Three-dimensional graphic physically based simulator of rainbows together with the background scene.
This paper presents a single scattering 3D graphics simulator of rainbows that includes the thickness of the rain shaft and the background scenery. The simulator is devised so that we can find a good configuration of the sun, the viewers, and the volume of water drops in a complicated geometric setting. The background-scene geometry and light-reflecting properties are modelled using 3D graphics tools. The simulator allows both the light reflected from the background surface and the light scattered by water drops to contribute to the final image by taking the depth to the background surface into account. The simulator generates an image of the rainbow by using the radiative transfer equation (RTE). We use ray optics to compute the average scattering cross section and the average phase function of particles that are the main parameters of the RTE. Depending on the density distribution of the water drops, the rainbow is perceived to be translucent, and the background scene is visible through the rainbow. We simulate other effects of the variation of the water-dropdensity and the location of the viewer, e.g., the visibility of the secondary rainbow, the brightness of the sky around the rainbow, the close-up view of the rainbow, and the full-circle rainbow. We explain these effects partly by computing the luminance contrasts of the primary and secondary bows against their local backgrounds.


CD24 overexpression in cancer development and progression: a meta-analysis.
CD24 has emerged as a new oncogene and metastasis promoter. However, there is a controversy as to whether CD24 expression is a prognostic factor for poor outcomes in many human cancers. To shed light on this controversy, we performed a meta-analysis of the relationship between CD24 expression and prognostic parameters in different carcinomas. Studies published in the period 1990-2009 were reviewed for the meta-analysis and selected according to defined criteria. The effect sizes of prognostic parameters and overall survival were calculated by an odds ratio (OR) or an adjusted hazard ratio (HR). Twenty-eight studies reported CD24 expression for 2,925 cases. The frequency of CD24 expression by immunohistochemistry was 68% in all the carcinomas of the breast, female genital tract, gastrointestinal tract, biliary tract and pancreas, urinary system, prostate and skin. Overall, CD24 was more frequently overexpressed in their carcinomas than their benign lesions (OR=4.21; 95% CI, 1.826-9.731; P=0.001) and was significantly associated with lymph node metastasis (OR=2.41; CI, 1.013-5.720; P=0.047), advanced clinical stages (OR=1.59; 95% CI, 1.244-2.032; P<0.001) and shortened overall survival (HR=2.13; 95% CI, 1.656-2.730; P<0.001). CD24 expression was highly associated with lymph node metastases in breast cancer (OR=3.55; 95% CI, 1.664-7.554; P=0.001), advanced clinical stages (OR=2.22; 95% CI, 1.442-3.418; P<0.001) and lymphovascular invasions (OR=2.78; 95% CI, 1.522-5.068; P=0.001) in urothelial carcinomas and with higher grades in endometrial adenocarcinomas (OR=3.88; 95% CI, 1.548-9.715; P=0.004). CD24 was more frequently and strongly expressed in breast (OR=35.80; 95% CI, 8.907-143.921; P<0.001) and ovarian carcinomas (OR=35.92; CI, 7.156-180.311; P<0.001), than in their benign counterparts. In conclusion, the meta-analysis strongly supports the idea that CD24 is an important marker of malignancy and poor prognosis in various cancers. In particular, CD24 may promote cancer development and progression in the breast, ovary and urinary bladder.


Toward the human cellular microRNAome.
MicroRNAs are short RNAs that serve as regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell-autonomously, and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data have caused considerable confusion, and comprehensive cell-level data do not yet exist. Here, we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent superenhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 495 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder, suggesting DROSHA- and DICER1-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to de-convolute variable cellular composition of colon and adipose tissue samples, highlighting one use of these cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.


A comparative effect of various surface chemical treatments on the resin composite-composite repair bond strength.
The aim of this in vitro study was an attempt to investigate the effect of different surface treatments on the bond strength between pre-existing composite and repair composite resin. Forty acrylic blocks were prepared in a cuboidal mould. In each block, a well of 5 mm diameter and 5 mm depth was prepared to retain the composite resin (Filtek™ Z350, 3M/ESPE). Aging of the composite discs was achieved by storing them in water at 37°C for 1 week, and after that were divided into 5 groups (n = 8) according to surface treatment: Group I- 37% phosphoric acid, Group II-10% hydrofluoric acid, Group III-30% citric acid, Group IV-7% maleic acid and Group V- Adhesive (no etchant). The etched surfaces were rinsed and dried followed by application of bonding agent (Adper™ Single Bond 2. 3M/ESPE). The repair composite was placed on aged composite, light-cured for 40 seconds and stored in water at 37°C for 1 week. Shear bond strength between the aged and the new composite resin was determined with a universal testing machine (crosshead speed of 0.5 mm/min). The compressive shear strengths were compared for differences using ANOVA test followed by Tamhane's T2 post hoc analysis. The surface treatment with 10% hydrofluoric acid showed the maximum bond strength followed by 30% citric acid, 7% maleic acid and 37% phosphoric acid in decreasing order. The use of 10% hydrofluoric acid can be a good alternative for surface treatment in repair of composite resin restoration as compared to commonly used 37% orthophosphoric acid.


Chronic stress experience in young physicians: impact of person- and workplace-related factors.
The objectives of the present study are to investigate and compare the relative impact of workplace-related factors and personal characteristics on chronic psychosocial stress experience in young physicians. In a prospective study, a cohort of Swiss medical school graduates was followed up, beginning in 2001. In their fourth and eighth year after graduation, 443 physicians assessed their workplace conditions, the experienced effort-reward imbalance, the received professional and emotional support as well as their personal characteristics. The chronic stress experience was measured by the Trier Inventory for the Assessment of Chronic Stress-Screening Subscale of Chronic Stress (TICS-SCSS), 7 years after graduation. The model of influencing factors on chronic stress experience was tested with a hierarchical regression analysis. The mean in chronic stress (TICS-SCSS) in our study sample is significantly higher (p < 0.001) compared to an age-matched population representative sample. In the prediction of chronic stress, the workplace-related factor effort-reward imbalance as well as the personal characteristic overcommitment turned out to be the most important risk factors. Stress protective are high satisfaction with career support, sense of coherence and occupational self-efficacy. The whole set of variables used in the regression model explains 51% of the variance of chronic stress experience. In the prediction of chronic stress, gender has no significant moderator effect. It is a matter of concern that young physicians report to feel chronically stressed early in their professional career. Actions have to be taken to reduce the stress level mainly in regard to re-establish reciprocity between perceived effort invested and rewards received, in the form of esteem, monetary gain and career opportunities including job security.


Varying gestational age patterns in cesarean delivery: an international comparison.
While international variations in overall cesarean delivery rates are well documented, less information is available for clinical sub-groups. Cesarean data presented by subgroups can be used to evaluate uptake of cesarean reduction policies or to monitor delivery practices for high and low risk pregnancies based on new scientific evidence. We studied differences and patterns in cesarean delivery rates by multiplicity and gestational age in Europe and the United States. This study used routine aggregate data from 17 European countries and the United States on the number of singleton and multiple live births with cesarean versus vaginal delivery by week of gestation in 2008. Overall and gestation-specific cesarean delivery rates were analyzed. We computed rate differences to compare mode of delivery (cesarean vs vaginal birth) between selected gestational age groups and studied associations between rates in these subgroups namely: very preterm (26-31 weeks GA), moderate preterm (32-36 weeks GA), near term (37-38 weeks GA), term (39-41 weeks GA) and post-term (42+ weeks GA) births, using Spearman's rank tests. High variations in cesarean rates for singletons and multiples were observed everywhere. Rates for singletons varied from 15% in The Netherlands and Slovenia, to over 30% in the US and Germany. In singletons, rates were highest for very preterm births and declined to a nadir at 40 weeks of gestation, ranging from 8.0% in Sweden and Norway, to 22.5% in the US. These patterns differed across countries; the average rate difference between very preterm and term births was 43 percentage points, but ranged from 14% to 61%. High variations in rate differences were also observed for near term versus term births. For multiples, rates declined by gestational age in some countries, whereas in others rates were similar across all weeks of gestation. Countries' overall cesarean rates were highly correlated with gestation-specific subgroup rates, except for very preterm births. Gestational age patterns in cesarean delivery were heterogeneous across countries; these differences highlight areas where consensus on best practices is lacking and could be used in developing strategies to reduce cesareans.


Executive Leadership and Physician Well-being: Nine Organizational Strategies to Promote Engagement and Reduce Burnout.
These are challenging times for health care executives. The health care field is experiencing unprecedented changes that threaten the survival of many health care organizations. To successfully navigate these challenges, health care executives need committed and productive physicians working in collaboration with organization leaders. Unfortunately, national studies suggest that at least 50% of US physicians are experiencing professional burnout, indicating that most executives face this challenge with a disillusioned physician workforce. Burnout is a syndrome characterized by exhaustion, cynicism, and reduced effectiveness. Physician burnout has been shown to influence quality of care, patient safety, physician turnover, and patient satisfaction. Although burnout is a system issue, most institutions operate under the erroneous framework that burnout and professional satisfaction are solely the responsibility of the individual physician. Engagement is the positive antithesis of burnout and is characterized by vigor, dedication, and absorption in work. There is a strong business case for organizations to invest in efforts to reduce physician burnout and promote engagement. Herein, we summarize 9 organizational strategies to promote physician engagement and describe how we have operationalized some of these approaches at Mayo Clinic. Our experience demonstrates that deliberate, sustained, and comprehensive efforts by the organization to reduce burnout and promote engagement can make a difference. Many effective interventions are relatively inexpensive, and small investments can have a large impact. Leadership and sustained attention from the highest level of the organization are the keys to making progress.


Simple bond patterns predict the stability of Diels-Alder adducts of empty fullerenes.
We present an extensive and systematic study on the regioselectivity of Diels-Alder (DA) cycloadditions to empty fullerenes, covering the whole range of cage sizes from C60 to C180. Reaction energies obtained from DFT calculations, which correlate with activation barriers, can be well reproduced by using a simple Hückel model, indicating that π electronic effect is the key factor determining the relative stability of DA adducts. Based on these results, we propose a couple of simple rules of thumb, in terms of a set of bond patterns, as a visual guide for approximate prediction of DA reactive sites. Moreover, we suggest two quantitative descriptors for the stability of DA regioadducts of empty fullerenes; one combines the π free valences and bond orders involved in the DA addition, and the other characterizes the local π aromaticity around the addition site. The latter criterion allows us to easily rationalize the proposed rules.


Multi-stakeholder perspectives in defining health-services quality in cataract care.
To develop a method to define a multi-stakeholder perspective on health-service quality that enables the expression of differences in systematically identified stakeholders' perspectives, and to pilot the approach for cataract care. Mixed-method study between 2014 and 2015. Cataract care in the Netherlands. Stakeholder representatives. We first identified and classified stakeholders using stakeholder theory. Participants established a multi-stakeholder perspective on quality of cataract care using concept mapping, this yielded a cluster map based on multivariate statistical analyses. Consensus-based quality dimensions were subsequently defined in a plenary stakeholder session. Stakeholders and multi-stakeholder perspective on health-service quality. Our analysis identified seven definitive stakeholders, as follows: the Dutch Ophthalmology Society, ophthalmologists, general practitioners, optometrists, health insurers, hospitals and private clinics. Patients, as dependent stakeholders, were considered to lack power by other stakeholders; hence, they were not classified as definitive stakeholders. Overall, 18 stakeholders representing ophthalmologists, general practitioners, optometrists, health insurers, hospitals, private clinics, patients, patient federations and the Dutch Healthcare Institute sorted 125 systematically collected indicators into the seven following clusters: patient centeredness and accessibility, interpersonal conduct and expectations, experienced outcome, clinical outcome, process and structure, medical technical acting and safety. Importance scores from stakeholders directly involved in the cataract service delivery process correlated strongly, as did scores from stakeholders not directly involved in this process. Using a case study on cataract care, the proposed methods enable different views among stakeholders concerning quality dimensions to be systematically revealed, and the stakeholders jointly agreed on these dimensions. The methods helped to unify different quality definitions and facilitated operationalisation of quality measurement in a way that was accepted by relevant stakeholders.


Sennetsu neorickettsiosis: a probable fish-borne cause of fever rediscovered in Laos.
Neorickettsia sennetsu has been described from Japan and Malaysia, causing a largely forgotten infectious mononucleosis-like disease. Because it is believed to be contracted from eating raw fish, frequently consumed in the Lao PDR, we looked for evidence of N. sennetsu among Lao patients and fish. A buffy coat from 1 of 91 patients with undifferentiated fever was positive by 16S rRNA amplification and sequencing and real-time polymerase chain reactions (PCR) targeting two N. sennetsu genes. Lao blood donors and patients with fever, hepatitis, or jaundice (N = 1,132) had a high prevalence (17%) of immunofluorescence assay IgG anti-N. sennetsu antibodies compared with 4% and 0% from febrile patients (N = 848) in Thailand and Malaysia, respectively. We found N. sennetsu DNA by PCR, for the first time, in a fish (Anabas testudineus). These data suggest that sennetsu may be an under-recognized cause of fever and are consistent with the hypothesis that it may be contracted from eating raw fish.


Analysis of the social network development of a virtual community for Australian intensive care professionals.
Social media platforms can create virtual communities, enabling healthcare professionals to network with a broad range of colleagues and facilitate knowledge exchange. In 2003, an Australian state health department established an intensive care mailing list to address the professional isolation experienced by senior intensive care nurses. This article describes the social network created within this virtual community by examining how the membership profile evolved from 2003 to 2009. A retrospective descriptive design was used. The data source was a deidentified member database. Since 2003, 1340 healthcare professionals subscribed to the virtual community with 78% of these (n = 1042) still members at the end of 2009. The membership profile has evolved from a single-state nurse-specific network to an Australia-wide multidisciplinary and multiorganizational intensive care network. The uptake and retention of membership by intensive care clinicians indicated that they appeared to value involvement in this virtual community. For healthcare organizations, a virtual community may be a communications option for minimizing professional and organizational barriers and promoting knowledge flow. Further research is, however, required to demonstrate a link between these broader social networks, enabling the exchange of knowledge and improved patient outcomes.


Cationic Surfactants: Potential Surface Disinfectants to Manage Agrobacterium tumefaciens Biovar 1 Contamination of Grafting Tools.
Nursery production of walnut seedlings is a 2-year process, during which crown gall, caused by Agrobacterium tumefaciens, often develops at grafting wounds. In this study, the spread of crown gall via contaminated tools and the efficacy of several disinfectants against A. tumefaciens were demonstrated. The cationic surfactants benzalkonium chloride (BC), cetyltrimethylammonium bromide (CTAB), and Physan 20 eliminated 100% of the A. tumefaciens population in water suspensions treated at 7, 5, and 2 ppm, respectively. Sodium hypochlorite eliminated 100% of the A. tumefaciens population at 0.5 ppm. Sodium hypochlorite efficacy, however, was reduced by 64% in the presence of total solids (0.7 g/ml) which are commonly found in field situations. At similar concentrations of total solids, the efficacy of cationic surfactants decreased, on average, by only 13%. The minimum effective treatment needed to eliminate A. tumefaciens on infested scalpels was a 5-s exposure to BC or CTAB at 5,000 ppm (0.5%). Infested scalpels treated with BC or CTAB at less than 5,000 ppm caused gall formation in 14 ± 7% of cuts made on Datura stramonium stems. This was significantly less than the tumor incidence (100%) in cuts made with inoculated blades not treated BC or CTAB.


Effect of Drying Methods on the Steroidal Alkaloid Content of Potato Peels, Shoots and Berries.
The present study has found that dried potato samples yielded significantly higher levels of steroidal alkaloids such as α-solanine and α-chaconine than the corresponding fresh samples, as determined by the UPLC-MS/MS technique. Among the drying techniques used, air drying had the highest effect on steroidal alkaloid contents, followed by freeze drying and vacuum oven drying. There was no significant difference between the freeze dried and vacuum oven dried samples in their α-chaconine contents. However, freeze dried potato shoots and berries had significantly higher α-solanine contents (825 µg/g dry weight (DW) in shoots and 2453 µg/g DW in berries) than the vacuum oven dried ones (325 µg/g dry weight (DW) in shoots and 2080 µg/g DW in berries). The kinetics of steroidal alkaloid contents of potato shoots during air drying were monitored over a period of 21 days. Both α-solanine and α-chaconine content increased to their maximum values, 875 µg/g DW and 3385 µg/g DW, respectively, after 7 days of drying. The steroidal alkaloid contents of the shoots decreased significantly at day 9, and then remained unchanged until day 21. In line with the potato shoots, air dried potato tuber peels also had higher steroidal alkaloid content than the freeze dried and vacuum oven dried samples. However, a significant decrease of steroidal alkaloid content was observed in air dried potato berries, possibly due to degradation during slicing of the whole berries prior to air drying. Remarkable variation in steroidal alkaloid contents among different tissue types of potato plants was observed with the potato flowers having the highest content.


Primary oral tuberculosis: A case series of a rare disease.
Tuberculosis (TB) is still one of the most life-threatening infectious diseases, resulting in high mortality in adults and is commonly found in developing countries. Lung is primarily affected while extrapulmonary TB is rarely encountered. Oral lesions, although rare, can be seen in both primary and secondary stages of TB. Primary oral TB may present a diagnostic challenge as its clinical features can be nonspecific that mimics other diseases and is usually misdiagnosed. Thus, it is very important to be aware and be highly suspicious of oral TB especially in endemic area. We share 4 such cases of primary oral TB with uncommon presentations (two on the gingiva, one on the palate and one on the tongue) The diagnosis was made by histopathological examination, polymerase chain reaction analysis and Mantoux test. They were successfully treated with antituberculous treatment. In secondary TB, the oral manifestations may be accompanied by lesions in the lungs, lymph nodes or in any other part of the body and can be detected by a systemic examination.


Development of Machine Learning Models to Validate a Medication Regimen Complexity Scoring Tool for Critically Ill Patients.
The Medication Regimen Complexity -Intensive Care Unit (MRC-ICU) is the first tool for measuring medication regimen complexity in critically ill patients. This study tested machine learning (ML) models to investigate the relationship between medication regimen complexity and patient outcomes. This study was a single-center, retrospective observational evaluation of 130 adults admitted to the medical ICU. The MRC-ICU score was utilized to improve the inpatient model's prediction accuracy. Three models were proposed: model I, demographic data without medication data; model II, demographic data and medication regimen complexity variables; and model III: demographic data and the MRC-ICU score. A total of 6 ML classifiers was developed: k-nearest neighbor (KNN), naïve Bayes (NB), random forest, support vector machine, neural network, and logistic classifier (LC). They were developed and tested using electronic health record data to predict inpatient mortality. The results demonstrated that adding medication regimen complexity variables (model II) and the MRC-ICU score (model III) improved inpatient mortality prediction.. The LC outperformed the other classifiers (KNN and NB), with an overall accuracy of 83%, sensitivity (Se) of 87%, specificity of 67%, positive predictive value of 93%, and negative predictive value of 46%. The APACHE III score and the MRC-ICU score at the 24-hour interval were the 2 most important variables. Inclusion of the MRC-ICU score improved the prediction of patient outcomes on the previously established APACHE III score. This novel, proof-of-concept methodology shows promise for future application of the MRC-ICU scoring tool for patient outcome predictions.


Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative.
Background and Purpose- We examine the association between self-reported consumption of artificially sweetened beverages (ASB) and stroke and its subtypes, coronary heart disease, and all-cause mortality in a cohort of postmenopausal US women. Methods- The analytic cohort included 81 714 women from the Women's Health Initiative Observational Study, a multicenter longitudinal study of the health of 93 676 postmenopausal women of ages 50 to 79 years at baseline who enrolled in 1993 to 1998. This prospective study had a mean follow-up time of 11.9 years (SD of 5.3 years.) Participants who completed a follow-up visit 3 years after baseline were included in the study. Results- Most participants (64.1%) were infrequent consumers (never or <1/week) of ASB, with only 5.1% consuming ≥2 ASBs/day. In multivariate analyses, those consuming the highest level of ASB compared to never or rarely (<1/wk) had significantly greater likelihood of all end points (except hemorrhagic stroke), after controlling for multiple covariates. Adjusted models indicated that hazard ratios and 95% confidence intervals were 1.23 (1.02-1.47) for all stroke; 1.31 (1.06-1.63) for ischemic stroke; 1.29 (1.11-1.51) for coronary heart disease; and 1.16 (1.07-1.26) for all-cause mortality. In women with no prior history of cardiovascular disease or diabetes mellitus, high consumption of ASB was associated with more than a 2-fold increased risk of small artery occlusion ischemic stroke hazard ratio =2.44 (95% confidence interval, 1.47-4.04.) High consumption of ASBs was associated with significantly increased risk of ischemic stroke in women with body mass index ≥30; hazard ratio =2.03 (95% confidence interval, 1.38-2.98). Conclusions- Higher intake of ASB was associated with increased risk of stroke, particularly small artery occlusion subtype, coronary heart disease, and all-cause mortality. Although requiring replication, these new findings add to the potentially harmful association of consuming high quantities of ASB with these health outcomes.


Element content and expression of genes of interest in guard cells are connected to spatiotemporal variations in stomatal conductance.
Element content and expression of genes of interest on single cell types, such as stomata, provide valuable insights into their specific physiology, improving our understanding of leaf gas exchange regulation. We investigated how far differences in stomatal conductance (gs ) can be ascribed to changes in guard cells functioning in amphistomateous leaves. gs was measured during the day on both leaf sides, on well-watered and drought-stressed trees (two Populus euramericana Moench and two Populus nigra L. genotypes). In parallel, guard cells were dissected for element content and gene expressions analyses. Both were strongly arranged according to genotype, and drought had the lowest impact overall. Normalizing the data by genotype highlighted a structure on the basis of leaf sides and time of day both for element content and gene expression. Guard cells magnesium, phosphorus, and chlorine were the most abundant on the abaxial side in the morning, where gs was at the highest. In contrast, genes encoding H+ -ATPase and aquaporins were usually more abundant in the afternoon, whereas genes encoding Ca2+ -vacuolar antiporters, K+ channels, and ABA-related genes were in general more abundant on the adaxial side. Our work highlights the unique physiology of each leaf side and their analogous rhythmicity through the day.


NTP Toxicology and Carcinogenesis Studies of 1,3-Butadiene (CAS No. 106-99-0) in B6C3F1 Mice (Inhalation Studies).
1,3-Butadiene is produced in large volumes for use in the manufacture of synthetic rubber and of thermoplastic resins. In previous inhalation studies conducted by the NTP (NTP, 1984) there was clear evidence of multiple organ carcinogenicity in male and female mice exposed to 625 or 1,250 ppm 1,3-butadiene for 60 or 61 weeks. To better characterize exposure-response relationships for neoplasms and nonneoplastic lesions, toxicology and carcinogenesis studies were conducted by exposing groups of male and female B6C3F1 mice to air containing 1,3-butadiene (greater than 99% pure) for up to 2 years. An additional study in male B6C3F1 mice, in which exposure to 1,3-butadiene was stopped after limited exposure periods (13, 26, 40, or 52 weeks), was performed to assess the effects of varying concentration and duration of exposure on the incidences of 1,3-butadiene-induced neoplasms. In vitro genetic toxicology studies were conducted in Salmonella typhimurium and mouse lymphoma cells. In vivo genetic effects were assayed in germ cells of male Drosophila melanogaster and in bone marrow and peripheral blood cells of B6C3F1 mice. 2-Year Studies: Groups of 70 male and 70 female mice were exposed to air containing 0, 6.25, 20, 62.5, or 200 ppm 1,3-butadiene for 6 hours per day, 5 days per week for up to 2 years; groups of 90 male and 90 female mice were exposed to 625 ppm 1,3-butadiene on the same schedule. Up to 10 animals from each group were examined after 9 and 15 months of exposure. Survival and Body Weight in the 2-Year Studies: Two-year survival was decreased for males and females exposed to concentrations of 20 ppm or above, primarily due to the development of chemical-related malignant neoplasms. No female mice exposed to 200 or 625 ppm or males exposed to 625 ppm survived to the end of the studies (males: 35/50, 39/50, 24/50, 22/50, 4/50, 0/70; females: 37/50, 33/50, 24/50, 11/50, 0/50, 0/70). Mean body weights of exposed male and female mice were similar to those of the controls. Hematologic Effects in the 2-Year Studies: Hematologic parameters were evaluated after 9 and 15 months of exposure. At 9 months, decreases in erythrocyte counts, hemoglobin concentration, and packed red cell volume were observed in male mice exposed to 62.5 ppm or above and in female mice exposed to 200 or 625 ppm. Mean erythrocyte volume was increased in male mice exposed to 625 ppm and in females exposed to 200 or 625 ppm. At 15 months, decreases in erythrocyte counts, hemoglobin concentration, and packed red cell volume and increases in mean erythrocyte volume were observed in male and female mice exposed to 625 ppm. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: Exposure of mice to 1,3-butadiene induced benign and malignant neoplasms at multiple sites. Statistically significant increases in the incidences of neoplasms at one or more sites were seen at concentrations of 20 ppm and higher in males and 6.25 ppm and higher in females. There was no exposure level in this study at which a significant carcinogenic response was not observed. Statistically significant increases occurred in the incidences of malignant lymphoma; histiocytic sarcoma; cardiac hemangiosarcoma; harderian gland adenoma; hepatocellular adenoma and carcinoma; alveolar/bronchiolar adenoma and carcinoma; mammary gland carcinoma, adenoacanthoma, and malignant mixed tumor (females only); benign and malignant ovarian granulosa cell tumor; and forestomach squamous cell papilloma and carcinoma. Low incidences of uncommon neoplasms also occurred in exposed male and female mice, including intestinal carcinomas in males, renal tubule adenomas in males and females, skin sarcomas (all types combined) in females, and Zymbal's gland adenomas and carcinomas in females. Lymphocytic lymphomas appeared as early as week 23 and were the principal cause of death of male and female mice exposed to 625 ppm 1,3-butadiene. The early and extensive development of lethal lymphocytic lymphomas in mice exposed to 625 ppm resulted in a reduced number of mice at risk for neoplasms developing laterg later at other sites. Exposure-response relationships for 1,3-butadiene-induced neoplasms were more clearly characterized at concentrations below 625 ppm and after adjustment for intercurrent mortality. Increased incidences of nonneoplastic lesions in exposed mice included bone marrow atrophy; testicular atrophy; ovarian atrophy, angiectasis, germinal epithelial hyperplasia, and granulosa cell hyperplasia; uterine atrophy; cardiac endothelial hyperplasia and mineralization; alveolar epithelial hyperplasia; forestomach epithelial hyperplasia; and harderian gland hyperplasia. Stop-Exposure Study: The stop-exposure study consisted of groups of 50 male mice exposed to 1,3-butadiene at concentrations of 200 ppm for 40 weeks, 625 ppm for 13 weeks, 312 ppm for 52 weeks, or 625 ppm for 26 weeks. After the exposures were completed, these groups were placed in control chambers for the remainder of the 2-year study. The total exposure of 1,3-butadiene (concentration times duration of exposure) of the 13- and 40-week stop-exposure groups was approximately 8,000 ppm-weeks, while that of the 26- and 52-week stop-exposure groups was approximately 16,000 ppm-weeks. The survival of all stop-exposure groups was markedly lower than that of the controls. The incidences of lymphocytic lymphoma, histiocytic sarcoma, cardiac hemangiosarcoma, alveolar/bronchiolar adenoma and carcinoma, forestomach squamous cell papilloma and carcinoma, hepatocellular adenoma, harderian gland adenoma and adenocarcinoma, and preputial gland carcinoma were significantly increased. Neoplasms were induced at most of these sites after only 13 weeks of exposure to 1,3-butadiene. Additionally, low numbers of malignant gliomas and neuroblastomas of the brain and Zymbal's gland carcinomas occurred in one or more stop-exposure groups. At similar total exposures, the incidence of lymphocytic lymphoma was greater with exposure to a higher concentration of 1,3-butadiene for a short time compared with exposure to a lower concentration for an extended period (34% at 625 ppm for 13 weeks versus 12% at 200 ppm for 40 weeks; 60% at 625 ppm for 26 weeks versus 8% at 312 ppm for 52 weeks). Genetic Toxicology: 1,3-Butadiene has been tested both in vitro and in vivo for mutagenic activity. In vitro, positive results were obtained in the Salmonella typhimurium gene mutation assay with strain TA1535; mutagenic activity was not observed in other S. typhimurium strains (TA100, TA97, and TA98). 1,3-Butadiene was negative in the mouse lymphoma assay for induction of trifluorothymidine resistance in L5178Y cells with and without S9. In vivo, 1,3-butadiene did not induce sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster; however, it did induce significant increases in chromosomal aberrations and sister chromatid exchanges in bone marrow cells of mice exposed for 2 weeks by inhalation. In addition, significant increases in micronucleated erythrocytes were observed in peripheral blood samples obtained from male and female mice exposed to 1,3-butadiene for 2 or 13 weeks or 15 months by inhalation. Conclusions: The previous inhalation studies of 1,3-butadiene (TR-288) in male and female B6C3F1 mice provided clear evidence of carcinogenicity at exposure concentrations of 625 or 1,250 ppm. The present inhalation studies - 2-year exposures of 6.25, 20, 62.5, 200, or 625 ppm or shorter duration exposures of 200, 312, or 625 ppm - provide a better characterization of the concentration-dependent responses for 1,3-butadiene-induced neoplasms and nonneoplastic lesions. The present studies confirmed the clear evidence of carcinogenicity of 1,3-butadiene in male B6C3F1 mice based on increased incidences of neoplasms in the hematopoietic system, heart, lung, forestomach, liver, harderian gland, preputial gland, brain, and kidney. There was clear evidence of carcinogenicity of 1,3-butadiene in female B6C3F1 mice based on increased incidences of neoplasms in the hematopoietic system, heart, lung, forestomach, liver, harderian gland, ovary, and mammary gland. Low incidences of intestinal carcinomas in male mice, Zymbal's gland carcinomas in male and female mice, and renal tubule adenomas and skin sarcomas in female mice may also have been related to administration of 1,3-butadiene. Synonyms: alpha,gamma-Butadiene; bivinyl; divinyl; erythrene; vinylethylene; biethylene; pyrrolylene


Larval digenean community parasitizing the freshwater snail, Biomphalaria peregrina (Pulmonata: Planorbidae), from a temporary pond in Patagonia, Argentina.
Knowledge of population dynamics of parasites in freshwater snails from South America is scarce. The objective of the present study was to describe the infection dynamics of larval digeneans in the planorbid snail, Biomphalaria peregrina , during 2 sampling periods in a Patagonian temporary pond. In total, 1,003 snails were examined. Rediae of Notocotylus biomphalariae and Echinoparyphium sp., sporocysts of Cotylurus sp., and metacercariae of the 2 latter species were found. The overall prevalence was significantly higher in the second sampling period, always as single-species infections in the hepatopancreas. The presence of larvae in the first sampled snails of the second hydroperiod indicated that parasitized snails survive drought. Both species exhibited different seasonal prevalence patterns, with Echinoparyphium sp. present in all sampling months. Metacercariae of Echinoparyphium sp. occurred in the heart and kidney, and those of Cotylurus sp. between organs. No significant differences in overall prevalence of metacercariae were found, and a progressive rise in prevalence from spring to summer for both species was observed. Almost all size classes of B. peregrina were infected with metacercariae of both species, but rediae and sporocysts were present only in snails larger than 3.1 mm. The predictability of the hydroperiod year after year, the tolerance of B. peregrina to drought, and the survival of infected specimens allows the parasite community to show a similar pattern of infection over time. This is the first study in Argentina analyzing the infection dynamics of digeneans of a pulmonate snail from a temporary pond.


Shoot traits and their relevance in terminal drought tolerance of chickpea (Cicer arietinum L.).
Chickpea is the second most important legume crop largely grown under semi-arid tropics where terminal drought is one of the major constraints for its productivity. A trait-based selection had been considered more beneficial in drought tolerance breeding to overcome the environmental influence on drought yields. Large number of traits had been suggested in literature, with less indication on their importance and priority, for use in such breeding programs resulting in poor utilization of critical traits in drought tolerance breeding. To identify the most critical traits that contribute to grain yield under drought, 12 chickpea genotypes, with well-defined drought response, were field evaluated by sampling at regular intervals during the cropping period. Large range of variation was observed for shoot biomass productivity, specific leaf area (SLA) and leaf area index (LAI) at different days after sowings (DAS), canopy temperature depression (CTD) at mid-reproductive stages, growth duration and both morphological and analytical yield components. Grain yield under drought was closely associated with the rate of partitioning (p), crop growth rate (C), CTD, phenology, LAI at mid-pod fill stage, pod number m-2 at maturity, shoot biomass at reproductive growth stages and SLA at physiological maturity. The shoot trait(s) were prioritized based on their significance and contribution to drought tolerance. The trait(s) that conferred tolerance varied across genotypes. The order of traits/plant functions identified as important and critical for the drought tolerance were p, C, CTD, growth duration and other related traits. Relatively less important traits were LAI, SLA at the mid reproductive stage and pod number per unit area at maturity. The traits Dr, seeds pod-1 and 100-seed weight were found to be least important. Breeding for the best combination of p and C with the right phenology was proposed to be the best selection strategy to enhance terminal drought tolerance in chickpea.


Suicide risk assessment received prior to suicide death by Veterans Health Administration patients with a history of depression.
To examine the quality of suicide risk assessment provided to veterans with a history of depression who died by suicide between 1999 and 2004. We conducted a case-control study of suicide risk assessment information recorded in 488 medical charts of veterans previously diagnosed with major depression, depression not otherwise specified, dysthymia, or other, less common ICD-9-CM depression codes. Patients dying by suicide from April 1999 through September 2004 or comparison patients (n = 244 pairs) were matched for age, sex, entry year, and region. Seventy-four percent of patients with a history of depression received a documented assessment of suicidal ideation within the past year, and 59% received more than 1 assessment. However, 70% of those who died of suicide did not have a documented assessment for suicidal ideation at their final Veterans Health Administration (VHA) visit, even if that visit occurred within 0 through 7 days prior to suicide death. Most patients dying by suicide denied suicidal ideation when assessed (85%; 95% CI, 75%-92%), even just 0 through 7 days prior to suicide death (73%; 95% CI, 39%-94%). Suicidal ideation was assessed more frequently during outpatient final visits with mental health providers (60%) than during outpatient final visits with primary care (13%) or other non-mental health providers (10%, P < .0001). Most VHA patients with a history of depression received some suicide risk assessment within the past year, but suicide risk assessments were infrequently administered at the final visit of patients who eventually died by suicide. Among patients who had assessments, denial of suicidal ideation appeared to be of limited value. Practice changes are needed to improve suicide risk assessment among patients with histories of depression, including the development of assessment and prevention strategies that are less dependent on the presence or disclosure of suicidal ideation at scheduled medical visits.


Veno-occlusive disease in snow leopards (Panthera uncia) from zoological parks.
Livers from 54 snow leopards, 4 days to 23 years old, that had died in 23 US zoos, were evaluated histopathologically to determine if the hepatic fibrosis, which has been noted to be prevalent in this species, was due to chronic active hepatitis from hepadnaviral infection, Ito cell proliferation, or hemosiderosis. Forty-two of 54 snow leopards had subintimal vascular fibrosis with partial or total occlusion of central and sublobular veins (veno-occlusive disease) of unknown origin. All 21 leopards older than 5 years were affected. Four leopards had chronic active hepatitis, and 12 leopards had cholangiohepatitis; but these lesions were not connected anatomically to central and sublobular venous fibrosis. Hepatocellular and Kupffer cell siderosis and Ito cell proliferation were prevalent and often coexisted with perisinusoidal, central, and sublobular venous fibrosis; but fibrosis was present in leopards without siderosis or Ito cell proliferation. The pattern and prevalence of veno-occlusive disease in these leopards was similar to that reported in captive cheetah (Acinonyx jubatus), suggesting that a common extrinsic factor may cause the majority of hepatic disease in these large felid animals in captivity.


Molecular matchmakers.
Molecular matchmakers are a class of proteins that use the energy released from the hydrolysis of adenosine triphosphate to cause a conformational change in one or both components of a DNA binding protein pair to promote formation of a metastable DNA-protein complex. After matchmaking the matchmaker dissociates from the complex, permitting the matched protein to engage in other protein-protein interactions to bring about the effector function. Matchmaking is most commonly used under circumstances that require targeted, high-avidity DNA binding without relying solely on sequence specificity. Molecular matchmaking is an extensively used mechanism in repair, replication, and transcription and most likely in recombination and transposition reactions, too.


A Retrospective Review of an Off-label Bromelain-based Selective Enzymatic Debridement (Nexobrid®) in the Treatment of Deep, Partial, and Full Thickness Burns and Hard to Heal Wounds.
Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting. To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer's guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds. This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement. Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer's guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds. Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.


Relationship between polyethylene wear and osteolysis in hips with a second-generation porous-coated cementless cup after seven years of follow-up.
The development of osteolysis, a commonly reported complication after total hip arthroplasty without cement, is perceived to be related to the amount of polyethylene particles generated from the bearing surfaces. Although the literature has suggested that the prevalence of osteolysis increases with increasing rates of polyethylene wear, this relationship has never been quantified. The goals of this study were to quantify the relationship between the prevalence of osteolysis and both linear and volumetric wear and to evaluate the risk of osteolysis as a function of wear in a currently used, porous-coated cup design. Polyethylene wear and osteolysis were examined in fifty-six hips with a Duraloc-100 acetabular cup articulating with a 28-mm femoral head. Penetration of the prosthetic head into the polyethylene liner was measured, with use of a validated computer-assisted technique, from anteroposterior pelvic radiographs of each patient. From these measurements, linear and volumetric wear rates were calculated. Each patient's series of radiographs was examined independently for the presence of osteolysis. A logistic regression analysis was performed to determine the risk of osteolysis associated with a given change in linear or volumetric wear rate. Osteolysis was found in twenty-three of the fifty-six hips. The hips with osteolysis had significantly higher linear (p < 0.001) and volumetric (p = 0.003) wear rates than the hips without osteolysis. Logistic regression revealed that every 0.1-mm/yr increase in the linear wear rate increased the likelihood of the development of osteolysis by a factor of four. Each 40-mm (3) /yr increase in volumetric wear raised the risk of osteolysis by about three times. To our knowledge, this study represents the first time that the relationship between polyethylene wear, as determined by both linear wear and volumetric wear, and the prevalence of osteolysis has been quantified. The use of the linear wear rate as a predictor of osteolysis can be a valuable tool in assessing the longevity of a particular implant. The results of our analysis provide quantitative support to the observation that a wear rate of 0.2 mm/yr seems to represent a "critical threshold" for the development of osteolysis. Close radiographic monitoring with the determination of linear wear rates to assess the risk of osteolysis is recommended for all patients after total hip arthroplasty.


Therapeutical relevance of MAP-kinase inhibitors in renal diseases: current knowledge and future clinical perspectives.
Renal failure, both acute and chronic, represents an important health problem by its social, sanitary and economic aspects. Mitogen-activated protein kinases (MAPK) are a family of mediators involved in the transduction of extracellular stimuli to intracellular responses. The best studied members of this family are extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), Jun NH(2)-terminal kinase (JNK), p38 kinase and extracellular signal regulated kinases 5 (ERK5) also known as big MAP Kinase 1 (BMK1). MAPKs plays a role in regulating renal function and all these pathways have been demonstrated to be activated in many "in vivo" and cellular models or renal failure. As MAP kinases are key regulators in the control of cell proliferation and cell death, many more or less specific inhibitors of these pathways are being developed for the treatment of tumors. The purpose of this review is to examine the data available on the role of MAPKs activation in "in vivo" models of renal failure, as well as in different renal cell types (especially in mesangial cells, podocytes, tubular epithelial cells and fibroblasts) subjected to stress or damage. We have also reviewed the effect of MAPKs inhibition on renal damage, both "in vivo" and "in vitro". Data collected allow to suggest that therapy of chronic and acute renal disease with MAPKs inhibitors is a promising therapeutic area, although much more basic and clinical studies are necessary before this kind of therapy can be used in the everyday clinic.


Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species-mediated ERK activation in HL-60 leukemia cells and xenograft.
Quercetin is a plant-derived bioflavonoid that was recently shown to have multiple anticancer activities in various solid tumors. Here, novel molecular mechanisms through which quercetin exerts its anticancer effects in acute myeloid leukemia (AML) cells were investigated. Results from Western blot and flow cytometric assays revealed that quercetin significantly induced caspase-8, caspase-9, and caspase-3 activation, poly ADP-ribose polymerase (PARP) cleavage, and mitochondrial membrane depolarization in HL-60 AML cells. The induction of PARP cleavage by quercetin was also observed in other AML cell lines: THP-1, MV4-11, and U937. Moreover, treatment of HL-60 cells with quercetin induced sustained activation of extracellular signal-regulated kinase (ERK), and inhibition of ERK by an ERK inhibitor significantly abolished quercetin-induced cell apoptosis. MitoSOX red and 2',7'-dichlorofluorescin fluorescence, respectively, showed that mitochondrial superoxide and intracellular peroxide levels were higher in quercetin-treated HL-60 cells compared with the control group. Moreover, both N-acetylcysteine and the superoxide dismutase mimetic, MnTBAP, reversed quercetin-induced intracellular reactive oxygen species production, ERK activation, and subsequent cell death. The in vivo xenograft mice experiments revealed that quercetin significantly reduced tumor growth through inducing intratumoral oxidative stress while activating the ERK pathway and subsequent cell apoptosis in mice with HL-60 tumor xenografts. In conclusions, our results indicated that quercetin induced cell death of HL-60 cells in vitro and in vivo through induction of intracellular oxidative stress following activation of an ERK-mediated apoptosis pathway.


Evidence for Training-Dependent Structural Neuroplasticity in Brain-Injured Patients: A Critical Review.
Acquired brain injury (ABI) is associated with a range of cognitive and motor deficits, and poses a significant personal, societal, and economic burden. Rehabilitation programs are available that target motor skills or cognitive functioning. In this review, we summarize the existing evidence that training may enhance structural neuroplasticity in patients with ABI, as assessed using structural magnetic resonance imaging (MRI)-based techniques that probe microstructure or morphology. Twenty-five research articles met key inclusion criteria. Most trials measured relevant outcomes and had treatment benefits that would justify the risk of potential harm. The rehabilitation program included a variety of task-oriented movement exercises (such as facilitation therapy, postural control training), neurorehabilitation techniques (such as constraint-induced movement therapy) or computer-assisted training programs (eg, Cogmed program). The reviewed studies describe regional alterations in white matter architecture and/or gray matter volume with training. Only weak-to-moderate correlations were observed between improved behavioral function and structural changes. While structural MRI is a powerful tool for detection of longitudinal structural changes, specific measures about the underlying biological mechanisms are lacking. Continued work in this field may potentially see structural MRI metrics used as biomarkers to help guide treatment at the individual patient level.


Estrogen receptor beta protects against acoustic trauma in mice.
The hormone estradiol affects the auditory system both by itself and by its interaction with neuroprotective factors. In this study, we examined the role of estrogen receptors (ERs) in response to auditory trauma. We found a ligand-dependent protective role for ERbeta in the auditory system by investigating mice deficient in ERalpha (ERKO mice), ERbeta (BERKO mice), and aromatase (ARKO mice). Basal auditory brainstem response (ABR) thresholds were similar in all animals. An acoustic trauma causing a temporary hearing loss raised ABR thresholds in male and female BERKO and ARKO mice compared with WT and ERKO mice. The ERalpha-selective agonist, propyl(1H) pyrazole-1,3,5-triyl-trisphenol (PPT), partially protected ARKO mice from trauma, while the ERbeta-selective agonist, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN), protected WT and ARKO mice. Immunohistochemistry and western blotting confirmed the expression of ERbeta in cochlea of WT males and females. Levels of brain-derived neurotrophic factor (BDNF), a neuroprotective peptide that can be induced by estrogen, was lower in BERKO and ARKO mice compared with WT. DPN treatment increased BDNF expression in ARKO mice. These data indicate ERbeta-mediated neuroprotection involving BDNF in the auditory system of males and females.


Quality parameters and fertility of ram semen cryopreserved in egg yolk and soybean lecithin supplemented extenders.
The aim of the study was to investigate the effect of soybean lecithin as a substitute for egg yolk in milk and tris based extenders in ram semen cryopreservation. Twenty ejaculates were col- lected from four healthy, mature Wrzosówka rams (2-3 years of age). Each ejaculate was divided into four equal aliquots and diluted with four different extenders: 1) milk extender containing 5% egg yolk, 2) milk extender containing 1.5% soybean lecithin, 3) tris extender containing 20% egg yolk, 4) tris extender containing 1.5% soybean lecithin. Extended semen was loaded into 0.25 ml French straws, cooled and frozen in liquid nitrogen vapor. Total motility, curvilinear velocity, plasma membrane integrity and fertilizing ability of sperm were assessed after thawing. Total mo- tility was lower (p⟨0.05) in tris-soybean lecithin extender when compared to other extenders. Curvilinear velocity was higher (p⟨0.05) for spermatozoa cryopreserved in milk-soybean lecithin extender compared to other extenders tested. For the percentage of live sperm no significant difference was observed between extenders. The lambing rate were higher (not statistically signifi- cant) in ewes inseminated with semen doses frozen in milk-soybean lecithin extender (42.9%) than in the tris-egg yolk extender (16.7%). In conclusion, replacing the egg yolk with soybean lecithin was effective in milk but not in tris extender.


Delays in assessment of patients with rheumatoid arthritis: variations across Europe.
The first 3 months after symptom onset represent an important therapeutic window for rheumatoid arthritis (RA). This study investigates the extent and causes of delay in assessment of patients with RA in eight European countries. Data on the following levels of delay were collected from 10 centres (Berlin, Birmingham, Heraklion, Lund, Prague, Stockholm, Umeå, Vienna, Warsaw and Zurich): (1) from onset of RA symptoms to request to see healthcare professional (HCP); (2) from request to see HCP to assessment by that HCP; (3) from initial assessment by HCP to referral to rheumatologist; and (4) from referral to rheumatologist to assessment by that rheumatologist. Data were collected from 482 patients with RA. The median delay across the 10 centres from symptom onset to assessment by the rheumatologist was 24 weeks, with the percentage of patients seen within 12 weeks of symptom onset ranging from 8% to 42%. There were important differences in the levels underlying the total delays at individual centres. This research highlights the contribution of patients, professionals and health systems to treatment delay for patients with RA in Europe. Although some centres have strengths in minimising certain types of delay, interventions are required in all centres to ensure timely treatment for patients.


DNA structure and flexibility in the sequence-specific binding of papillomavirus E2 proteins.
The papillomavirus E2 proteins are transcriptional regulators that bind to a consensus DNA sequence ACCG NNNN CGGT. Multiple copies of this binding site are found in the viral genomes. The affinities of the naturally occurring binding sites for the E2 proteins are predominantly dependent upon the sequence of the NNNN spacer. The hierarchies of binding site affinities among the sites present in the viral genomes result in differential occupancy during the viral life-cycle. In turn, this differential binding regulates transcription from viral promoters, including those for the oncogenes E6 and E7. Structural and biochemical studies have shown that E2 proteins bend the DNA to which they specifically bind. Atomic resolution structures of complexes of the bovine papillomavirus strain 1 (BPV-1) E2 protein and DNA show that the protein does not contact the spacer DNA. A direct comparison of the binding of the DNA-binding domains of the E2 proteins from BPV-1 and human papillomavirus strain 16 (HPV-16) to a series of binding sites as a function of the sequence of their central spacer and/or the presence of a nick or gap in one strand of the spacer DNA is presented in this paper. The BPV-1 E2 DNA-binding domain is only moderately sensitive to the nature of the central spacer; less than several fold differences in affinity were observed when the DNA sequence of the spacer was varied and/or a nick or gap was introduced. In contrast, the HPV-16 E2 DNA-binding domain binds to sites containing A:T-rich central spacers with significantly increased affinity. The introduction of a nick or gap into the spacer of these high affinity sequences is very detrimental to HPV-16 E2 binding while comparable nicks or gaps have only small effects in the low affinity sequences. These results suggest that the HPV-16 E2 protein recognizes the structure of the DNA spacer and that the mechanism of DNA-sequence specific binding of the homologous HPV-16 E2 and BPV-1 E2 proteins is significantly different.


A prospective audit of the usefulness of evacuating proctography.
Fifty-nine evacuating proctograms were performed over a 4 month period. We sought to identify how useful this technique is in diagnosing the cause of various anorectal symptoms and indicating which treatment option may be beneficial to the patient. The main reasons for referral were faecal soiling (60%) and obstructed defaecation (47%). Of the proctograms, 90% revealed some pathology. The most common abnormalities detected were rectocele (56%), rectal intussusception (39%), enterocele (19%) and rectal prolapse (12%). Of the patients, 45% were treated with an operation specific to the pathology detected on the proctogram; 29% did not require any active treatment and the remainder were managed with biofeedback conditioning or injection sclerotherapy. Evacuating proctography is of value in providing a diagnosis in patients with anorectal symptoms and thereby allowing specific treatment, operative or nonoperative, to be directed to the underlying pathology.


Production of biomedical cell products: requirements for the quality of donor material and excipients of animal origin (review).
Donor biological materials and excipients of animal origin are important components in the production of biomedical cell products (BMCPs). Their quality ensures the stability, safety, effectiveness and purity of the final product. This review discusses quality requirements for biological excipients intended for the production of biomedical cell products, in terms of the necessary information that should be included in the BMCP registration dossier during state registration and is subject to expert assessment during quality control. Considering that there is currently no production of biomedical cell products in the Russian Federation, the authors considered international approaches to ensuring the safety of donor material and excipients for the manufacturing of human cell- and tissue-based products (BMCP analogues).


School-based intervention for improving the oral health of children in southern Thailand.
A two-year study assessed the benefit of an enhanced oral health promotion program combined with a closely supervised tooth brushing program in schools, using toothpaste containing 1,450 ppm F- and 1.5% arginine, on oral health and dental caries. 15 southern Thailand schools and 3,706 pre-school children were recruited: 8 schools with 1,766 children as controls; 7 schools with 1,940 children in the intervention groups. Of the intervention schools five were classified as cooperative school and two as non-cooperative schools, based on the criteria of 80% participation in the prescribed tooth brushing activities. The DMFT and DMFS increments ("enamel and dentine") were 1.19 and 1.91 for the control group and 1.04 and 1.59 for the intervention groups. These represent 12.6% and 16.8% reductions in caries respectively. The DMFT and DMFS increments ("dentine threshold") were 0.26 and 0.44 for the control group and 0.19 and 0.29 for the intervention group, representing 26.9%, and 34.1% reductions in caries incidence respectively. For the more cooperative schools the benefits were greater: up to a 40.9% reduction in caries for DMFS ("dentine threshold"). At the 24 month examination there were significant improvements in dental plaque scores with greater improvements seen in the intervention group, greater still in the cooperative schools. This study documents the positive effect from use of fluoridated toothpaste (1,450 ppm F- and 1.5% arginine) administered by schoolteachers and undertaken via an enhanced school oral health program. Optimising oral health interventions for young children in Thai schools may have a significant impact on caries incidence resulting in reductions of up to 34% reductions in caries for all schools included in the study and up to 41% for the most cooperative.


Characterization of children of bipolar parents by parent report CBCL.
In past research the Child Behavior Checklist (CBCL) has differentiated among various diagnostic categories for children and adolescents. However, research has not been conducted on whether the CBCL differentiates among diagnostic categories for children at high risk for development of psychopathology. This study compares four diagnostic groups [bipolar disorder (BD), attention/deficit-hyperactivity disorder (ADHD), Depressed/Anxious and No Diagnosis] within a cohort of 58 children of bipolar parents to determine whether their CBCL scores will replicate the scores of children not at high risk for bipolar disorder. The cohort of children of bipolar parents received elevated scores on the CBCL scales in comparison with non-clinical populations. In addition, the CBCL distinguished between children of bipolar parents with and without clinical disorders. Finally the BD group differed from the ADHD group only on the Aggressive Behaviors, Withdrawn and Anxious/Depressed subscales of the CBCL. Therefore the CBCL did not discriminate between the BD and ADHD groups as it had in previous studies of children with BD and unspecified family history. It is possible that this discrepancy is due to a group of children of bipolar parents with ADHD who are currently prodromal for bipolar disorder and therefore received higher scores on the CBCL based on prodromal symptomatology. A longitudinal follow-up of this cohort is necessary to ascertain whether this is the case.


Ellipsometric investigation of rough zinc arsenide epilayers.
We report single-wavelength ellipsometric measurements of the complex index of refraction of rough Zn3As2 films on InP substrates. What we believe to be a novel technique, based on surface roughness measurements by atomic-force microscopy, is discussed to extract useful information from the ellipsometry results. The anticipated presence of a thin oxide layer is confirmed by Auger electron spectroscopy.


Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease.
The Apolipoprotein E (APOE) epsilon 4 allele is an important risk factor for Alzheimer's disease (AD). Given the interest in early identification of at-risk individuals, we examined memory decline as a function of APOE status and age in cognitively intact participants aged 48-77 years old (yo). Participants were grouped by age (<60 versus > or =60) and APOE (epsilon4+/-). Longitudinal analysis of several components of memory over a 2-year interval showed a significant Age-by-APOE interaction reflecting a decline in new learning for the > or =60 epsilon4+ group only. Among epsilon4+, 76% of the > or =60 participants showed a decline versus 32% of the <60, but the amount of decline in new learning over the 2-year interval within the > or =60 group was not further influenced by age. That is, the size of the 2-year change was the same for 60 and 70 year old participants. This suggests that longitudinal study of new learning is a sensitive measure for detecting early cognitive changes in at-risk individuals that precede the symptomatic onset of mild cognitive impairment and AD.


Active and Passive Coping Strategies: Comparing Psychological Distress, Cortisol, and Proinflammatory Cytokine Levels in Breast Cancer Survivors.
Breast cancer survivors can experience psychological distress, such as anxiety and depression, long after treatment has ended, and the development of such negative affective states has been related to the coping strategy used. This pilot study aims to determine whether different coping strategies are associated with differences in psychological distress, cortisol, and tumor necrosis factor alpha (TNF-a) levels in breast cancer survivors. 54 breast cancer survivors completed the Stress Coping Questionnaire and the Hospital Anxiety and Depression Scale and provided a blood sample for cortisol and proinflammatory cytokine measures. Passive coping strategies were associated with higher psychological distress, cortisol, and TNF-a levels. The passive group had more avoidance and negative self-targeting and less positive reappraisal and focusing on a problem's solution.


Evaluation of chondrogenesis within PEGT: PBT scaffolds with high PEG content.
Porous poly(ethylene glycol) terephthalate:poly (butylene terephthalate) (PEGT:PBT) scaffolds with high PEG molecular weight (1000 g/mole) and PEGT content (60%) were fabricated using two different processes-paraffin templating and compression molding-for cartilage engineering applications. This polymer composition has previously been shown to enable chondrocyte adhesion and maintain differentiated phenotype in 2D monolayer culture. The influence of 3D polymer scaffold processing on the formation of cartilaginous tissue was studied by seeding primary immature bovine chondrocytes within cylindrical scaffolds in mixed flask reactors for 3 days, followed by cultivation in culture plates for a total of 10 or 24 days. Tissue-polymer constructs were evaluated morphologically by SEM and histology, and quantitatively for cellularity, total collagen, and glycosaminoglycan content, all of which remained statistically equivalent for each time point tested, irrespective of fabrication method. These data demonstrate that the polymers engineered for this study were able to support chondrogenesis independent of scaffold fabrication process, with the influence of pore architecture lessened by the highly hydrated scaffold microenvironments induced by high PEG content.


Chemotherapy-related change in cognitive function: a conceptual model.
To develop a conceptual model of chemotherapy-related changes in cognitive function. MEDLINE, CINAHL, HealthStar, and PsycINFO databases. Patients undergoing chemotherapy often complain of forgetfulness, absentmindedness, and an inability to focus when performing a variety of daily tasks. Changes in cognitive function have been referred to by the colloquial term "chemo-brain." The authors conducted an examination of the literature to investigate relationships among concepts and to synthesize current knowledge. Cognitive function, defined as higher-order mental processes, may be altered along two distinct and interacting pathways: (a) the cancer diagnosis, which can lead to anxiety, stress, distress, and depression; and (b) the direct physiologic effects of cancer treatment. The Chemotherapy-Related Change in Cognitive Function conceptual model is informed by a review of literature that illustrates antecedents, moderators, mediators, and consequences that may be relevant to this issue. When a patient presents with cognitive complaints, the problems can be evaluated for intervention when an overall understanding exists of chemotherapy-related cognitive changes based on a conceptual model that continues to be informed through well-conceptualized and well-designed research.


Postoperative Cerebral Vasospasm Following Transsphenoidal Pituitary Adenoma Surgery.
Cerebral vasospasm following a transsphenoidal resection of a pituitary adenoma is a devastating occurrence that can lead to delayed cerebral ischemia and poor neurologic outcome if not diagnosed and treated in a timely manner. The etiology of this condition is not well understood but can lead to significant arterial vasospasm that causes severe ischemic insults. In this paper, we identify common presenting symptoms and essential management strategies to treat this harmful disease. A retrospective case report and literature review of presentation, treatment, and outcome of cerebral vasospasm following transsphenoidal surgery. We present 1 case and review 12 known cases in the literature on vasospasm following transsphenoidal surgery. Mean age was 48 (±13.8) years. There were 46.2% male patients. Factors associated with vasospasm, such as cerebral spinal fluid leaks following surgery, were seen in 38.5% of cases, and postoperative subarachnoid hemorrhage (SAH) was seen in 84.6% of cases. Hemiparesis was the presenting symptom of delayed cerebral ischemia in 61.5% of cases. For management, maintaining at least a euvolemic volume status was used in 76.9%, induced hypertension was used in 61.5%, and nimodipine was administered in 46.2% of cases. Patients returned to their neurologic baseline in 61.5% of cases, had new permanent deficits in 7.7% of cases, and died in 30.8% of cases. Cerebral vasospasm following transsphenoidal surgery is a dangerous disease that can lead to a high likelihood of mortality if not identified and treated. Early postoperative events, such as peritumoral subarachnoid hemorrhage and hemiparesis, may be factors associated with post-transsphenoidal surgery vasospasm. Effective treatment options used in patients that regained complete neurologic recovery were by inducing hypertension, maintaining euvolemia, and administering nimodipine.


Effect of Mentally Challenging Occupations on Incident Dementia Differs Between African Americans and Non-Hispanic Whites.
Engaging in mentally challenging activities may protect against dementia in late life. However, little is known whether the association between mentally challenging activities and dementia risk varies with race/ethnicity. The current study investigates whether having jobs with higher mental stimulation is differentially associated with a decreased risk of dementia between African Americans (AAs) and non-Hispanic Whites (nHWs). The sample consisted of 1,079 individuals (66% nHWs, 28% AAs; age = 78.6±5.3) from the longitudinal Einstein Aging Study. Occupation information of each participant was collected retrospectively at baseline and was linked to the substantive complexity of work score from the Dictionary of Occupational Titles. Cox proportional hazards models were used to evaluate the associations of occupational complexity with risk of dementia. Individuals whose jobs had moderate-to-high levels of complexity, compared to those with the lowest complexity, were at modestly decreased risk for incident dementia. When stratified by race, moderate-to-high levels of occupational complexity were significantly associated with lower risk of developing dementia for AAs (HR = 0.35). When risk of dementia was evaluated based on the combinations of race×occupational complexity, AAs with lowest occupational complexity showed the highest risk of developing dementia, while other combinations exhibited lower risk of developing dementia (HRs = 0.36~0.43). Our results suggest that moderate-to-high levels of complexity at work are associated with a decreased risk of incident dementia in AAs. Understanding the differential effects of mentally challenging occupations across race/ethnicity may suggest important intervention strategies that could mitigate racial disparities in dementia rates.


Study of serum vitamin D levels in men with premature androgenetic alopecia.
Vitamin D deficiency had been associated with various hair loss disorders, such as telogen effluvium, alopecia areata, and female pattern hair loss. However, previous studies have not found a correlation between serum vitamin D levels and the severity of androgenetic alopecia. A case-control study was conducted for a period of one year in a public tertiary care hospital. Fifty males clinically diagnosed with androgenetic alopecia and 50 age-matched healthy controls were recruited. Serum vitamin D levels in both cases and controls were measured by radioimmunoassay technique, and the results were compared. A total of 50 cases and 50 controls were recruited and analyzed. The mean age of the cases was 23 years and that of controls was 24.2 years. The mean levels of serum vitamin D significantly decreased in cases, compared to controls (20.10 vs. 29.34 ng/mL; P ≤ 0.001). Eighty-six percent of the cases had deficiency of vitamin D (<30 nmol/L), while 14% had insufficient vitamin D levels (31-50 nmol/L). There was a positive correlation between vitamin D deficiency and severity of androgenetic alopecia (AGA), which was statistically significant (P ≤ 0.5). However, there was no correlation between the duration of sun exposure and serum vitamin D levels (2.36 ± 1.2 in cases and 3.23 ± 1.6 in controls, P value = 0.98). Our study showed a significant correlation between vitamin D deficiency and the severity of androgenetic alopecia. This suggests that vitamin D may play a role in the premature onset of androgenetic alopecia. However, further studies on a larger population and the effect of vitamin D supplementation on the progression of androgenetic alopecia are required to validate the above findings.


Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA.
Malonyl-coenzyme A is an important precursor metabolite for the biosynthesis of polyketides, flavonoids and biofuels. However, malonyl-CoA naturally synthesized in microorganisms is consumed for the production of fatty acids and phospholipids leaving only a small amount available for the production of other metabolic targets in recombinant biosynthesis. Here we present an integrated computational and experimental approach aimed at improving the intracellular availability of malonyl-CoA in Escherichia coli. We used a customized version of the recently developed OptForce methodology to predict a minimal set of genetic interventions that guarantee a prespecified yield of malonyl-CoA in E. coli strain BL21 Star™. In order to validate the model predictions, we have successfully constructed an E. coli recombinant strain that exhibits a 4-fold increase in the levels of intracellular malonyl-CoA compared to the wild type strain. Furthermore, we demonstrate the potential of this E. coli strain for the production of plant-specific secondary metabolites naringenin (474mg/L) with the highest yield ever achieved in a lab-scale fermentation process. Combined effect of the genetic interventions was found to be synergistic based on a developed analysis method that correlates genetic modification to cell phenotype, specifically the identified knockout targets (ΔfumC and ΔsucC) and overexpression targets (ACC, PGK, GAPD and PDH) can cooperatively force carbon flux towards malonyl-CoA. The presented strategy can also be readily expanded for the production of other malonyl-CoA-derived compounds like polyketides and biofuels.


Is "huh?" a universal word? Conversational infrastructure and the convergent evolution of linguistic items.
A word like Huh?--used as a repair initiator when, for example, one has not clearly heard what someone just said--is found in roughly the same form and function in spoken languages across the globe. We investigate it in naturally occurring conversations in ten languages and present evidence and arguments for two distinct claims: that Huh? is universal, and that it is a word. In support of the first, we show that the similarities in form and function of this interjection across languages are much greater than expected by chance. In support of the second claim we show that it is a lexical, conventionalised form that has to be learnt, unlike grunts or emotional cries. We discuss possible reasons for the cross-linguistic similarity and propose an account in terms of convergent evolution. Huh? is a universal word not because it is innate but because it is shaped by selective pressures in an interactional environment that all languages share: that of other-initiated repair. Our proposal enhances evolutionary models of language change by suggesting that conversational infrastructure can drive the convergent cultural evolution of linguistic items.


Factors determining the variability of arterial pressure in hypertension.
1. Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Pressure was analysed beat by beat by computer and variability measured as the standard deviation of the normally distributed frequency histogram. 2. Variability was strongly influenced by physical activity, being least during sleep and increasing progressively with bed rest and ambulation. Variability during daytime was not related to time. 3. Systolic variability correlated directly with systolic pressure. An independent inverse relationship with baroreflex sensitivity was observed. Systolic variability tended to increase with obesity. 4. None of the following were related independently with variability: age; race; sex; plasma renin activity; plasma angiotensin II; plasma noradrenaline; plasma adrenaline.


Surveillance for respiratory and diarrheal pathogens at the human-pig interface in Sarawak, Malaysia.
The large livestock operations and dense human population of Southeast Asia are considered a hot-spot for emerging viruses. To determine if the pathogens adenovirus (ADV), coronavirus (CoV), encephalomyocarditis virus (EMCV), enterovirus (EV), influenza A-D (IAV, IBV, ICV, and IDV), porcine circovirus 2 (PCV2), and porcine rotaviruses A and C (RVA and RVC), are aerosolized at the animal-interface, and if humans working in these environments are carrying these viruses in their nasal airways. This cross-sectional study took place in Sarawak, Malaysia among 11 pig farms, 2 abattoirs, and 3 animal markets in June and July of 2017. Pig feces, pig oral secretions, bioaerosols, and worker nasal wash samples were collected and analyzed via rPCR and rRT-PCR for respiratory and diarrheal viruses. In all, 55 pig fecal, 49 pig oral or water, 45 bioaerosol, and 78 worker nasal wash samples were collected across 16 sites. PCV2 was detected in 21 pig fecal, 43 pig oral or water, 3 bioaerosol, and 4 worker nasal wash samples. In addition, one or more bioaerosol or pig samples were positive for EV, IAV, and RVC, and one or more worker samples were positive for ADV, CoV, IBV, and IDV. This study demonstrates that nucleic acids from a number of targeted viruses were present in pig oral secretions and pig fecal samples, and that several viruses were detected in bioaerosol samples or in the nasal passages of humans with occupational exposure to pigs. These results demonstrate the need for future research in strengthening viral surveillance at the human-animal interface, specifically through expanded bioaerosol sampling efforts and a seroepidemiological study of individuals with exposure to pigs in this region for PCV2 infection.


Multivalent benzoboroxole functionalized polymers as gp120 glycan targeted microbicide entry inhibitors.
Microbicides are women-controlled prophylactics for sexually transmitted infections. The most important class of microbicides target HIV-1 and contain antiviral agents formulated for topical vaginal delivery. Identification of new viral entry inhibitors that target the HIV-1 envelope is important because they can inactivate HIV-1 in the vaginal lumen before virions can come in contact with CD4+ cells in the vaginal mucosa. Carbohydrate binding agents (CBAs) demonstrate the ability to act as entry inhibitors due to their ability to bind to glycans and prevent gp120 binding to CD4+ cells. However, as proteins they present significant challenges in regard to economical production and formulation for resource-poor environments. We have synthesized water-soluble polymer CBAs that contain multiple benzoboroxole moieties. A benzoboroxole-functionalized monomer was synthesized and incorporated into linear oligomers with 2-hydroxypropylmethacrylamide (HPMAm) at different feed ratios using free radical polymerization. The benzoboroxole small molecule analogue demonstrated weak affinity for HIV-1BaL gp120 by SPR; however, the 25 mol % functionalized benzoboroxole oligomer demonstrated a 10-fold decrease in the K(D) for gp120, suggesting an increased avidity for the multivalent polymer construct. High molecular weight polymers functionalized with 25, 50, and 75 mol % benzoboroxole were synthesized and tested for their ability to neutralize HIV-1 entry for two HIV-1 clades and both R5 and X4 coreceptor tropism. All three polymers demonstrated activity against all viral strains tested with EC(50)s that decrease from 15000 nM (1500 microg mL(-1)) for the 25 mol % functionalized polymers to 11 nM (1 microg mL(-1)) for the 75 mol % benzoboroxole-functionalized polymers. These polymers exhibited minimal cytotoxicity after 24 h exposure to a human vaginal cell line.


BAS: balanced acceptance sampling of natural resources.
To design an efficient survey or monitoring program for a natural resource it is important to consider the spatial distribution of the resource. Generally, sample designs that are spatially balanced are more efficient than designs which are not. A spatially balanced design selects a sample that is evenly distributed over the extent of the resource. In this article we present a new spatially balanced design that can be used to select a sample from discrete and continuous populations in multi-dimensional space. The design, which we call balanced acceptance sampling, utilizes the Halton sequence to assure spatial diversity of selected locations. Targeted inclusion probabilities are achieved by acceptance sampling. The BAS design is conceptually simpler than competing spatially balanced designs, executes faster, and achieves better spatial balance as measured by a number of quantities. The algorithm has been programed in an R package freely available for download.


Wolbachia successfully replicate in a newly established horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae) cell line.
Haematobia spp., horn flies (HF) and buffalo flies (BF), are economically important ectoparasites of dairy and beef cattle. Control of these flies relies mainly on treating cattle with chemical insecticides. However, the development of resistance to commonly used compounds is compromising the effectiveness of these treatments and alternative methods of control are required. Wolbachia are maternally transmitted endosymbiotic bacteria of arthropods that cause various reproductive distortions and fitness effects, making them a potential candidate for use in the biological control of pests. The first step towards this is the establishment and adaptation of xenobiotic infections of Wolbachia in target host cell lines. Here, we report the successful establishment of a continuous HF cell line (HIE-18) from embryonic cells and its stable transinfection with Wolbachia strains wAlbB native to mosquitoes, and wMel and wMelPop native to Drosophila melanogaster. HIE-18 cells were typically round and diploid with ten chromosomes (2n = 10) or tetraploid with 20 chromosomes (4n = 20), with a doubling time of 67.2 h. Wolbachia density decreased significantly in HIE-18 cells in the first 48 h of infection, possibly due to overexpression of antimicrobial peptides through the Imd immune signalling pathway. However, density recovered after this time and HIE-18 cell lines stably infected with the three strains of Wolbachia have now each been subcultured more than 50 times as persistently infected lines. The amenability of HF cells to infection with different strains of Wolbachia and the establishment of stable sustaining infections suggest the potential for use of Wolbachia in novel approaches for the control of Haematobia spp. Further, the availability of the HIE-18 cell line will provide an important resource for the study of genetics, host-parasite interactions and chemical resistance in Haematobia populations. © 2020 Society of Chemical Industry.


Autoimmune diseases and infections: controversial issues.
The etiology and pathogenesis of certain types of disease remain controversial and stand like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Infection, for example, may initiate a disease, although it is the genetic regulation in the host, the interplay between virus or bacteria persistence and autoimmunity that produces the later phases of disease, the antigenic determinants responsible for inducing autoimmune disease, and the pathogenetic effector mechanisms. Infections agents cause pericarditis, but in 85% of cases it is "idiopathic". It has also been shown that persistent Clamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori infections cause host immunity and promote atherogenesis. A number of infectious agents have been suggested as potential triggers for primary biliary cirrhosis. Infections and vaccinations have also been linked to the pathogenesis of fibromyalgia syndrome, a common, chronic syndrome of widespread pain. Many factors are also responsible for fever of unknown origin such as: infections, autoimmunity disease, etc. However, it is difficult to determine a direct correlation between the infections agents in such a large group of diseases. The aim of this review is to analyze some of the controversies about the role of infections in autoimmune diseases.


Bifocal juvenile papillomatosis as a marker of breast cancer: A case report and review of the literature.
Juvenile papillomatosis (JP), also termed Swiss cheese disease, is a rare and benign type of proliferative breast tumor that is specifically observed in children and adolescents. The majority of JP patients are Caucasian and exhibit a single breast mass. The current report presents an unusual case of bifocal JP in an 11-year-old Chinese female. The patient presented with a slow-growing palpable mass in the upper outer quadrant of the left breast. Ultrasonography identified a further impalpable lesion in the lower outer quadrant of the ipsilateral breast. The preoperative clinical diagnosis of the two masses was fibroadenoma, however, following complete excision of the two tumors, histopathology revealed JP. Furthermore, the patient had a family history of breast cancer. The current report describes a review of the literature regarding the presentation, pathology, diagnosis, and treatment of JP and its association with breast carcinoma. In the current case, JP was associated with an increased risk of breast cancer in the patient, as well as the patient's elder female relatives; therefore, a more thorough medical follow-up may prove prudent for those individuals with a high risk of developing breast cancer.


Attraction of Anopheles gambiae to odour baits augmented with heat and moisture.
The search for a standard human surrogate in the form of a synthetic mosquito attractant has been the goal of many laboratories around the world. Besides alleviating the occupational risk subjected to volunteers participating in vector surveillance and control, discovery of potent attractants underpins the development and deployment of mass trapping devices for controlling mosquito-borne diseases. A dual-port olfactometer was used to assess behavioural responses of female Anopheles gambiae mosquitoes towards synthetic versus natural (whole human emanations and worn socks) attractants. The synthetic attractants included a standard blend consisting of ammonia, carbon dioxide and water; and Ifakara blend 1 (IB1) consisting of various aliphatic carboxylic acids. Natural attractants were obtained from two males known to be less and highly attractive (LA and HA, respectively) to the mosquitoes. Mosquito responses to the volunteers' worn socks were also investigated. The effect of heat (25-27 degrees C) and moisture (75-85%) on the mosquito behavioural responses was determined. A significantly higher proportion of mosquitoes was attracted to each volunteer when compared to the standard blend. Whereas the proportion of mosquitoes attracted to person LA versus IB1 (49% versus 51%, respectively; P = 0.417) or his worn socks did not differ (61% versus 39%, respectively; P = 0.163), far more mosquitoes were attracted to person HA relative to IB1 (96% versus 4%; P = 0.001) or his worn socks (91% versus 9%; P = 0.001). Person HA attracted a significantly higher proportion of mosquitoes than his worn socks, the standard blend and IB1 when these were augmented with heat, moisture or both (P = 0.001). Similar results were obtained with person LA except that the proportion of mosquitoes attracted to him versus his worn sock augmented with heat (P = 0.65) or IB1 augmented with heat and moisture (P = 0.416) did not differ significantly. These findings indicate that olfactory cues are key mediators of the mosquito host-seeking process and that heat and moisture play a minor role. The need for a standard, highly stringent positive control for screening synthetic attractants is strongly highlighted.


Effects of acute and chronic sleep deprivation on cardiovascular regulation.
Sleep is a fundamental physiological process, characterized by the activation of several cortical and subcortical neural networks. The relation between sleep and cardiovascular system is complex and bidirectional: sleep disorders may alter cardiovascular system, leading to an increased cardiovascular risk, while, on the contrary, cardio- vascular diseases are characterized by an alteration of physiological sleep. Autonomic nervous system (ANS) plays a key role in the regulation of cardiovascular functions during different sleep stages, with sympatho-vagal balance dynamically shifting towards sympathetic or vagal predominance across different sleep stages. Sleep deprivation (SD) has becoming one of the most relevant health problem in modern societies. SD can be related to aging, which is associated with increased sleep fragmentation, and to sleep disorders, such as sleep disordered breathing and neurological disorders. Experimental studies in animals showed that SD significantly affects cardiovascular functions, altering heart rate and blood pressure responses, and increasing sympathetic activity and neuroendocrine response to stressor stimuli. Clinical studies in humans have shown that SD, either due to experimental sleep loss and to sleep disorders, can affect different biological pathways, such as cardiovascular autonomic control, inflammation, immunity responses and metabolism. All these alterations may predispose subjects with SD to an increased cardiovascular risk. Hence, it is fundamental to identify the presence of a sleep disorder, which could be per se responsible for sleep loss, or the presence of sleep deprivation due to other factors, such as social life, habits etc., in order to identify subjects at high risk for cardiovascular events.


Using information technology to improve the quality and safety of emergency care.
With the 2010 federal health care reform passage, a renewed focus has emerged for the integration of electronic health records (EHRs) into the U.S. health care system. A consensus conference in October 2009 met to discuss the future research agenda with regard to using information technology (IT) to improve the future quality and safety of emergency department (ED) care. The literature is mixed as to how the use of computerized provider order entry (CPOE), clinical decision support (CDS), EHRs, and patient tracking systems has improved or degraded the safety and quality of ED care. Such mixed findings must be considered in the national push for rapid implementation of health IT. We present a research agenda addressing the major questions that are posed by the introduction of IT into ED care; these questions relate to interoperability, patient flow and integration into clinical work, real-time decision support, handoffs, safety-critical computing, and the interaction between IT systems and clinical workflows.


Evaluation of TNF-alpha and IL-1 blockade in collagen-induced arthritis and comparison with combined anti-TNF-alpha/anti-CD4 therapy.
We have evaluated the effects of anti-TNF-alpha, anti-IL-1, and combined anti-TNF-alpha/anti-CD4 therapy in collagen-induced arthritis. Blockade of TNF-alpha or IL-1 before disease onset delayed, but did not prevent, the induction of arthritis. When treatment was initiated after onset of arthritis, anti-TNF-alpha, anti-IL-1beta, and anti-IL-1R (which blocks IL-1alpha and IL-1beta) were all found to be effective in reducing the severity of arthritis, with anti-IL-1R and anti-IL-1beta showing greater efficacy than anti-TNF-alpha. Anti-IL-1beta was equally as effective as anti-IL-1R, indicating that IL-1beta plays a more prominent role than IL-1alpha in collagen-induced arthritis. An additive effect was observed between anti-TNF-alpha and anti-IL-1R in the prevention of joint erosion and in normalization of the levels of serum amyloid P. Combined anti-TNF-alpha/anti-CD4 therapy also caused normalization of serum amyloid P levels. The therapeutic effect of anti-TNF-alpha plus anti-CD4 was comparable to that of anti-TNF-alpha plus anti-IL-1R, suggesting that combined anti-TNF-alpha/anti-CD4 therapy prevents both TNF-alpha- and IL-1-mediated pathology. Anti-TNF-alpha treatment reduced IL-1beta expression in the joint and, conversely, anti-IL-1beta treatment reduced TNF-alpha expression. Combined anti-TNF-alpha/anti-CD4 treatment almost completely blocked the expression of IL-1beta, thereby confirming the ability of this form of combination therapy to prevent IL-1ss-mediated pathology.