Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.
Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.


Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells.
Activating length mutations in the juxtamembrane domain (FLT3-LM) and mutations in the tyrosine kinase domain (FLT3-TKD) of FLT3 represent the most frequent genetic alterations in acute myeloid leukemia (AML). However, the functional role of active FLT3 mutants in primary AML blast cells is not well characterized. We analyzed the transforming potential and the signaling of FLT3-ITD mutants in Ba/F3 cells and in primary AML blasts. FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation. In contrast to the FLT3-ITD mutants, the ligand-stimulated FLT3-WT receptor was unable to transduce a fully proliferative response in Ba/F3 and monocytic OCI-AML5 cells. The ligand-stimulated FLT3-WT receptor activated AKT and MAPK, but not STAT5. In primary blast cells from 60 patients with AML, FLT3 was expressed in 91.9% of patients carrying a FLT3-LM/TKD mutation compared with 77.8% in FLT3-LM/TKD-negative patients. STAT3 and STAT5 were constitutively activated in 76 and 63% of patients, respectively. In accordance with the results in Ba/F3 cells, a high FLT3 expression and the presence of a FLT3-LM was strongly associated with the STAT5 but not with the STAT3 activation in primary AML blast cells. Moreover, the constitutive tyrosine phosphorylation of STAT5 was efficiently down-regulated by a FLT3 protein tyrosine kinase inhibitor in AML cells expressing an active FLT3 mutant. Active FLT3 receptor mutants have transforming potential in hematopoietic cells and induce a strong activation of STAT5 in primary AML cells. The FLT3-STAT5 pathway contributes to the malignant phenotype and represents a promising molecular therapeutic target structure in AML.


Genital tuberculosis at Tygerberg Hospital--prevalence, clinical presentation and diagnosis.
Over a period of 30 months (1 July 1986-31 December 1988) 57 cases of genital tuberculosis were diagnosed at Tygerberg Hospital. Forty of these cases were diagnosed as a result of routine screening in 650 patients who presented with infertility and the other 17 were diagnosed in patients admitted to the gynaecological wards. The prevalence in patients presenting with infertility was 6.15%. The commonest gynaecological presenting symptom was infertility (73.7%). Dysmenorrhoea in 29.8% and deep dyspareunia in 12.3% were the only other frequently occurring gynaecological symptoms. Menstruation was normal in 50 patients (87.7%). Seven per cent of patients were postmenopausal. Abdominal symptoms were only present in 15.8%. These findings re-emphasise that genital tuberculosis is often a disease of absent or few symptoms. General, abdominal and pelvic examinations were normal in 56.1% of patients and even when clinical signs were present they were nonspecific. Menstrual fluid collection and culture proved to be the most reliable diagnostic procedure, since it was positive in 11 patients in whom premenstrual endometrial sample cultures were negative and also in 17 patients in whom histological examination of premenstrual endometrial samples for tuberculosis were negative. The possible reasons for this and its clinical importance are discussed. Other than histological examination of operation and/or biopsy specimens, special investigations proved to be of little help in the diagnosis of genital tuberculosis.


Cardiac arrhythmias during rewarming of patients with accidental hypothermia.
Accidental hypothermia has a high mortality and is associated with cardiac arrhythmias. To determine the incidence of arrhythmias and their importance 22 patients with accidental hypothermia (core temperature less than 35 degrees C) were studied by 12 lead electrocardiography and continuous recording of cardiac rhythm. Although 14 of the patients died (64%), only six died while hypothermic. Prolongation of the Q-T interval and the presence of J waves were related to the severity of the hypothermia. Supraventricular arrhythmias, including atrial fibrillation, were common (nine cases) and benign. Ventricular extrasystoles were also common (10 cases), but ventricular tachycardia or fibrillation did not occur during rewarming. In eight patients who died while being monitored the terminal rhythm was asystole. There was no correlation between the severity of hypothermia or the rate of rewarming and the clinical outcome. In the absence of malignant arrhythmias there is no indication for using prophylactic antiarrhythmic treatment in patients with accidental hypothermia. The presence or absence of severe underlying disease is the main determinant of prognosis.


GITIRBio: A Semantic and Distributed Service Oriented-Architecture for Bioinformatics Pipeline.
The need to process large quantities of data generated from genomic sequencing has resulted in a difficult task for life scientists who are not familiar with the use of command-line operations or developments in high performance computing and parallelization. This knowledge gap, along with unfamiliarity with necessary processes, can hinder the execution of data processing tasks. Furthermore, many of the commonly used bioinformatics tools for the scientific community are presented as isolated, unrelated entities that do not provide an integrated, guided, and assisted interaction with the scheduling facilities of computational resources or distribution, processing and mapping with runtime analysis. This paper presents the first approximation of a Web Services platform-based architecture (GITIRBio) that acts as a distributed front-end system for autonomous and assisted processing of parallel bioinformatics pipelines that has been validated using multiple sequences. Additionally, this platform allows integration with semantic repositories of genes for search annotations. GITIRBio is available at: http://c-head.ucaldas.edu.co:8080/gitirbio.


Atrial Fibrillation Impact Questionnaire (AFImpact): Validity and reliability of the Turkish version.
Guidelines recommend measuring and addressing health-related quality of life in the management of atrial fibrillation (AF); however, a disease-specific questionnaire is lacking for the Turkish language. Our aim was to translate and adapt the Atrial Fibrillation Impact Questionnaire (AFImpact) into Turkish and to explore its psychometric properties. This cross-sectional study was conducted in two phases, including the translation and cultural adaptation of AFImpact into Turkish language and the analysis of psychometric properties of the translated questionnaire. 98 patients diagnosed with AF were evaluated using the Turkish version of AFImpact, Short Form-36 (SF-36) and Pittsburg Sleep Quality Index (PSQI). Reliability, validity, and factor structure of the Turkish version of AFImpact was explored. Cronbach's alpha coefficients for vitality, emotional distress, and sleep domains of AFImpact was 0.956, 0.955, and 0.819, respectively, indicating good-to-excellent internal consistency. No significant difference was detected between the initial and retest scores, and intraclass correlation coefficients of each domain varied between 0.991 and 0.996, indicating excellent test-retest reliability. Each domain of AFImpact highly correlated with similar domains of SF-36 and PSQI, having correlation coefficients between -0.484 and -0.699. AFImpact was able to discriminate between the patients in different functional classes, confirming know-groups validity. Factor analysis revealed AFImpact had the same factorial structure as the original questionnaire. The Turkish version of AFImpact is a valid and reliable questionnaire for evaluating health-related quality of life in patients with AF.


Tailoring the hexagonal boron nitride nanomesh on Rh(111) with gold.
It is known that the hexagonal boron nitride (h-BN) monolayer has a periodically corrugated structure on Rh(111), termed "nanomesh", while the h-BN layer is planar on the close packed surfaces of coinage metals (Cu, Ag, Au) due the weak interactions. Our studies are aimed at understanding the metal-h-BN interaction, when both Rh and Au are present. On the one hand, the growth and thermal properties of gold deposited on h-BN nanomesh prepared on Rh(111) were studied. On the other hand, the formation of h-BN was examined on Au/Rh surface alloys prepared by the deposition of Au on Rh(111) and subsequent annealing at 1000 K. In each case, the h-BN was prepared by the decomposition of borazine at about 1000 K. Low energy ion scattering (LEIS), X-ray photoelectron spectroscopy (XPS) and scanning tunneling microscopy (STM) measurements revealed that the growth of Au on h-BN/Rh(111) at room temperature leads to the formation of mainly three dimensional (3D) gold nanoparticles, although at low coverages (<0.2 ML) 2D particles formed as well. Stepwise annealing to higher temperatures induces the intercalation of Au below the nanomesh, which was complete at around 1050 K. Some agglomeration and desorption of Au also took place. Interestingly, the nanomesh structure was observable after intercalation up to relatively large Au coverages. Measurements performed in the reverse order, namely exposing a Au/Rh(111) surface alloy to borazine, revealed that Rh atoms get covered by h-BN (or by its precursors) at significantly smaller borazine exposures than Au atoms. The nanomesh structure was essentially present up to a gold coverage of 0.9 ML, but with a smaller pore diameter, while it gradually disappeared at higher gold amounts. In this way the application of surface alloy supports provides a key for gradual tuning of the mesh morphology. Density functional theory calculations confirmed the decreased pore diameter of the BN layer upon the formation of a surface Rh-Au alloy layer.


Tumoral and tissue-specific expression of the major human beta-tubulin isotypes.
The beta-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on beta-tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex beta-tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT-PCR technique that accurately determines the mRNA expression of the eight human beta-tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell-specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total beta-tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex beta-tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule-binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response.


Family history of colorectal cancer as a marker of potential malignancy within a screening program.
Epidemiologic studies have shown that asymptomatic adult relatives of colorectal cancer patients are at increased risk for developing this tumor. A prospective, published pilot study confirmed this added risk and demonstrated the importance of the family history of cancer as a marker of potential malignancy. The study group was enlarged to include 471 asymptomatic adult, first degree relatives of patients having large bowel neoplasia (cancer or adenomatous polyps) but without polyposis syndromes. These first degree relatives were screened by fecal occult blood examinations and flexible sigmoidoscopy, followed by colonoscopy when indicated. Adenomatous polyps or cancer were found in 8.1% of the study group as compared with 3.7% in a comparison group of screens, not having the same family history of neoplasia and undergoing similar screening tests. Of the study group the age-adjusted rate for colorectal adenomas or cancer increased threefold (P less than 0.001) for subjects older than 40 years and an even higher fivefold relative risk was found for large bowel cancer only (P = 0.01). This was true even if there was only one relative with colorectal neoplasia (P less than 0.01) but was even more pronounced among those having more than one affected relative. The results confirm the usefulness of the family history, of even one member with large bowel neoplasia, in isolating a group at high risk for these lesions. This group would most likely benefit from regular cancer and adenomatous polyp screening particularly when older than 40 years.


Aging in place versus nursing home care: comparison of costs to Medicare and Medicaid.
The objective of this study was to compare the community-based, long-term care program called Aging in Place (AIP) and nursing home care, in terms of cost to the Medicare and Medicaid programs. A retrospective cohort design was used in this study of 39 nursing home residents in the Midwest who were matched with 39 AIP participants. The AIP program consisted of a combination of Medicare home health, Medicaid home and community-based services (HCBS), and intensive nurse care coordination. Controlling for high inpatient Medicare cost in the 6 months prior and the 10 most frequently occurring chronic conditions, multiple regression was used to estimate the relationship of the AIP program on Medicare and Medicaid costs. Total Medicare and Medicaid costs were $1,591.61 lower per month in the AIP group (p < 0.01) when compared with the nursing home group over a 12-month period. The findings suggest that the provision of nurse-coordinated HCBS and Medicare home health services has potential to provide savings in the total cost of health care to the Medicaid program while not increasing the cost of the Medicare program.


Gas visualization of industrial hydrocarbon emissions.
Gases leaking from a polyethene plant and a cracker plant were visualized with the gas-correlation imaging technique. Ethene escaping from flares due to incomplete or erratic combustion was monitored. A leakage at a high-pressure reactor tank could be found and visualized by scanning the camera system over the industrial site. The image processing methods rely on the information from three simultaneously captured images. A direct and a gas-filtered infrared image are recorded with a split-mirror telescope through a joint band-pass filter. The resulting path-integrated gas concentration image, derived from the two infrared images, is combined with a visible image of the scene. The gas-correlation technique also has the potential to estimate the flux in the gas plume by combining a wind vector map, derived by cross-correlating the images in time, with a calibrated gas path-integrated concentration image. The principles of the technique are outlined and its potential discussed.


High post-anthesis temperature effects on bread wheat (Triticum aestivum L.) grain transcriptome during early grain-filling.
High post-anthesis (p.a) temperatures reduce mature grain weights in wheat and other cereals. However, the causes of this reduction are not entirely known. Control of grain expansion by the maternally derived pericarp of the grain has previously been suggested, although this interaction has not been investigated under high p.a. temperatures. Down-regulation of pericarp localised genes that regulate cell wall expansion under high p.a. temperatures may limit expansion of the encapsulated endosperm due to a loss of plasticity in the pericarp, reducing mature grain weight. Here the effect of high p.a. temperatures on the transcriptome of the pericarp and endosperm of the wheat grain during early grain-filling was investigated via RNA-Seq and is discussed alongside grain moisture dynamics during early grain development and mature grain weight. High p.a. temperatures applied from 6-days after anthesis (daa) and until 18daa reduced the grain's ability to accumulate water, with total grain moisture and percentage grain moisture content being significantly reduced from 14daa onwards. Mature grain weight was also significantly reduced by the same high p.a. temperatures applied from 6daa for 4-days or more, in a separate experiment. Comparison of our RNA-Seq data from whole grains, with existing data sets from isolated pericarp and endosperm tissues enabled the identification of subsets of genes whose expression was significantly affected by high p.a. temperature and predominantly expressed in either tissue. Hierarchical clustering and gene ontology analysis resulted in the identification of a number of genes implicated in the regulation of cell wall expansion, predominantly expressed in the pericarp and significantly down-regulated under high p.a. temperatures, including endoglucanase, xyloglucan endotransglycosylases and a β-expansin. An over-representation of genes involved in the 'cuticle development' functional pathway that were expressed in the pericarp and affected by high p.a. temperatures was also observed. High p.a. temperature induced down-regulation of genes involved in regulating pericarp cell wall expansion. This concomitant down-regulation with a reduction in total grain moisture content and grain weight following the same treatment period, adds support to the theory that high p.a. temperatures may cause a reduction in mature grain weight as result of decreased pericarp cell wall expansion.


Continuous Intraoperative Neuromonitoring (C-IONM) Technique with the Automatic Periodic Stimulating (APS) Accessory for Conventional and Endoscopic Thyroid Surgery.
One of the most important trends in intraoperative neural monitoring (IONM) in thyroid surgery is currently the real-time monitoring of the vagus nerve (VN) in order to prevent recurrent laryngeal nerve (RLN) iatrogenic damages. Notably, continuous intraoperative neuromonitoring (C-IONM) seems to be superior to intermitted intraoperative neural monitoring (I-IONM) because it enhances standardization by permanent vagus nerve (VN) stimulation, and it provides entire and constant RLN function monitoring as the surgeon dissects and removes the thyroid gland. It also has to be highlighted that the surgical maneuvers for the automatic periodic stimulating (APS) placement must be accurate and standardized in order to avoid a potential iatrogenic morbidity on the VN function. We recommend the experienced surgeon be very careful in each step, with cautious dissection. With this review article we provide a comprehensive analyses of C-IONM technique with the APS accessory for conventional and endoscopic thyroid surgery.


Pixel-based skin segmentation in psoriasis images.
In this paper, we present a detailed comparison study of skin segmentation methods for psoriasis images. Different techniques are modified and then applied to a set of psoriasis images acquired from the Royal Melbourne Hospital, Melbourne, Australia, with aim of finding the best technique suited for application to psoriasis images. We investigate the effect of different colour transformations on skin detection performance. In this respect, explicit skin thresholding is evaluated with three different decision boundaries (CbCr, HS and rgHSV). Histogram-based Bayesian classifier is applied to extract skin probability maps (SPMs) for different colour channels. This is then followed by using different approaches to find a binary skin map (SM) image from the SPMs. The approaches used include binary decision tree (DT) and Otsu's thresholding. Finally, a set of morphological operations are implemented to refine the resulted SM image. The paper provides detailed analysis and comparison of the performance of the Bayesian classifier in five different colour spaces (YCbCr, HSV, RGB, XYZ and CIELab). The results show that histogram-based Bayesian classifier is more effective than explicit thresholding, when applied to psoriasis images. It is also found that decision boundary CbCr outperforms HS and rgHSV. Another finding is that the SPMs of Cb, Cr, H and B-CIELab colour bands yield the best SMs for psoriasis images. In this study, we used a set of 100 psoriasis images for training and testing the presented methods. True Positive (TP) and True Negative (TN) are used as statistical evaluation measures.


Feline calicivirus p32, p39 and p30 proteins localize to the endoplasmic reticulum to initiate replication complex formation.
In common with other positive-strand RNA viruses, replication of feline calicivirus (FCV) results in rearrangement of intracellular membranes and production of numerous membrane-bound vesicular structures on which viral genome replication is thought to occur. In this study, bioinformatics approaches have identified three of the FCV non-structural proteins, namely p32, p39 and p30, as potential transmembrane proteins. These proteins were able to target enhanced cyan fluorescent protein to membrane fractions where they behaved as integral membrane proteins. Immunofluorescence microscopy of these proteins expressed in cells showed co-localization with endoplasmic reticulum (ER) markers. Further electron microscopy analysis of cells co-expressing FCV p39 or p30 with a horseradish peroxidase protein containing the KDEL ER retention motif demonstrated gross morphological changes to the ER. Similar reorganization patterns, especially for those produced by p30, were observed in naturally infected Crandel-Rees feline kidney cells. Together, the data demonstrate that the p32, p39 and p30 proteins of FCV locate to the ER and lead to reorganization of ER membranes. This suggests that they may play a role in the generation of FCV replication complexes and that the endoplasmic reticulum may represent the potential source of the membrane vesicles induced during FCV infection.


Cadherin-11 blockade reduces inflammation-driven fibrotic remodeling and improves outcomes after myocardial infarction.
Over one million Americans experience myocardial infarction (MI) annually, and the resulting scar and subsequent cardiac fibrosis gives rise to heart failure. A specialized cell-cell adhesion protein, cadherin-11 (CDH11), contributes to inflammation and fibrosis in rheumatoid arthritis, pulmonary fibrosis, and aortic valve calcification but has not been studied in myocardium after MI. MI was induced by ligation of the left anterior descending artery in mice with either heterozygous or homozygous knockout of CDH11, wild-type mice receiving bone marrow transplants from Cdh11-deficient animals, and wild-type mice treated with a functional blocking antibody against CDH11 (SYN0012). Flow cytometry revealed significant CDH11 expression in noncardiomyocyte cells after MI. Animals given SYN0012 had improved cardiac function, as measured by echocardiogram, reduced tissue remodeling, and altered transcription of inflammatory and proangiogenic genes. Targeting CDH11 reduced bone marrow-derived myeloid cells and increased proangiogenic cells in the heart 3 days after MI. Cardiac fibroblast and macrophage interactions increased IL-6 secretion in vitro. Our findings suggest that CDH11-expressing cells contribute to inflammation-driven fibrotic remodeling after MI and that targeting CDH11 with a blocking antibody improves outcomes by altering recruitment of bone marrow-derived cells, limiting the macrophage-induced expression of IL-6 by fibroblasts and promoting vascularization.


Creation of a gilded trap by the high economic value of the Maine lobster fishery.
Unsustainable fishing simplifies food chains and, as with aquaculture, can result in reliance on a few economically valuable species. This lack of diversity may increase risks of ecological and economic disruptions. Centuries of intense fishing have extirpated most apex predators in the Gulf of Maine (United States and Canada), effectively creating an American lobster (Homarus americanus) monoculture. Over the past 20 years, the economic diversity of marine resources harvested in Maine has declined by almost 70%. Today, over 80% of the value of Maine's fish and seafood landings is from highly abundant lobsters. Inflation-corrected income from lobsters in Maine has steadily increased by nearly 400% since 1985. Fisheries managers, policy makers, and fishers view this as a success. However, such lucrative monocultures increase the social and ecological consequences of future declines in lobsters. In southern New England, disease and stresses related to increases in ocean temperature resulted in more than a 70% decline in lobster abundance, prompting managers to propose closing that fishery. A similar collapse in Maine could fundamentally disrupt the social and economic foundation of its coast. We suggest the current success of Maine's lobster fishery is a gilded trap. Gilded traps are a type of social trap in which collective actions resulting from economically attractive opportunities outweigh concerns over associated social and ecological risks or consequences. Large financial gain creates a strong reinforcing feedback that deepens the trap. Avoiding or escaping gilded traps requires managing for increased biological and economic diversity. This is difficult to do prior to a crisis while financial incentives for maintaining the status quo are large. The long-term challenge is to shift fisheries management away from single species toward integrated social-ecological approaches that diversify local ecosystems, societies, and economies.


Protonation states of membrane-embedded carboxylic acid groups in rhodopsin and metarhodopsin II: a Fourier-transform infrared spectroscopy study of site-directed mutants.
A method was developed to measure Fourier-transform infrared (FTIR) difference spectra of detergent-solubilized rhodopsin expressed in COS cells. Experiments were performed on native bovine rhodopsin, rhodopsin expressed in COS cells, and three expressed rhodopsin mutants with amino acid replacements of membrane-embedded carboxylic acid groups: Asp-83-->Asn (D83N), Glu-122-->Gln (E122Q), and the double mutant D83N/E122Q. Each of the mutant opsins bound 11-cis-retinal to yield a visible light-absorbing pigment. Upon illumination, each of the mutant pigments formed a metarhodopsin II-like species with maximal absorption at 380 nm that was able to activate guanine nucleotide exchange by transducin. Rhodopsin versus metarhodopsin II-like photoproduct FTIR-difference spectra were recorded for each sample. The COS-cell rhodopsin and mutant difference spectra showed close correspondence to that of rhodopsin from disc membranes. Difference bands (rhodopsin/metarhodopsin II) at 1767/1750 cm-1 and at 1734/1745 cm-1 were absent from the spectra of mutants D83N and E122Q, respectively. Both bands were absent from the spectrum of the double mutant D83N/E122Q. These results show that Asp-83 and Glu-122 are protonated both in rhodopsin and in metarhodopsin II, in agreement with the isotope effects observed in spectra measured in 2H2O. A photoproduct band at 1712 cm-1 was not affected by either single or double replacements at positions 83 and 122. We deduce that the 1712 cm-1 band arises from the protonation of Glu-113 in metarhodopsin II.


Characterization of a Novel Compound That Stimulates STING-Mediated Innate Immune Activity in an Allele-Specific Manner.
The innate immune response to cytosolic DNA involves transcriptional activation of type I interferons (IFN-I) and proinflammatory cytokines. This represents the culmination of intracellular signaling pathways that are initiated by pattern recognition receptors that engage DNA and require the adaptor protein Stimulator of Interferon Genes (STING). These responses lead to the generation of cellular and tissue states that impair microbial replication and facilitate the establishment of long-lived, antigen-specific adaptive immunity. Ultimately this can lead to immune-mediated protection from infection but also to the cytotoxic T cell-mediated clearance of tumor cells. Intriguingly, pharmacologic activation of STING-dependent phenotypes is known to enhance both vaccine-associated immunogenicity and immune-based anti-tumor therapies. Unfortunately, the STING protein exists as multiple variant forms in the human population that exhibit differences in their reactivity to chemical stimuli and in the intensity of molecular signaling they induce. In light of this, STING-targeting drug discovery efforts require an accounting of protein variant-specific activity. Herein we describe a small molecule termed M04 that behaves as a novel agonist of human STING. Importantly, we find that the molecule exhibits a differential ability to activate STING based on the allelic variant examined. Furthermore, while M04 is inactive in mice, expression of human STING in mouse cells rescues reactivity to the compound. Using primary human cells in ex vivo assays we were also able to show that M04 is capable of simulating innate responses important for adaptive immune activation such as cytokine secretion, dendritic cell maturation, and T cell cross-priming. Collectively, this work demonstrates the conceivable utility of a novel agonist of human STING both as a research tool for exploring STING biology and as an immune potentiating molecule.


Comparing glaucomatous disc change using stereo disc viewing and the MatchedFlicker programme in glaucoma experts and trainees.
The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change. Three experienced glaucoma specialists, two resident ophthalmologists and one glaucoma fellow from multiple institutions independently evaluated the same 140 image pairs from 100 glaucomatous/ocular hypertensive eyes using a handheld stereo viewer and the MatchedFlicker programme. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and endpoint committee, and 50 more were negative controls for progression with photos taken a few minutes apart. Twenty photo pairs from each of the two groups were duplicated for reviewer variability analysis. The initial viewing method was randomised and then alternated for each group of 70 image pairs. Reviewer accuracy and evaluation time for each method were measured. Evaluators averaged 8.6 s faster per image pair (26%) with the MatchedFlicker programme than with the stereo viewer (p=0.0007). Evaluators correctly identified more image pairs when using the MatchedFlicker software over the stereo viewer (p=0.0003). There was no significant difference between the expert and trainee group in speed or overall accuracy for either method. Experts were significantly more consistent than trainees with the duplicate image pairs (p=0.029). Trainees appeared more reluctant to designate eyes as showing glaucoma progression than experts. Both expert glaucoma specialists and ophthalmologists in various stages of training had greater accuracy and speed with the MatchedFlicker programme than with a handheld stereoscopic viewer.


A role for pheromones in mate choice in a lekking sandfly.
There is increasing evidence to suggest that pheromone-mediated communication may play an important role in mate choice in many insects. We investigated the possible role of pheromones in mate choice in the lekking sandfly, Lutzomyia longipalpis, and explored whether males or females display any behavioural traits that predict patterns of male mating success. Pairs of virgin males were introduced into a small mating chamber and allowed to interact for approximately 10 min prior to the introduction of a single virgin female. The trial continued until the female copulated with one of the males. We recorded trials on video for later analysis. After a successful copulation, we determined the quantity of pheromone remaining in the glands of both males and measured the size of the pheromone glands and tergites. We corrected behaviours and measurements for body size (tergite width). Mated males had significantly more pheromone present in their glands after a trial than unmated males. Males differed in how much time they invested in wing fanning. Members of each pair of males spent similar amounts of time wing fanning but mated males and males with more residual pheromone spent more time wing fanning than their counterparts throughout the trial. The time spent wing fanning and the amount of residual pheromone were not correlated, however. A male's ability to win fights did not relate to his reproductive success. Finally, a female was equally likely to wing-fan directly at, or walk away from, either male in a given pair. The possible relationships between the amount of pheromone released and the residual pheromones left in the glands, and the level of male wing fanning and pheromone productivity, are discussed. Copyright 1998 The Association for the Study of Animal Behaviour.


GABAA and GABAC receptors on hybrid bass retinal bipolar cells.
1. gamma-Aminobutyric acid (GABA) responses from solitory hybrid bass retinal bipolar cells were studied with the use of conventional and perforated whole cell patch-clamp recording. 2. GABA elicited a chloride current in bipolar cells that had both transient and sustained components. The transient component was sensitive to bicuculline and resembled GABAA-mediated currents, whereas the more sustained component was resistant to bicuculline and resembled the responses mediated by GABAC receptors. 3. The bicuculline-resistant GABA responses recorded from the bipolar cells could not be modulated by either diazepam or pentobarbital sodium, and they were unaffected by phaclofen and 2-hydroxysaclofen, GABAB receptor antagonists. On the other hand, the bicuculline-resistant GABA responses could be blocked substantially by imidazole-4-acetic acid (I4AA), a competitive antagonist of GABAC receptors. 4. Noise analysis of the GABA-elicited currents suggested a different single channel conductance for GABAA (10.1 pS) and GABAC receptors (3.6 pS). 5. Zinc, a putative modulator of synaptic transmission, strongly inhibited the GABAC responses on bipolar cells, whereas the GABAA responses were not significantly affected by zinc. 6. The proportion of the GABAC to GABAA responses varied widely between bipolar cells. Local application of GABA onto dendrites or axon terminals showed that both types of GABA receptors are present on both regions of the cell. 7. The distinct properties of these two GABA receptor types suggest that they play different roles in retinal function.


Complementary and alternative medicine use among women receiving chemotherapy for ovarian cancer in 2 patient populations.
The authors evaluated attitudes toward complementary and alternative medicine (CAM) use in 2 populations of women receiving chemotherapy for epithelial ovarian cancer (EOC). Women with EOC currently being treated with chemotherapy at 2 tertiary cancer centers, in Canada and the United Kingdom, completed a self-administered questionnaire on attitudes and perceptions of CAM and types of CAM used within the previous month. One hundred ninety-two patients (94 from Canada, 98 from United Kingdom) completed the questionnaire. Overall, 85 women (44%) were identified as CAM users. Complementary and alternative medicine use was more common among Canadian women (52%) compared with women from the United Kingdom (37%), P = 0.02. Participants used 71 different types of CAM, the majority (61%) taking multiple CAM. The frequency of CAM use was the same in primary compared with recurrent disease. Eighty-nine percent of CAM users considered it important for their oncologist to be aware of CAM use. Canadian women, however, were less likely to inform their physician (Canada: 50%; United Kingdom: 81%), P = 0.02. Motivations for CAM use were the same in both populations including assist healing (60%), boost the immune system (57%), improve quality of life (48%), and relieve symptoms (45%). Thirteen percent thought CAM could cure cancer, whereas 17% thought it would prevent recurrence. Complementary and alternative medicine use is common in women receiving chemotherapy for EOC. Increasingly, interactions between CAM and prescribed medication are being identified. Oncologists should be aware and actively inquire about CAM use. Although patterns of CAM use differed, the motivation for starting CAM was similar, highlighting the need to address supportive care in all patients.


Spatial but not temporal numerosity thresholds correlate with formal math skills in children.
Humans and other animals are able to make rough estimations of quantities using what has been termed the approximate number system (ANS). Much evidence suggests that sensitivity to numerosity correlates with symbolic math capacity, leading to the suggestion that the ANS may serve as a start-up tool to develop symbolic math. Many experiments have demonstrated that numerosity perception transcends the sensory modality of stimuli and their presentation format (sequential or simultaneous), but it remains an open question whether the relationship between numerosity and math generalizes over stimulus format and modality. Here we measured precision for estimating the numerosity of clouds of dots and sequences of flashes or clicks, as well as for paired comparisons of the numerosity of clouds of dots. Our results show that in children, formal math abilities correlate positively with sensitivity for estimation and paired-comparisons of the numerosity of visual arrays of dots. However, precision of numerosity estimation for sequences of flashes or sounds did not correlate with math, although sensitivities in all estimations tasks (for sequential or simultaneous stimuli) were strongly correlated with each other. In adults, we found no significant correlations between math scores and sensitivity to any of the psychophysical tasks. Taken together these results support the existence of a generalized number sense, and go on to demonstrate an intrinsic link between mathematics and perception of spatial, but not temporal numerosity. (PsycINFO Database Record


Suppression of the Fix- phenotype of Rhizobium meliloti exoB mutants by lpsZ is correlated to a modified expression of the K polysaccharide.
The rhizobial production of extracellular polysaccharide (EPS) is generally required for the symbiotic infection of host plants that form nodules with an apical meristem (indeterminate nodules). One exception is Rhizobium meliloti AK631, an exoB mutant of Rm41, which is deficient in EPS production yet infects and fixes nitrogen (i.e., is Fix+) on alfalfa, an indeterminate nodule-forming plant. A mutation of lpsZ in AK631 results in a Fix- strain with altered phage sensitivity, suggesting that a cell surface factor may substitute for EPS in the alfalfa-AK631 symbiosis. Biochemical analyses of the cell-associated polysaccharides of AK631 and Rm5830 (AK631 lpsZ) demonstrated that the lpsZ mutation affected the expression of a surface polysaccharide that is analogous to the group II K polysaccharides of Escherichia coli; the polysaccharide contains 3-deoxy-D-manno-2-octulosonic acid or a derivative thereof in each repeating unit. Rm5830 produced a polysaccharide with altered chromatographic and electrophoretic properties, indicating a difference in the molecular weight range. Similar results were obtained in a study of Rm1021, a wild-type isolate that lacks the lpsZ gene: the introduction of lpsZ into Rm1021 exoB (Rm6903) both suppresses the Fix- phenotype and results in a modified expression of the K polysaccharide. Chromatography and electrophoresis analysis showed that the polysaccharide extracted from Rm6903 lpsZ+ differed from that of Rm6903 in molecular weight range. Importantly, the effect of LpsZ is not structurally specific, as the introduction lpsZ+ into Rhizobium fredii USDA257 also resulted in a molecular weight range change in the structurally distinct K polysaccharide produced by that strain. This evidence suggests that LpsZ has a general effect on the size-specific expression of rhizobial K polysaccharides.


Transmission of infectious diseases en route to habitat hotspots.
The spread of infectious diseases in wildlife populations is influenced by patterns of between-host contacts. Habitat "hotspots"--places attracting a large numbers of individuals or social groups--can significantly alter contact patterns and, hence, disease propagation. Research on the importance of habitat hotspots in wildlife epidemiology has primarily focused on how inter-individual contacts occurring at the hotspot itself increase disease transmission. However, in territorial animals, epidemiologically important contacts may primarily occur as animals cross through territories of conspecifics en route to habitat hotspots. So far, the phenomenon has received little attention. Here, we investigate the importance of these contacts in the case where infectious individuals keep visiting the hotspots and in the case where these individuals are not able to travel to the hotspot any more. We developed a simulation epidemiological model to investigate both cases in a scenario when transmission at the hotspot does not occur. We find that (i) hotspots still exacerbate epidemics, (ii) when infectious individuals do not travel to the hotspot, the most vulnerable individuals are those residing at intermediate distances from the hotspot rather than nearby, and (iii) the epidemiological vulnerability of a population is the highest when the number of hotspots is intermediate. By altering animal movements in their vicinity, habitat hotspots can thus strongly increase the spread of infectious diseases, even when disease transmission does not occur at the hotspot itself. Interestingly, when animals only visit the nearest hotspot, creating additional artificial hotspots, rather than reducing their number, may be an efficient disease control measure.


The signaling domain of the erythropoietin receptor rescues prolactin receptor-mutant mammary epithelium.
The cytokine hormones prolactin and erythropoietin mediate tissue-specific developmental outcomes by activating their cognate receptors, prolactin receptor (PrlR) and erythropoietin receptor (EpoR), respectively. The EpoR is essential for red blood cell formation, whereas a principal function of PrlR is in the development of the mammary gland during pregnancy and lactation [Ormandy, C., et al. (1997) Genes Dev. 11, 167-178]. The instructive model of differentiation proposes that such distinct, cytokine-dependent developmental outcomes are a result of cytokine receptor-unique signals that bring about induction of lineage-specific genes. This view was challenged by our finding that an exogenously expressed PrlR could rescue EpoR(-/-) erythroid progenitors and mediate their differentiation into red blood cells. Together with similar findings in other hematopoietic lineages, this suggested that cytokine receptors do not play an instructive role in hematopoietic differentiation. Here, we show that these findings are not limited to the hematopoietic system but are of more general relevance to cytokine-dependent differentiation. We demonstrate that the developmental defect of PrlR(-/-) mammary epithelium is rescued by an exogenously expressed chimeric receptor (prl-EpoR) containing the PrlR extracellular domain joined to the EpoR transmembrane and intracellular domains. Like the wild-type PrlR, the prl-EpoR rescued alveologenesis and milk secretion in PrlR(-/-) mammary epithelium. These results suggest that, in cell types as unrelated as erythrocytes and mammary epithelial cells, cytokine receptors employ similar, generic signals that permit the expression of predetermined, tissue-specific differentiation programs.


Motivational Salience Guides Attention to Valuable and Threatening Stimuli: Evidence from Behavior and Functional Magnetic Resonance Imaging.
Rewarding and aversive outcomes have opposing effects on behavior, facilitating approach and avoidance, although we need to accurately anticipate each type of outcome to behave effectively. Attention is biased toward stimuli that have been learned to predict either type of outcome, and it remains an open question whether such orienting is driven by separate systems for value- and threat-based orienting or whether there exists a common underlying mechanism of attentional control driven by motivational salience. Here, we provide a direct comparison of the neural correlates of value- and threat-based attentional capture after associative learning. Across multiple measures of behavior and brain activation, our findings overwhelmingly support a motivational salience account of the control of attention. We conclude that there exists a core mechanism of experience-dependent attentional control driven by motivational salience and that prior characterizations of attention as being value driven or supporting threat monitoring need to be revisited.


Genetic variation in peroxisome proliferator-activated receptor gamma, soy, and mammographic density in Singapore Chinese women.
PPARγ is a transcription factor important for adipogenesis and adipocyte differentiation. Data from animal studies suggest that PPARγ may be involved in breast tumorigenesis, but results from epidemiologic studies on the association between PPARγ variation and breast cancer risk have been mixed. Recent data suggest that soy isoflavones can activate PPARγ. We investigated the interrelations of soy, PPARγ, and mammographic density, a biomarker of breast cancer risk in a cross-sectional study of 2,038 women who were members of the population-based Singapore Chinese Health Study Cohort. We assessed mammographic density using a computer-assisted method. We used linear regression to examine the association between 26 tagging single-nucleotide polymorphisms (SNP) of PPARγ and their interaction with soy intake and mammographic density. To correct for multiple testing, we calculated P values adjusted for multiple correlated tests (P(ACT)). Out of the 26 tested SNPs in the PPARγ, seven SNPs were individually shown to be statistically significantly associated with mammographic density (P(ACT) = 0.008-0.049). A stepwise regression procedure identified that only rs880663 was independently associated with mammographic density which decreased by 1.89% per-minor allele (P(ACT) = 0.008). This association was significantly stronger in high-soy consumers as mammographic density decreased by 3.97% per-minor allele of rs880663 in high-soy consumers (P(ACT) = 0.006; P for interaction with lower soy intake = 0.017). Our data support that PPARγ genetic variation may be important in determining mammographic density, particularly in high-soy consumers. Our findings may help to identify molecular targets and lifestyle intervention for future prevention research.


Physical inactivity and health inequality during coronavirus: a novel opportunity or total lockdown?
Government-restricted movement during the coronavirus pandemic in various countries around the world has led to rapid and fundamental changes in our health behaviour. As well as being at a higher risk of contracting and being hospitalised with COVID-19, the elderly, those with chronic disease and lower socioeconomic groups are also disproportionately affected by restriction of movement, further widening the physical activity health inequality. In this viewpoint we discuss the physiological sequelae of physical inactivity, and the additional burden of ageing and inflammation. We provide recommendations for public health promotion and interventions to try to mitigate the detrimental effects of physical inactivity and rebalance the health inequality.


Renal Cortical Necrosis; Five Consecutive Cases within Short Span of Time.
Renal cortical necrosis (RCN) is characterized by patchy or diffuse destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients of AKI. In contrast, the incidence of RCN is higher in developing countries ranging from 6%-7%. Obstetric complication is the main cause of RCN, earlier it was about 20%-30% which has been declining to 5% in the Indian subcontinent during the past two decades. The aim of this study is to review five consecutive cases of RCN diagnosed within very short span of time. Histopathologically, diagnosed five cases of RCN during one-month span in September 2016 at Armed Forces Institute of Pathology, Dhaka were included in this study. All the cases were referred cases from a tertiary level obstetric center of Dhaka city; the mean age was 24.2 ± 3.4 years. All the cases had the history of postpartum hemorrhage followed by septicemia. They all presented with acute renal failure dependent on hemodialysis for >21 days. On histological examination, three (60%) had patchy RCN and two (40%) had diffuse RCN. Two (40%) showed coagulative necrosis of all the glomeruli, two (40%) showed coagulative necrosis of >50% of glomeruli, and in one (20%) case necrosis of about 25% of glomeruli. One of the glomeruli showed global sclerotic change of most of the glomeruli. In all the cases, interstitium showed moderate focal lymphocytic infiltration and mild edema. Among all, one (20%) was found with immunoglobulin A nephropathy as an associated diagnosis. RCN is still encountered as an obstetric complication in our setting and this type of grave consequences should be prevented by better monitoring of pregnancies.


Metabolic syndrome and kidney disease: a systematic review and meta-analysis.
Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS AND POPULATION: We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m(2) were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies. Eleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m(2) (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m(2) for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS. MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m(2) and microalbuminuria or overt proteinuria.


Improving NO(x) cap-and-trade system with adjoint-based emission exchange rates.
Cap-and-trade programs have proven to be effective instruments for achieving environmental goals while incurring minimum cost. The nature of the pollutant, however, affects the design of these programs. NO(x), an ozone precursor, is a nonuniformly mixed pollutant with a short atmospheric lifetime. NO(x) cap-and-trade programs in the U.S. are successful in reducing total NO(x) emissions but may result in suboptimal environmental performance because location-specific ozone formation potentials are neglected. In this paper, the current NO(x) cap-and-trade system is contrasted to a hypothetical NO(x) trading policy with sensitivity-based exchange rates. Location-specific exchange rates, calculated through adjoint sensitivity analysis, are combined with constrained optimization for prediction of NO(x) emissions trading behavior and post-trade ozone concentrations. The current and proposed policies are examined in a case study for 218 coal-fired power plants that participated in the NO(x) Budget Trading Program in 2007. We find that better environmental performance at negligibly higher system-wide abatement cost can be achieved through inclusion of emission exchange rates. Exposure-based exchange rates result in better environmental performance than those based on concentrations.


Systematic review of combined functional near-infrared spectroscopy and transcranial direct-current stimulation studies.
Significance: Combining transcranial direct-current stimulation (tDCS) with functional near-infrared spectroscopy (fNIRS) is a recent approach to exploring brain activation evoked by neurostimulation. Aim: To critically evaluate studies combining tDCS and fNIRS and provide a consolidated overview of cortical hemodynamic responses to neurostimulation. Approach: Key terms were searched in three databases (MEDLINE, EMBASE, and PsycINFO) with cross-referencing and works from Google Scholar also evaluated. All studies reporting on fNIRS-derived hemoglobin changes evoked by tDCS were included. Results: Literature searches revealed 474 articles, of which 28 were included for final review (22 in healthy individuals: 9 involving rest and 13 with tasks; 6 in the clinical setting). At rest, an overall increase in cortical activation was observed in fNIRS responses at the site of stimulation, with evidence suggesting nonstimulated brain regions are also similarly affected. Conversely, during tasks, reduced cortical activation was observed during online stimulation. Offline and poststimulation effects were less consistent, as is the impact on clinical populations and their symptom correlation. Conclusion: This review explores the methodological frameworks for fNIRS-tDCS evaluations and summarizes hemodynamic responses associated with tDCS in all populations. Our findings provide further evidence of the impact of tDCS on neuronal activation within functionally connected networks.


Advanced error diagnostics of the CMAQ and Chimere modelling systems within the AQMEII3 model evaluation framework.
The work here complements the overview analysis of the modelling systems participating in the third phase of the Air Quality Model Evaluation International Initiative (AQMEII3) by focusing on the performance for hourly surface ozone by two modelling systems, Chimere for Europe and CMAQ for North America. The evaluation strategy outlined in the course of the three phases of the AQMEII activity, aimed to build up a diagnostic methodology for model evaluation, is pursued here and novel diagnostic methods are proposed. In addition to evaluating the "base case" simulation in which all model components are configured in their standard mode, the analysis also makes use of sensitivity simulations in which the models have been applied by altering and/or zeroing lateral boundary conditions, emissions of anthropogenic precursors, and ozone dry deposition. To help understand of the causes of model deficiencies, the error components (bias, variance, and covariance) of the base case and of the sensitivity runs are analysed in conjunction with timescale considerations and error modelling using the available error fields of temperature, wind speed, and NO x concentration. The results reveal the effectiveness and diagnostic power of the methods devised (which remains the main scope of this study), allowing the detection of the timescale and the fields that the two models are most sensitive to. The representation of planetary boundary layer (PBL) dynamics is pivotal to both models. In particular, (i) the fluctuations slower than ~ 1.5 days account for 70-85 % of the mean square error of the full (undecomposed) ozone time series; (ii) a recursive, systematic error with daily periodicity is detected, responsible for 10-20 % of the quadratic total error; (iii) errors in representing the timing of the daily transition between stability regimes in the PBL are responsible for a covariance error as large as 9 ppb (as much as the standard deviation of the network-average ozone observations in summer in both Europe and North America); (iv) the CMAQ ozone error has a weak/negligible dependence on the errors in NO2, while the error in NO2 significantly impacts the ozone error produced by Chimere; (v) the response of the models to variations of anthropogenic emissions and boundary conditions show a pronounced spatial heterogeneity, while the seasonal variability of the response is found to be less marked. Only during the winter season does the zeroing of boundary values for North America produce a spatially uniform deterioration of the model accuracy across the majority of the continent.


Food preferences and weight change during low-fat and low-carbohydrate diets.
Understanding associations between food preferences and weight loss during various effective diets could inform efforts to personalize dietary recommendations and provide insight into weight loss mechanisms. We conducted a secondary analysis of data from a clinical trial in which participants were randomized to either a 'choice' arm, in which they were allowed to select between a low-fat diet (n = 44) or low-carbohydrate diet (n = 61), or to a 'no choice' arm, in which they were randomly assigned to a low-fat diet (n = 49) or low-carbohydrate diet (n = 53). All participants were provided 48 weeks of lifestyle counseling. Food preferences were measured at baseline and every 12 weeks thereafter with the Geiselman Food Preference Questionnaire. Participants were 73% male and 51% African American, with a mean age of 55. Baseline food preferences, including congruency of food preferences with diet, were not associated with weight outcomes. In the low-fat diet group, no associations were found between changes in food preferences and weight over time. In the low-carbohydrate diet group, increased preference for low-carbohydrate diet congruent foods from baseline to 12 weeks was associated with weight loss from 12 to 24 weeks. Additionally, weight loss from baseline to 12 weeks was associated with increased preference for low-carbohydrate diet congruent foods from 12 to 24 weeks. Results suggest that basing selection of low-carbohydrate diet or low-fat diet on food preferences is unlikely to influence weight loss. Congruency of food preferences and weight loss may influence each other early during a low-carbohydrate diet but not low-fat diet, possibly due to different features of these diets. NCT01152359.


Prediction of recidivism in exhibitionists: psychological, phallometric, and offense factors.
Exhibitionists have traditionally been regarded as nuisance offenders. However, empirical studies show that some offenders can be highly recidivistic and can escalate to incidents of Hands-on sexual assault. The objective of this study was to investigate predictors of recidivism in exhibitionists and clarify the differences between Hands-on and Hands-off sexual recidivists. The hundred and twenty-one exhibitionists were assessed at a university teaching hospital between 1983 and 1996. Archival data came from medical files and police files. The Psychopathy Checklist-Revised (PCL-R) was assessed retrospectively. Results indicated that over a mean follow-up period of 6.84 years, 11.7, 16.8, and 32.7% of exhibitionists were charged with or convicted of sexual, violent, or criminal offenses, respectively. Sexual reoffending recidivists were less educated, and had more prior sexual and criminal offenses. Violent, recidivists were also less educated, had lower Derogatis Sexual Functioning Inventory (DSFI) scores, higher PCL-R Totals, and more prior sexual, violent, and criminal offenses. Criminal recidivists were younger, less educated, had lower DSFI scores, higher PCL-R scores, higher Pedophile Indices, and more prior sexual, violent, and criminal offenses. Hands-on sexual recidivists demonstrated higher PCL-R ratings, higher Pedophile and Rape indices, and more prior sexual, violent, and criminal offenses than did Hands-off counterparts.


Thinning of Inner Retinal Layers after Vitrectomy with Silicone Oil versus Gas Endotamponade in Eyes with Macula-Off Retinal Detachment.
To evaluate retinal layer thickness with optical coherence tomography (OCT) in eyes with macula-off retinal detachment after silicone oil (SiO) or gas endotamponade. Cross-sectional study of 40 eyes with macula-off rhegmatogenous retinal detachment that underwent vitrectomy. 20 eyes received SiO tamponade and 20 matched eyes received gas. 33 healthy fellow eyes served as controls. Macular spectral domain OCT was performed with automated layer detection in the 5 inner subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. Comparing the SiO group with the gas group, the ganglion cell layer showed a significant thinning in all fields of the inner ring of the ETDRS map, the inner plexiform layer in the nasal, superior and temporal quadrants, and the outer plexiform layer in the nasal quadrant. Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade.


Fine-tuning the brain: MicroRNAs.
The brain is of bewildering complexity and numerous genes and signaling molecules have been described that affect the architecture and functioning of specific neuronal circuits. Recent evidence from genome analysis revealed the existence of a large group of novel RNA molecules with unexpected properties. One such group is called microRNAs, which are small 21-23 nucleotides RNA molecules that are transcribed by the genome. However, they are not translated into proteins but rather control translation of coding mRNA. Particularly in the brain, numerous different microRNAs are expressed in a cell type specific fashion both during development and in adulthood. Aberrant microRNA expression has been implicated in several human diseases including CNS diseases. The aim of this review is to emphasize their role in the development of the brain and their function. In addition, we highlight recent findings on the evolution of mammalian microRNAs and their effect on steroid signaling in the brain.


Selection for resistance to a fungal pathogen in Drosophila melanogaster.
An artificial selection experiment designed to explore the evolution of resistance to a fungal pathogen, Beauveria bassiana, in Drosophila melanogaster is reported here. The experiment was designed to test whether there is sufficient additive genetic variation in this trait for increased resistance to evolve, and, if so, whether there are correlated responses that might represent a cost to defence. After 15 generations of selection, flies from selected lines did not have higher overall fitness after infection compared with control lines. The response to selection for resistance against this pathogen is thus much weaker than against other species, in particular, parasitoids. There was, however, evidence for increased late-life fecundity in selected lines, which may indicate evolved tolerance of fungal infection. This increase was accompanied by reduced early-life fitness, which may reflect the well-known trade-off between early and late reproduction. In the absence of fungal infection, selected flies had lower fitness than control flies, and the possibility that this is also a trade-off with increased tolerance is explored.


Best Practice Recommendations for Stroke Patients with Dysphagia: A Delphi-Based Consensus Study of Experts in Turkey-Part I: Management, Diagnosis, and Follow-up.
Dysphagia is one of the most common and important complications of stroke. It is an independent marker of poor outcome after acute stroke and may become chronic after the acute period and continues to affect all aspects of the patient's life. Patients with stroke may encounter any of the medical branches in the emergency room or outpatient clinic, and as in our country, there may not be specialists specific for dysphagia, such as speech-language pathologists (SLP), in every hospital. This study aimed to raise awareness and create a common opinion of medical specialists for stroke patients with dysphagia. This recommendation paper has been written by a multidisciplinary team and offers 45 recommendations for stroke patients with dysphagia. It was created using the eight-step Delphi round via e-mail. This study is mostly specific to Turkey. However, since it contains detailed recommendations from the perspective of various disciplines associated with stroke, this consensus-based recommendation paper is not only a useful guide to address clinical questions in practice for the clinical management of dysphagia in terms of management, diagnosis, and follow-up, but also includes detailed comments for these topics.


HIV testing and high risk sexual behaviour among London's migrant African communities: a participatory research study.
To describe the demographic and behavioural factors associated with HIV testing among migrant Africans in London. A cross sectional survey of migrants from five sub-Saharan African communities (Congo, Kenya, Uganda, Zambia, Zimbabwe) resident in London was carried out. The study formed part of a larger community based participatory research initiative with migrant African communities in London-the MAYISHA project. Trained, ethnically matched interviewers recruited study participants in a variety of community venues. A brief self completion questionnaire collected data on demographic characteristics, utilisation of sexual health services, HIV testing history, sexual behaviour, and attitudes. Valid questionnaires were obtained from 748 participants (396 men and 352 women), median ages 31 and 27 years, respectively. Median length of UK residence was 6 years. 34% of men and 30% of women reported ever having had an HIV test. HIV testing was significantly associated with age and previous STI diagnosis among women; and additionally, nationality, education, employment, and self perceived risk of acquiring HIV among men. After controlling for significant demographic variables, previous diagnosis of an STI (adjusted odds ratio and 95% confidence interval for men: 2.96, 1.63 to 5.38, and women 2.03, 1.06 to 3.88) and perceived risk of acquiring HIV for men (adjusted OR 2.28, 95%CI 1.34 to 3.90) remained independently associated. Among these high HIV prevalence migrant communities, these data suggest that HIV testing remains largely associated with an individual's STI history or self perceived risk. This strategy may be inappropriate given the potential for onward and vertical transmission. Antenatal HIV testing combined with proactive targeted HIV testing promotion should be prioritised.


Collective-Intelligence Recommender Systems: Advancing Computer Tailoring for Health Behavior Change Into the 21st Century.
What is the next frontier for computer-tailored health communication (CTHC) research? In current CTHC systems, study designers who have expertise in behavioral theory and mapping theory into CTHC systems select the variables and develop the rules that specify how the content should be tailored, based on their knowledge of the targeted population, the literature, and health behavior theories. In collective-intelligence recommender systems (hereafter recommender systems) used by Web 2.0 companies (eg, Netflix and Amazon), machine learning algorithms combine user profiles and continuous feedback ratings of content (from themselves and other users) to empirically tailor content. Augmenting current theory-based CTHC with empirical recommender systems could be evaluated as the next frontier for CTHC. The objective of our study was to uncover barriers and challenges to using recommender systems in health promotion. We conducted a focused literature review, interviewed subject experts (n=8), and synthesized the results. We describe (1) limitations of current CTHC systems, (2) advantages of incorporating recommender systems to move CTHC forward, and (3) challenges to incorporating recommender systems into CTHC. Based on the evidence presented, we propose a future research agenda for CTHC systems. We promote discussion of ways to move CTHC into the 21st century by incorporation of recommender systems.


Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A through oxidative stress.
We previously demonstrated that indoxyl sulfate (IS), a uremic toxin, induces aortic calcification in hypertensive rats and induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells. This study aimed to clarify whether IS stimulates senescence of cultured human aortic smooth muscle cells (HASMCs) and aorta in Dahl salt-sensitive hypertensive rats and whether AST-120, an oral sorbent, prevents senescence of aorta in subtotally nephrectomized uremic rats. IS increased the mRNA expression of p53 and p21 in HASMCs, whereas it did not change that of p16 and retinoblastoma protein (pRb). The IS-induced expression of p53 and p21 was suppressed by N-acetylcysteine, an antioxidant. IS promoted protein expression of p53, p21, and senescence-associated β-galactosidase (SA-β-gal) activity in HASMCs, and N-acetylcysteine and pifithrin-α,p-nitro, a p53 inhibitor, blocked these effects. IS upregulated prelamin A, a hallmark of vascular smooth muscle cell senescence, and downregulated FACE1/Zempste24 protein expression in HASMCs, and N-acetylcysteine suppressed these effects. Administration of IS to hypertensive rats increased expression of SA-β-gal, p53, p21, prelamin A, and oxidative stress markers such as 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in the cells embedded in the calcification area of arcuate aorta. Further, the uremic rat model showed positive staining for SA-β-gal, p53, p21, prelamin A, 8-OHdG, and MDA in the cells embedded in the calcification area of arcuate aorta, whereas AST-120 reduced the expression of these biomarkers. Taken together, IS accelerates vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A and downregulation of FACE1 through oxidative stress.


Kisspeptin: A Potential Factor for Unexplained Infertility and Impaired Embryo Implantation.
Kisspeptin (KP) is a neuropeptide that causes the release of the gonadotropin releasing hormone, which controls hypothalamo pituitary ovarian axis and exerts a number of peripheral effects on reproductive organs. The primary objective of this study was to compare baseline KP levels in females with different types of infertility and identify possible correlations with risk of failure to conceive, preclinical abortion and pregnancy after intracytoplasmic sperm injection (ICSI). A longitudinal cohort study was carried out from August 2014 until May 2015 by recruiting 124 female patients undergoing ICSI, after obtaining ethical approval from the Australian Concept Infertility Medical Center. Cause of infertility due to male, female and unexplained factors was at a frequency of 32 (24%), 33 (31%) and 59 (45%) among the individuals respectively. KP levels were measured by ELISA assay before the initiation of the ICSI treatment protocol. Outcome of ICSI was categorized into three groups of non-pregnant with beta-human chorionic gonadotropin (β-hCG)<5-25 mIU/ml, preclinical abortion with β-hCG>25 mIU/ml and no cardiac activity, and clinical pregnancy declared upon confirmation of cardiac activity. Results based on cause of infertility and outcome groups were analyzed by one-way ANOVA. Females with unexplained infertility had significantly lower levels of KP when compared with those with male factor infertility (176.69 ± 5.03 vs. 397.6 ± 58.2, P=0.001). Clinical pregnancy was observed in 28 (23%) females of which 17 (71%) had a female cause of infertility. In the non-pregnant group of 66 (53%) females, common cause of infertility was unexplained 56(85%). A weak positive correlation of KP levels with fertilized oocytes and endometrial thickness was observed (P=0.04 and 0.01 respectively). Deficiency of KP in females with unexplained infertility was associated with reduced chances of implantation after ICSI.


Effects of soft tissue augmentation procedures on peri-implant health or disease: A systematic review and meta-analysis.
To review the dental literature in terms of soft tissue augmentation procedures and their influence on peri-implant health or disease in partially and fully edentulous patients. A MEDLINE search from 1966 to 2016 was performed to identify controlled clinical studies comparing soft tissue grafting versus no soft tissue grafting (maintenance) or two types of soft tissue grafting procedures at implant sites. The soft tissue grafting procedures included either an increase of keratinized tissue or an increase of the thickness of the peri-implant mucosa. Studies reporting on the peri-implant tissue health, as assessed by bleeding or gingival indices, were included in the review. The search was complemented by an additional hand search of all selected full-text articles and reviews published between 2011 and 2016. The initial search yielded a total number of 2,823 studies. Eligible studies were selected based on the inclusion criteria (finally included: four studies on gain of keratinized tissue; six studies on gain of mucosal thickness) and quality assessments conducted. Meta-analyses were applied whenever possible. Soft tissue grafting procedures for gain of keratinized tissue resulted in a significantly greater improvement of gingival index values compared to maintenance groups (with or without keratinized tissue) [n = 2; WMD = 0.863; 95% CI (0.658; 1.067); p < .001]. For final marginal bone levels, statistically significant differences were calculated in favor of an apically positioned flap (APF) plus autogenous grafts versus all control treatments (APF alone; APF plus a collagen matrix; maintenance without intervention [with or without residual keratinized tissue]) [n = 4; WMD = -0.175 mm; 95% CI: (-0.313; -0.037); p = .013]. Soft tissue grafting procedures for gain of mucosal thickness did not result in significant improvements in bleeding indices over time, but in significantly less marginal bone loss over time [WMD = 0.110; 95% CI: 0.067; 0.154; p < .001] and a borderline significance for marginal bone levels at the study endpoints compared to sites without grafting. Within the limitations of this review, it was concluded that soft tissue grafting procedures result in more favorable peri-implant health: (i) for gain of keratinized mucosa using autogenous grafts with a greater improvement of bleeding indices and higher marginal bone levels; (ii) for gain of mucosal thickness using autogenous grafts with significantly less marginal bone loss.


Walnut leaf extract acts as a fertility agent in male Wistar albino rats - A search for herbal male fertility enhancer.
Background Walnut leaf is one of the many medicinal plants used in folklore as male fertility enhancers. The present work was therefore undertaken with an aim to scientifically validate this claim. As such, we evaluated the effect of the aqueous extract from walnut leaves on biomolecules related to fertility in adult male rats and its mode of action as fertility-enhancing agent. Methods Twenty-five rats were randomly divided into five groups of five animals each; Group 1 served as control and received normal (0.9%) saline only; Groups II, III, IV received 50, 500, 1,000 mg/kg body weight (BW) of T. conophorum leaf extract orally, while Group V served as standard and was given suspension of clomiphene citrate orally at the dose of 1.04 mg/kg/ml BW. The extract and drug were given daily and the experiment lasted for 21 consecutive days. Results The testicular biochemical parameters in treated groups showed significant (p<0.05) increase in lactate dehydrogenase activity activity, Glucose-6-phosphate dehydrogenase (G-6PDH) activity, glycogen content, 3β and 17β hydroxysteroid dehydrogenase activities and testicular and epididymal Zn and Se contents with a significant decrease in cholesterol content. A significant increase in testis weight and epididymis weight were also observed. Also, a significant (p<0.05) increase in the level of serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone, sperm count, motility, viability and a decrease in sperm abnormality were observed in the various treated groups when compared with the control group. This increment was concentration dependent, while the extract at the highest concentration showed a more pronounced effect than the standard drug. Also, no sperm DNA fragmentation index was found in all the treatment groups. Photomicrographs from light and scanning electron microscopy showed large fenestrae of interstitial tissue, large fluid space and intact seminiferous epithelium layers fully packed with spermatogenic cells in treated groups than the control group. Conclusions The present study has demonstrated that Tetracarpidium conophorum leaf possesses fertility-enhancing property and have useful effects on spermatogenesis and sperm parameters in rats.


Side-Channel Sensing: Exploiting Side-Channels to Extract Information for Medical Diagnostics and Monitoring.
Information within systems can be extracted through side-channels; unintended communication channels that leak information. The concept of side-channel sensing is explored, in which sensor data is analysed in non-trivial ways to recover subtle, hidden or unexpected information. Practical examples of side-channel sensing are well known in domains such as cybersecurity (CYB), but are not formally recognised within the domain of medical diagnostics and monitoring (MDM). This article reviews side-channel usage within CYB and MDM, identifying techniques and methodologies applicable to both domains. We establish a systematic structure for the use of side-channel sensing in MDM that is comparable to existing structures in CYB, and promote cross-domain transferability of knowledge, mindsets, and techniques.


Pediatric nephrolithiasis: does treatment affect renal growth?
The long-term effects of shock wave lithotripsy on the growth of pediatric kidneys are not well defined. Likewise, no long-term data regarding renal growth after ureteroscopy or percutaneous nephrolithotomy have been published. We studied the effect of urolithiasis on renal growth in our pediatric patient population. A total of 165 children were treated for urolithiasis at St. Louis Children's Hospital from March 1993 to December 2003. Of these 165 children, 74 were available for long-term follow-up. Four groups were evaluated: those who underwent shock wave lithotripsy, ureteroscopy, or percutaneous nephrolithotomy, and those who received no intervention. The expected renal length was calculated using Chen's nomogram, and the observed renal length was measured using renal ultrasonography. All measurements were performed by one pediatric radiologist. The expected and observed renal growth was determined by subtracting the renal length at baseline from the length at follow-up, divided by the number of months of follow-up. Statistical analysis used paired data for each treatment group, and comparisons were made on a nonparametric single-rank method. Of the 74 children, 39 were boys and 35 were girls, with a mean age at treatment of 9 years (range 9 months to 14 years) and a mean follow-up of 6.2 years (range 1.3 to 13.1). In all groups, the comparison between the treated side and nontreated side for expected and actual kidney size and growth was calculated as described. None of the groups had statistically significant differences in the observed or predicted renal growth rates. Shock wave lithotripsy, ureteroscopic stone extraction, and percutaneous nephrolithotomy do not appear to impair renal growth.


Pediatric plastic bronchitis: case report and retrospective comparative analysis of epidemiology and pathology.
Plastic bronchitis (PB) is a pathologic condition in which airway casts develop in the tracheobronchial tree causing airway obstruction. There is no standard treatment strategy for this uncommon condition. We report an index patient treated using an emerging multimodal strategy of directly instilled and inhaled tissue plasminogen activator (t-PA) as well as 13 other cases of PB at our institution between 2000 and 2012. The majority of cases (n = 8) occurred in patients with congenital heart disease. Clinical presentations, treatments used, histopathology of the casts, and patient outcomes are reviewed. Further discussion is focused on the epidemiology of plastic bronchitis and a systematic approach to the histologic classification of casts. Comorbid conditions identified in this study included congenital heart disease (8), pneumonia (3), and asthma (2). Our institutional prevalence rate was 6.8 per 100,000 patients, and our case fatality rate was 7%.


An individual differences analysis of memory control.
Performance on a wide variety of memory tasks can be hypothesized to be influenced by processes associated with controlling the contents of memory. In this project 328 adults ranging from 18 to 93 years of age performed six tasks (e.g., multiple trial recall with an interpolated interference list, directed forgetting, proactive interference, and retrieval inhibition) postulated to yield measures of the effectiveness of memory control. Although most of the patterns from earlier studies were replicated, only a few of the measures of memory control were reliable at the level of individual differences. Furthermore, the memory control measures had very weak relations with the age of the participant. Analyses examining the relations between established cognitive abilities and variables from the experimental tasks revealed that most of the variables were related only to episodic memory ability.


Novel multiple phosphorescence in nanostructured zinc oxide and calculations of correlated colour temperature.
The design and development of novel and high quantum efficiency luminescent materials, such as phosphors, having tuneability in properties, have received tremendous interest among scientists. In this paper, we have achieved for the first-time multiple phosphorescence (blue and green) having a life-time of ∼10 μs in nanostructured zinc oxide that was synthesized using an easy and facile sol-gel method. Importantly, the photoluminescence (PL) intensity and the phosphorescence life-time could be tuned by controlling the annealing temperature under a reducing atmosphere. Temperature and atmosphere dependent variation of [VO] and has been interpreted by the detailed thermodynamic analysis of defect chemistry, for the first time. These nanostructured zinc oxide particles being sufficiently large in size (around 160 nm) are extremely stable and expected to show photoluminescence for a longer period of time than nanorods and quantum dots. The quantum yield was found to be as high as 13-15% which is comparable to the order of magnitude of that of quantum dots. The calculated correlated colour temperature is found to be suitable for cool lighting applications.


Pathomechanisms and the diagnosis of arterial hypertension in pediatric renal allograft recipients.
Arterial hypertension is common in pediatric renal allograft recipients. While the causes are multifactorial, including chronic graft rejection, immunosuppressive therapy, and renal vascular disorders, the effect of hypertension on renal allograft function is detrimental. As in adults, if not treated early and aggressively, hypertension may lead to cardiovascular damage and graft failure. Pathophysiological changes in the arteries and kidney af-ter renal transplantation and the impact of receptor regulation have not been studied extensively in children. For identifying children with hypertension following renal transplantation casual blood pressure measurements do not accurately reflect average arterial blood pressure and circadian blood pressure rhythm. Ambulatory 24-h blood pressure monitoring should regularly be applied in trans-plant patients. The purpose of this review is to analyze pathophysiological aspects of risk factors for arterial hypertension and underline the importance of regular blood pressure monitoring and early therapeutic intervention.


Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes.
Previous reports have indicated that Helicobacter pylori heat-shock protein 60 (H. pylori-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which H. pylori-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which H. pylori-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact H. pylori, heat-killed H. pylori and H. pylori recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-kappaB (NF-kappaB)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-kappaB activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in H. pylori-HSP60-induced IL-8 secretion.


Urolithiasis, Urinary Cancer, and Home Drinking Water Source in the United States Territory of Guam, 2006-2010.
We reviewed patient records with a first-listed diagnosis of urolithiasis-also known as urinary tract or kidney stone disease, nephrolithiasis-upon discharge from Guam's sole civilian hospital during 2006 to 2010 and urinary cancer mortality records from the Guam Cancer Registry for 1970 to 2009 to determine the source of municipal water supplied to the patients' residence. The objective was to investigate a possible relationship between the sources of municipal water supplied to Guam villages and the incidence of urolithiasis and urinary cancer. We analyzed hospital discharge diagnoses of urolithiasis or renal calculi by calculating the incidence of first-mentioned discharge for urolithiasis or renal calculi and comparing rates across demographic or geographic categories while adjusting by age, sex, and ethnicity/race. We reviewed cancer registry records of urinary cancer deaths by patient residence. The annual incidence of hospitalization for urolithiasis was 5.22 per 10,000. Rates adjusted for sex or age exhibited almost no change. The rate of 9.83 per 10,000 among Chamorros was significantly higher (p < 0.05) than the rates among any other ethnic group or race. When villages were grouped by water source, rates of patients discharged with a first-listed diagnosis of urolithiasis, adjusted for ethnicity/race, were similar for villages using either well water (5.44 per 10,000) or mixed source water (5.39 per 10,000), and significantly greater than the rate for villages using exclusively reservoir water (1.35 per 10,000). No statistically significant differences were found between the water source or village of residence and urinary cancer mortality. Some Guam residents living in villages served completely or partly by deep well water high in calcium carbonate may be at increased risk for urolithiasis compared with residents living in villages served by surface waters. Although the risk appears to be highest in villagers of Chamorro ethnicity, residents should be aware of other contributing risk factors and steps to take to avoid developing this health problem.


Morphine: new aspects in the study of an ancient compound.
Morphine is the most widely used compound among narcotic analgesics and remains the gold standard when the effects of other analgetic drugs are compared. Apart from its presence in the poppy plant Papaver somniferum, morphine has been shown to be present in milk, cerebrospinal fluid and also in nervous tissue extracts. Recent evidence suggests that biosynthetic pathways for morphine exist in animal and even human tissues such as liver, blood and brain. The most characteristic effect of morphine is the modulation of pain perception resulting in an increase in the threshold of noxious stimuli. Antinociception induced by morphine is mediated via opioid receptors and therefore can be inhibited by opioid antagonists, e.g., naloxone. Nevertheless, consideration of morphine as endogenous ligand for opioid receptors seems to be speculative. Recently, the primary receptor for morphine-type drugs called the mu-opioid receptor has been cloned from rat brain. There is accumulating evidence that morphine actions are, at least partly, due to one of its major metabolite morphine-6-glucuronide in man. It is concluded that further investigations are necessary to elucidate the mechanisms, whereby multiple actions of morphine are expressed in the nervous system.


Sulfate availability drives divergent evolution of arsenic speciation during microbially mediated reductive transformation of schwertmannite.
The effect of SO4(2-) availability on the microbially mediated reductive transformation of As(V)-coprecipitated schwertmannite (Fe8O8(OH)3.2(SO4)2.4(AsO4)0.004) was examined in long-term (up to 400 days) incubation experiments. Iron EXAFS spectroscopy showed siderite (FeCO3) and mackinawite (FeS) were the dominant secondary Fe(II) minerals produced via reductive schwertmannite transformation. In addition, ∼ 25% to ∼ 65% of the initial schwertmannite was also transformed relatively rapidly to goethite (αFeOOH), with the extent of this transformation being dependent on SO4(2-) concentrations. More specifically, the presence of high SO4(2-) concentrations acted to stabilize schwertmannite, retarding its transformation to goethite and allowing its partial persistence over the 400 day experiment duration. Elevated SO4(2-) also decreased the extent of dissimilatory reduction of Fe(III) and As(V), instead favoring dissimilatory SO4(2-) reduction. In contrast, where SO4(2-) was less available, there was near-complete reduction of schwertmannite- and goethite-derived Fe(III) as well as solid-phase As(V). As a result, under low SO4(2-) conditions, almost no Fe(III) or As(V) remained toward the end of the experiment and arsenic solid-phase partitioning was controlled mainly by sorptive interactions between As(III) and mackinawite. These As(III)-mackinawite interactions led to the formation of an orpiment (As2S3)-like species. Interestingly, this orpiment-like arsenic species did not form under SO4(2-)-rich conditions, despite the prevalence of dissimilatory SO4(2-) reduction. The absence of an arsenic sulfide species under SO4(2-)-rich conditions appears to have been a consequence of schwertmannite persistence, combined with the preferential retention of arsenic oxyanions by schwertmannite. The results highlight the critical role that SO4(2-) availability can play in controlling solid-phase arsenic speciation, particularly arsenic-sulfur interactions, under reducing conditions in soils, sediments, and shallow groundwater systems.


Environment-adjusted total-factor energy efficiency of Taiwan's service sectors.
This study computes the pure technical efficiency (PTE) and energy-saving target of Taiwan's service sectors during 2001-2008 by using the input-oriented data envelopment analysis (DEA) approach with the assumption of a variable returns-to-scale (VRS) situation. This paper further investigates the effects of industry characteristics on the energy-saving target by applying the four-stage DEA proposed by Fried et al. (1999). We also calculate the pre-adjusted and environment-adjusted total-factor energy efficiency (TFEE) scores in these service sectors. There are three inputs (labor, capital stock, and energy consumption) and a single output (real GDP) in the DEA model. The most energy efficient service sector is finance, insurance and real estate, which has an average TFEE of 0.994 and an environment-adjusted TFEE (EATFEE) of 0.807. The study utilizes the panel-data, random-effects Tobit regression model with the energy-saving target (EST) as the dependent variable. Those service industries with a larger GDP output have greater excess use of energy. The capital-labor ratio has a significantly positive effect while the time trend variable has a significantly negative impact on the EST, suggesting that future new capital investment should also be accompanied with energy-saving technology in the service sectors.


Smoking and finances: baseline characteristics of low income daily smokers in the FISCALS cohort.
Financial stress is a barrier to successful smoking cessation and a key predictor of relapse. Little is known about the financial situation of low-income Australian daily smokers. This study aims to describe and investigate associations between the financial functioning, tobacco use and quitting behaviours of low income daily smokers. Low-income Australian adult smokers in the 'Financial Intervention for Smoking Cessation Among Low-income Smokers (FISCALS) randomised clinical trial completed a structured telephone questionnaire. The median number of cigarettes typically smoked by the 1047 participants was 23 per day. The median spent on tobacco per week was AU$80. Three quarters (73.0%) reported some financial stress and 43.2% reported smoking-induced deprivation. Financial stress was significantly associated with deprivation (IRR: 1.23, 95% CI 1.21, 1.26, p < 0.001). There were no significant associations either between adjusted financial stress or deprivation and motivation to quit or certainty of quit success. Financial stress and smoking induced deprivation were prevalent among low-income daily smokers, but they were not associated with motivation to quit. Smoking cessation interventions need to be responsive to the role financial stress plays in reducing quit attempts and increasing relapse. Australian and New Zealand Clinical trials Registry ACTRN12612000725864 6/07/2012.


Non-invasive cerebral perfusion pressure (nCPP): evaluation of the monitoring methodology in head injured patients.
The method of direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number, which not always adequately expresses brain perfusion. We investigated an alternative non-invasive method, based on waveform analysis of Transcranial Doppler blood flow velocity in Middle Cerebral Arteries (MCA). 25 consecutive head injured patients, paralysed, sedated and ventilated were studied. Intracranial pressure (ICP) arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (116 measurements) using a purpose-built transcranial Doppler monitor (Deltex Ltd, Chichester, U.K.) with software capable of the non-invasive estimation of CPP. Time averaged values of ABP, mean and diastolic flow velocities (FVm, FVd) were calculated and CPPe was computed as: ABP*FVd/FVm + 14. An absolute difference between real CPP and CPPe was less than 10 mm Hg in 82% of measurements and less than 13 mm Hg in 90% of measurements. The method demonstrated a high potential to detect both short-term and long-term changes in CPP. The method is of potential benefit for the intermittent measurement and continuous monitoring of changes in brain perfusion pressure in situations where the direct measurement of CPP is not available or its reliability is in question.