Five Years Malaria Trend Analysis in Woreta Health Center, Northwest Ethiopia.
An estimated 68% of the Ethiopian population, living in 75% of the landmass, is at risk of contracting malaria at any time making it the leading public health problem. The temporal analysis of malaria data could be important to evaluate the performance of malaria prevention programmes. Thus, the aim of this study was to determine the trend of malaria at Woreta Health Center (WHC) over a period of five years. We analyzed the records of 8,057 presumptive malaria patients registered in 2012 to 2016. The following patient data were retrieved from laboratory registration logbook for analysis: sex, age, residence, blood film (BF) microscopy result, type of malaria parasite identified, year and month when the patients visited WHC. Logistic regression was employed to assess the association between potential associated factors and positive BF result; p < 0.05 was considered significant. Among the total presumptive individuals, 4447(55.2%) were females. The prevalence of malaria in each year ranged from 4.1% to 6.7%. The overall prevalence of malaria was 5.4% (95%CI: 4.9%-5.9%). The two most important species of malaria parasite identified were P. falciparum at 233(53.7%) and P. vivax at 184(42.4%). Relatively higher proportions of cases were documented in the months of November, December and June (11.1%, 8.1% and 7.2%, respectively). Patients who visited the health center in the month of December were >4 times more likely to be infected as compared with those who came to the health center in September [AOR: 4.2, 95%CI (2.374-7.560)]. Females were 1.3 times more likely to be infected than males, [AOR: 1.3, 95%CI (1.101-1.638)]. Similarly, patients in the age group above 15 were 1.9 times more likely to be infected than individuals < 5, [AOR: 1.9 95%CI (1.498-2.455), p value 0.000]. In the studied area, malaria remains a major public health challenge. Hence, interventions to decrease the impact of the disease have to be evaluated and strengthened.


Loneliness, Mental Health, and Substance Use among US Young Adults during COVID-19.
As COVID-19 converges with loneliness and addiction epidemics in the US, both public health and mental health experts forecast dramatic increases in substance use and mental health conditions. This cross-sectional study evaluated relationships of loneliness with depression, anxiety, alcohol use, and drug use during COVID-19, and assessed perceived increases in these symptoms in young adults. Between April 22 and May 11, 2020, 1,008 participants ages 18-35 were recruited through social media to a one-time, online anonymous survey. Symptomatology was assessed using six scales. Perceived changes since COVID-19 were evaluated using 5-point Likert scales. Forty-nine percent of respondents reported loneliness scores above 50; 80% reported significant depressive symptoms; 61% reported moderate to severe anxiety; 30% disclosed harmful levels of drinking. While only 22% of the population reported using drugs, 38% reported severe drug use. Loneliness was associated with higher levels of mental health symptomatology. Participants reported significant increases across mental health and substance use symptoms since COVID-19. While direct impacts of COVID-19 could only be calculated with pre-pandemic assessments of these symptoms, estimates indicate elevated psychosocial symptomatology and suggest that symptoms could have worsened since the pandemic. Findings underscore the importance of prevention and intervention to address these public health problems.


Characterization of a carboxypeptidase inhibitor from the tick Haemaphysalis longicornis.
A carboxypeptidase inhibitor called HlTCI was isolated from Haemaphysalis longicornis in this study. The full-length cDNA of HlTCI contains an open reading frame (ORF) of 291bp, encoding 96 amino acid residues consisting of a predicted 19-residue signal peptide and a putative mature 77-residue protein. The expected mature protein is cysteine-rich and has 12 cysteine residues assumed to construct six disulfide bridges. The deduced peptide sequence shows 63.9% homology to the carboxypeptidase inhibitor from another ixodid tick, Rhipicephalus bursa. Reverse-transcription PCR (RT-PCR) indicated that HlTCI was specifically expressed in the ovary from partially engorged adult ticks. The recombinant protein of HlTCI (rHlTCI) with glutathione S-transferase (GST) was expressed in Escherichia coli strain BL21 (DE3) and purified by glutathione-Sepharose 4B beads. rHlTCI showed inhibitory activity against digestive metallocarboxypeptidases A and B, but the activity was affected by the increase of the temperature treatment. High concentrations of rHlTCI were shown to significantly accelerate fibrinolysis in vitro. This effect of rHlTCI on clot lysis suggests its promising potential for use in some thrombotic disorders.


[Descending necrotising mediastinitis: report of two cases].
Descending necrotising mediastinitis is a severe infection spreading from the cervical region to the mediastinal connective tissue. It represents a virulent form of mediastinal infection, requiring prompt diagnosis and treatment to reduce the high mortality associated. An optimal debridement and drainage through an open thoracotomy access are the keys for a successful outcome. Two patients, males, 70 and 75-years-old with descending necrotising mediastinitis were treated in our Institution in April '05. One had an odontogenic abscess and the other had a retropharyngeal abscess. Operative procedures included thoracotomy with radical surgical debridement of the mediastinum and excision of necrotic tissue associated with transcervical surgical debridement and drainage. Postoperatively mediastinum-pleural and cervical irrigation with iodopovidone 2 per thousand was performed until a culture of pleural effusion become negative. Postoperatively both patients suffered from severe complication including septic shock and acute respiratory distress syndrome. The 70-years-old patient had an acute renal failure too. Postoperatively the length of the intensive care unit stay was 40 and 42 days, respectively. The outcome was favorable in both patients. Early detection and immediate open surgical treatment could be the best way to reduce morbidity and mortality rate. Descending Necrotising Mediastinitis cannot be adequately treated without mediastinal and cervical excision of necrotic tissue and drainage including an open thoracic and cervical approach.


Reverse osmosis followed by activated carbon filtration for efficient removal of organic micropollutants from river bank filtrate.
Drinking water utilities in Europe are faced with a growing presence of organic micropollutants in their water sources. The aim of this research was to assess the robustness of a drinking water treatment plant equipped with reverse osmosis and subsequent activated carbon filtration for the removal of these pollutants. The total removal efficiency of 47 organic micropollutants was investigated. Results indicated that removal of most organic micropollutants was high for all membranes tested. Some selected micropollutants were less efficiently removed (e.g. the small and polar NDMA and glyphosate, and the more hydrophobic ethylbenzene and napthalene). Very high removal efficiencies for almost all organic micropollutants by the subsequent activated carbon, fed with the permeate stream of the RO element were observed except for the very small and polar NDMA and 1,4-dioxane. RO and subsequent activated carbon filtration are complementary and their combined application results in the removal of a large part of these emerging organic micropollutants. Based on these experiments it can be concluded that the robustness of a proposed treatment scheme for the drinking water treatment plant Engelse Werk is sufficiently guaranteed.


Communication-based assessment of developmental age for young children with developmental disabilities.
In this study, the authors compared a multiple-domain strategy for assessing developmental age of young children with developmental disabilities who were at risk for long-term reliance on augmentative and alternative communication (AAC) with a communication-based strategy composed of receptive language and communication indices that may be less affected by physically challenging tasks than traditional developmental age scores. Participants were 42 children (age 9-27 months) with developmental disabilities and who were at risk for long-term reliance on AAC. Children were assessed longitudinally in their homes at 3 occasions over 18 months using multiple-domain and communication-based measures. Confirmatory factor analysis examined dimensionality across the measures, and age-equivalence scores under each strategy were compared, where possible. The communication-based latent factor of developmental age demonstrated good reliability and was almost perfectly correlated with the multiple-domain latent factor. However, the mean age-equivalence score of the communication-based assessment significantly exceeded that of the multiple-domain assessment by 5.3 months across ages. Clinicians working with young children with developmental disabilities should consider a communication-based approach as an alternative developmental age assessment strategy for characterizing children's capabilities, identifying challenges, and developing interventions. A communication-based developmental age estimation is sufficiently reliable and may result in more valid inferences about developmental age for children whose developmental or cognitive age scores may otherwise be limited by their physical capabilities.


A survey of sedation practices for colonoscopy in Canada.
There are limited data regarding the use of sedation for colonoscopy and concomitant monitoring practices in different countries. A survey was mailed to 445 clinician members of the Canadian Association of Gastroenterology and 80 members of the Canadian Society of Colon and Rectal Surgeons in May and June 2009. Sixty-five per cent of Canadian Association of Gastroenterology members and 69% of Canadian Society of Colon and Rectal Surgeons members responded with the full survey. Most endoscopists reported using sedation for more than 90% of colonoscopies. The most common sedation regimen was a combination of midazolam and fentanyl. Propofol, either alone or with another drug, was used in 12% of cases. A higher proportion (94%) of adult gastroenterologists who routinely used propofol were highly satisfied compared with those using other sedative agents (45%; P<0.001). Fifty per cent of adult gastroenterologists and 29% of surgeons who were not currently using propofol expressed interest in starting to use it for routine colonoscopies. Only a single nurse was present in the endoscopy room during colonoscopy performed by two-thirds of the endoscopists. Results of the present survey suggest that gastroenterologists in Canada use sedation for colonoscopy in more than 90% of their patients. There was higher satisfaction among gastroenterologists who used propofol routinely for all colonoscopies. Most endoscopy rooms were staffed by a single nurse, which may limit further increases in the use of propofol. Further studies are needed to determine optimal staffing of endoscopy units with and without the use of propofol. Sedation practices of general surgery endoscopists need to be evaluated.


EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location.
Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.


Estimating Informal Caregiving Time from Patient EQ-5D Data: The Informal CARE Effect (iCARE) Tool.
Families and friends provide a considerable proportion of care for patients and elderly people. Caregiving can have substantial effects on caregivers' lives, health, and well-being. However, because clinical trials rarely assess these effects, no information on caregiver burden is available when evaluating the cost effectiveness of treatments. This study develops an algorithm for estimating caregiver time using information that is typically available in clinical trials: the EQ-5D scores of patients and their gender. Four datasets with a total of 8012 observations of dyads of caregivers and a gamma model with a log-link estimated with the Bayesian approach were used to estimate the statistical association between patient scores on the EQ-5D-3L dimensions and the numbers of hours of care provided by caregivers during the previous week. The model predicts hours of care as mean point estimates with 95% credible intervals or entire distributions. Model predictions of hours of care based on the five EQ-5D dimensions ranged from 13.06 (12.7-14.5) h/week for female patients reporting no health problems but receiving informal care to 52.82 (39.38-66.26) for male patients with the highest level of problems on all EQ-5D dimensions. The iCARE algorithm developed in this study allows researchers who only have patient-level EQ-5D data to estimate the mean hours of informal care received per week, including a 95% Bayesian credible interval. Caregiver time can be multiplied with a monetary value for caregiving, enabling the inclusion of informal care costs in economic evaluations. We recommend using the tool for samples that fall within the confidence intervals of the characteristics of our samples: men (age range 47.0-104.2 years), women (age range 55-103 years).


Progress and future challenges in aging and diversity research in the United States.
In 2016, the UC Davis Latino Aging Research Resource Center and UC Davis Alzheimer's Disease Center brought together experts from across the country to consolidate current knowledge and identify future directions in aging and diversity research. This report disseminates the research priorities that emerged from this conference, building on an earlier Gerontological Society of America preconference. We review key racial/ethnic differences in cognitive aging and dementia and identify current knowledge gaps in the field. We advocate for a systems-level framework for future research whereby environmental, sociocultural, behavioral, neuropathological, genetic, and psychometric levels of analysis are examined together to identify pathways and mechanisms that influence disparities. We then discuss steps to increase the recruitment and retention of racial/ethnic minorities in aging studies, as none of the recommendations will be possible without strong collaboration between racial/ethnic minority communities and researchers. This approach is consistent with the National Institute on Aging Health Disparities Research Framework.


A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.
Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.


Complete genome sequence of Rhodothermus marinus type strain (R-10).
Rhodothermus marinus Alfredsson et al. 1995 is the type species of the genus and is of phylogenetic interest because the Rhodothermaceae represent the deepest lineage in the phylum Bacteroidetes. R. marinus R-10(T) is a Gram-negative, non-motile, non-spore-forming bacterium isolated from marine hot springs off the coast of Iceland. Strain R-10(T) is strictly aerobic and requires slightly halophilic conditions for growth. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the genus Rhodothermus, and only the second sequence from members of the family Rhodothermaceae. The 3,386,737 bp genome (including a 125 kb plasmid) with its 2914 protein-coding and 48 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.


The design and implementation of a randomized controlled trial of a risk reduction and human immunodeficiency virus prevention videogame intervention in minority adolescents: PlayForward: Elm City Stories.
To address the need for risk behavior reduction and human immunodeficiency virus prevention interventions that capture adolescents "where they live," we created a tablet-based videogame to teach skills and knowledge and influence psychosocial antecedents for decreasing risk and preventing human immunodeficiency virus infection in minority youth in schools, after-school programs, and summer camps. We developed PlayForward: Elm City Stories over a 2-year period, working with researchers, commercial game designers, and staff and teens from community programs. The videogame PlayForward provides an interactive world where players, using an avatar, "travel" through time, facing challenges such as peer pressure to drink alcohol or engage in risky sexual behaviors. Players experience how their choices affect their future and then are able to go back in time and change their choices, creating different outcomes. A randomized controlled trial was designed to evaluate the efficacy of PlayForward. Participants were randomly assigned to play PlayForward or a set of attention/time control games on a tablet at their community-based program. Assessment data were collected during face-to-face study visits and entered into a web-based platform and unique real-time "in-game" PlayForward data were collected as players engaged in the game. The innovative methods of this randomized controlled trial are described. We highlight the logistical issues of conducting a large-scale trial using mobile technology such as the iPad(®), and collecting, transferring, and storing large amounts of in-game data. We outline the methods used to analyze the in-game data alone and in conjunction with standardized assessment data to establish correlations between behaviors during gameplay and those reported in real life. We also describe the use of the in-game data as a measure of fidelity to the intervention. In total, 333 boys and girls, aged 11-14 years, were randomized over a 14-month period: 166 were assigned to play PlayForward and 167 to play the control games. To date (as of 1 March 2016), 18 have withdrawn from the study; the following have completed the protocol-defined assessments: 6 weeks: 271 (83%), 3 months: 269 (84%), 6 months: 254 (79%), 12 months: 259 (82%), and 24 months: is ongoing with 152 having completed out of the 199 participants (76%) who were eligible to date (assessment windows were still open). Videogames can be developed to address complex behaviors and can be subject to empiric testing using community-based randomized controlled trials. Although mobile technologies pose challenges in their use as interventions and in the collection and storage of data they produce, they provide unique opportunities as new sources of potentially valid data and novel methods to measure the fidelity of digitally delivered behavioral interventions.


A novel framework to classify marginal land for sustainable biomass feedstock production.
To achieve food and energy security, sustainable bioenergy has become an important goal for many countries. The use of marginal lands to produce energy crops is one strategy for achieving this goal, but what is marginal land? Current definitions generally focus on a single criterion, primarily agroeconomic profitability. Herein, we present a framework that incorporates multiple criteria including profitability of current land use, soil health indicators (erosion, flooding, drainage, or high slopes), and environmental degradation resulting from contamination of surface water or groundwater resources. We tested this framework for classifying marginal land in the state of Nebraska and estimated the potential for using marginal land to produce biofuel crops. Our results indicate that approximately 1.6 million ha, or 4 million acres, of land (approximately 8% of total land area) could be classified as marginal on the basis of at least two criteria. Second-generation lignocellulosic bioenergy crops such as switchgrass ( Panicum virgatum L.), miscanthus (Miscanthus giganteus), native prairie grasses, and short-rotation woody crops could be grown on this land in redesigned landscapes that meet energy and environmental needs, without significant impacts on food or feed production. Calculating tradeoffs between the economics of redesigned landscapes and current practices at the field scale is the next step for determining functional designs for integrating biofuel feedstock production into current land management practices.


The decrease in growth hormone (GH) response after repeated stimulation with GH-releasing hormone is partly caused by an elevation of somatostatin tonus.
Repeated injection of GHRH leads to a decrease in the GH response in normal subjects. Arginine (Arg) stimulates GH secretion by suppression of hypothalamic somatostatin. To confirm these findings, eight normal men were examined in a series of five settings: test 1 (GHRH/GHRH-TRH), 100 micrograms GHRH injected iv, followed by 100 micrograms GHRH, iv, after 120 min and 200 micrograms TRH, iv, after 150 min; test 2 (GHRH/Arg-TRH), like test 1, but instead of the second GHRH injection, a 30 g Arg infusion over 30 min; test 3 (GHRH/GHRH-Arg-TRH), like test 1, but additionally a 30 g Arg infusion after 120 min; test 4 (GHRH-Arg-TRH), iv GHRH and Arg infusion initially, followed by iv TRH after 30 min; and test 5 (TRH), 200 micrograms TRH, iv, at 0 min. For statistical evaluation, the area under the GH curve (AUC) from 0-120 min was compared with the AUC from 120-240 min. The GH response to the second administration of GHRH was significantly lower (P < 0.02) than the first increase [AUC, 0.5 +/- 0.01 min.mg/L (mean +/- SE) vs. 1.2 +/- 0.3]. No significant differences were found between the GH responses to either GHRH or Arg alone (AUC, 0.9 +/- 0.2 min.mg/L vs. 0.9 +/- 0.2). A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3). The GH response (P < 0.02) to GHRH-Arg stimulation was lower after previous GHRH injection than after GHRH-Arg stimulation alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 3.5 +/- 0.9). There was a statistically significant difference between the TRH-stimulated TSH response in test 4 compared to that in test 5. We could show that decreasing GH responses to repeated GHRH can be avoided by a combined stimulation with GHRH/Arg. These findings suggest that the decreased GH response to a second GHRH bolus may be partly due to an elevated hypothalamic somatostatin secretion, which can be suppressed by Arg. The lower GH response to GHRH-Arg stimulation after a previous GHRH bolus suggests, furthermore, that the readily available GH pool in the human pituitary may be limited.


Can microcarrier-expanded chondrocytes synthesize cartilaginous tissue in vitro?
Tissue engineering is a promising approach for articular cartilage repair; however, it is challenging to produce adequate amounts of tissue in vitro from the limited number of cells that can be extracted from an individual. Relatively few cell expansion methods exist without the problems of de-differentiation and/or loss of potency. Recently, however, several studies have noted the benefits of three-dimensional (3D) over monolayer expansion, but the ability of 3D expanded chondrocytes to synthesize cartilaginous tissue constructs has not been demonstrated. Thus, the purpose of this study was to compare the properties of engineered cartilage constructs from expanded cells (monolayer and 3D microcarriers) to those developed from primary chondrocytes. Isolated bovine chondrocytes were grown for 3 weeks in either monolayer (T-Flasks) or 3D microcarrier (Cytodex 3) expansion culture. Expanded and isolated primary cells were then seeded in high density culture on Millicell™ filters for 4 weeks to evaluate the ability to synthesize cartilaginous tissue. While microcarrier expansion was twice as effective as monolayer expansion (microcarrier: 110-fold increase, monolayer: 52-fold increase), the expanded cells (monolayer and 3D microcarrier) were not effectively able to synthesize cartilaginous tissue in vitro. Tissues developed from primary cells were substantially thicker and accumulated significantly more extracellular matrix (proteoglycan content: 156%-292% increase; collagen content: 70%-191% increase). These results were attributed to phenotypic changes experienced during the expansion phase. Monolayer expanded chondrocytes lost their native morphology within 1 week, whereas microcarrier-expanded cells were spreading by 3 weeks of expansion. While the use of 3D microcarriers can lead to large cellular yields, preservation of chondrogenic phenotype during expansion is required in order to synthesize cartilaginous tissue.


Cardiometabolic Impact of Changing Sitting, Standing, and Stepping in the Workplace.
According to cross-sectional and acute experimental evidence, reducing sitting time should improve cardiometabolic health risk biomarkers. Furthermore, the improvements obtained may depend on whether sitting is replaced with standing or ambulatory activities. Based on data from the Stand Up Victoria multicomponent workplace intervention, we examined this issue using compositional data analysis-a method that can examine and compare all activity changes simultaneously. Participants receiving the intervention (n = 136 ≥ 0.6 full-time equivalent desk-based workers, 65% women, mean ± SD age = 44.6 ± 9.1 yr from seven worksites) were asked to improve whole-of-day activity by standing up, sitting less, and moving more. Their changes in the composition of daily waking hours (activPAL-assessed sitting, standing, and stepping) were quantified then tested for associations with concurrent changes in cardiometabolic risk (CMR) scores and 14 biomarkers concerning body composition, glucose, insulin, and lipid metabolism. Analyses were by mixed models, accounting for clustering (3 months, n = 105-120; 12 months, n = 80-97). Sitting reduction was significantly (P < 0.05) associated only with lower systolic blood pressure at 3 months, and with CMR scores, weight, body fat, waist circumference, diastolic blood pressure, and fasting triglycerides, total/HDL cholesterol, and insulin at 12 months. Significant differences between standing and stepping were only observed for systolic blood pressure and insulin; both favored stepping. However, replacing sitting with standing was significantly associated only with improvements in CMR scores, whereas replacing sitting with stepping was significantly associated with CMR scores and six biomarkers. Improvements in several cardiometabolic health risk biomarkers were significantly associated with sitting reductions that occurred in a workplace intervention. The greatest degree and/or widest range of cardiometabolic benefits appeared to occur with long-term changes, and when increasing ambulatory activities. ACTRN1211000742976.


Cancer Risk after Fat Transfer: A Multicenter Case-Cohort Study.
Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers. A multicenter, case-cohort study was performed. Eligible patients from four centers (Memorial Sloan Kettering, M. D. Anderson Cancer Center, Alvin J. Siteman Cancer Center, and the University of Chicago) were identified by each site's institutional tumor registry or cancer data warehouse. Eligibility criteria were as follows: mastectomy with immediate breast reconstruction between 2006 and 2011, age older than 21 years, female sex, and incident diagnosis of invasive ductal carcinoma (stage I, II, or III). Cases consisted of all recurrences during the study period, and controls consisted of a 30 percent random sample of the study population. Cox proportional hazards regression was used to evaluate for association between fat transfer and time to recurrence in bivariate and multivariate models. The time to disease recurrence unadjusted hazard ratio for fat transfer was 0.99 (95 percent CI, 0.56 to 1.7). After adjustment for age, body mass index, stage, HER2/Neu receptor status, and estrogen receptor status, the hazard ratio was 0.97 (95 percent CI, 0.54 to 1.8). In this population of breast cancer patients who had mastectomy with immediate reconstruction, fat transfer was not associated with a higher risk of cancer recurrence. Therapeutic, III.


RAR1, ROR1, and the actin cytoskeleton contribute to basal resistance to Magnaporthe grisea in barley.
The fungus Magnaporthe grisea, the causal agent of rice blast disease, is a major pathogen of rice and is capable of producing epidemics on other cultivated cereals, including barley (Hordeum vulgare). We explored the requirements for basal resistance of barley against a compatible M. grisea isolate using both genetic and chemical approaches. Mutants of the RAR1 gene required for the function of major resistance gene-mediated resistance and mutants of the ROR1 and ROR2 genes required for full expression of cell-wall-penetration resistance against powdery mildew pathogens were examined for macroscopic and microscopic alterations in M. grisea growth and symptoms. RAR1 contributed to resistance in epidermis and mesophyll at different stages of fungal infection dependent on the MLO/mlo-5 status. Whereas no ROR2 effect was detected, ROR1 was found to contribute to cell-wall-penetration resistance, at least in the epidermis. Application of the actin agonist cytochalasin E promoted cell wall penetration by M. grisea in a dose-dependent manner, demonstrating an involvement of the actin cytoskeleton in penetration resistance.


Challenges in the anesthetic management of ambulatory patients in the MRI suites.
MRI is becoming an indispensable diagnostic tool. The need for prolonged motion-free periods has substantially increased the need for deep sedation or anesthesia in a challenging environment. This review summarises recent literature with respect to pharmacological sedative strategies, nonpharmacological alternative approaches, airway management and safety issues in the ambulatory setting. Most literature researches the pediatric patient population. The American Society of Pediatrics published guidelines for monitoring and management of pediatric patients during sedation for diagnostic procedures. Dexmedetomidine is the most researched agent for sedation. It remains uncertain what the clinical implications are of the potential neurotoxicity of repeat sedation or anesthesia in young children. Airway strategies highlight the use of end-tidal carbon dioxide monitoring. Technical imaging advancement and nonpharmacological sedation alternatives allow for shorter procedures with a lower need for sedation. The anesthetic management of ambulatory patients in the MRI environment has its specific challenges and safety issues. However, the implementation of safety guidelines, new pharmacological and alternative nonpharmacological sedation strategies offer interesting perspectives to tackle these challenges.


Atherofibrosis - a unique and common process of the disease pathogenesis of atherosclerosis and fibrosis - lessons for biomarker development.
The hallmark of a variety of fibrotic diseases such as liver fibrosis, lung fibrosis, skin fibrosis and atherosclerosis is extensive extracellular matrix remodeling (ECMr) of the disease affected tissue. Inflammation often leads to tissue disruption and destruction, upon which locally released battery of proteases such as matrix metalloproteinases and cysteine proteases degrade the surrounding matrix. The degradation products of ECM proteins, the co-called neoepitopes, are released into the systemic circulation. By recent development of Enzyme-Linked Immunosorbent Assays (ELISAs) detecting the pathological tissue turnover in atherosclerosis and liver fibrosis, we have introduced a novel class of biomarkers into the field of fibrotic diseases, which have been proved efficient in the early diagnosis. This work has resulted in identification of common mechanisms involving specific cell types, proteins and proteases as well as pathways shared among the fibrotic diseases. In this analysis we seek to answer following questions: a) Are there common disease mechanisms and cell types involved in both atherosclerosis and fibrosis? b) Can the lessons learned in developing fibrosis biomarkers be used for the development of atherosclerosis biomarkers? Our hypothesis is that by answering the above questions, we may be able to improve general understanding of the early-stage disease initiation and progression of fibrotic diseases, which in turn may aid in early diagnosis, prognosis and ultimately patient management.


Glomerular filtrate proteins in acute cardiorenal syndrome.
Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.


The Economic Burden of Road Traffic Injuries on Households in South Asia.
Globally, road traffic injuries accounted for about 1.36 million deaths in 2015 and are projected to become the fourth leading cause of disability-adjusted life years (DALYs) lost by 2030. One-fifth of these deaths occurred in South Asia where road traffic injuries are projected to increase by 144% by 2020. Despite this rapidly increasing disease burden there is limited evidence on the economic burden of road traffic injuries on households in South Asia. We applied a novel coarsened exact matching method to assess the household economic burden of road traffic injuries using nationally representative World Health Survey data from five South Asian countries- Bangladesh, India, Nepal, Pakistan and Sri Lanka collected during 2002-2003. We examined the impact of road traffic injuries on household out-of-pocket (OOP) health spending, household non-medical consumption expenditure and the employment status of the traffic injury-affected respondent. We exactly matched a household (after 'coarsening') where a respondent reported being involved in a road traffic injury to households where the respondent did not report a road traffic injury on each of multiple observed household characteristics. Our analysis found that road traffic injury-affected households had significantly higher levels of OOP health spending per member (I$0.75, p<0.01), higher OOP spending on drugs per member (I$0.30, p = 0.03), and higher OOP hospital spending per member (I$0.29, p<0.01) in the four weeks preceding the survey. Indicators of "catastrophic spending" were also significantly higher in road traffic injury-affected households: 6.45% (p<0.01) for a threshold of OOP health spending to total household spending ratio of 20%, and 7.40% (p<0.01) for a threshold of OOP health spending to household 'capacity to pay' ratio of 40%. However, no statistically significant effects were observed for household non-medical consumption expenditure, and employment status of the road traffic injury-affected individual. Our analysis points to the need for financial risk protection against the road traffic injury-related OOP health expenditure and a focus on prevention.


A clinical instrument to guide brief interventions for adolescents with substance use concerns.
Adolescent substance use is an important public health problem in New Mexico and the United States. The New Mexico Department of Health school-based health centers (SBHCs) universally administer a validated screen, the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), for adolescent substance use concerns; however, quality assurance efforts revealed that SBHC providers needed more information at the point of screening to initiate brief interventions for students with positive CRAFFT screens. The CHISPA (Cocaine, Heroin, IV drugs, Synthetic pot, Pot, Alcohol) was developed to gather specific information on recent substance use experience to guide brief interventions. This paper describes the development and initial reliability and validity of data obtained using the CHISPA instrument. In 2015, 99 high school-aged SBHC users in Albuquerque, New Mexico, completed the CRAFFT and CHISPA twice over 2 weeks using standard test-retest methods. Using the CHISPA, students reported for the prior 3 months substances used, frequency of use, and signs of addiction or acute danger (adverse events). Retest reliability for the CRAFFT score was 0.82. CHISPA retest reliabilities were 0.75 for alcohol use; 0.91 for having used any substances; 0.92 for number of substances used; 0.81 for frequency of substance use; and 0.79 for number of adverse events. CRAFFT scores correlated with CHISPA measures of number of substances used at 0.62; with frequency of substance use at 0.58; and with number of adverse events at 0.64. CHISPA measures show preliminary evidence of reliability and validity. SBHC providers and other providers in primary care settings who use the CRAFFT screen may benefit from using the CHISPA to define recent substance use experience to guide brief interventions for adolescents with substance use concerns. The CHISPA instrument is currently being tested in electronic form in selected SBHCs in the state of New Mexico.


Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.
A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. Glucose tolerance tests were performed on days 2 and 3 of treatment with vehicle (HF-V) or proapoptotic peptide (HF-PP) and mice pair-fed to HF-PP (HF-PF) in obese mice on a high-fat diet (HFD). Serum metabolic variables, including lipid profile, adipokines, individual fatty acids, and acylcarnitines, were measured. Microarray analysis was performed in epididymal fat of lean or obese mice treated with vehicle or proapoptotic peptide (PP). PP rapidly and potently improved glucose tolerance of obese mice in a weight- and food intake-independent manner. Serum insulin and triglycerides were decreased in HF-PP relative to HF-V. Levels of fatty acids and acylcarnitines were distinctive in HF-PP compared with HF-V or HF-PF. Microarray analysis in AT revealed that pathways involved in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation were changed by exposure to HFD and were reversed by PP administration. These studies suggest a novel role of the AT vasculature in glucose homeostasis and lipid metabolism.


Dendrimer solutions: a Monte Carlo study.
We study the conformational properties of dendrimers with flexible spacers in solutions over a wide range of concentrations from dilute solutions to melts. By combining large scale computer simulations using the bond fluctuation model with scaling arguments we identify the semi-dilute regime of dendrimers which is controlled by the concentration behavior of the linear spacers. Associated with this observation we find that the decrease in the size of flexible dendrimers is accompanied by increasing interpenetration between the molecules with increasing concentration of the solution. In the melt state we show that the size of individual dendrimers follows the scaling prediction for isolated dendrimers at the θ-point rather than that of collapsed dendrimers. The pair correlation functions between the centers of dendrimers indicate that for short spacers dendrimer solutions retain the morphological characteristics of simple liquids. For long spacers the functions reveal high penetration of neighboring dendrimers in the melt state. Our studies show that flexible dendrimers in solution can be understood with arguments similar to those of linear polymers. The role of generation is to influence the particular form of the crossover-function.


Molecular characterization of blaESBL-producing Escherichia coli cultured from pig farms in Ireland.
To characterize ESBL-encoding Escherichia coli cultured from pigs and their plasmids carrying these genes following conjugation into recipient strains. Six ESBL-producing E. coli were recovered from faecal samples taken from pigs along with a further isolate from the environment of a farrowing house on three pig farms in Ireland. These isolates were characterized by phylogenetic grouping, MLST and ESBL genotype analyses. Conjugation experiments were carried out in broth mating assays. S1-nuclease PFGE was used to determine the plasmid profiles. Whole-genome sequences of the seven E. coli were determined and subsequently analysed. Phylogenetic groups and the corresponding MLST STs identified among the seven tested E. coli isolates included A/ST10, A/ST34, C/ST23 and C/ST1629. All seven isolates carried one or more high-molecular-weight plasmids and demonstrated the ability to transfer their cefotaxime resistance phenotype at high frequencies. Five transmissible plasmid replicon types were detected, including IncK/B (n = 3), IncI1 (n = 2), IncFIA (n = 1), IncFIB (n = 1) and IncN (n = 1). ESBL-encoding genes, including blaCTX-M-14, blaCTX-M-15 and blaTEM-20, were identified. As the first report from pig sources in Ireland, characterization of these ESBL-encoding isolates and their transmissible plasmids extends our understanding on these resistance markers from porcine E. coli.


Meditation awareness training for the treatment of workaholism: A controlled trial.
Background and aims Workaholism is a form of behavioral addiction that can lead to reduced life and job satisfaction, anxiety, depression, burnout, work-family conflict, and impaired productivity. Given the number of people affected, there is a need for more targeted workaholism treatments. Findings from previous case studies successfully utilizing second-generation mindfulness-based interventions (SG-MBIs) for treating behavioral addiction suggest that SG-MBIs may be suitable for treating workaholism. This study conducted a controlled trial to investigate the effects of an SG-MBI known as meditation awareness training (MAT) on workaholism. Methods Male and female adults suffering from workaholism (n = 73) were allocated to MAT or a waiting-list control group. Assessments were performed at pre-, post-, and 3-month follow-up phases. Results MAT participants demonstrated significant and sustained improvements over control-group participants in workaholism symptomatology, job satisfaction, work engagement, work duration, and psychological distress. Furthermore, compared to the control group, MAT participants demonstrated a significant reduction in hours spent working but without a decline in job performance. Discussion and conclusions MAT may be a suitable intervention for treating workaholism. Further controlled intervention studies investigating the effects of SG-MBIs on workaholism are warranted.


Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy.
This is an update of a Cochrane review first published in The Cochrane Library in Issue 3, 2010.For many patients with head and neck cancer, oral nutrition will not provide adequate nourishment during treatment with radiotherapy or chemoradiotherapy due to the acute toxicity of treatment, obstruction caused by the tumour, or both. The optimal method of enteral feeding for this patient group has yet to be established. To compare the effectiveness of different enteral feeding methods used in the nutritional management of patients with head and neck cancer receiving radiotherapy or chemoradiotherapy using the clinical outcomes, nutritional status, quality of life and rates of complications. Our extensive search included the Cochrane ENT Group Trials Register, CENTRAL, PubMed, EMBASE, CINAHL, AMED and ISI Web of Science. The date of the most recent search was 13 February 2012. Randomised controlled trials comparing one method of enteral feeding with another, e.g. nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) feeding, for adult patients with a diagnosis of head and neck cancer receiving radiotherapy and/or chemoradiotherapy. Two authors independently assessed trial quality and extracted data using standardised forms. We contacted study authors for additional information. One randomised controlled trial met the criteria for inclusion in this review. No further studies were identified when we updated the searches in 2012.Patients diagnosed with head and neck cancer, being treated with chemoradiotherapy, were randomised to PEG or NG feeding. In total only 33 patients were eligible for analysis as the trial was terminated early due to poor accrual. A high degree of bias was identified in the study.Weight loss was greater for the NG group at six weeks post-treatment than for the PEG group (P = 0.001). At six months post-treatment, however, there was no significant difference in weight loss between the two groups. Anthropometric measurements recorded six weeks post-treatment demonstrated lower triceps skin fold thickness for the NG group compared to the PEG group (P = 0.03). No statistically significant difference was found between the two different enteral feeding techniques in relation to complication rates or patient satisfaction. The duration of PEG feeding was significantly longer than for the NG group (P = 0.0006). In addition, the study calculated the cost of PEG feeding to be 10 times greater than that of NG, though this was not found to be significant. There was no difference in the treatment received by the two groups. However, four PEG fed patients and two NG fed patients required unscheduled treatment breaks of a median of two and six days respectively.We identified no studies of enteral feeding involving any form of radiologically inserted gastrostomy (RIG) feeding or comparing prophylactic PEG versus PEG for inclusion in the review. There is not sufficient evidence to determine the optimal method of enteral feeding for patients with head and neck cancer receiving radiotherapy and/or chemoradiotherapy. Further trials of the two methods of enteral feeding, incorporating larger sample sizes, are required.


Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences.
Changes in gene regulation are suspected to comprise one of the driving forces for evolution. To address the extent of cis-regulatory changes and how they impact on gene regulatory networks across eukaryotes, we systematically analyzed the evolutionary dynamics of target gene batteries controlled by 16 different transcription factors. We found that gene batteries show variable conservation within vertebrates, with slow and fast evolving modules. Hence, while a key gene battery associated with the cell cycle is conserved throughout metazoans, the POU5F1 (Oct4) and SOX2 batteries in embryonic stem cells show strong conservation within mammals, with the striking exception of rodents. Within the genes composing a given gene battery, we could identify a conserved core that likely reflects the ancestral function of the corresponding transcription factor. Interestingly, we show that the association between a transcription factor and its target genes is conserved even when we exclude conserved sequence similarities of their promoter regions from our analysis. This supports the idea that turnover, either of the transcription factor binding site or its direct neighboring sequence, is a pervasive feature of proximal regulatory sequences. Our study reveals the dynamics of evolutionary changes within metazoan gene networks, including both the composition of gene batteries and the architecture of target gene promoters. This variation provides the playground required for evolutionary innovation around conserved ancestral core functions.


The Language of Cigar Use: Focus Group Findings on Cigar Product Terminology.
The consumption of cigar products has increased since 2000. The multiple product types within this category, combined with the varied language with which consumers refer to them, present challenges for accurately assessing the prevalence of cigar product use. Surveillance is also complicated by the fact that these products can be used to smoke marijuana, as "blunts"-cigars in which the tobacco is removed and replaced with marijuana. Few studies exist regarding the language and terminology used to describe these products. Sixteen focus groups were conducted in five cities in the United States between March and May of 2014. Participants (N = 123) included adults who had used cigars, cigarillos, or little cigars in the past 30 days. A semi-structured moderator guide was used to gather data on the terms used to identify cigar product subtypes and the language used to describe the products and their use. Participants used a variety of terms for each product subtype. Brand names were often used, as well as slang terms, including terms describing cigars modified for marijuana use. Some subtypes were less likely than others to be considered "cigars." Participants had mixed opinions about whether users of cigar products are "smokers." Users of cigar products may classify or label products differently from researchers and policy makers, and many refer to their product by brand name or a slang term. These findings have implications for future research, instrument design, and public health messaging about cigar products. This study adds to the body of evidence highlighting the challenges for measurement and surveillance of non-cigarette tobacco products, including cigars. Findings illustrate the myriad terms used by consumers to describe their use of cigar product subtypes, as well as the complexity of distinguishing between use of cigar products as intended, versus as a vehicle for smoking marijuana. Future research aimed to enhance specificity of cigar use measures will enable policy-makers and public health practitioners to more fully characterize prevalence and patterns of use by cigar subtype.


Trends in stroke incidence and mortality in Hawaiian Japanese men.
Vital statistics show a sharp decline in stroke mortality since the late 1960s. It is not clear whether this has been associated with a decline in stroke incidence. Since 1966 the Honolulu Heart Program has monitored the incidence and mortality of coronary heart disease and stroke in a target population of 11,136 men of Japanese ancestry living on Oahu. Trends were analyzed from January 1, 1969, through December 31, 1988. Of 7893 men aged 45 to 68 years and free of stroke at entry examination, 530 developed first episodes of stroke in the period 1969 to 1988 (389 cases of thromboembolic stroke, 124 cases of hemorrhagic stroke, and 17 cases of stroke of unknown type). Age-adjusted annual stroke incidence declined from 5.1 per 1000 person-years in 1969 to 1972 to 2.4 in 1985 to 1988. The incidences of thromboembolic stroke, hemorrhagic stroke, and total stroke decreased 3.5%, 4.2%, and 4.4% per year, respectively. The 1-month case-fatality rates for thromboembolic stroke decreased moderately; those for hemorrhagic stroke fell dramatically. These findings suggest that the decline in stroke mortality in the past two or three decades results from a decline in both incidence rates and early case-fatality rates in thromboembolic and hemorrhagic stroke and stroke of unknown type. The decreases may be related to changes in risk factors, such as the decline in blood pressure and the decrease in cigarette smoking, as well as improvements in diagnosis and treatment.


Microbes as Engines of Ecosystem Function: When Does Community Structure Enhance Predictions of Ecosystem Processes?
Microorganisms are vital in mediating the earth's biogeochemical cycles; yet, despite our rapidly increasing ability to explore complex environmental microbial communities, the relationship between microbial community structure and ecosystem processes remains poorly understood. Here, we address a fundamental and unanswered question in microbial ecology: 'When do we need to understand microbial community structure to accurately predict function?' We present a statistical analysis investigating the value of environmental data and microbial community structure independently and in combination for explaining rates of carbon and nitrogen cycling processes within 82 global datasets. Environmental variables were the strongest predictors of process rates but left 44% of variation unexplained on average, suggesting the potential for microbial data to increase model accuracy. Although only 29% of our datasets were significantly improved by adding information on microbial community structure, we observed improvement in models of processes mediated by narrow phylogenetic guilds via functional gene data, and conversely, improvement in models of facultative microbial processes via community diversity metrics. Our results also suggest that microbial diversity can strengthen predictions of respiration rates beyond microbial biomass parameters, as 53% of models were improved by incorporating both sets of predictors compared to 35% by microbial biomass alone. Our analysis represents the first comprehensive analysis of research examining links between microbial community structure and ecosystem function. Taken together, our results indicate that a greater understanding of microbial communities informed by ecological principles may enhance our ability to predict ecosystem process rates relative to assessments based on environmental variables and microbial physiology.


Drought and exogenous abscisic acid alter hydrogen peroxide accumulation and differentially regulate the expression of two maize RD22-like genes.
Increased biosynthesis of abscisic acid (ABA) occurs in plants in response to water deficit, which is mediated by changes in the levels of reactive oxygen species such as H2O2. Water deficit and ABA induce expression of some RD22-like proteins. This study aimed to evaluate the effect of water deficit and exogenous ABA (50 µM ABA applied every 24 hours for a total of 72 hours) on H2O2 content in Zea mays (maize) and to characterise genes encoding two putative maize RD22-like proteins (designated ZmRD22A and ZmRD22B). The expression profiles of the two putative maize RD22-like genes in response to water deficit and treatment with ABA were examined in leaves. In silico analyses showed that the maize RD22-like proteins share domain organisation with previously characterized RD22-like proteins. Both water deficit and exogenous ABA resulted in increased H2O2 content in leaves but the increase was more pronounced in response to water deficit than to exogenous ABA. Lignin content was not affected by exogenous ABA, whereas it was decreased by water deficit. Expression of both RD22-like genes was up-regulated by drought but the ZmRD22A gene was not influenced by exogenous ABA, whereas ZmRD22B was highly responsive to exogenous ABA.


Correction of hysteretic respiratory motion in SPECT myocardial perfusion imaging: Simulation and patient studies.
Amplitude-based respiratory gating is known to capture the extent of respiratory motion (RM) accurately but results in residual motion in the presence of respiratory hysteresis. In our previous study, we proposed and developed a novel approach to account for respiratory hysteresis by applying the Bouc-Wen (BW) model of hysteresis to external surrogate signals of anterior/posterior motion of the abdomen and chest with respiration. In this work, using simulated and clinical SPECT myocardial perfusion imaging (MPI) studies, we investigate the effects of respiratory hysteresis and evaluate the benefit of correcting it using the proposed BW model in comparison with the abdomen signal typically employed clinically. The MRI navigator data acquired in free-breathing human volunteers were used in the specially modified 4D NCAT phantoms to allow simulating three types of respiratory patterns: monotonic, mild hysteresis, and strong hysteresis with normal myocardial uptake, and perfusion defects in the anterior, lateral, inferior, and septal locations of the mid-ventricular wall. Clinical scans were performed using a Tc-99m sestamibi MPI protocol while recording respiratory signals from thoracic and abdomen regions using a visual tracking system (VTS). The performance of the correction using the respiratory signals was assessed through polar map analysis in phantom and 10 clinical studies selected on the basis of having substantial RM. In phantom studies, simulations illustrating normal myocardial uptake showed significant differences (P < 0.001) in the uniformity of the polar maps between the RM uncorrected and corrected. No significant differences were seen in the polar map uniformity across the RM corrections. Studies simulating perfusion defects showed significantly decreased errors (P < 0.001) in defect severity and extent for the RM corrected compared to the uncorrected. Only for the strong hysteretic pattern, there was a significant difference (P < 0.001) among the RM corrections. The errors in defect severity and extent for the RM correction using abdomen signal were significantly higher compared to that of the BW (severity = -4.0%, P < 0.001; extent = -65.4%, P < 0.01) and chest (severity = -4.1%, P < 0.001; extent = -52.5%, P < 0.01) signals. In clinical studies, the quantitative analysis of the polar maps demonstrated qualitative and quantitative but not statistically significant differences (P = 0.73) between the correction methods that used the BW signal and the abdominal signal. This study shows that hysteresis in respiration affects the extent of residual motion left in the RM-binned data, which can impact wall uniformity and the visualization of defects. Thus, there appears to be the potential for improved accuracy in reconstruction in the presence of hysteretic RM with the BW model method providing a possible step in the direction of improvement.


Identification and initial characterisation of a protein involved in Campylobacter jejuni cell shape.
Campylobacter jejuni is the leading cause of bacterial food borne illness. While helical cell shape is considered important for C. jejuni pathogenesis, this bacterium is capable of adopting other morphologies. To better understand how helical-shaped C. jejuni maintain their shape and thus any associated colonisation, pathogenicity or other advantage, it is first important to identify the genes and proteins involved. So far, two peptidoglycan modifying enzymes Pgp1 and Pgp2 have been shown to be required for C. jejuni helical cell shape. We performed a visual screen of ∼2000 transposon mutants of C. jejuni for cell shape mutants. Whole genome sequence data of the mutants with altered cell shape, directed mutants, wild type stocks and isolated helical and rod-shaped 'wild type' C. jejuni, identified a number of different mutations in pgp1 and pgp2, which result in a change in helical to rod bacterial cell shape. We also identified an isolate with a loss of curvature. In this study, we have identified the genomic change in this isolate, and found that targeted deletion of the gene with the change resulted in bacteria with loss of curvature. Helical cell shape was restored by supplying the gene in trans. We examined the effect of loss of the gene on bacterial motility, adhesion and invasion of tissue culture cells and chicken colonisation, as well as the effect on the muropeptide profile of the peptidoglycan sacculus. Our work identifies another factor involved in helical cell shape.


Assessment of hand-transmitted vibration exposure from motorized forks used for beach-cleaning operations.
Motorized vibrating manure forks were used in beach-cleaning operations following the massive Deepwater Horizon oil spill in the Gulf of Mexico during the summer of 2010. The objectives of this study were to characterize the vibration emissions of these motorized forks and to provide a first approximation of hand-transmitted vibration exposures to workers using these forks for beach cleaning. Eight operators were recruited to operate the motorized forks during this laboratory study. Four fork configurations were used in the study; two motor speeds and two fork basket options were evaluated. Accelerations were measured near each hand as the operators completed the simulated beach-cleaning task. The dominant vibration frequency for these tools was identified to be around 20 Hz. Because acceleration was found to increase with motor speed, workers should consider operating these tools with just enough speed to get the job done. These forks exhibited considerable acceleration magnitudes when unloaded. The study results suggest that the motor should not be operated with the fork in the unloaded state. Anti-vibration gloves are not effective at attenuating the vibration frequencies produced by these forks, and they may even amplify the transmitted vibration and increase hand/arm fatigue. While regular work gloves are suitable, vibration-reducing gloves may not be appropriate for use with these tools. These considerations may also be generally applicable for the use of motorized forks in other workplace environments.


Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma.
Harmine hydrochloride (Har-hc), a derivative from Harmine which is a natural extractive from plants, has been considered for treatment of kinds of cancers and cerebral diseases. In this study, we found that Har-hc clearly decreased cell viability, induced apoptosis and inhibited Akt phosphorylation in glioblastoma cell lines. Moreover, Har-hc had the ability to inhibit self-renewal and promote differentiation of glioblastoma stem like cells (GSLCs) accompanied by inhibition of Akt phosphorylation. Especially, we demonstrated that Har-hc inhibited neurosphere formation of human primary GSLCs. In vivo test also confirmed Har-hc decreased the tumorigenicity of GSLCs. Thus we conclude that Har-hc has potent anti-cancer effects in glioblastoma cells, which is at least partially via inhibition of Akt phosphorylation. Administration of Har-hc may act as a new approach to glioblastoma treatment.


Plasma concentrations of asymmetric dimethylarginine, nitric oxide and homocysteine in patients with slow coronary flow.
Slow coronary flow (SCF) is slow progression of contrast agent in the coronary arteries in the absence of stenosis in epicardial coronary vessels. Endothelial dysfunction and diffuse atherosclerosis have been proposed for the etiology of SCF. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, levels are associated with an increased risk of endothelial dysfunction and atherosclerosis. ADMA levels may be increased by homocysteine. The aim of this study was to evaluate the relationship between ADMA, nitric oxide and homocysteine in patients with SCF. The study group consisted of 50 patients with SCF. An age- and gender-matched control group was composed of 30 patients with normal coronary arteries and normal coronary flow on coronary angiography. We measured ADMA, nitric oxide and homocysteine plasma concentrations in all patients. Plasma nitric oxide concentrations were significantly lower in the SCF group than in the control group (11.4 ± 6, 16.1 ± 9, p = 0.02). Plasma ADMA concentrations (0.9 ± 0.3, 0.7 ± 0.3, p = 0.01) and plasma homocysteine concentrations (12.4 ± 5, 9.8 ± 2, p = 0.03) were significantly higher in the SCF group than control group. The mean TIMI frame count (TFC) was significantly correlated with plasma ADMA (r = 0.26, p = 0.02) and homocysteine (r = 0.28, p = 0.02) concentrations, but not with nitric oxide concentrations (r = - 0.18, p = 0.13). In linear regression analysis, plasma ADMA concentrations (β = 4.6, p = 0.005) and homocysteine concentrations (β = 0.2, p = 0.03) were independently and positively associated with mean TFC. Our results suggest that plasma concentrations of ADMA and homocysteine are increased in SCF and also that these are independent predictors of SCF.


Structural and thermodynamic basis for the enhanced transcriptional control by the human papillomavirus strain-16 E2 protein.
Strain 16 of the human papillomavirus is responsible for the largest number of cases of cervical cancers linked to this virus, and the E2 protein is the transcriptional regulator of all viral genes. We present the first structure for the DNA binding domain of HPV16 E2 bound to DNA, and in particular, to a natural cognate sequence. The NMR structure of the protein backbone reveals that the overall conformation remains virtually unchanged, and chemical shift analysis of the protein bound to a shorter DNA duplex uncovered a contact out of the minimal E2 DNA binding site, made by lysine 349. This contact was confirmed by titration calorimetry and mutagenesis, with a contribution of 1.0 kcal mol(-)(1) to binding energy. HPV16 E2 has the highest DNA binding affinity and exerts a strict transcriptional control, translated into the repression of the E6 and E7 oncogenes. These novel features provide the structural and thermodynamic basis for this tight transcriptional control, the loss of which correlates with carcinogenesis.


The association between socio-economic position and diet quality in Australian adults.
We aimed to investigate the association between multiple measures of socio-economic position (SEP) and diet quality, using a diet quality index representing current national dietary guidelines, in the Australian adult population. Cross-sectional study. Linear regression analyses were used to estimate the association between indicators of SEP (educational attainment, level of income and area-level disadvantage) and diet quality (measured using the Dietary Guideline Index (DGI)) in the total sample and stratified by sex and age (≤55 years and >55 years). A large randomly selected sample of the Australian adult population. Australian adults (n 9296; aged ≥25 years) from the Australian Diabetes, Obesity and Lifestyle Study. A higher level of educational attainment and income and a lower level of area-level disadvantage were significantly associated with a higher DGI score, across the gradient of SEP. The association between indicators of SEP and DGI score was consistently stronger among those aged ≤55 years compared with their older counterparts. The most disadvantaged group had a DGI score between 2 and 5 units lower (depending on the marker of SEP) compared with the group with the least disadvantage. A higher level of SEP was consistently associated with a higher level of diet quality for all indicators of SEP examined. In order to reduce socio-economic inequalities in diet quality, healthy eating initiatives need to act across the gradient of socio-economic disadvantage with a proportionate focus on those with greater socio-economic disadvantage.


Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors.
The selection of Drosophila melanogaster sense organ precursors (SOPs) for sensory bristles is a progressive process: each neural equivalence group is transiently defined by the expression of proneural genes (proneural cluster), and neural fate is refined to single cells by Notch-Delta lateral inhibitory signalling between the cells. Unlike sensory bristles, SOPs of chordotonal (stretch receptor) sense organs are tightly clustered. Here we show that for one large adult chordotonal SOP array, clustering results from the progressive accumulation of a large number of SOPs from a persistent proneural cluster. This is achieved by a novel interplay of inductive epidermal growth factor-receptor (EGFR) and competitive Notch signals. EGFR acts in opposition to Notch signalling in two ways: it promotes continuous SOP recruitment despite lateral inhibition, and it attenuates the effect of lateral inhibition on the proneural cluster equivalence group, thus maintaining the persistent proneural cluster. SOP recruitment is reiterative because the inductive signal comes from previously recruited SOPs.


What is the future of magnetic nanoparticles in the axillary management of breast cancer?
Magnetic nanoparticles (MNPs) possess unique properties, which make them highly attractive for medical applications. The use of MNPs in surgery has mainly been focused on their role in the identification of metastatic lymph node involvement. There have been developments within this field, including ongoing and newly conducted clinical trials. The current published evidence for the use of MNPs in assessing metastatic lymph node spread using sentinel lymph node biopsy and non-invasive imaging modalities is reviewed and future applications considered.


Nutrient movement and mycelial reorganization in established systems of Phanerochaete velutina, following arrival of colonized wood resources.
The effect of arrival of wood resources, pre-colonized by Coriolus versicolor, Phlebia radiata, Stereum hirsutum, and Vuilleminia comedens, on mycelial systems of Phanerochaete velutina was studied in trays of nonsterile soil in the laboratory over 5 months. Morphological responses were quantified non-destructively using image analysis. In a parallel series of experiments, nutrient movement was also quantified non-destructively using (32)P monitoring with a scintillation probe and subsequently by destructively harvesting after 155 days. The presence of a fungus occupying a newly arriving resource had major effects on deployment of biomass and on the uptake and allocation of phosphorus in the established Pha. velutina system. The effects varied depending on the species occupying the new resource. Hyphal coverage was greater in the half of the system to which new resources were added. Following addition of new resources, there was massive redeployment of biomass away from regions with no new resource when the new resource was (1) uncolonized, (2) colonized by V. comedens, or (3) colonized by S. hirsutum (although to a lesser extent with the latter), but not with others. (32)P was taken up by Pha. velutina both in the vicinity of the inoculum and the new resource and was translocated to the new resource from both sites of uptake; however, the local supply contributed most. Bidirectional translocation also occurred. The results are discussed in relation to mycelial foraging strategies, nutrient translocation, and partitioning within mycelial cord systems.


Normal contrast enhancement of extraocular muscles: fat-suppressed MR findings.
To evaluate contrast enhancement of normal extraocular muscles in the orbit. Noncontrast and contrast-enhanced T1-weighted images of the orbit were acquired using a fat-suppression MR technique in eight patients with no orbital disease. Contrast enhancement of 64 extraocular muscles was evaluated and compared with that of 16 temporal muscles. Compared with temporal muscles, all extraocular muscles markedly enhanced after administration of contrast material. Because normal extraocular muscles enhanced markedly with contrast material, more attention should be paid to these muscles when using contrast-enhanced, fat-suppressed T1-weighted MR imaging to evaluate pathologic conditions.


Frontal electroencephalographic correlates of individual differences in emotion expression in infants: a brain systems perspective on emotion.
Emotion expressions can be characterized by both the type of emotion displayed and the intensity with which the emotion is expressed. Individual differences in these two aspects of emotion appear to vary independently and may perhaps account for distinct dimensions of temperament, personality, and vulnerability to psychopathology. We reviewed several sets of data gathered in our laboratory that indicate that these two dimensions of emotion expression are associated with distinct and independent patterns of frontal EEG activity in infants. Specifically, whereas the type of emotion expression was found to be associated with asymmetries in frontal EEG activity, the intensity of emotion expression was found to be associated with generalized activation of both the right and the left frontal regions. Moreover, we reviewed and provided evidence that measures of asymmetrical frontal activity are better predictors of individual differences in the tendency to express certain emotions, such as distress and sadness, whereas measures of generalized frontal activity are better predictors of individual differences in emotional reactivity and emotion intensity. The neuroanatomical bases of emotion were discussed with special reference to the role of the frontal lobe in emotion regulation. It was hypothesized that the frontal activation asymmetries that have been found to accompany emotion expressions reflect specific regulation strategies. The left frontal region is specialized for regulation strategies involving action schemes that serve to maintain continuity and stability of the organism-environment relation and of ongoing motor schemes, such as those involved in language and the expression of happiness and interest. In contrast, the right frontal region appears to be specialized for regulation strategies that involve processing novel stimuli that disrupt ongoing activity, such as might occur during the expression of fear, disgust, and distress. Furthermore, it was proposed that individual differences in patterns of frontal EEG asymmetries during emotion may be related to socialization influences rather than solely innate factors. It was speculated that the pattern of generalized frontal lobe activation that accompanies the experience of intense emotions may reflect, in part, the relatively diffuse influence of subcortical structures on the cortex and may serve to increase the infant's general readiness to receive and respond to significant external stimuli.


A conceptual model of the role of complexity in the care of patients with multiple chronic conditions.
Effective healthcare for people with multiple chronic conditions (MCC) is a US priority, but the inherent complexity makes both research and delivery of care particularly challenging. As part of AHRQ Multiple Chronic Conditions Research Network (MCCRN) efforts, the Network developed a conceptual model to guide research in this area. To synthesize methodological and topical issues relevant to MCC patient care into a framework that can improve the delivery of care and advance future research about caring for patients with MCC. The Network synthesized essential constructs for MCC research identified from roundtable discussion, input from expert advisors, and previously published models. The AHRQ MCCRN conceptual model defines complexity as the gap between patient needs and healthcare services, taking into account both the multiple considerations that affect the needs of MCC patients, as well as the contextual factors that influence service delivery. The model reframes processes and outcomes to include not only clinical care quality and experience, but also patient health, well being, and quality of life. The single-condition paradigm for treating needs one-by-one falls apart and highlights the need for care systems to address dynamic patient needs. Defining complexity in terms of the misalignment between patient needs and services offers new insights in how to research and develop solutions to patient care needs.


Orexin regulates bone remodeling via a dominant positive central action and a subordinate negative peripheral action.
Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here, we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R null mice exhibit low bone mass owing to elevated circulating leptin, whereas central administration of an OX2R-selective agonist augments bone mass. Conversely, orexin also functions peripherally through orexin receptor 1 (OX1R) in the bone to suppress bone formation. OX1R null mice exhibit high bone mass owing to a differentiation shift from marrow adipocyte to osteoblast that results from higher osseous ghrelin expression. The central action is dominant because bone mass is reduced in orexin null and OX1R2R double null mice but enhanced in orexin-overexpressing transgenic mice. These findings reveal orexin as a critical rheostat of skeletal homeostasis that exerts a yin-yang dual regulation and highlight orexin as a therapeutic target for osteoporosis.


Addressing tri-morbidity (hepatitis C, psychiatric disorders, and substance use): the importance of routine mental health screening as a component of a comanagement model of care.
Recent studies suggest that most patients with hepatitis C virus (HCV) infection commonly present to medical clinics with active psychiatric and substance use disorders. However, routine screening for these disorders is generally not done. The purpose of our study was to assess prospectively the frequency of psychiatric and substance use disorders in patients presenting for initial assessment of a positive HCV antibody test result. A sample of 293 patients represented the majority of patients scheduled for their initial hepatology clinic visit at the Portland Veterans Affairs Medical Center between September 2002 and September 2003. The patient screening questionnaire, Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and the Beck Depression Inventory (BDI-II) were administered to all patients. At screening, 93% of the patients had a current or past history of at least 1 psychiatric disorder, and 73% had >or=2 disorders. The most common disorders included depression (81%), posttraumatic stress disorder (62%), any substance use disorder (58%), bipolar disorder (20%), and other psychotic disorders (17%). One hundred two patients (35%) had baseline BDI-II scores in the moderate-to-severe range of depression (>19), and 61 (21%) had AUDIT-C scores indicating current heavy alcohol use (>or=4). Psychiatric and substance use disorders are highly prevalent among veterans with chronic hepatitis C. Thirty-five percent have significant symptoms of depression before the initiation of treatment with interferon (IFN). Routine screening for underlying psychiatric and substance use disorders and early treatment intervention before initiating antiviral therapy is essential to prevent worsening of depression and to optimize the outcome of treatment with IFN. Comanagement treatment models involving mental health care may expand the pool of patients eligible to receive treatment with IFN, as well as enhance treatment outcomes.


Lipophilic index, kidney function, and kidney function decline.
Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended re-examination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction ≥30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m2 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m2, p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). A high LI was associated with lower kidney function, kidney function decline, and CKD progression.


Accessory plantaris muscle: anatomy and prevalence.
Accessory and anomalous muscles have been described in humans, but only a few at the level of the knee. The aim of this retrospective cohort analysis was to determine the prevalence of a new accessory muscle located at the level of the knee detected with magnetic resonance imaging (MRI). The accessory muscle is designated an accessory plantaris muscle in this study due to its intimate origin with the normal plantaris muscle. Retrospective review of 1,000 consecutive MRI exams of the knee performed on patients presenting with acute or chronic knee symptoms revealed an accessory plantaris muscle in 63 of the 1,000 patients (6.3%)-38 males (7.5%) and 25 females (5.1%). Origin of 62 of 63 of the accessory plantaris muscles merged with the origin of the normal plantaris muscle, and one of 63 merged with the origin of the lateral head of the gastrocnemius muscle. These accessory plantaris muscles inserted into the iliotibial band, the lateral patellar retinaculum, or the iliotibial tract.


Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition.
PTPN11 encodes the Shp2 non-receptor protein-tyrosine phosphatase implicated in several signaling pathways. Activating mutations in Shp2 are commonly associated with juvenile myelomonocytic leukemia but are not as well defined in other neoplasms. Here we report that Shp2 mutations occur in human acute myeloid leukemia (AML) at a rate of 6.6% (6/91) in the ECOG E1900 data set. We examined the role of mutated Shp2 in leukemias harboring MLL translocations, which co-occur in human AML. The hyperactive Shp2E76K mutant, commonly observed in leukemia patients, significantly accelerated MLL-AF9-mediated leukemogenesis in vivo. Shp2E76K increased leukemic stem cell frequency and affords MLL-AF9 leukemic cells IL3 cytokine hypersensitivity. As Shp2 is reported to regulate anti-apoptotic genes, we investigated Bcl2, Bcl-xL and Mcl1 expression in MLL-AF9 leukemic cells with and without Shp2E76K. Although the Bcl2 family of genes was upregulated in Shp2E76K cells, Mcl1 showed the highest upregulation in MLL-AF9 cells in response to Shp2E76K. Indeed, expression of Mcl1 in MLL-AF9 cells phenocopies expression of Shp2E76K, suggesting Shp2 mutations cooperate through activation of anti-apoptotic genes. Finally, we show Shp2E76K mutations reduce sensitivity of AML cells to small-molecule-mediated Mcl1 inhibition, suggesting reduced efficacy of drugs targeting MCL1 in patients with hyperactive Shp2.


Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria.
Cyanobacteria have played a significant role in the formation of past and modern carbonate deposits at the surface of the Earth using a biomineralization process that has been almost systematically considered induced and extracellular. Recently, a deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, was reported to form intracellular amorphous Ca-rich carbonates. However, the significance and diversity of the cyanobacteria in which intracellular biomineralization occurs remain unknown. Here, we searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria. We discovered that diverse unicellular cyanobacterial taxa form intracellular amorphous Ca-carbonates with at least two different distribution patterns, suggesting the existence of at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles. This pattern seems to be linked with the nucleation of the inclusions at the septum of the cells, showing an intricate and original connection between cell division and biomineralization. These findings indicate that intracellular Ca-carbonate biomineralization by cyanobacteria has been overlooked by past studies and open new perspectives on the mechanisms and the evolutionary history of intra- and extracellular Ca-carbonate biomineralization by cyanobacteria.


Treatment of early Lyme disease.
To compare the safety and efficacy of azithromycin, amoxicillin/probenecid, and doxycycline for the treatment of early Lyme disease, to identify risk factors for treatment failure, and to describe the serologic response in treated patients. Fifty-five patients with erythema migrans and two patients with flu-like symptoms alone and fourfold changes in antibody titers to Borrelia burgdorferi were randomized to receive (1) oral azithromycin, 500 mg on the first day followed by 250 mg once a day for 4 days; (2) oral amoxicillin 500 mg and probenecid 500 mg, three times a day for each for 10 days; or (3) doxcycline, 100 mg twice a day for 10 days. If symptoms were still present at 10 days, treatment was extended with amoxicillin/probenecid or doxycycline for 10 more days. Evaluations were done at study entry and 10, 30, and 180 days later. Three of the patients who initially had symptoms suggestive of spread of the spirochete to the nervous system, one from each antibiotic treatment group, subsequently developed neurologic abnormalities, but symptoms in the other 54 patients resolved within 3 to 30 days after study entry. Six of the 19 patients (32%) (95% confidence interval, 13% to 57%) given amoxicillin/probenecid developed a drug eruption, whereas none of the patients given azithromycin or doxycycline had this complication. The presence of dysesthesias at study entry was the only risk factor significantly associated with treatment failure (p less than 0.001). By convalescence, 72% of the patients were seropositive, and 56% still had detectable IgM responses to the spirochete 6 months later. The three antibiotic regimens tested in this study were generally effective for the treatment of early Lyme disease, but the regimens differ in the frequency of side effects and in ease of administration.


Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas.
Since the introduction of chemoradiotherapy with temozolomide as the new standard of care for patients with glioblastoma, there has been an increasing awareness of progressive and enhancing lesions on MRI, noted immediately after the end of treatment, which are not related to tumour progression, but which are a treatment effect. This so-called pseudoprogression can occur in up to 20% of patients who have been treated with temozolomide chemoradiotherapy, and can explain about half of all cases of increasing lesions after the end of this treatment. These lesions decrease in size or stabilise without additional treatments and often remain clinically asymptomatic. Additionally, there is evidence that treatment-related necrosis occurs more frequently and earlier after temozolomide chemotherapy than after radiotherapy alone. The mechanisms behind these events have not yet been fully elucidated, but the likelihood is that chemoradiotherapy causes a higher degree of (desired) tumour-cell and endothelial-cell killing. This increased cell kill might lead to secondary reactions, such as oedema and abnormal vessel permeability in the tumour area, mimicking tumour progression, in addition to subsequent early treatment-related necrosis in some patients and milder subacute radiotherapy reactions in others. In patients managed with temozolomide chemoradiotherapy who have clinically asymptomatic progressive lesions at the end of treatment, adjuvant temozolomide should be continued; in clinically symptomatic patients, surgery should be considered. If mainly necrosis is noted during surgery, continuation of adjuvant temozolomide is logical. Trials on the treatment of recurrent malignant glioma should exclude patients with progression within the first 3 months after temozolomide chemoradiotherapy unless histological confirmation of tumour recurrence is available. Further research is needed to establish reliable imaging parameters that distinguish between true tumour progression and pseudoprogression or treatment-related necrosis.


Catchment vegetation and temperature mediating trophic interactions and production in plankton communities.
Climatic factors influence the interactions among trophic levels in an ecosystem in multiple ways. However, whereas most studies focus on single factors in isolation, mainly due to interrelation and correlation among drivers complicating interpretation and analyses, there are still only few studies on how multiple ecosystems respond to climate related factors at the same time. Here, we use a hierarchical Bayesian model with a bioenergetic predator-prey framework to study how different climatic factors affect trophic interactions and production in small Arctic lakes. Natural variation in temperature and catchment land-cover was used as a natural experiment to exemplify how interactions between and production of primary producers (phytoplankton) and grazers (zooplankton) are driven by direct (temperature) and indirect (catchment vegetation) factors, as well as the presence or absence of apex predators (fish). The results show that increased vegetation cover increased phytoplankton growth rate by mediating lake nutrient concentration. At the same time, increased temperature also increased grazing rates by zooplankton. Presence of fish increased zooplankton mortality rates, thus reducing grazing. The Arctic is currently experiencing an increase in both temperature and shrub vegetation cover due to climate change, a trend, which is likely to continue. Our results point towards a possible future general weakening of zooplankton grazing on phytoplankton and greening of arctic lakes with increasing temperatures. At the same time, the impact of the presence of an apex predator indicate considerable local variation in the response. This makes direction and strength of global change impacts difficult to forecast.


Colopancreatic Fistula: An Uncommon Complication of Recurrent Acute Pancreatitis.
Colonic complications, including colopancreatic fistulas (CPFs), are uncommon after acute and chronic pancreatitis. However, they have been reported and are serious. CPFs are less likely to close spontaneously and are associated with a higher risk of complications. Therefore, more definitive treatment is required that includes surgical and endoscopic options. We present a case of a 62-year-old male patient with a history of heavy alcohol intake and recurrent acute pancreatitis who presented with a 6-month history of watery diarrhea and abdominal pain. His abdominal imaging showed a possible connection between the colon and the pancreas. A further multidisciplinary workup by the gastroenterology and surgery teams, including endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and colonoscopy, resulted in a diagnosis of CPF. A distal pancreatectomy and left hemicolectomy were performed, and the diagnosis of CPF was confirmed intraoperatively. The patient showed improvement afterward.


Release of endothelium-derived relaxing factor from freshly harvested porcine endothelial cells.
Vascular relaxation in rabbit aortic preparations induced by acetylcholine is endothelium-dependent. The nature of the endothelium-derived relaxing factor (EDRF) has not been ascertained because it is very labile (reported half-life 6-50 seconds). To obtain a stable source of EDRF, a system was developed in which the relaxing factor was continuously produced by freshly harvested porcine endothelial cells. Endothelial cells were collected from aortas by exposing the endothelial lining to collagenase 0.1%. Cells were washed and concentrated by repeated centrifugation to obtain a high cell count (7.2 X 10(6) cells/ml). Endothelium-deprived aortic strips from rabbits were incubated in these cells suspended in tissue culture medium and fetal calf serum. The strips were precontracted with histamine. Acetylcholine was added to induce EDRF release. Significant relaxation of endothelium-deprived aortic strips was observed. Superoxide dismutase, an enzyme known to protect EDRF against inactivation, caused further relaxation, which was inhibited by the addition of hemoglobin, an agent known to inhibit the relaxing action of EDRF. Even without the addition of acetylcholine, hemoglobin caused contraction of the denuded aortic strips in suspension of porcine endothelial cells, demonstrating spontaneous EDRF release. Hemoglobin had no effect in cell-free medium. Endothelial-cell-dependent relaxation occurred without attachment of endothelial cells to the endothelium-deprived aortic strips: when the cell suspension was replaced by cell-free medium, relaxation did not occur after acetylcholine. Scanning electron microscopy showed no attachment of endothelial cells to the subendothelial layer. It can be concluded that freshly harvested endothelial cells produce endothelium-derived relaxing factor with an without stimulation by acetylcholine.