinson's disease patients suggests that this brain area has a role in the symptoms of Parkinson's disease and/or the beneficial/side-effects of treatment.


Different Typologies of Gamers Are Associated with Mental Health: Are Students DOOMed?
(1) Background: The inclusion of Internet Gaming Disorder in the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) led to a rapid development of assessment instruments based on the suggested diagnosis. However, previous studies suggest that some of the symptoms in the diagnosis reflect engagement in gaming rather than a disorder or addiction. The aim of the present cross-sectional study was to investigate mental health associations with different typologies of gamers. (2) Methods: Data stemmed from a large national survey of students (SHoT2022) that was conducted between February and April 2022 (N = 59,544). Participants were categorized into non-gamers, recreational gamers, engaged gamers, problematic gamers, and addicted gamers. Logistic regression models adjusted for age were analyzed with and without gender-stratification for mental distress and life satisfaction as dependent variables across gaming categories. (3) Results: The proportion reporting case-level mental distress was lower for recreational gamers compared to non-gamers, indicating fewer mental health problems for recreational gamers. However, after stratifying the analysis by gender, female recreational gamers had higher levels of mental distress compared to female non-gamers, reflecting Simpson's paradox. (4) Conclusions: Future studies investigating mental health and gaming should include a gender perspective.


Red food coloring stain: new, safer procedures for staining nematodes in roots and egg masses on root surfaces.
Acid fuchsin and phloxine B are commonly used to stain plant-parasitic nematodes in roots and egg masses on root surfaces, respectively. Both stains can be harmful to both the user and the environment and require costly waste disposal procedures. We developed safer methods to replace both stains using McCormick Schilling red food color. Eggs, juveniles, and adults of Meloidogyne incognita stained in roots with red food color were equally as visible as those stained with acid fuchsin. Egg masses stained with red food color appeared as bright-red spheres on the root surfaces and were highly visible even without magnification. Replacement of acid fuchsin and phloxine B with red food color for staining nematodes is safer for the user and the environment, and eliminates costly waste disposal of used stain solutions.


The evolution of endometrial cycles and menstruation.
According to a recent hypothesis, menstruation evolved to protect the uterus and oviducts from sperm-borne pathogens by dislodging infected endometrial tissue and delivering immune cells to the uterine cavity. This hypothesis predicts the following: (1) uterine pathogens should be more prevalent before menses than after menses, (2) in the life histories of females, the timing of menstruation should track pathogen burden, and (3) in primates, the copiousness of menstruation should increase with the promiscuity of the breeding system. I tested these predictions and they were not upheld by the evidence. I propose the alternative hypothesis that the uterine endometrium is shed/resorbed whenever implantation fails because cyclical regression and renewal is energetically less costly than maintaining the endometrium in the metabolically active state required for implantation. In the regressed state, oxygen consumption (per mg protein/h) in human endometria declines nearly sevenfold. The cyclicity in endometrial oxygen consumption is one component of the whole body cyclicity in metabolic rate caused by the action of the ovarian steroids on both endometrial and nonendometrial tissue. Metabolic rate is at least 7% lower, on average, during the follicular phase than during the luteal phase in women, which signifies an estimated energy savings of 53 MJ over four cycles, or nearly six days worth of food. Thus the menstrual cycle revs up and revs down, economizing on the energy costs of reproduction. This economy is greatest during the nonbreeding season and other periods of amenorrhea when the endometrium remains in a regressed state and ovarian cycling is absent for a prolonged period of time. Twelve months of amenorrhea save an estimated 130 MJ, or the energy required by one woman for nearly half a month. By helping females to maintain body mass, energy economy will promote female fitness in any environment in which fecundity and survivorship is constrained by the food supply. Endometrial economy may be of ancient evolutionary origin because similar reproductive structures, such as the oviducts of lizards, also regress when a fertilized egg is unlikely to be present. Regression of the endometrium is usually accompanied by reabsorption, but in some species as much as one third of the endometrial and vascular tissue is shed as the menses. Rather than having an adaptive basis in ecology or behavior, variation in the degree of menstrual bleeding in primates shows a striking correlation with phylogeny. The endometrial microvasculature is designed to provide the blood supply to the endometrium and the placenta, and external bleeding appears to be a side effect of endometerial regression that arises when there is too much blood and other tissue for complete reabsorption. The copious bleeding of humans and chimps can be attributed to the large size of the uterus relative to adult female body size and to the design of the microvasculature in catarrhines.


Basic math in monkeys and college students.
Adult humans possess a sophisticated repertoire of mathematical faculties. Many of these capacities are rooted in symbolic language and are therefore unlikely to be shared with nonhuman animals. However, a subset of these skills is shared with other animals, and this set is considered a cognitive vestige of our common evolutionary history. Current evidence indicates that humans and nonhuman animals share a core set of abilities for representing and comparing approximate numerosities nonverbally; however, it remains unclear whether nonhuman animals can perform approximate mental arithmetic. Here we show that monkeys can mentally add the numerical values of two sets of objects and choose a visual array that roughly corresponds to the arithmetic sum of these two sets. Furthermore, monkeys' performance during these calculations adheres to the same pattern as humans tested on the same nonverbal addition task. Our data demonstrate that nonverbal arithmetic is not unique to humans but is instead part of an evolutionarily primitive system for mathematical thinking shared by monkeys.


What are the predictors and prevalence of pseudotumor and elevated metal ions after large-diameter metal-on-metal THA?
Soft tissue masses, or "pseudotumors," around metal-on-metal total hip arthroplasty (MoM THA) have been reported frequently; however, their prevalence remains unknown. Several risk factors, including elevated metal ion levels, have been associated with the presence of pseudotumor, although this remains controversial. The goals of this study were to (1) determine the prevalence of pseudotumors after large-diameter head MoM THA; (2) identify risk factors associated with pseudotumor formation and elevated metal ion levels; and (3) determine the early failure rate of large-diameter MoM THA. Between December 2005 and November 2012, 258 hips (215 patients) underwent large-diameter head primary MoM THA at our institution. Clinical followup was obtained in 235 hips (91%). Using an inclusion criteria of a minimum followup of 1 year, a subset of 191 hips (mean followup, 4 years; range, 1-7 years) was recruited for high-resolution ultrasound screening for the presence of pseudotumor. Whole blood cobalt and chromium ion levels, UCLA activity level, WOMAC score, patient demographics as well as surgical, implant, and radiographic data were collected. Bivariate correlations and multivariate log-linear regression models were used to compare the presence of pseudotumor and elevated metal ions with all other factors. Ultrasound detected a solid, cystic, or mixed mass in 20% hips (38 of 191). No correlation was found between the presence of pseudotumor and any risk factor that we examined. After controlling for confounding variables, elevated cobalt ions were correlated (p<0.001, R=0.50, R2=0.25) with smaller femoral head size, the presence of bilateral MoM THA, and female sex. Elevated chromium ions were correlated (p<0.001, R=0.59, R2=0.34) with smaller femoral head size, presence of bilateral MoM THA, and lower body mass index. The overall survival of MoM THA was 96% at a mean followup of 4.5 years (range, 2-8 years). With the numbers available, we found no associations between the presence of pseudotumor and the potential risk factors we analyzed, including elevated metal ion levels. Further work is needed to explain why larger femoral head sizes resulted in lower metal ion levels despite being associated with higher early failure rates in joint registry data. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Design of a cluster-randomized controlled trial of a diabetes prevention program within African-American churches: The Fit Body and Soul study.
Evidence from varied community settings has shown that the Group Lifestyle Balance (GLB) Program and other adaptations of the Diabetes Prevention Program (DPP) intervention are effective in lowering diabetes risk. Most DPP data originated from studies of pre-diabetic whites, with only sparse evidence of the effect of DPP in African Americans (AAs) in community settings. This paper describes the design, methods, baseline characteristics and cost effective measures, of a single-blinded, cluster-randomized trial of a faith-based adaptation of the GLB program, Fit Body and Soul (FBAS). The major aims are to test efficacy and cost utility of FBAS in twenty AA churches. Randomization occurred at the church level and 604 AA overweight/obese (BMI≥25kg/m(2)) adults with fasting plasma glucose range from normal to pre-diabetic received either FBAS or a health-education comparison program. FBAS is a group-based, multi-level intervention delivered by trained church health advisors (health professionals from within the church), with the goal of ≥7% weight loss, achieved through increasing physical activity, healthy eating and behavior modification. The primary outcome is weight change at 12weeks post intervention. Secondary outcomes include hemoglobin A1C, fasting plasma glucose, waist circumference, blood pressure, physical activity level, quality of life measures, and cost-effectiveness. FBAS is the largest known cohort of AAs enrolled in a faith-based DPP translation. Reliance on health professionals from within the church for program implementation and the cost analysis are unique aspects of this trial. The design provides a model for faith-based DPPs and holds promise for program sustainability and widespread dissemination.


Commute times, food retail gaps, and body mass index in North Carolina counties.
The prevalence of obesity is higher in rural than in urban areas of the United States, for reasons that are not well understood. We examined correlations between percentage of rural residents, commute times, food retail gap per capita, and body mass index (BMI) among North Carolina residents. We used 2000 census data to determine each county's percentage of rural residents and 1990 and 2000 census data to obtain mean county-level commute times. We obtained county-level food retail gap per capita, defined as the difference between county-level food demand and county-level food sales in 2008, from the North Carolina Department of Commerce, and BMI data from the 2007 North Carolina Behavioral Risk Factor Surveillance System. To examine county-level associations between BMI and percentage of rural residents, commute times, and food retail gap per capita, we used Pearson correlation coefficients. To examine cross-sectional associations between individual-level BMI (n = 9,375) and county-level commute times and food retail gap per capita, we used multilevel regression models. The percentage of rural residents was positively correlated with commute times, food retail gaps, and county-level BMI. Individual-level BMI was positively associated with county-level commute times and food retail gaps. Longer commute times and greater retail gaps may contribute to the rural obesity disparity. Future research should examine these relationships longitudinally and should test community-level obesity prevention strategies.


The repeat structure of two paralogous genes, Yersinia ruckeri invasin (yrInv) and a "Y. ruckeri invasin-like molecule", (yrIlm) sheds light on the evolution of adhesive capacities of a fish pathogen.
Inverse autotransporters comprise the recently identified type Ve secretion system and are exemplified by intimin from enterohaemorrhagic Escherichia coli and invasin from enteropathogenic Yersiniae. These proteins share a common domain architecture and promote bacterial adhesion to host cells. Here, we identified and characterized two putative inverse autotransporter genes in the fish pathogen Yersinia ruckeri NVH_3758, namely yrInv (for Y. ruckeri invasin) and yrIlm (for Y. ruckeri invasin-like molecule). When trying to clone the highly repetitive genes for structural and functional studies, we experienced problems in obtaining PCR products. PCR failures and the highly repetitive nature of inverse autotransporters prompted us to sequence the genome of Y. ruckeri NVH_3758 using PacBio sequencing, which produces some of the longest average read lengths available in the industry at this moment. According to our sequencing data, YrIlm is composed of 2603 amino acids (7812bp) and has a molecular mass of 256.4kDa. Based on the new genome information, we performed PCR analysis on four non-sequenced Y. ruckeri strains as well as the sequenced. Y. ruckeri type strain. We found that the genes are variably present in the strains, and that the length of yrIlm, when present, also varies. In addition, the length of the gene product for all strains, including the type strain, was much longer than expected based on deposited sequences. The internal repeats of the yrInv gene product are highly diverged, but represent the same bacterial immunoglobulin-like domains as in yrIlm. Using qRT-PCR, we found that yrIlm and yrInv are differentially expressed under conditions relevant for pathogenesis. In addition, we compared the genomic context of both genes in the newly sequenced Y. ruckeri strain to all available PacBio-sequenced Y. ruckeri genomes, and found indications of recent events of horizontal gene transfer. Taken together, this study demonstrates and highlights the power of Single Molecule Real-Time technology for sequencing highly repetitive proteins, and sheds light on the genetic events that gave rise to these highly repetitive genes in a commercially important fish pathogen.


Injuries and medical issues in synchronized Olympic sports.
Spectators of the Olympic Games can enjoy a wide variety of sports, including strength, team, timed, endurance, and artistic sports. In the Olympic program, there are two synchronized events: synchronized diving and synchronized swimming. The precision of the synchronization of the athlete's movements and skills is an added feature of entertainment. Synchronized athletes have additional training requirements to perfect the synchronization of their skills. The physical demands on the athlete from the repetition of training required for the perfection of synchronization result in injuries unique to these sports. Although both traumatic and overuse injuries occur, overuse injuries are more common. As these disciplines are artistic, judged sports, these athletes also are susceptible to eating disorders and the female athlete triad. This article reviews the training regimen of these athletes and outlines the injuries and health concerns that are common in the synchronized sports.


Structure and dynamics of the membrane attaching nitric oxide transporter nitrophorin 7.
Nitrophorins represent a unique class of heme proteins that are able to perform the delicate transportation and release of the free-radical gaseous messenger nitric oxide (NO) in a pH-triggered manner. Besides its ability to bind to phospholipid membranes, the N-terminus contains an additional Leu-Pro-Gly stretch, which is a unique sequence trait, and the heme cavity is significantly altered with respect to other nitrophorins. These distinctive features encouraged us to solve the X-ray crystallographic structures of NP7 at low and high pH and bound with different heme ligands (nitric oxide, histamine, imidazole). The overall fold of the lipocalin motif is well preserved in the different X-ray structures and resembles the fold of other nitrophorins. However, a chain-like arrangement in the crystal lattice due to a number of head-to-tail electrostatic stabilizing interactions is found in NP7. Furthermore, the X-ray structures also reveal ligand-dependent changes in the orientation of the heme, as well as in specific interactions between the A-B and G-H loops, which are considered to be relevant for the biological function of nitrophorins. Fast and ultrafast laser triggered ligand rebinding experiments demonstrate the pH-dependent ligand migration within the cavities and the exit route. Finally, the topological distribution of pockets located around the heme as well as from inner cavities present at the rear of the protein provides a distinctive feature in NP7, so that while a loop gated exit mechanism to the solvent has been proposed for most nitrophorins, a more complex mechanism that involves several interconnected gas hosting cavities is proposed for NP7.


Metagenomic sequencing of an in vitro-simulated microbial community.
Microbial life dominates the earth, but many species are difficult or even impossible to study under laboratory conditions. Sequencing DNA directly from the environment, a technique commonly referred to as metagenomics, is an important tool for cataloging microbial life. This culture-independent approach involves collecting samples that include microbes in them, extracting DNA from the samples, and sequencing the DNA. A sample may contain many different microorganisms, macroorganisms, and even free-floating environmental DNA. A fundamental challenge in metagenomics has been estimating the abundance of organisms in a sample based on the frequency with which the organism's DNA was observed in reads generated via DNA sequencing. We created mixtures of ten microbial species for which genome sequences are known. Each mixture contained an equal number of cells of each species. We then extracted DNA from the mixtures, sequenced the DNA, and measured the frequency with which genomic regions from each organism was observed in the sequenced DNA. We found that the observed frequency of reads mapping to each organism did not reflect the equal numbers of cells that were known to be included in each mixture. The relative organism abundances varied significantly depending on the DNA extraction and sequencing protocol utilized. We describe a new data resource for measuring the accuracy of metagenomic binning methods, created by in vitro-simulation of a metagenomic community. Our in vitro simulation can be used to complement previous in silico benchmark studies. In constructing a synthetic community and sequencing its metagenome, we encountered several sources of observation bias that likely affect most metagenomic experiments to date and present challenges for comparative metagenomic studies. DNA preparation methods have a particularly profound effect in our study, implying that samples prepared with different protocols are not suitable for comparative metagenomics.


Surgical Treatment of Osteoporotic Vertebral Fracture with Neurological Deficit-A Nationwide Multicenter Study in Japan.
The prevalence of patients with osteoporosis continues to increase in aging societies, including Japan. The first choice for managing osteoporotic vertebral compression fracture (OVF) is conservative treatment. Failure in conservative treatment for OVF may lead to non-union or vertebral collapse, resulting in neurological deficit and subsequently requiring surgical intervention. This multicenter nationwide study in Japan was conducted to comprehensively understand the outcomes of surgical treatments for OVF non-union. This multicenter, retrospective study included 403 patients (89 males, 314 females, mean age 73.8 ± 7.8 years, mean follow-up 3.9 ± 1.7 years) with neurological deficit due to vertebral collapse or non-union after OVF at T10-L5 who underwent fusion surgery with a minimum 1-year follow-up. Radiological and clinical outcomes at baseline and at the final follow-up (FU) were evaluated. OVF was present at a thoracolumbar junction such as T12 (124 patients) and L1 (117 patients). A majority of OVF occurred after a minor trauma, such as falling down (55.3%) or lifting objects (8.4%). Short segment fusion, including affected vertebra, was conducted (mean 4.0 ± 2.0 vertebrae) with 256.8 minutes of surgery and 676.1 g of blood loss. A posterior approach was employed in 86.6% of the patients, followed by a combined anterior and posterior (8.7%), and an anterior (4.7%) approach. Perioperative complications and implant failures were observed in 18.1% and 41.2%, respectively. VAS scores of low back pain (74.7 to 30.8 mm) and leg pain (56.8 to 20.7 mm) improved significantly at FU. Preoperatively, 52.6% of the patients were unable to walk and the rate of non-ambulatory patients decreased to 7.5% at FU. This study demonstrated that substantial improvement in activity of daily living (ADL) was achieved by fusion surgery. Although there was a considerable rate of complications, fusion surgery is beneficial for elderly OVF patients with non-union.