Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years.
The number of people living with dementia is expected to exceed 130 million by 2050, which will have serious personal, social and economic implications. Employing successful intervention and treatment strategies focused on disease prevention is currently the only available approach that can have an impact on the projected rates of dementia, with risk assessment being a key component of population-based risk reduction for identification of at-risk individuals. We evaluated a risk index comprising lifestyle, medical and demographic factors (the Australian National University Alzheimer's Disease Risk Index [ANU-ADRI]), as well as a genetic risk score (GRS), for assessment of the risk of progression to mild cognitive impairment (MCI). The ANU-ADRI was computed for the baseline assessment of 2078 participants in the Personality and Total Health (PATH) Through Life project. GRSs were constructed on the basis of 25 single-nucleotide polymorphisms previously associated with Alzheimer's disease (AD). Participants were assessed for clinically diagnosed MCI and dementia as well as psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models were used to estimate the odds of transitioning from cognitively normal (CN) to MCI, dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS. A higher ANU-ADRI score was associated with increased risk of progressing from CN to both MCI and MCI-TB (HR 1.07 [95% CI 1.04-1.11]; 1.07 [1.04-1.09]). The GRS was associated with transitions from CN to dementia (HR 4.19 [95% CI 1.72-10.20), but not to MCI or MCI-TB (HR 1.05 [95% CI 0.86-1.29]; 1.03 [0.87-1.21]). Limitations of our study include that the ethnicity of participants in the PATH project is predominately Caucasian, potentially limiting the generalisability of the results of this study to people of other ethnicities. Biomarkers of AD were not available to define MCI attributable to AD. Not all the predictive variables for the ANU-ADRI were available in the PATH project. In the general population, the ANU-ADRI, comprising lifestyle, medical and demographic factors, is associated with the risk of progression from CN to MCI, whereas a GRS comprising the main AD risk genes was not associated with this risk. The ANU-ADRI may be used for population-level risk assessment and screening.


A minimally invasive method for gender determination in the prehensile-tailed porcupine (Coendou prehensilis).
Prehensile-tailed porcupines (Coendou prehensilis), like other rodents, lack external sexual traits, making it difficult to non-invasively determine their gender. By exploiting genetic differences between the X and the Y chromosome, we developed a simple genetic test to determine the gender of Coendous from shed quills. We Sanger sequenced a short portion (195 bp) of the zinc finger protein gene of known male (XY) Coendous to identify positions that are polymorphic between the X and Y chromosomes at this locus. By directly sequencing this fragment, we were able to correctly determine (confirmed via anatomical sexing) the gender of male and female Coendous by the presences or absence of polymorphisms in the resulting chromatograms. This assay is simple, quick and is applicable to other porcupine species.


Comparison of the RT3 Research Tracker and Tritrac R3D accelerometers during a backpacking expedition by a single subject.
This study compared the RT3 Research Tracker accelerometer and the Tritrac R3D accelerometer in a field setting. A six-day backpacking expedition (122.4 km in length) was completed by a single subject in the Grand Canyon National Park, Arizona. The overall correlation between the counts of vector magnitude activity for the RT3 and R3D was moderate (r =.75, p<.001), with the overall calculated bias [mean difference (RT3 minus R3D) and standard deviation of the differences] across all six days estimated at 235+/-436 vector magnitude activity counts. However, agreement between the instruments is problematic; the RT3 might be 201 activity counts below or 671 activity counts above the R3D in assessing physical activity during backpacking.


Electro-optical co-simulation for integrated CMOS photonic circuits with VerilogA.
We present a Cadence toolkit library written in VerilogA for simulation of electro-optical systems. We have identified and described a set of fundamental photonic components at the physical level such that characteristics of composite devices (e.g. ring modulators) are created organically - by simple instantiation of fundamental primitives. Both the amplitude and phase of optical signals as well as optical-electrical interactions are simulated. We show that the results match other simulations and analytic solutions that have previously been compared to theory for both simple devices, such as ring resonators, and more complicated devices and systems such as single-sideband modulators, WDM links and Pound Drever Hall Locking loops. We also illustrate the capability of such toolkit for co-simulation with electronic circuits, which is a key enabler of the electro-optic system development and verification.


Total Force Fitness Education: A Critical Enabler of Human Performance Optimization.
Military health education has historically been focused on conveying the consequences of risky behaviors, informing about external resources, and addressing disease through mitigation and prevention. Total Force Fitness (TFF) and Human Performance Optimization (HPO) provide a broad and holistic framework for preventing health issues and bolstering performance. The Consortium for Health and Military Performance convened a workgroup at the TFF Summit in 2021 to discuss the current state of TFF/HPO in military health education efforts and to identify areas for improvement. An education workgroup of 42 attendees gathered to discuss the current state of TFF/HPO-based health education in the military. Four questions were posed to all members for discussion. Notes were taken and consolidated to obtain feedback and promote discussion from the attendees in a larger audience at the TFF Summit. The education workgroup identified several education formats, goals, initiatives, and opportunities for improving the development and dissemination of TFF/HPO-based health education throughout the Services. Workgroup members reached a consensus on health education formats (development, dissemination, and audience) and that the primary goal of education is knowledge dissemination and increasing awareness. They also identified several stellar examples of existing TFF/HPO initiatives and explored how health education can increase impact and be more sustainable. The workgroup outcomes were shared with the TFF Summit audience to generate further discussion and to outline action items. Seven action items were identified to improve the development and dissemination of TFF/HPO resources and ensure productive and effective initiatives and programs throughout the Department of Defense. The TFF Summit outlined several actionable items that would improve the development and dissemination of TFF/HPO-based health education throughout the Department of Defense's initiatives and programs. A broader approach to military health education that uses a TFF/HPO framework will directly impact the health and performance of the force. Ultimately, embedding TFF/HPO information into the fabric of military health education would shift the focus toward a holistic, proactive, preventive, and performance-based culture.


Promoter polymorphism (rs3755724, -55C/T) of tissue inhibitor of metalloproteinase 4 (TIMP4) as a risk factor for Kawasaki disease with coronary artery lesions in a Korean population.
Kawasaki disease (KD) is an acute febrile vasculitis that predominantly affects infants and young children. Tissue inhibitors of matrix metalloproteinases (TIMPs) comprise a family of four members, of which TIMP4 is characterized by its restriction to cardiovascular structures. In KD pathophysiology, TIMP4 is considered to be involved in the development of coronary artery lesions (CALs). Therefore, this study investigated single-nucleotide polymorphisms (SNPs) of the TIMP4 gene as risk factors for KD with CALs in Korean children. To observe this association, two SNPs (rs3755724, -55C/T, promoter; rs17035945, 3'-untranslated region) were genotyped in TIMP4 using direct sequencing. There were no SNPs in the coding region of TIMP4, and two SNPs were selected in the exon and promoter regions. This study recruited 250 control and 101 KD subjects. For data analysis, SNPStats, SNPAnalyzer, and Helixtree programs were used. These SNPs were not associated with KD. However, in the recessive model, a significant association was found between rs3755724 and the development of CALs in KD (P = 0.02; odds ratio, 0.31; 95% confidence interval, 0.11-0.85). The minor allele (C) of rs3755724 showed the susceptibility of CALs to risk in KD patients. These results suggest that TIMP4 is related to the development of KD with CALs in Korean children.


[Hypersplenism].
Hypersplenism is characterized by a significant reduction in one or more of the cellular elements of the blood in the presence of normocellular or hypercellular bone marrow and splenomegaly. The incidence of hypersplenism in patients with cirrhosis and portal hypertension is high. In rare cases the hyperslenism is symptomatic with bleeding disorders or hemolytic anemia. In this situation the splenectomy is the therapy of choice. The arterial partial embolisation is a good alternative procedure in patients with high risk of operation.


Mycobacterium bovis bacillus Calmette-Guérin secreting active cathepsin S stimulates expression of mature MHC class II molecules and antigen presentation in human macrophages.
A successful Th cell response to bacterial infections is induced by mature MHC class II molecules presenting specific Ag peptides on the surface of macrophages. In recent studies, we demonstrated that infection with the conventional vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) specifically blocks the surface export of mature class II molecules in human macrophages by a mechanism dependent on inhibition of cathepsin S (Cat S) expression. The present study examined class II expression in macrophages infected with a rBCG strain engineered to express and secrete biologically active human Cat S (rBCG-hcs). Cat S activity was completely restored in cells ingesting rBCG-hcs, which secreted substantial levels of Cat S intracellularly. Thus, infection with rBCG-hcs, but not parental BCG, restored surface expression of mature MHC class II molecules in response to IFN-gamma, presumably as result of MHC class II invariant chain degradation dependent on active Cat S secreted by the bacterium. These events correlated with increased class II-directed presentation of mycobacterial Ag85B to a specific CD4(+) T cell hybridoma by rBCG-hcs-infected macrophages. Consistent with these findings, rBCG-hcs was found to accelerate the fusion of its phagosome with lysosomes, a process that optimizes Ag processing in infected macrophages. These data demonstrated that intracellular restoration of Cat S activity improves the capacity of BCG-infected macrophages to stimulate CD4(+) Th cells. Given that Th cells play a major role in protection against tuberculosis, rBCG-hcs would be a valuable tuberculosis vaccine candidate.


DTI segmentation using an information theoretic tensor dissimilarity measure.
In recent years, diffusion tensor imaging (DTI) has become a popular in vivo diagnostic imaging technique in Radiological sciences. In order for this imaging technique to be more effective, proper image analysis techniques suited for analyzing these high dimensional data need to be developed. In this paper, we present a novel definition of tensor "distance" grounded in concepts from information theory and incorporate it in the segmentation of DTI. In a DTI, the symmetric positive definite (SPD) diffusion tensor at each voxel can be interpreted as the covariance matrix of a local Gaussian distribution. Thus, a natural measure of dissimilarity between SPD tensors would be the Kullback-Leibler (KL) divergence or its relative. We propose the square root of the J-divergence (symmetrized KL) between two Gaussian distributions corresponding to the diffusion tensors being compared and this leads to a novel closed form expression for the "distance" as well as the mean value of a DTI. Unlike the traditional Frobenius norm-based tensor distance, our "distance" is affine invariant, a desirable property in segmentation and many other applications. We then incorporate this new tensor "distance" in a region based active contour model for DTI segmentation. Synthetic and real data experiments are shown to depict the performance of the proposed model.


Incidence, causes, and consequences of preventable adverse drug reactions occurring in inpatients: A systematic review of systematic reviews.
Preventable adverse drug reactions (PADRs) in inpatients are associated with harm, including increased length of stay and potential loss of life, and result in elevated costs of care. We conducted an overview of reviews (i.e., a systematic review of systematic reviews) to determine the incidence of PADRs experienced by inpatients. Secondary review objectives were related to assessment of the effects of patient age, setting, and clinical specialty on PADR incidence. The protocol was registered in PROSPERO (CRD42016043220). We performed a search of Medline, Embase, and the Cochrane Library, limiting languages of publication to English and French. We included published systematic reviews that reported quantitative data on the incidence of PADRs in patients receiving acute or ambulatory care in a hospital setting. The full texts of all primary studies for which PADR data were reported in the included reviews were obtained and data relevant to review objectives were extracted. Quality of the included reviews was assessed using the AMSTAR-2 tool. Both narrative summaries of findings and meta-analyses of primary study data were undertaken. Thirteen systematic reviews encompassing 37 unique primary studies were included. Across primary studies, the PADR incidence was highly varied, ranging from 0.006 to 13.3 PADRs per 100 patients, with a pooled incidence estimate of 0.59 PADRs per 100 patients. Substantial heterogeneity was present across both reviews and primary studies with respect to review/study objectives, patient age, hospital setting, medical discipline, definitions and assessment tools used, event detection methods, endpoints of interest, and units of measure. Thirteen primary studies used prospective event detection methods and had a pooled PADR incidence of 3.13 (2.87-3.38) PADRs per 100 patients; however, extreme statistical heterogeneity (I2 = 97%) indicated this finding should be considered with caution. Subgroup meta-analyses demonstrated that PADR incidence varied significantly with event detection method (prospective > retrospective > voluntary reporting methods), hospital setting (ICU > wards), and medical discipline (medical > surgical). High statistical heterogeneity (I2 > 80%) was present across all analyses, indicating results should be interpreted with caution. Effects of patient age could not be assessed due to poor reporting of age groups used in primary studies. The method of event detection appeared to significantly influence PADR incidence, with prospective methods having the highest reported PADR rate. This finding is in agreement with the background literature. High methodological and statistical heterogeneity across primary studies evaluating adverse drug events reduces the validity of the overall PADR incidence derived from the meta-analyses of the pooled data. Data pooled from studies using only prospective methods of event detection should provide an overall estimate closest to the true PADR incidence; however, our estimate should be considered with caution due to the statistical heterogeneity found in this group of studies. Future studies should employ prospective methods of detection. This review demonstrates that the true overall incidence of PADRs is likely much greater than the overall pooled incidence estimate of 0.59 PADRs per 100 patients obtained when event detection method was not taken into consideration.


Prospects for personalized combination immunotherapy for solid tumors based on adoptive cell therapies and immune checkpoint blockade therapies.
Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors. However, gene-engineered T cells possess strong killing activity and cytokine production capacity, which can induce antigen spreading and modulate the TME of non-T cell-inflamed tumors seen in non-responders to ICB therapy. Immune responses against cancer are highly heterogeneous, not only between tumor types, but also within a patient or between different patients with the same type of cancer, indicating that personalized immunotherapy should be employed, based on the immune status of the individual patient. Here, we offer our perspective for personalized combination immunotherapy for solid tumors based on ACT and ICB therapies.


Cost implications of improving the quality of child care using integrated clinical algorithms: evidence from Northeast Brazil.
Previous research has shown that providers trained in the Integrated Management of Childhood Illness offered higher quality care for under-fives than those providing routine care in several settings including Northeast Brazil. The objective of this paper is to examine if such quality improvements adds to total costs or is cost saving. The additional costs associated with treating children based on IMCI clinical algorithms in northeast Brazil are estimated by comparing the total costs of under-five care in 22 municipalities with IMCI with 22 matched municipalities providing routine care. Multivariate analysis was also used to isolate the effect of IMCI on costs at primary facilities, controlling for other possible determinants. For 2001, there was no statistically significant difference in the cost per child of caring for under-fives in IMCI municipalities (US$ 95) relative to the comparison municipalities (US$ 98). Moreover, IMCI training had no independent effect on unit costs at primary facilities, the largest component in overall costs per child (79%). Case load was the most important determinant. Our findings suggest that scaling up IMCI-based care could increase child health outcomes in Brazil without increasing overall health costs.


Applying Thienyl Side Chains and Different π-Bridge to Aromatic Side-Chain Substituted Indacenodithiophene-Based Small Molecule Donors for High-Performance Organic Solar Cells.
A pair of linear tetrafluorinated small molecular donors, named as ThIDTTh4F and ThIDTSe4F, which are with tetrathienyl-substituted IDT as electron-rich central core, electron-deficient difluorobenzothiadiazole as acceptor units, and donor end-capping groups, but having differences in the π-bridge (thiophene and selenophene), were successfully synthesized and evaluated as donor materials in organic solar cells. Such π-bridge and core units in these small molecules play a decisive role in the formation of the nanoscale separation of the blend films, which were systematically investigated through absorption spectra, grazing incidence X-ray diffraction pattern, transmission electron microscopy images, resonant soft X-ray scattering profiles, and charge mobility measurement. The ThIDTSe4F (with selenophene π-bridge)-based device exhibited superior performance than devices based on ThIDTh4F (with thiophene π-bridge) after post annealing treatment owing to optimized film morphology and improved charge transport. Power conversion efficiency of 7.31% and fill factor of ∼0.70 were obtained by using a blend of ThIDTSe4F and PC71BM with thermal annealing and solvent vapor annealing treatments, which is the highest PCE from aromatic side-chain substituted IDT-based small molecular solar cells. The scope of this study is to reveal the structure-property relationship of the aromatic side-chain substituted IDT-based donor materials as a function of π-bridge and the post annealing conditions.


Customized topography-guided photorefractive keratectomy with the MEL-70 platform and mitomycin C to correct hyperopia after radial keratotomy.
To evaluate topography-guided photorefractive keratectomy (PRK) for correcting hyperopia and astigmatism after radial keratotomy (RK). Prospective study of 12 consecutive patients (19 eyes) who were treated with topography-guided PRK with 0.02% mitomycin C using an Asclepion-Meditec MEL-70 excimer laser with a 9.5-mm ablation zone. All eyes were operated by the same surgeon and followed for 1 year. Thirteen eyes had complete epithelialization by day 7 and all eyes by day 10. At 1 year, uncorrected visual acuity was 20/25 or better in 42.1% of eyes and 20/40 or better in 68.4%. Preoperative mean spherical equivalent refraction was +3.80+/-2.47 diopters (D) and +0.24+/-2.36 D (P<.001) 1 year postoperative, with 47.4% of eyes being within +/-1.00 D and 73.7% within +/-2.00 D. Preoperative mean cylinder was -2.30+/-1.41 D and -0.62+/-0.73 D (P<.001) 1 year postoperative. At 1 year, 68.4% of eyes gained at least 1 line of best-spectacle corrected visual acuity, 36.8% gained more than 1 line, and only 2 eyes lost 1 line (one due to corneal haze). Three eyes developed central haze. Mean regression from 6 to 12 months in these 3 eyes was +1.83 D and in the remaining 16 eyes was -0.50 D. Topography-guided PRK with mitomycin C was safe and reasonably effective for the treatment of hyperopia after RK.


New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones.
Basic proteins and nucleic acids are assembled into complexes in a reaction that must be facilitated by nuclear chaperones in order to prevent protein aggregation and formation of non-specific nucleoprotein complexes. The nucleophosmin/nucleoplasmin (NPM) family of chaperones [NPM1 (nucleophosmin), NPM2 (nucleoplasmin) and NPM3] have diverse functions in the cell and are ubiquitously represented throughout the animal kingdom. The importance of this family in cellular processes such as chromatin remodeling, genome stability, ribosome biogenesis, DNA duplication and transcriptional regulation has led to the rapid growth of information available on their structure and function. The present review covers different aspects related to the structure, evolution and function of the NPM family. Emphasis is placed on the long-term evolutionary mechanisms leading to the functional diversification of the family members, their role as chaperones (particularly as it pertains to their ability to aid in the reprogramming of chromatin), and the importance of NPM2 as an essential component of the amphibian chromatin remodeling machinery during fertilization and early embryonic development.


Knowledge mapping visualization analysis of the military health and medicine papers published in the web of science over the past 10 years.
Military medicine is a research field that seeks to solve the medical problems that occur in modern war conditions based on public medicine theory. We explore the main research topics of military health and medical research in the web of science™ core collection (WoSCC) from 2007 to 2016, and the goal of this work is to serve as a reference for orientation and development in military health and medicine. Based on CiteSpace III, a reference co-citation analysis is performed for 7921 papers published in the WoSCC from 2007 to 2016. In addition, a cluster analysis of research topics is performed with a comprehensive analysis of high-yield authors, outstanding research institutions and their cooperative networks. Currently, the research topics in military health and medicine mainly focus on the following seven aspects: mental health diagnoses and interventions, an army study to assess risk and resilience in service members (STARRS), large-scale military action, brain science, veterans, soldier parents and children of wartime, and wound infection. We also observed that the annual publication rate increased with time. Wessely S, Greenberg N, Fear NT, Smith TC, Smith B, Jones N, Ryan MAK, Boyko EJ, Hull L, and Rona RJ were the top 10 authors in military health and medicine research. The top 10 institutes were the Uniformed Services University of the Health Sciences, the United States Army, the United States Navy, Kings College London, Walter Reed National Military Medical Center, Boston University, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Naval Health Research Center, and the VA Boston Healthcare System. We are able to perform a comprehensive analysis of studies in military health and medicine research and summarize the current research climate and the developmental trends in the WoSCC. However, further studies and collaborations are needed worldwide. Overall, our findings provide valuable information and new perspectives and shape future research directions for further research in the area of military health and medicine.


Stereotactic vacuum-assisted breast biopsy: our experience and comparison with stereotactic automated needle biopsy.
To evaluate and compare the outcome of stereotactically guided percutaneous, directional, vacuum-assisted breast biopsy (VAB) with the outcome of those performed with 14-gauge automated gun. Between January 2008 and January 2011, altogether 257 stereotactic biopsies were performed in our institute; 193 with the 14-gauge automated needle and 64 with a directional, vacuum-assisted instrument. Patients with malignant or high risk lesions were encouraged to undergo an excisional biopsy. We evaluated and compared concordance between the biopsy results and subsequent examinations (surgical excision or follow up) for both methods. VAB demonstrated 57 (89 %) benign lesions, 2 (3 %) high risk and 5 (8 %) malignant lesions. We obtained post-bioptic mammographic or histological evaluation for altogether 51 lesions, with one (12.5 %) false negative case, one case of underestimation of borderline lesion, and no false positive cases. Clusters of microcalcifiation were completely removed in 18 lesions (28 %). Vacuum-assisted biopsy outperformed the 14-gauge automated needle biopsy with a lower disease underestimation, sensitivity and false-negative rates; however these differences were not statistically significant due to small data files and relatively small number of identified malignant lesions in the vacuum-assisted biopsy group.VAB completely removed significantly more clusters of microcalcifications in comparison to the automated needle biopsy, which significantly reduced the need for surgery in benign lesions (Tab. 7, Fig. 3, Ref. 32).


Analysis of proliferating cell nuclear antigen expression aids histological diagnosis and is predictive of progression of human cardiac allograft rejection.
A quantitative immunohistological analysis was undertaken of 558 sequential paraffin-embedded and 22 snap-frozen endomyocardial biopsies (EMBs) from nine consecutive patients undergoing cardiac transplantation and followed for up to 1 year post-surgery. Serial monitoring was performed to assess whether 1) the phenotypic characteristics, 2) level of immune activation, or 3) expression of proliferation-associated antigens by intragraft leukocytes were useful in determining the grade of rejection or predicting further rejection episodes. Particular attention was given to those patients whose most recent EMBs showed grade 2 rejection, because these patients present a common problem in clinical management wherein a decision must be made as to whether or not to increase immunosuppression. Comparison of EMBs displaying various grades of rejection showed that whereas the absolute number of leukocytes (CD45), memory T cells (UCHL1/CD45RO), helper T cells (OPD4), and macrophages (Mac387) increased with increasing grade of rejection, the proportions of each subset remained similar. Cell proliferation was determined by labeling with monoclonal antibodies to proliferating cell nuclear antigen (cyclin) and Ki-67, and immune activation was assessed using an anti-interleukin-2 receptor (CD25) monoclonal antibody. The numbers of intragraft proliferating cell nuclear antigen-positive Ki-67+ or interleukin-2 receptor-positive cells were found to increase with increasing grades of rejection. Moreover, comparison of EMBs with equivalent histological features of rejection (grade 2) showed significantly (P < 0.0001) greater numbers of proliferating cell nuclear antigen-positive cells in EMBs preceding an episode of higher grade or persisting rejection versus EMB from patients whose rejection resolved, as seen on subsequent biopsy, without increased immunosuppression. These data suggest that the identification of proliferating or immunologically activated cells may aid in the histological diagnosis of clinical rejection and provide a valuable indicator predictive of likely further rejection episodes of increasing severity if grade 2 rejection is left untreated.


Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats.
Administration of a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 20 or 80 micrograms/kg) resulted in significantly decreased hepatic and uterine estrogen receptor (ER) levels in 25-day-old female Long-Evans rats. By contrast, estradiol (5 and 15 micrograms/kg) administration increased hepatic and uterine ER levels, while a combination of 2,3,7,8-TCDD plus estradiol resulted in uterine and hepatic ER levels which were similar or lower than those observed after treatment with only 2,3,7,8-TCDD. In addition, 2,3,7,8-TCDD significantly decreased the effects of estradiol on uterine wet weight increase. Competitive binding studies showed that estradiol did not bind to the aryl hydrocarbon (Ah) receptor and that 2,3,7,8-TCDD did not bind to the ER. The effects of structure on the activity of polychlorinated dibenzo-p-dioxin congeners on their activity to down-regulate hepatic and uterine ER levels were determined by using 2,3,7,8-TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,3,7,8-TCDD, and 1,2,4,7,8-PeCDD. Both 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD exhibit high affinities for the Ah receptor and at dose levels of 80 micrograms/kg the hepatic ER levels were decreased 42 and 41%, respectively, and uterine ER levels were decreased 53 and 49%, respectively. 1,3,7,8-TCDD and 1,2,4,7,8-PeCDD bind less avidly to the Ah receptor and at dose levels of 400 micrograms/kg these compounds decreased hepatic ER levels 36 and 40%, respectively, and uterine ER levels 21 and 24%, respectively. These results support a role for the Ah receptor in the down-regulation of uterine and hepatic ER levels in the female rat by 2,3,7,8-TCDD and this effect may be associated with the decrease in spontaneous mammary and uterine tumors observed in female rats treated with 2,3,7,8-TCDD.


Health-related behaviours of people with diabetes and those with cardiometabolic risk factors: results from SHIELD.
The study assessed knowledge, attitudes and behaviours towards health, diabetes, diet and exercise among respondents with type 2 diabetes mellitus and those with cardiometabolic risk factors. Respondents in the SHIELD study reported their health conditions, exercise, diet and weight loss. Three groups were assessed: (i) type 2 diabetes, (ii) high risk (HR) defined as 3-5 of the following factors: abdominal obesity, BMI > or = 28 kg/m(2), reported diagnosis of dyslipidaemia, hypertension, coronary heart disease or stroke and (iii) low risk (LR) defined as < or = 2 factors. Comparisons across groups were made using analysis of variance. More type 2 diabetes and HR respondents (> 46%) received recommendations to change their lifestyle habits (increase exercise and change eating habits), compared with < 29% of LR respondents, p < 0.0001. Less than 25% of respondents agreed that type 2 diabetes is not as serious as type 1 diabetes and > 85% agreed that obesity can aggravate or contribute to onset of chronic conditions. Mean number of healthcare visits was highest in type 2 diabetes (11.0) than HR (9.4) and LR (6.1) groups, p < 0.05. Type 2 diabetes and HR respondents were least likely to report exercising regularly (26%), compared with LR (37%), p < 0.05. More type 2 diabetes (70%) and HR (72%) respondents reported trying to lose weight vs. LR respondents (55%), p < 0.05. Type 2 diabetes and HR respondents reported attitudes and knowledge conducive to good health, but the majority of respondents did not translate these positive traits into healthy behaviour with respect to diet, exercise and weight loss.


Lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone Japanese quail.
The purpose of this study was to characterize the lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone (HAP) Japanese quail. HAP and commercially available (CA) Japanese quail were fed either a semi-purified diet containing 1% cholesterol or a cholesterol-free diet for two weeks. The lipoproteins of CA and HAP quail fed cholesterol-free diet were composed of two fractions: densities ranging from 1.02 to 1.09 and from 1.09 to 1.21. The lipoprotein distribution patterns obtained from both strains showed an HDL-predominant pattern. A protein of 26 kDa was the major apoprotein in the entire density range of the lipoprotein class. Marked increases in the cholesterol ester levels were observed in the lower density fractions (1.006 < d < 1.055: chylomicron and VLDL fractions) of the cholesterol-fed quail, accounting for 46% of the total lipids in CA quail and 54% in HAP quail. In addition, the presence of a protein of 470 kDa was exclusively observed in the lower density fractions (1.006 < d < 1.055) of the cholesterol-fed HAP quail. The fatty-acid compositions of the chylomicron and VLDL fractions were affected by the dietary cholesterol in both strains: a decrease in concentration of 16: 0 and increase in 18: 0 (weight %). However, cholesterol feeding had no effect on the level of cholesterol, chemical composition or fatty-acid composition of the HDL fractions in either strain. Although the lipoprotein and apoprotein profiles of HAP quail showed resemblances to those of the CA quail, expression of the 470 kDa protein in the lipoproteins (d < 1.055) appeared to be pronounced in HAP quail. The relevance of these lipoprotein and apoprotein profiles to the genesis of atherosclerosis was discussed in this study.


Förster resonance energy transfer efficiency measurements on vinculin tension sensors at focal adhesions using a simple and cost-effective setup.
Forces inside cells play a fundamental role in tissue growth, affecting important processes such as cancer cell migration or tissue repair after injury. Förster resonance energy transfer (FRET)-based tension sensors are a remarkable tool for studying these forces and should be made easier to use. We prove that absolute FRET efficiency can be measured on a simple setup, an order of magnitude more cost-effective than a standard FRET microscopy setup, by applying it to vinculin tension sensors (VinTS) at the focal adhesions of live CHO-K1 cells. Our setup located at Université Paris-Saclay acquires donor and acceptor fluorescence in parallel on two low-cost CMOS cameras and uses two LEDs for rapid switching of the excitation wavelength at a reduced cost. The calibration required to extract FRET efficiency was achieved using a single construct (TSMod). FRET efficiencies were measured for VinTS and the tail-less control VinTL, lacking the actin-binding domain of vinculin. Measurements were confirmed on the same cell type using a more standard intensity-based setup located at Rutgers University. The average FRET efficiency of VinTS (22.0%±4%) over more than 10,000 focal adhesions is significantly lower (p<10-6) than that of VinTL (30.4%±5%), our control that is insensitive to force, in agreement with the force exerted on vinculin at focal adhesions. Attachment of the CHO-K1 cells on fibronectin decreases FRET efficiency, thus increasing the force, compared with poly-lysine. FRET efficiency for the VinTL control is consistent with all measurements currently available in the literature, confirming the validity of our measurements and hence of our simpler setup. Force measurements, resolved spatially inside a cell, can be achieved using FRET-based tension sensors with a cost effective intensity-based setup. This will facilitate combining FRET with techniques for applying controlled forces such as optical tweezers.


Infection in a dish: high-throughput analyses of bacterial pathogenesis.
Diverse aspects of host-pathogen interactions have been studied using non-mammalian hosts such as Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio for more than 20 years. Over the past two years, the use of these model hosts to dissect bacterial virulence mechanisms has been expanded to include the important human pathogens Vibrio cholerae and Yersinia pestis. Innovative approaches using these alternative hosts have also been developed, enabling the isolation of new antimicrobials through screening large libraries of compounds in a C. elegans Enterococcus faecalis infection model. Host proteins required by Mycobacterium and Listeria during their invasion and intracellular growth have been uncovered using high-throughput dsRNA screens in a Drosophila cell culture system, and immune evasion mechanisms deployed by Pseudomonas aeruginosa during its infection of flies have been identified. Together, these reports further illustrate the potential and relevance of these non-mammalian hosts for modelling many facets of bacterial infection in mammals.


Increased Runx2 expression associated with enhanced Wnt signaling in PDLLA internal fixation for fracture treatment.
Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and β-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3β, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling.


Early morphologic alterations in mouse skin after topical application of 3-methylcholanthrene and its metabolites.
The effects of topical administration of 3-methylcholanthrene (MCA) or its metabolites on BALB/cKi mice were reported on inflammatory skin reactions, the alterations in epidermal thickness, the number of nucleated cells, pyknotic nuclei and/or nuclear fragments, and mitotic figures in the interfollicular epidermis (IFE). In the two-stage carcinogenesis system, MCA, the powerful complete carcinogen, induced an ordered sequence of cell changes strikingly similar to those caused by tumor-promoting agents such as the phorbol esters. These changes were absent after application of the "K-region" oxide of MCA. Other MCA metabolites also failed to induce notable inflammation, epidermal hyperplasia, and/or hypertrophy. Several MCA derivatives, however, caused a thinning of IFE paralleled by an increase in the relative number of pyknotic nuclei and a decrease in the total number of epithelial cells. The inhibitor of polycyclic hydrocarbon metabolism alpha-naphthoflavone did not prevent MCA-mediated skin reactions but, under suitable conditions, apparently potentiated the hyperplastic effects of MCA. The findings indicate that important events in the promotion phase of MCA-mediated skin carcinogenesis might be associated with the parent compound rather than with one of its metabolites.


Patients with non-ambulatory cerebral palsy have higher sclerostin levels and lower bone mineral density than patients with ambulatory cerebral palsy.
Bone loss is a serious clinical issue in patients with cerebral palsy (CP). Sclerostin has garnered interest as a key mechanosensor in osteocytes, leading to considerations of the therapeutic utilization of anti-sclerostin medications. This study was undertaken to determine associations among mechanical unloading, sclerostin levels, and bone imbalance in patients with CP. A total of 28 patients with CP participated in this cross-sectional study. The following measurements were taken: anthropometrics, clinical diagnosis of CP subtype and ambulatory status, bone mineral density (BMD) z-scores at the lumbar spine and hip, and blood biochemical markers, including sclerostin, parathyroid hormone (PTH), osteocalcin, C-terminal telopeptide, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, creatinine, calcium, and phosphorus. In analysis according to CP subtype, patients with spastic CP showed significantly lower BMD z-scores at the lumbar spine and femur neck regions than patients with dyskinetic CP. In analysis according to ambulatory status, patients with non-ambulatory CP showed significantly lower BMD z-scores at all lumbar spine and femoral sites, lower PTH and creatinine levels, and higher plasma sclerostin levels than patients with ambulatory CP. In regression analysis, ambulatory status was a significant determinant of plasma sclerostin levels. This study is the first to report on sclerostin levels and BMD in patients with CP, based on the hypothesis that patients who lack sufficient weight-bearing activities would show increased sclerostin levels and decreased BMD scores, compared with patients who sustain relatively sufficient physical activity. Therefore, this report may provide clinical insights for clinicians considering ambulatory status, sclerostin levels, and bone loss in patients with CP.


Tinnitus--a study of its prevalence and characteristics.
Three thousand six hundred randomly selected adults in the city of Gothenburg (425,000 inhabitants) stratified by age and gender, were questioned by mail concerning tinnitus. We received 66% useful answers, 14.2% suffered from tinnitus 'often' or 'always'. Tinnitus was more common in males than in females. Tinnitus was much more common in the left than in the right ear. 2.4% of the whole population suffered from the worst severity degree, 'tinnitus plagues me all day'. Tinnitus was clearly more common with hearing loss than with subjectively normal hearing. Sleep disturbances were common and increased with tinnitus severity. A majority of the questioned subjects wanted further examination and treatment.


Association between transforming growth factor β1 and atrial fibrillation in essential hypertensive patients.
Transforming growth factor β1 (TGFβ1) was one of the main factors for accelerating atrial fibrosis and has been reported with significantly higher level in plasma of the patients with essential hypertension (EH), especially in those with target organ damage. The contribution of TGFβ1 in the pathogenesis of atrial fibrillation (AF) in EH patients remains unknown. 75 EH patients with documented AF were divided into the paroxysmal AF group (EH+pAF, n = 44) or the chronic AF group (EH+cAF, n = 31), and 37 EH patients with sinus rhythm (SR) were assigned into the EH+SR group. All data including EH duration, blood pressure, lipids, glucose and left atrial diameter (LAD) measured by ultrasonic cardiogram were recorded. The serum levels of TGFβ1 and connective tissue growth factor (CTGF) were detected, and compared with normal controls (NC group, n = 36). The serum levels of TGFβ1 and CTGF in all EH groups were significantly higher than those in the NC group (p < 0.001, respectively). Among the EH groups, TGFβ1 and CTGF levels were highest in the cAF group, followed by the pAF and the SR groups (p < 0.005). However, no significant difference was observed in TGFβ1 and CTGF levels between the cAF group and the pAF group. The serum TGFβ1 in AF patients was independently correlated with LAD, the presence of AF, aldosterone, CTGF and age. The serum TGFβ1 promotes CTGF synthesis and causes left atrial enlargement and remodeling, which is possibly involved in the pathogenesis of AF in EH patients.


Induction of chemoresistance in a cultured canine cell line by retroviral transduction of the canine multidrug resistance 1 gene.
To induce chemoresistance in a normal canine cell line through the transduction of the canine multidrug resistance 1 gene (mdr1). Madin-Darby canine kidney (MDCK) epithelial cell line. The full-length canine mdr1 cDNA clone isolated in our laboratory was inserted into a Moloney murine leukemia virus-based vector to construct the retroviral vector, pLNC-cMDR1. After retroviral transduction of pLNC-cMDR1 into MDCK cells, the expression and function of the P-glycoprotein, a product of mdr1, were assessed by immunoblotting, measurement of rhodamine123 (Rh123) retention, and drug sensitivity assays. P-glycoprotein was strongly expressed in cells transduced with pLNC-cMDR1. This P-glycoprotein was fully functional, as demonstrated by the decreased Rh123 retention and the increased resistance to chemotherapeutic drugs. Measured as 50% inhibitory concentrations, resistance increased 59 times to vincristine and 25 times to doxorubicin in MDCK cells after transduction of pLNC-cMDR1. Transduction of canine mdr1 is an effective method for inducing chemoresistance in normal canine cells. This system may be applicable to the induction of drug resistance in hematopoietic cells.


Histone H1 isoforms purified from rat liver bind nonspecifically to the nuclear factor 1 recognition sequence and serve as generalized transcriptional repressors.
Two polypeptides with molecular masses of 34 and 30 kDa were copurified from rat liver during DNA affinity purification of a sequence-specific transcription factor binding to the footprint II sequence within the P2 promoter of the rat alpha1B adrenergic receptor (alpha1B AR) gene, and were identified by microsequencing their endoproteinase Lys-C-derived peptides as histone H1d and histone H1c, respectively. Histone H1 was previously reported to bind to the nuclear factor 1 (NF1) recognition sequence, although the specificity of this binding has been controversial. Here, DNA mobility shift and supershift assays, DNase I footprinting and mutational analyses indicated that the binding of histone H1 to the NF1 sites located within footprint II of the alpha1B AR gene P2 promoter is nonspecific. Transient cotransfections into Hep3B cells of histone H1d cDNA with CAT constructs containing promoter regions of different genes resulted in generalized and non-specific suppression of CAT activity. The histone H1d-mediated repression of the activities of the alpha1B AR gene P2/CAT or beta2 AR gene P(-186/1307)/CAT constructs was reversed by the cotransfection of a cDNA encoding the sequence-specific transcription factor NF1/X, and the fold increase in CAT activities was similar to that obtained in the absence of histone H1d. These results suggest that sequence-specific transcription factors counteract the histone H1-mediated transcriptional repression in vivo by a true activation, which is different from the in vitro antirepression in histone H1-repressed chromatin templates (Laybourn and Kadonaga, (1991) Science 254: 238-245).


Hypocholesterolemia in patients treated with recombinant interleukin-2: appearance of remnant-like lipoproteins.
Reversible acute hypocholesterolemia was observed during treatment of metastatic cancer with high-dose intravenous recombinant interleukin-2 (IL-2). Further analysis revealed virtual disappearance of high-density lipoproteins (HDLs) and marked reduction in the concentration of low-density lipoproteins (LDL); the remaining LDL and intermediate-density lipoproteins (IDL) were enriched in triglyceride relative to cholesterol and had broad-beta electrophoretic mobility, properties reminiscent of remnant lipoproteins. These changes differ qualitatively and quantitatively from those previously reported for other cytokines such as tumor necrosis factor (TNF) or the interferons (IFNs).


Formation of Au-Pt bimetallic nanoparticles in a two-layer SiO2 films doped with Au and Pt, respectively, through interlayer diffusion.
Bimetallic Au-Pt nanoparticles have been generated inside a relatively porous SiO2 film matrix by a two-layer (2L) coating methodology. Two overlapping coating layers were deposited on glass substrates from Au- and Pt-doped inorganic-organic hybrid silica sols and air dried at 60 degrees C. The 2L coating assembly was then UV- and followed by heat-treated at 450 and 550 degrees C in air. UV-treatment decomposes AuCl(4)(-) and PtCl(6)(2-) ions in the respective layers and the subsequent heat treatment in air influences the diffusion of Au and Pt nanometals to each other to form bimetallic Au-Pt nanoparticles inside the silica matrix. A UV-visible study showed damping of Au-plasmon after heat treatments. GIXRD and TEM analyses reveal the formation of a partial Au/Pt solid solution with a small fraction of Pt ( approximately 16%), while the major fraction of Pt remains fused with the Au(Pt) solid solution.


Application of microautologous fat transplantation in the correction of sunken upper eyelid.
Although fat grafting has been clinically applied by surgeons in esthetic and reconstructive surgery, it has widely evolved in processes such as harvesting, processing, and placement of fat, using the fat-grafting procedure, which dates back over 100 years. Surgeons frequently use fat grafting to recontour, augment, or fill soft-tissue defects, facial wrinkles, or skin problems such as depressions or scars. However, fat grafting has not been thoroughly understood and has not been conclusively standardized to ensure superior clinical results. This study was intended to determine the role of microautologous fat transplantation (MAFT) under evidence-based medicine, particularly in accurate delivery of small fat parcels. The research method involved the conceptualization of MAFT and the development of an innovative surgical instrument for fat placement. Clinically, 168 patients with sunken upper eyelids with multiple folds underwent this procedure. The major findings suggested that MAFT exhibits promising clinical results and offers a superior guideline for fat placement. Details of the technique and theoretical implications are also discussed. The therapeutic effects of MAFT and the long-term clinical results of patients with sunken upper eyelids with multiple folds indicated satisfactory outcomes. Based on the results, MAFT offers an alternative option to surgeons for performing fat grafting and provides a more favorable option for the benefit and welfare of patients by reducing the potential complications.


Biochemical and endocrine properties of a mechanism-based inhibitor of aromatase.
The conversion of androgens to estrogens by aromatase represents a major alteration in hormonal expression, and its regulation offers a promising method for therapeutic control of disease processes that are hormonally dependent. The design of suicide inhibitors based on enzyme-activated mechanisms provides an attractive approach for regulation of estrogen biosynthesis. MDL 18,962, (10-2(-propynyl)estr-4-ene-3,17-dione), a C-10 substituted analog of the natural substrate androstenedione, was evaluated as a suicide inhibitor of aromatase. Appropriate kinetic evaluations of MLD 18,962 established it to be a highly potent [inhibition constant (Ki) = 4.5 +/- 1.3 nM] irreversible inhibitor of human placental aromatase. The 2-propynyl group was necessary for time-dependent inactivation, as this activity was lost in related compounds. The inactivation process was specific for aromatase, since other P450 enzyme systems are not inactivated by MDL 18,962. This compound exhibited minimal intrinsic hormonal properties, since weak binding affinities were observed for cytosolic androgen, estrogen, or progestin receptors. The stimulation of ovarian aromatase activity by gonadotropins in immature mice was inhibited in animals implanted with 10-mm MDL 18,962 Silastic implants. This inhibition of estrogen biosynthesis suppressed estrogen-dependent uterine growth in these mice.


Action-specific influences on distance perception: a role for motor simulation.
Perception is influenced by the perceiver's ability to perform intended actions. For example, when people intend to reach with a tool to targets that are just beyond arm's reach, the targets look closer than when they intend to reach without the tool (J. K. Witt, D. R. Proffitt, & W. Epstein, 2005). This is one of several examples demonstrating that behavioral potential affects perception. However, the action-specific processes that are involved in relating the person's abilities to perception have yet to be explored. Four experiments are presented that implicate motor simulation as a mediator of these effects. When a perceiver intends to perform an action, the perceiver runs a motor simulation of that action. The perceiver's ability to perform the action, as determined by the outcome of the simulation, influences perceived distance.


Molecular recognition at the myo-inositol 1,4,5-trisphosphate receptor. 3-position substituted myo-inositol 1,4,5-trisphosphate analogues reveal the binding and Ca2+ release requirements for high affinity interaction with the myo-inositol 1,4,5-trisphosphate receptor.
Several novel D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3] analogues equatorially substituted at the 3-position have been synthesized to probe the structure-activity relationship of the Ins(1,4,5)P3-receptor subsite adjacent to the native 3-hydroxy (3-OH) of Ins(1,4,5)P3. This study was prompted, in part, by our observation that myo-inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), the 3-position phosphorylated product of Ins(1,4,5)P3 was a full agonist at the Ca(2+)-mobilizing Ins(1,4,5)P3 receptor of SH-SY5Y cells (Wilcox, R.A., Challiss, R. A. J., Liu, C., Potter, B. V. I., and Nahorski, S. R. (1993) Mol. Pharmacol. 44, 810-817). The 3-position Ins(1,4,5)P3 analogues were equatorially substituted with groups spanning the steric range between the 3-OH of Ins(1,4,5)P3 and the 3-phosphate of Ins(1,3,4,5)P4; in order of increasing 3-position steric bulk these were: 3-fluoro-, 3-chloro-, 3-amino-, 3-bromo-, 3-methoxy-, and 3-phosphorothioate-Ins(1,4,5)P3. The analogues were assessed at the specific Ins(1,4,5)P3 binding-site of bovine adrenal cortex and for Ca2+ mobilizing activity in saponin-permeabilized SH-SY5Y human neuroblastoma cells. A correlation was observed between increasing molecular volume of the 3-position substituent and respective decreases in both affinity and Ca2+ mobilizing efficacy. Further analysis of the data also revealed that Ins(1,4,5)P3 analogues with equatorial 3-OH, 3-phosphate, and 3-phosphorothioate substituents interacted more favorably with Ins(1,4,5)P3 recognition sites than would be predicted by purely steric considerations. In contrast, 3-C-trifluoromethyl-Ins(1,4,5)P3 (which is axially substituted, but retains the native 3-OH of Ins(1,4,5)P3) interacted with Ins(1,4,5)P3 recognition sites with virtually the same potency as Ins(1,4,5)P3, indicating that the binding pocket of the Ins(1,4,5)P3-receptor was not sterically restrictive with respect to axially oriented 3-position substituents. We conclude that the Ins(1,4,5)P3 receptor has favorable non-covalent binding interactions with the equatorial 3-position substituents of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 and that these interactions significantly ameliorate the steric constraints of the Ins(1,4,5)P3 receptor binding pocket.


[Effects of three different adult stem cells on inflammatory status of lipopolysaccharide- induced RAW264.7 cells].
To compare the modulatory effects of human amniotic epithelial cells (H-AECs), human amniotic mesenchymal cell (HA-MSCs), umbilical mesenchymal cells (UC-MSCs) on the inflammatory status of lipopolysaccharide (LPS)-induced RAW264.7 cells. RAW264.7 cells stimulated with LPS were co-cultured with H-AECs, HA-MSCs, or UC-MSCs or cultured in conditioned media of the 3 stem cells to assess the changes of the inflammatory status of RAW264.7 cells. The migration ability, nitric oxide concentration, and expressions of the pro-inflammatory and anti-inflammatory genes, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), and inducible nitric oxide synthase (NOS-2) of M1 macrophages, and Arg-1, CD206, and CD36 of M2 macrophages, were detected in the co-cultures. Compared with the control macrophages, RAW264.7 cells cultured in the conditioned media of H-AECs, HA-MSCs, and UC-MSCs all showed significantly lowered migration abilities (P<0.05). Co-culture with H-AECs, but not the other two stem cells, resulted in a significant reduction of NO production (P<0.05) and significant down-regulation of IL-1β, TNFα, NOS-2, and INFβ expressions in RAW264.7 cells; co-culture with HA-MSCs and UC-MSCs only caused a down-regulation of INFβ mRNA expression. In all the 3 RAW264.7 and stem cell co-cultures, the expressions of the inflammation related genes including Arg-1, CD206, and CD36 were up-regulated significantly. H-AECs, HA-MSCs, and UC-MSCs can all prevent RAW264.7 cells from differentiating into M2 macrophages, but their effects and mechanisms are different from one another.


Global Health Perspectives on Race in Research: Neocolonial Extraction and Local Marginalization.
Best practices in global health training prioritize leadership and engagement from investigators from low- and middle-income countries (LMICs), along with conscientious community consultation and research that benefits local participants and autochthonous communities. However, well into the 20th century, international research and clinical care remain rife with paternalism, extractive practices, and racist ideation, with race presumed to explain vulnerability or protection from various diseases, despite scientific evidence for far more precise mechanisms for infectious disease. We highlight experiences in global research on health and illness among indigenous populations in LMICs, seeking to clarify what is both scientifically essential and ethically desirable in research with human subjects; we apply a critical view towards race and racism as historically distorting elements that must be acknowledged and overcome.


[Selection and identification of human keratinocyte stem cells in vitro].
To investigate the selection and identification of human keratinocyte stem cells(KSC) in vitro. According to the characteristics of KSC which can adhere to extracellular matrix very fast, we selected 3 groups of different time(5 minutes, 20 minutes and 60 minutes) and unselected as control group. And the cells were identified by monoclone antibody of beta 1-integrin and cytokeratin 19 (Ck19), then the image analysis was done. Furthermore we analyzed the cultured cells with flow cytometer(FCM) and observed the ultrastructure of the cell by transmission electron microscope(TEM). The cell clones formed in all groups after 10 to 14 days, while the cells of 5 minute group grew more slowly than those of the other groups, however, the clones of this group were bigger. The expression of beta 1-integrin and Ck19 were found in all groups. The positive rate of beta 1-integrin was significant difference between 5 minute group and the other groups (P < 0.05). And the expression of Ck19 was no significant difference between 5 minute group and 20 minute group(P > 0.05), and between 60 minute group and control group. But significant difference was observed between the former and the later groups(P < 0.05). The result of FCM showed that most cells of the 5 minute group lied in G1 period of cell cycle, which was different from those of the other groups. At the same time, the cells of 5 minute group were smaller and contained fewer organelles than those of the other groups. The above results demonstrate that the cells of 5 minute group have a slow cell cycle, characteristics of immaturity, and behaving like clonogenic cells in vitro. The cells have the general anticipated properties for KSC. So the KSC can be selected by rapid attachment to extracellular matrix and identified by monoclone antibody of beta 1-integrin and Ck19.


Validity of new phage typing scheme against Vibrio cholerae 01 biotype ElTor strains.
A total of 538 strains of V. cholerae 01 biotype ElTor were phage typed by the conventional Basu and Mukerjee and also the new typing scheme developed at the National Institute of Cholera and Enteric Diseases, Calcutta. The strains could be clustered into seven types by the new scheme as against only two by the conventional method. The results provide conclusive evidence on the validity of the new scheme for phage typing of V. cholerae strains.


On-chip grown ZnO nanosheet-array with interconnected nanojunction interfaces for enhanced optoelectronic NO2 gas sensing at room temperature.
Herein, we demonstrated the on-chip growth of nanostructured ZnO films with abundant nanojunctions for the fabrication of high-performance optoelectronic NO2 sensors. A fast solution approach allowed the controllable growth of ZnO nanorod- and nanosheet-arrays directly on flexible substrates, which were endowed with abundant nanojunctions. Electron microscopy observations revealed the existence of two types of the nanojunction interfaces, i.e., the attached and interconnected interfaces within the nanostructure networks. Compared with the attached nanorods, the optoelectronic NO2 sensors based on interconnected ZnO nanosheets showed higher responses and faster response/recovery rates under UV illumination at room temperature. The responses of the nanosheet-based sensor ranged from 28% to 610% toward NO2 concentrations of 10 ppb to 1000 ppb. Moreover, the optoelectronic sensors exhibited excellent reversibility, and mechanical and long-term stabilities along with low detection limits. The enhanced optoelectronic NO2 sensing properties of the interconnected ZnO nanosheets could be attributed to different types of nanojunction interfaces, which played a key role in modulating the interfacial potential barrier heights of the nanojunctions according to the surface depletion model. The presently developed strategy of nanojunction interface engineering is expected to have wide interest for semiconductor-based sensor applications.


Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV).
A T-cell tropic lentivirus of macaques the simian immunodeficiency virus (SIV), has morphologic, growth, and antigenic properties that indicate that it is related to the human immunodeficiency virus (HIV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Six juvenile macaques developed persistent lymphadenopathy (greater than 3 months in duration) after inoculation with SIV. The histologic appearance of the lymph nodes was characterized by marked follicular hyperplasia with abundant proliferative B cells infiltrating into the paracortex. The number of T8-positive lymphocytes equaled or exceeded the number of T4-positive lymphocytes in the paracortex. These findings, in association with immunologic abnormalities and a previously observed fatal immunodeficiency syndrome in SIV-infected macaques, provide further evidence of the importance of SIV-induced disease in macaques as a model for the study of AIDS.


[Myocardial revascularization in patients with ischemic heart disease and left ventricular dysfunction].
Operative morbidity and mortality in coronary artery bypass surgery has decreased over the last decades and coronary artery bypass surgery offers an increase in long-term survival in selected patients with lower ejection fraction. We do not know exactly the results of the surgery and evolution of our patients with chronic lower ejection fraction. To evaluate clinical results of myocardial revascularization in patients with ischemic heart disease and chronic lower ejection fraction. We analyzed the experience between January 2000 and December 2001 of patients with ejection fraction = 30% treated with surgical myocardial revascularization. The procedure was carried out with cardiopulmonary bypass and moderate hypothermia (30 degrees C), and myocardial protection with intermittent cold crystalloid cardioplegia. We evaluated demographic characteristics, surgical procedure carried out, length-of-stay in intensive postoperative care unit, and morbidity and mortality in perioperative period and in middle term follow-up. During this period, 738 patients were treated with aorto-coronary bypass surgery Thirty eight patients were patients with chronic lower ejection fraction (5.14%) and were included in this evaluation. Six patients were female (15.78%), and 32 males (84.21%). Range of duration of cardiopulmonary bypass was 65-245 min (mean, 123 min), range of aortic cross-clamping time was 30-120 min (mean, 59 min). Twelve month follow-up showed improvement in two functional classes in 15 patients (39.4%), and improvement in one functional class in 10 patients (26.3%); two patients remained in the same functional class (5.2%), and one patient decreased his/her functional class (2.6%). Mean of length-of-stay in intensive care unit was 6.5 days and in hospital, 12.5 days. Perioperative morbility was 34.2% and same-period mortality was 26%; 12 month survival was 74%. It was concluded that even with high mortality as in other series, survival and quality of life of these patients is better with than medical therapy.


Synthesis and Characterization of High Glycolic Acid Content Poly(glycolic acid-co-butylene adipate-co-butylene terephthalate) and Poly(glycolic acid-co-butylene succinate) Copolymers with Improved Elasticity.
Poly(glycolic acid) (PGA) is a biodegradable polymer with high gas barrier properties, mechanical strength, and heat deflection temperature. However, PGA's brittleness severely limits its application in packaging, creating a need to develop PGA-based copolymers with improved elasticity that maintain its barrier properties and hydrolytic degradability. In this work, a series of PGBAT (poly(glycolic acid-co-butylene) adipate-co-butylene terephthalate) copolymers containing 21-92% glycolic acid (nGA) with Mw values of 46,700-50,600 g mol-1 were synthesized via melt polycondensation, and the effects of altering the nGA on PGBAT's thermomechanical properties and hydrolysis rate were investigated. Poly(glycolic acid-co-butylene succinate) (PGBS) and poly(glycolic acid-co-butylene terephthalate) (PGBT) copolymers with high nGA were synthesized for comparison. DSC analysis revealed that PGBAT21 (nGA = 21%) and PGBAT92 were semicrystalline, melting between 102.8 and 163.3 °C, while PGBAT44, PGBAT86-89, PGBT80, and PGBS90 were amorphous, with Tg values from -19.0 to 23.7 °C. These high nGA copolymers showed similar rates of hydrolysis to PGA, whereas those containing <50% GA showed almost no mass loss over the testing period. Their mechanical properties were highly dependent upon their crystallinity and improved significantly after annealing. Of the high nGA copolymers, annealed PGBS90 (Mw 97,000 g mol-1) possessed excellent mechanical properties with a modulus of 588 MPa, tensile strength of 30.0 MPa, and elongation at break of 171%, a significant improvement on PGA's elongation at break of 3%. This work demonstrates the potential of enhancing PGA's flexibility by introducing minor amounts of low-cost diols and diacids into its synthesis.


Sulfasalazine treatment in juvenile chronic arthritis: an open study.
In an open study, the effect of sulfasalazine was evaluated in the treatment of juvenile chronic arthritis (JCA). Forty-one patients, i.e., 27 boys and 14 girls with JCA under 16 years of age, were included in the study. In all of them, treatment with nonsteroidal antiinflammatory drugs (NSAID) had been unable to control the disease. The patients were divided in 4 subgroups depending on the mode of onset and evolution (Type I = systemic onset, Type II = polyarticular form. Type IIIa and Type IIIb = pauciarticular form). Remission was achieved in 21 patients, significant improvement in 12. Status was unchanged in 4 patients and worsened in 3. In 5 patients side effects were observed, which forced interruption of treatment in 4. Sulfasalazine was stopped in 7 patients: for toxicity in 4 and for inefficacy in 3. In 7 other patients the treatment was terminated after a prolonged remission. These promising results must be confirmed in a double blind versus placebo study, preferably restricted to type III JCA.


[Three phase bone scintigraphy of reflex sympathetic dystrophy and its change with sympathetic blockade].
We examined three phase bone scintigraphy performed at various stages, covering 13 patients with reflex sympathetic dystrophy (RSD) of limbs. In three patients, changes following sympathetic nerve block were examined. In stage-1, radiation count in the affected limbs increased markedly in phases 1 to 3 as compared with the values in healthy limbs. In stage-2, radiation count decreased in phase-1, showed about the same level in phase-2, and maintained an increased level in phase-3. In stage-3, count decreased in phase-1 and 2, and showed about the same level in phase-3. In patients who received a chemical sympathectomy in its early stage, the count was found to have returned to normal level over a short period of time from phase 1 to 3. Three phase bone scintigraphy was considered useful in understanding the pathologic condition of RSD and follow-up evaluation of treatment mainly consisting of sympathetic nerve block.


Effects of hypertensive plasma on the responses of an isolated artery preparation to noradrenaline.
The effect of hypertensive plasma on the responses of an isolated artery preparation to noradrenaline were studied. In addition, because of the association between hypercholesterolaemia and hypertension, the effect of pure cholesterol and low density lipoprotein on the arterial responses to noradrenaline was also investigated. Both hypertensive plasma and low density lipoprotein potentiated the responses of the arterial preparation to noradrenaline.


Not one, but many: developing a multi-indication pricing model for medicines in Belgium.
Back ground: Current pricing and reimbursement models that focus on one indication at a time are not suited to address the market access of multi-indication medicines. Therefore, the aim of this study is to co-create with Belgian stakeholders a multi-indication pricing model and procedural pathway, to identify conditions for implementation, and to illustrate the multi-indication pricing model with a case study. Methods: Different multi-indication pricing models were identified from the literature, case studies and pilots in other countries. Semi-structured interviews were conducted with 21 representatives from the National Institute for Health and Disability Insurance, insurance funds, clinicians, patients, the policy cell of the Minister of Health, pharmaceutical industry and academia. These provided insight in the opinions of stakeholders about possible multi-indication pricing models and their feasibility in the Belgian context. Agreement on the preferred multi-indication pricing model and procedural pathway was reached in a multi-stakeholder round table. Results: The international review generated four main multi-indication pricing models that vary in terms of whether a uniform price or differential prices are applied, whether prices are adjusted for the volume and/or value of the medicine in each indication, and whether a proactive or retroactive dynamic pricing approach is used. However, Belgian stakeholders preferred a fifth model, which sets a single price as the volume- and value-weighted average price across all indications at launch. Over time, the price is adapted based on volume and value of the medicine in real-life practice for each indication. To implement this model, a legal framework, horizon scanning and early dialogue, data infrastructure, an evidence plan for the medicine, technical expertise and governance model need to be developed. Conclusion: Although the multi-indication pricing model preferred by Belgian stakeholders raises the administrative burden, it allows for the price of a medicine to vary during the lifecycle based on its initial and real-life performance in multiple indications.


Development of the main and accessory placentae in the Japanese long-fingered bat, Miniopterus schreibersii fuliginosus.
The placentae of the Japanese long-fingered bat were characterized by their morphological and functional transition from the main placenta to the accessory placentae. The main placenta transformed from an endotheliodichorial to a haemodichorial (one layer of syncytiotrophoblast and one layer of cytotrophoblast cells) condition. Degeneration of the main placenta was accompanied by development of two accessory placentae. These developed on both sides (fetal side) of the main placenta, and subsequently converted from a haemodichorial (two layers of cytotrophoblast cells) to a haemomonochorial condition.


Molecular typing of Malassezia species with PFGE and RAPD.
The currently recognized seven species of Malassezia all have different karyotypes which do not vary intraspecifically, except in M. furfur which displayed two different karyotypes. In contrast, random amplified polymorphic DNA (RAPD) typing showed the presence of genetic variation in all species. It is concluded that karyotype analysis is useful for species identification, and RAPD typing can be used in epidemiological investigations.


Occurrence of Salmonella, Listeria monocytogenes, and enterotoxigenic Staphylococcus in goat milk from small and medium-sized farms located in Minas Gerais State, Brazil.
Consumption of goat milk has been increasing due to its nutritional characteristics and health benefits. Therefore, assessment of the presence of foodborne pathogens in this product is critical to ensure its safety to consumers. The present study aimed to identify common foodborne pathogens in raw goat milk. Fifty-three samples of raw goat milk from 11 farms were collected and cultured for the presence of Salmonella spp. and Listeria monocytogenes, as well as for enumeration and isolation of coagulase-positive and coagulase-negative Staphylococcus (CPS and CNS, respectively). All samples tested negative for Salmonella spp. and L. monocytogenes. The CPS counts in raw goat milk samples were predominantly less than 2 log cfu/mL (n=39), and CNS counts were predominantly higher than 3 log cfu/mL (n=42). Based on Staphylococcus counts, 51 isolates were selected (CPS=26; CNS=25) and tested by PCR for the presence of classic enterotoxin-encoding genes (sea, seb, sec, sed, and see). Only 3 isolates (CPS=2, CNS=1) were negative for all enterotoxin-encoding genes tested, and the genotype sec and see was the most frequent (n=16), followed by sea, sec, and see (n=13) and sec (n=13); sed was not detected in any isolate. The frequencies of enterotoxin-encoding genes for CPS and CNS were similar, demonstrating the equivalence of both groups in harboring these virulent markers. These results suggest that Salmonella and L. monocytogenes are not frequent contaminants of raw goat milk, but that Staphylococcus spp. that are capable of producing enterotoxins are prevalent; therefore, consumers of raw goat milk and products made from raw milk are at risk.


Soil respiration variation along an altitudinal gradient in the Italian Alps: Disentangling forest structure and temperature effects.
On the mountains, along an elevation gradient, we generally observe an ample variation in temperature, with the associated difference in vegetation structure and composition and soil properties. With the aim of quantifying the relative importance of temperature, vegetation and edaphic properties on soil respiration (SR), we investigated changes in SR along an elevation gradient (404 to 2101 m a.s.l) in the southern slopes of the Alps in Northern Italy. We also analysed soil physicochemical properties, including soil organic carbon (SOC) and nitrogen (N) stocks, fine root C and N, litter C and N, soil bulk densities and soil pH at five forest sites, and also stand structural properties, including vegetation height, age and basal area. Our results indicated that SR rates increased with temperature in all sites, and 55-76% of SR variability was explained by temperature. Annual cumulative SR, ranging between 0.65-1.40 kg C m-2 yr-1, decreased along the elevation gradient, while temperature sensitivity (Q10) of SR increased with elevation. However, a high SR rate (1.27 kg C m-2 yr-1) and low Q10 were recorded in the mature conifer forest stand at 1731 m a.s.l., characterized by an uneven-aged structure and high dominant tree height, resulting in a nonlinear relationship between elevation and temperature. Reference SR at 10°C (SRref) was unrelated to elevation, but was related to tree height. A significant negative linear relationship was found between bulk density and elevation. Conversely, SOC, root C and N stock, pH, and litter mass were best fitted by nonlinear relationships with elevation. However, these parameters were not significantly correlated with SR when the effect of temperature was removed (SRref). These results demonstrate that the main factor affecting SR in forest ecosystems along this Alpine elevation gradient is temperature, but its regulating role can be strongly influenced by site biological characteristics, particularly vegetation type and structure, affecting litter quality and microclimate. This study also confirms that high elevation sites are rich in SOC and more sensitive to climate change, being prone to high C losses as CO2. Furthermore, our data indicate a positive relationship between Q10 and dominant tree height, suggesting that mature forest ecosystems characterized by an uneven-age structure, high SRref and moderate Q10, may be more resilient.


Consistent Principal Component Modes from Molecular Dynamics Simulations of Proteins.
Principal component analysis is a technique widely used for studying the movements of proteins using data collected from molecular dynamics simulations. In spite of its extensive use, the technique has a serious drawback: equivalent simulations do not afford the same PC-modes. In this article, we show that concatenating equivalent trajectories and calculating the PC-modes from the concatenated one significantly enhances the reproducibility of the results. Moreover, the consistency of the modes can be systematically improved by adding more individual trajectories to the concatenated one.


Efficacy of Computed Tomography (CT) Attenuation Values and CT Findings in the Differentiation of Pleural Effusion.
The aim of this study was to investigate the efficacy of computed tomography (CT) findings for characterizing pleural effusions with the use of attenuation values. One hundred and twenty eight patients with pleural effusions on thoracic CT who underwent thoracentesisis within two weeks were studied. Pleural effusions were classified as exudates or transudates according to the Light's criteria. A region of interest was placed for the measurement of Hounsfield Unit (HU) values in the area of the greatest amount of effusion on each slice of the three slices used. CT features that were evaluated for distinguishing pleural exudates from transudates included pleural nodules, pleural thickening and loculation. Thirty three (26%) of the 128 pleural effusions were transudates and 95 (74%) were exudates. The mean HU values of the exudates (8.82±7.04) were significantly higher than those of the transudates (2.91±8.53), (p<0.001). No statistically significant difference was found between transudate and exudate patients in terms of pleural thickness, pleural nodules and loculation (p>0.05). HU values can help in differentiating exudative pleural effusions from transudative pleural effusions. Because of overlapping HU values, correlation with clinical findings is essential.


Setting priorities for stroke care and research.
Recent publications describing the sobering global increase in stroke mortality and global life years lost due to stroke despite improvements in developed countries have drawn focus on the severe impact of stroke in the developing world. At the same time, three recent interventional trials that failed to demonstrate an important role for catheter-based therapies in acute stroke have called into question this expensive use of technology. Coupling all of this new data leads to the natural conclusion that a focus on stroke prevention for the developing world, and for the poor in developed countries, should be where we set our priorities for the foreseeable future.


The brittle bone: how to save women from osteoporosis.
For a woman, the risk of suffering an osteoporotic fracture during her lifetime is higher than the combined risk of breast, endometrial, and ovarian cancer. It is important to reduce the number of osteoporosis-related fractures. Therefore, it is necessary to emphasize various interventions and attitudes which will decrease both the risk of falling and that of breaking bones. Strategies should be followed to reach adulthood with an optimal bone mass through improved diet and exercise during childhood. Programs that identify women with the lowest bone mass at the time of menopause may be useful, since prophylactic measures against osteoporosis such as hormone replacement therapy (HRT) can be offered to them. Identification of women at risk can be achieved through bone densitometry; a decrease of each standard deviation of bone mineral mass below mean values predicts a doubling of the fracture risk. Some data suggest that physicians are more willing to prescribe HRT specifically to women with the lowest bone mass, and that the latter are more likely to stay on therapy for longer periods of time. The decision to use HRT should be taken by the patient after proper information of all benefits (diminished climacteric symptoms, decrease of cardiovascular risk) and potential risks (possible enhanced breast cancer risk, appearance of side effect). In women who do not want to take HRT, or for whom contraindications exist, alternative medications, such as calcium, vitamin D and biphosphonates can be considered, depending on fracture risk. For older and institutionalized women, programs should be developed to decrease the risk of falling. Likewise, it may be possible to reduce the consequences of a fall, for instance by promoting the development of energy-absorbing hip pads, which reduce fracture risk.


Effect of temporary school closure due to COVID-19 on musculoskeletal function in elementary school children.
Objective: In 2020, coronavirus disease-2019 (COVID-19) became the cause of a pandemic. In response, the Japan Sports Agency issued warnings about secondary damage to health, such as the threat to physical and mental well-being due to the lack of exercise in this situation. In this study, we report on cross-sectional and longitudinal examinations of standing trunk flexion to evaluate how temporary long-term school closures affected musculoskeletal function in elementary school students. Patients and Methods: All children in one public elementary school in T-city during the school years 2019 and 2020 were included in this study. A digital forward flexion meter was used to measure standing trunk flexion. Results: In this study, 284 (284/289: 98.3%) and 266 (266/274: 97.1%) children in school years 2020 and 2019, respectively, were found to have valid data for cross-sectional analysis. The standing trunk flexion did not show significant differences between grades or sexes. In the longitudinal analysis, the results of the comparison of standing trunk flexion in children for two consecutive years revealed significant differences only between grades 3 and 4 (P<0.05) and between girls in grades 3 and 4 (P<0.01), but no significant differences in other grades or among boys or girls were observed. Conclusion: Initially, we expected that there would be a difference in the results of functional assessment using standing trunk flexion depending on the period of absence from school. However, the results of this study showed no significant changes in standing trunk flexion. Moreover, since children's musculoskeletal functions may be affected by various factors during the COVID-19 pandemic, they should be carefully monitored in the future.


Effects of host extinction and vector preferences on vector-borne disease risk in phylogenetically structured host-hector communities.
Anthropogenic disturbance impacts the phylogenetic composition and diversity of ecological communities. While changes in diversity are known to dramatically change species interactions and alter disease dynamics, the effects of phylogenetic changes in host and vector communities on disease have been relatively poorly studied. Using a theoretical model, we investigated how phylogeny and extinction influence network structural characteristics relevant to disease transmission in disturbed environments. We modelled a multi-host, multi-vector community as a bipartite ecological network, where nodes represent host and vector species and edges represent connections among them through vector feeding, and we simulated vector preferences and threat status on host and parasite phylogenies. We then simulated loss of hosts, including phylogenetically clustered losses, to investigate how extinction influences network structure. We compared effects of phylogeny and extinction to those of host specificity, which we predicted to strongly increase network modularity and reduce disease prevalence. The simulations revealed that extinction often increased modularity, with higher modularity as species loss increased, although not as much as increasing host specificity did. These results suggest that extinction itself, all else being equal, may reduce disease prevalence in disturbed communities. However, in real communities, systematic patterns in species loss (e.g. favoring high competence species) or changes in abundance may counteract these effects. Unexpectedly, we found that effects of phylogenetic signal in host and vector traits were relatively weak, and only important when phylogenetic signal of host and vector traits were similar, or when these traits both varied.


Synthesis and luminescent properties of nanoscale Gd2Si2O7:Eu3+ phosphors.
Gd2Si2O7:Eu3+ nanoparticles were prepared by the sol-gel method with citric acid as an additive in the precursor solutions. The crystal structure was analyzed by means of X-ray diffraction (XRD). The results indicate that the alpha-Gd2Si2O7 powders in size 35 nm are obtained at a synthesis temperature of 1,100 degrees C, and the doping ion contents do not influence the crystal structure. The excitation and emission spectra of samples were measured. The dependence of photoluminescence intensity and lifetime of level on Eu3+ concentration and synthesis temperature of samples are also discussed.


The liberal arts connection.
Occupational therapists need to be critical of who teaches, what is taught, how it is taught, how it is applied, and to whom it is taught in the entire education program of prospective occupational therapists. Further, I recommend that occupational therapy educators on campus take the lead in initiating meetings and discussions that facilitate a functional conjoining of occupational therapy practice, occupational therapy theory, and liberal arts studies. An initial effort in this regard might be for the three mutually interdependent and equal partners in the education of occupational therapy students to read and discuss Ernest L. Boyer's work entitled, A Quest for Common Learning--The Aims of General Education. I believe that all occupational therapists would benefit from reading this text, individually and collectively, and the profession and our community would benefit. The question is not whether or not this subject should be incorporated into an occupational therapy student's curriculum. The question for discussion should be at what point in the student's education--the student's intellectual growth and development and professionalization--would this topic and this treatment be best applied? Perhaps from this beginning the three partners--practice, theory, and liberal arts--would recognize and respond to their mutually interdependent and equally important role and responsibility in the design and implementation of the entire occupational therapy educational program, which is future responsive and ensures the highest probability that graduates will be professionally competent.


Role of a children's hospital safety centre in injury control.
Over the past 13 years, child safety centres have been established at several Australian Children's hospitals. In a short time, they have developed an important role in community injury control programmes. These centres provide an efficient conduit for transferring up-to-date injury surveillance and prevention information to families, industry, health and education professionals, and government. The activities of the Child Safety Centre at the Royal Children's Hospital in Melbourne are described, together with ways in which a degree of self-funding can be achieved.


Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens.
Conscious cats were used to study the local release of prostaglandin (PG) E2 and thromboxane (Tx) B2 (the stable TxA2 by-product) from the preoptic-anterior hypothalamus (AH-POA) and the tuberal-posterior hypothalamus (PH-Tu) using a modified "push-pull" perfusion procedure. In the absence of fever, PGE2 release was steady from the 2nd h of perfusion onward, its rate at either site ranging between 0.08 and 0.12 pg/min. Local treatment with probenecid (1 mM) increased PGE2 release about threefold. Compared with PGE2, basal release of TxB2 was greater (0.15-0.43 pg/min) and, occasionally, tended to fall with time. Both compounds were found in higher amounts (2- to 10-fold increase) after locally injecting endotoxin, and the effect was greater in AH-POA than PH-Tu. Conversely, intravenous endotoxin (bolus) or interleukin 1 (IL-1) (bolus plus infusion) at doses causing a sustained fever selectively stimulated the formation of PGE2, but the response itself did not differ between AH-POA and PH-Tu. In either region, the degree of enhancement in PGE2 release correlated with the magnitude of the fever. Intravenous indomethacin (2 mg/kg) reversed both the fever and PGE2 elevation. These findings support an intermediary role for PGE2 in the central action of pyrogens and the ensuing fever. Blood-borne pyrogens may act at multiple sites in brain, which are tentatively identified with the circumventricular organs.


Bombus (Hymenoptera: Apidae) Microcolonies as a Tool for Biological Understanding and Pesticide Risk Assessment.
Bumble bees provide valuable pollination services to many wild and agricultural plants. Populations of some bumble bee species are in decline, prompting the need to better understand bumble bee biology and to develop methodologies for assessing the effects of environmental stressors on these bees. Use of bumble bee microcolonies as an experimental tool is steadily increasing. This review closely examines the microcolony model using peer-reviewed published literature identified by searching three databases through November 2018. Microcolonies have been successfully used for investigating a range of endpoints including behavior, the gut microbiome, nutrition, development, pathogens, chemical biology, and pesticides/xenobiotics. Methods for the initiation and monitoring of microcolonies, as well as the recorded variables were catalogued and described. From this information, we identified a series of recommendations for standardizing core elements of microcolony studies. Standardization is critical to establishing the foundation needed to support use of this model for biological response investigations and particularly for supporting use in pesticide risk assessment.


Complementary coding optical stealth transmission based on amplified spontaneous emission light source.
Complementary encoder of stealth signal is proposed and demonstrated for coding, modulating and enhancing the privacy of optical stealth transmission. With complementary encoding, the stealth signal carried by amplified spontaneous emission (ASE) light keeps the same characteristic to ASE noise and can be concealed well under public channel. The experiment results demonstrate the feasibility of the scheme and show the stealth signal has the same impact on public channel in transmission performance, compared to the ASE noise.


Appropriate methods to assess the effectiveness and efficacy of treatments or interventions to control cancer pain.
Pain is common in cancer patients. To ensure optimal pain management efficacy and effectiveness of new drugs and treatments have to be investigated in clinical trials. Efficacy trials such as randomised controlled trials (RCT) are experimental studies and estimate the maximum potential benefit to be derived from an intervention in ideal circumstances and under a controlled environment. RCTs are the only trial design to establish causal effects. A crossover study is a special type of RCT where patients serve as own controls. In efficacy studies the intervention and the control group should be as homogeneous as possible, confounding variables are controlled, bias is reduced, internal validity is high whereas external validity is low. Studies looking at effectiveness assess clinical practice and reflect real life circumstances. They rely high on external validity at the expense of careful controls, the study population is heterogeneous, confounding variables are examined. Cohort studies follow a group or groups of individuals with a common characteristic over a period of time to measure outcomes. Case-control studies start with the outcome and compare the characteristics of two groups of interest, those with the outcome and those without to identify factors which occur more or less often in the poor outcome group. Definition of outcome criteria is crucial both for efficacy and effectiveness studies and is often a primary problem. All clinical studies must use valid and reliable outcome measures.


Why distinctive information reduces false memories: evidence for both impoverished relational-encoding and distinctiveness heuristic accounts.
Two accounts explain why studying pictures reduces false memories within the Deese-Roediger-McDermott paradigm (J. Deese, 1959; H. L. Roediger & K. B. McDermott, 1995). The impoverished relational-encoding account suggests that studying pictures interferes with the encoding of relational information, which is the primary basis for false memories in this paradigm. Alternatively, the distinctiveness heuristic assumes that critical lures are actively withheld by the use of a retrieval strategy. When participants were given inclusion recall instructions to report studied items as well as related items, they still reported critical lures less often after picture encoding than they did after word encoding. As the impoverished relational-encoding account suggests, critical lures appear less likely to come to mind after picture encoding than they do after word encoding. However, the results from a postrecall recognition test provide evidence in favor of the distinctiveness heuristic.


Nicotinic acetylcholine receptor from chick optic lobe.
An alpha-bungarotoxin-sensitive nicotinic cholinergic receptor from chick optic lobe has been completely purified. Its standard sedimentation coefficient is 9.1 S. The value near 12 S reported for the related component from other brain regions can be reproduced when the initial extraction is by Triton X-100 (rather than Lubrol PX), but other protein is then complexed with it. A single subunit of apparent molecular weight 54,000 is detected, and this subunit is specifically labeled by bromo-[3H]acetylcholine, but only after disulfide reduction. The same size subunit likewise is labeled in the protein (purified similarly) from the rest of the chick brain which can also bind alpha-bungarotoxin and nicotinic ligands. Immunological crossreactivity is demonstrated between both of these proteins with an antiserum to pure acetylcholine receptor from skeletal muscle. The acetylcholine receptor from chick optic lobe and the alpha-bungarotoxin-binding protein from the rest of the brain appear similar or identical by a series of criteria and are related to (but with differences from) peripheral acetylcholine receptors.