Association of Number of Indoor Tanning Salons With Neighborhoods With Higher Concentrations of Male-Male Partnered Households.
Both indoor tanning and skin cancer are more common among sexual-minority men, defined as gay and bisexual men, than among heterosexual men. Convenient access to indoor tanning salons may influence use patterns. To investigate whether indoor tanning salons are disproportionately located in areas with higher concentrations of gay men. This cross-sectional study used geographic information systems to integrate census data and business location data obtained from ArcGIS and Google Maps for the 10 US cities with the largest lesbian, gay, bisexual, and transgender populations in 2010, ie, Los Angeles, California; Chicago, Illinois; San Francisco, California; Seattle, Washington; San Diego, California; Dallas, Texas; Phoenix, Arizona; Washington, DC; Portland, Oregon; and Denver, Colorado. The association of indoor tanning salon locations with proportions of gay men, using the concentration of male-male partnered households as a proxy measure for the latter, was examined. Data analysis was performed in October 2018. Census tracts with at least 1%, 5%, or 10% male-male partnered households, adjusting for median household income, percentage young women, and percentage non-Hispanic white residents. Presence of 1 or more indoor tanning salons within census tracts. Across the 10 cities and 4091 census tracts in this study, there were 482 823 unmarried partnered households, of which 35 164 (7.3%) were male-male. The median (interquartile range) percentage of male-male partnered households per census tract was 0% (0%-10.6%). Odds of indoor tanning salon presence in areas with at least 10% male-male households were more than twice those of areas with less than 10% male-male households (odds ratio, 2.17; 95% CI, 1.59-2.97). When sensitivity analyses using a 1-mile euclidian buffer around each tanning salon were conducted, this association remained significant (odds ratio, 2.48; 95% CI, 2.14-2.88). After adjusting for median household income, percentage young women, and percentage non-Hispanic white residents, the odds of an indoor tanning salon being within 1 mile of a census tract with at least 10% male-male households remained twice that of census tracts with less than 10% male-male households (odds ratio, 2.00; 95% CI, 1.71-2.35). In this study, indoor tanning salons were more likely to be located near neighborhoods with higher concentrations of male-male partnered households, possibly contributing to the disproportionate use of indoor tanning by sexual-minority men.


Introduction to grayscale calibration and related aspects of medical imaging grade liquid crystal displays.
Consistent presentation of digital radiographic images at all locations within a medical center can help ensure a high level of patient care. Currently, liquid crystal displays (LCDs) are the electronic display technology of choice for viewing medical images. As the inherent luminance (and thereby perceived contrast) properties of different LCDs can vary substantially, calibration of the luminance response of these displays is required to ensure that observer perception of an image is consistent on all displays. The digital imaging and communication in medicine (DICOM) grayscale standard display function (GSDF) defines the luminance response of a display such that an observer's perception of image contrast is consistent throughout the pixel value range of a displayed image. The main purpose of this work is to review the theoretical and practical aspects of calibration of LCDs to the GSDF. Included herein is a review of LCD technology, principles of calibration, and other practical aspects related to calibration and observer perception of images presented on LCDs. Both grayscale and color displays are considered, and the influence of ambient light on calibration and perception is discussed.


Survey of organizational research climates in three research intensive, doctoral granting universities.
The Survey of Organizational Research Climate (SOuRCe) is a new instrument that assesses dimensions of research integrity climate, including ethical leadership, socialization and communication processes, and policies, procedures, structures, and processes to address risks to research integrity. We present a descriptive analysis to characterize differences on the SOuRCe scales across departments, fields of study, and status categories (faculty, postdoctoral scholars, and graduate students) for 11,455 respondents from three research-intensive universities. Among the seven SOuRCe scales, variance explained by status and fields of study ranged from 7.6% (Advisor-Advisee Relations) to 16.2% (Integrity Norms). Department accounted for greater than 50% of the variance explained for each of the SOuRCe scales, ranging from 52.6% (Regulatory Quality) to 80.3% (Integrity Inhibitors). It is feasible to implement this instrument in large university settings across a broad range of fields, department types, and individual roles within academic units. Published baseline results provide initial data for institutions using the SOuRCe who wish to compare their own research integrity climates.


Texture segmentation using Gaussian-Markov random fields and neural oscillator networks.
We propose an image segmentation method based on texture analysis. Our method is composed of two parts. The first part determines a novel set of texture features derived from a Gaussian-Markov random fields (GMRF) model. Unlike a GMRF-based approach, our method does not employ model parameters as features or require the extraction of features for a fixed set of texture types a priori. The second part is a 2D array of locally excitatory globally inhibitory oscillator networks (LEGION). After being filtered for noise suppression, features are used to determine the local couplings in the network. When LEGION runs, the oscillators corresponding to the same texture tend to synchronize, whereas different texture regions tend to correspond to distinct phases. In simulations, a large system of differential equations is solved for the first time using a recently proposed method for integrating relaxation oscillator networks. We provide results on real texture images to demonstrate the performance of our method.


[Validity and reliability of the Spanish version of Yale-Brown obsessive-compulsive rating scale for children and adolescents].
The Children Yale-Brown Obsessive- Compulsive Scale (CY-BOCS) constitutes a very good instrument for the evaluation of obsessive-compulsive disorder (OCD) symptoms, by a clinical interview administered to the patient and parent, that includes summary score of the clinician. We are proposing a Spanish version of instrument, which is rated during a brief clinical interview to the parents and the patients. We are presenting data reliability and validity using two out-patient samples. After the translation to Spanish, a back translation and adaptation to Spanish of the CY-BOCS, twenty eight out-patients (75 % male) with a mean age 12.1 (+/- 2.7) from two clinical settings on Mexico City evaluated. Reliability was evaluated by computing the internal consistency (Cronbach's alpha) on all interviews. assess interrater agreement, the interviews were videotaped and scored by three independent raters and all of them included both the child and the parent interview. The CY-BOCS total scored was correlated with the K-SADS-PL diagnosis. The CY-BOCS total score for all subjects was 16.5 +/- 9.8. Cronbach's alpha coefficient was 0.87; Pearson correlation of total CY-BOCS score with the K-SADS-PL diagnosis was 0.60 (p < or = 0.05). The intraclass correlations coefficients for the parents, youngsters and clinician 0.96, 0.94 and 0.92, respectively. The Spanish version of the CY-BOCS reliable and valid instrument, useful for both clinicians and researchers in child and adolescent OCD assessment.


Dexamethasone fails to suppress hyperendorphinaemia of obese children.
In order to evaluate the origin of hyperendorphinaemia in obese patients, plasma B-endorphin (B-EP), B-lipotropin (B-LPH) and cortisol levels were measured in basal conditions and after overnight treatment with 1 mg of dexamethasone. Thirteen obese children (weight excess ranging from 44 to 100%) and 10 normal weight controls were studied. Weight gain started in prepuberty and could not be explained by concurrent diseases. Hormone levels were measured by RIA, either directly in the plasma (cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-EP and B-LPH). Basal B-EP levels in the obese children (19.4 +/- 4.9 pmol/l, mean +/- SEM) were significantly higher than in the controls (7.8 +/- 1.2, P less than 0.01), whereas B-LPH and cortisol was within normal range. In the controls, post-dexamethasone morning and afternoon hormone levels were significantly suppressed. In the obese children, B-EP concentrations remained unaffected by the treatment (14.6 +/- 5.3 and 14.9 +/- 5.2 at 08.00 and 16.00 h, respectively), whereas both B-LPH and cortisol values were significantly decreased. These data demonstrate that a short-term dexamethasone treatment is unable to correct the increased B-EP levels which characterize obese children, whereas it is effective on B-LPH and cortisol concentrations. It can be concluded that circulating B-EP in this condition loses the control of CRH. However, the origin of hyperendorphinaemia in obese patients still remains to be investigated.


Do associations between education and obesity vary depending on the measure of obesity used? A systematic literature review and meta-analysis.
Consistent evidence suggests a relationship between lower educational attainment and total obesity defined using body mass index (BMI); however, a comparison of the relationships between educational attainment and total obesity (BMI ≥30 kg/m2) and central obesity (waist circumference (WC) > 102 cm for men and WC > 88 cm for women) has yet to be carried out. This systematic literature review (SLR) and meta-analyses aimed to understand whether i) the associations between education and obesity are different depending on the measures of obesity used (BMI and WC), and ii) to explore whether these relationships differ by gender and region. Medline, Embase and Web of Science were searched to identify studies investigating the associations between education and total and central obesity among adults in the general population of countries in the Organisation for Economic Co-operation and Development (OECD). Meta-analyses and meta-regression were performed in a subset of comparable studies (n=36 studies; 724,992 participants). 86 eligible studies (78 cross-sectional and eight longitudinal) were identified. Among women, most studies reported an association between a lower education and total and central obesity. Among men, there was a weaker association between lower education and central than total obesity (OR central vs total obesity in men 0.79 (95% CI 0.60, 1.03)). The association between lower education and obesity was stronger in women compared with men (OR women vs men 1.66 (95% CI 1.32, 2.08)). The relationship between lower education and obesity was less strong in women from Northern than Southern Europe (OR Northern vs Southern Europe in women 0.37 (95% CI 0.27, 0.51)), but not among men. Associations between education and obesity differ depending on whether total or central obesity is used among men, but not in women. These associations are stronger among women than men, particularly in Southern European countries.


The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction.
Pathologic cutaneous scarring affects over 40 million people worldwide and costs billions of dollars annually. Understanding mechanisms of fibroblast activation and granulation tissue contraction is the first step toward preventing pathologic scarring. The authors hypothesize that nucleic acids increase fibroblast activation and cause granulation tissue contraction and that sequestration of nucleic acids by application of a nucleic acid scavenger dendrimer, polyamidoamine third-generation dendrimer, will decrease pathologic scarring. In vitro experiments were performed to assess the effect of nucleic acids on pathologic scar-associated fibroblast activity. The effect of nucleic acids on cytokine production and migration on mouse fibroblasts was evaluated. Immunofluorescence microscopy was used to determine the effect of nucleic acids on the differentiation of human primary fibroblasts into myofibroblasts. Using a murine model, the effect of polyamidoamine third-generation dendrimer on granulation tissue contraction was evaluated by gross and histologic parameters. Mouse fibroblasts stimulated with nucleic acids had increased cytokine production (i.e., transforming growth factor-β, monocyte chemotactic protein 1, interleukin-10, tumor necrosis factor-α, and interferon-γ), migration, and differentiation into myofibroblasts. Polyamidoamine third-generation dendrimer blocked cytokine production, migration, and differentiation into myofibroblasts. Using a murine model of granulation tissue contraction, polyamidoamine third-generation dendrimer decreased wound contraction and angiogenesis. Collagen deposition in polyamidoamine third-generation dendrimer-treated tissues was aligned more randomly and whorl-like compared with control tissue. The data demonstrate that nucleic acid-stimulated fibroblast activation and granulation tissue contraction are blocked by polyamidoamine third-generation dendrimer. Sequestration of pathogen-associated molecular patterns may be an approach for preventing pathologic scarring.


Prenatal Zika virus exposure is associated with lateral geniculate nucleus abnormalities in juvenile rhesus macaques.
Zika virus' neural tropism causes significant neural pathology, particularly in developing fetuses. One of the consistent findings from humans and animal models is that prenatal exposure to Zika virus (ZIKV) causes pathology in the eyes and visual pathways of the brain, although the extent to which this pathology persists over development is not clear. In the present report, we build upon our previous work which demonstrated that full-term rhesus monkey ( Macaca mulatta ) fetuses who were exposed to ZIKV early in gestation had significant pathological abnormalities to the organization of the lateral geniculate nucleus (LGN), a major hub of the visual network. The objective of the present work was to replicate those LGN findings and determine whether such pathology persisted across childhood development. We carried out histological analyses of the LGNs of two juvenile rhesus monkeys who were prenatally exposed to ZIKV and two age-matched controls. Pregnant rhesus monkeys were infected with ZIKV via the intravenous and intra-amniotic routes and tracked across development. Following sacrifice and perfusion, brains were subjected to quantitative neuroanatomical analyses with a focus on the size and structure of the LGN and its composite layers. Early fetal ZIKV exposure resulted in developmental abnormalities within the brains' visual pathway: specifically disorganization, blending of layers, laminar discontinuities, and regions of low cell density within the LGN. These abnormalities were not observed in the control animals. Our findings demonstrate that the ZIKV's damage to the LGN that occurs during fetal development persists into childhood.


Evolutionary implications of the relationship between genome size and body size in flatworms and copepods.
Genome and body sizes were measured in 38 species of turbellarian flatworms and 16 species of copepod crustaceans. Significant positive relationships existed between genome size and body size in both groups. The slopes of these regressions indicated that increases in cell volume are reinforced by increased cell numbers, or that cell volumes show positive allometric variation with genome size. Genome sizes appear to vary in a discontinuous fashion among congeneric species in both groups, indicating that such changes have occurred rapidly, and with potentially profound effects on important morphological characters.


Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial.
It is essential to optimize standard colonoscopy technique to be able to increase polyp detection. We sought to compare the performance of colonoscopy using a high-definition, wide-angle endoscope (HDE) versus a standard colonoscope (SC) for the detection of colorectal neoplasia. All consecutive consenting adult patients referred from primary care centers were included and randomly assigned at a 1:1 ratio to undergo HDE or SC. Times to reach and withdraw from the cecum were measured. Morphology, size, location, and pathologic diagnosis of each polyp were recorded. Sample size calculation resulted in a total of 682 patients needed. A total of 693 consecutive patients fulfilled all inclusion criteria (73 excluded owing to insufficient bowel preparation). Each arm included 310 patients with no baseline characteristic differences. Time to reach the cecum was slightly superior for SC (8.9 +/- 4.8 minutes vs 8.2 +/- 4.5 minutes; P = .055). Pathology examination was feasible in 418 lesions (272 adenomas, 109 hyperplastic polyps, and 37 inflammatory lesions). Both techniques detected a similar number and type of lesions, and there were no differences in the distribution along the colon, in the degree of dysplasia, or morphology of adenomas. The per-patient basis analyses demonstrated that there were no differences between the 2 arms of the study in the detection rates of polyps (SC, 0.84 +/- 1.59; HDE, 0.83 +/- 1.30), adenomas (0.45 +/- 1.07 vs 0.43 +/- 0.87), small adenomas (0.22 +/- 0.71 vs 0.28 +/- 0.78), flat adenomas (0.30 +/- 0.91 vs 0.21 +/- 0.63), or hyperplastic polyps (0.16 +/- 0.50 vs 0.18 +/- 0.54). HDE did not detect significantly more colorectal neoplasia than SC.


Elevated CO2 affects shell dissolution rate but not calcification rate in a marine snail.
As CO(2) levels increase in the atmosphere, so too do they in the sea. Although direct effects of moderately elevated CO(2) in sea water may be of little consequence, indirect effects may be profound. For example, lowered pH and calcium carbonate saturation states may influence both deposition and dissolution rates of mineralized skeletons in many marine organisms. The relative impact of elevated CO(2) on deposition and dissolution rates are not known for many large-bodied organisms. We therefore tested the effects of increased CO(2) levels--those forecast to occur in roughly 100 and 200 years--on both shell deposition rate and shell dissolution rate in a rocky intertidal snail, Nucella lamellosa. Shell weight gain per day in live snails decreased linearly with increasing CO(2) levels. However, this trend was paralleled by shell weight loss per day in empty shells, suggesting that these declines in shell weight gain observed in live snails were due to increased dissolution of existing shell material, rather than reduced production of new shell material. Ocean acidification may therefore have a greater effect on shell dissolution than on shell deposition, at least in temperate marine molluscs.


[Grief stages and responses of bereaved mother who lost her children with cancer].
This study was done to develop a bereaved family care program by identifying characteristics of a grief healing process in a child loss. The subjects were five bereaved mothers who have lost their children with cancer. Data was collected with in-depth interviews using grief phase assessment tool and grief reaction assessment tool from 1, February, 2001 to 31 August, 2002. Data was analyzed on the basis of two tools. Process of grief in general was as follows: evading phase was within one week - one month, confrontation phase was 5 - 12 months, and reconciliation phase was after 9 months and still going on when the study was finished. Grief reaction in five (physical, cognitive, emotional, social, and spiritual) dimensions was stabilized when the phase moved into reconciliation phase. Influencing factors were intimacy and expectation towards child, social support, personality, prior loss experience, coping style, religion, culture, family cohesion, openness of communication, and stress events. These results suggest that a bereaved family care program considering characteristics of Korean culture should be developed and activated.


Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy.
To date, immunotherapeutic approaches in glioblastoma (GBM) have had limited clinical efficacy as compared to other solid tumors. Here we explore autologous cell treatments that have the potential to circumvent treatment resistance to immunotherapy for GBM. We performed literature review and assessed clinical outcomes in phase 1 safety trials as well as phase 2 and 3 autologously-derived vaccines for the treatment of newly-diagnosed GBM. In one recent review of over 3,000 neuro-oncology phase 2 and phase 3 clinical trials, most trials were nonblinded (92%), single group (65%), nonrandomized (51%) and almost half were GBM trials. Only 10% involved a biologic and only 2.2% involved a double-blind randomized trial design. With this comparative literature review we conclude that our autologous cell product is uniquely antigen-inclusive and antigen-agnostic with a promising safety profile as well as unexpected clinical efficacy in our published phase 1b trial. We have since designed a rigorous double-blinded add-on placebo-controlled trial involving our implantable biologic drug device. We conclude that IGV-001 provides a novel immunotherapy platform for historically intransigent ndGBM in this ongoing phase 2b trial (NCT04485949).


Impact of extraneous proteins on the gastrointestinal fate of sunflower seed (Helianthus annuus) oil bodies: a simulated gastrointestinal tract study.
In this study, we examined the physicochemical nature of sunflower seed oil bodies (in the absence and presence of added protein) exposed to gastrointestinal conditions in vitro: crude oil bodies (COB); washed oil bodies (WOB); whey protein isolate-enriched oil bodies (WOB-WPI); and, sodium caseinate enriched-oil bodies (WOB-SC). All oil body emulsions were passed through an in vitro digestion model that mimicked the stomach and duodenal environments, and their physicochemical properties were measured before, during, and after digestion. Oil bodies had a positive charge under gastric conditions because the pH was below the isoelectric point of the adsorbed protein layer, but they had a negative charge under duodenal conditions which was attributed to changes in interfacial composition resulting from adsorption of bile salts. Oil bodies were highly susceptible to flocculation and coalescence in both gastric and duodenal conditions. SDS-PAGE analysis indicated degradation of oleosin proteins (ca. 18-21 kDa) to a greater or lesser extent (dependent on the emulsion) during the gastric phase in all emulsions tested; there is evidence that some oleosin remained intact in the crude oil body preparation during this phase of the digestion process. Measurements of protein displacement from the surface of COBs during direct exposure to bile salts, without inclusion of a gastric phase, indicated the removal of intact oleosin from native oil bodies.


Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer. A prospective, randomized trial.
To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy. Randomized trial with a median follow-up of 57 months. A single government institution--the National Cancer Institute. Consecutive sample of 96 patients with histologically confirmed small cell lung cancer that was confined to the hemithorax of origin or mediastinal and supraclavicular nodes, and which could be encompassed within a tolerable radiation portal ("limited stage"). All patients were followed until death or the end of the study period. Chemotherapy: Cyclophosphamide, methotrexate, and lomustine in 6-week cycles alternating with vincristine, adriamycin, and procarbazine in 6-week cycles, for a total of 48 weeks. Radiation therapy: Chest irradiation to 40 Gy in 15 fractions over 3 weeks, given simultaneously with the first chemotherapy cycle. The combined therapy led to a significantly higher response rate (complete responses, 81%, compared with partial responses, 43%; 95% Cl for the difference, 20% to 56%), significantly improved local control of the chest tumor (p less than 0.001), and significantly longer survival (p less than 0.035) (median, 15.0 months, compared with 11.6 for chemotherapy alone). The combined therapy produced significantly more myelosuppression, weight loss, esophagitis, and pulmonary dysfunction. There were more infections and deaths from toxicity in the combined treatment group, but the differences between groups were not statistically significant. A regimen of combined chemotherapy and chest radiation therapy given concurrently is superior to chemotherapy given alone in inducing remission and prolonging survival in patients with limited stage small cell lung cancer, and the benefit of combined therapy is reduced by its greater toxicity.


The immune system. Part II, Intravenous administration of immune globulin.
Part I of this article, published in the September/October 1991 issue of the Journal of Intravenous Nursing, reviews normal immune function, immune disorders, and diagnosis. The main treatment modality discussed in Part II is therapy with immune globulin IgG. History, indications, administration technique, and nursing care are highlighted.


Humanistic qualities in end-of-life care: lessons from the diving bell and the butterfly: a memoir of life in death-required reading in an end-of-life care curriculum for internal medicine residents.
Reading a literary account of a terminal illness to develop humanistic qualities and attitudes for effective end-of-life care. The Diving Bell and the Butterfly: A Memoir of Life in Death by Jean-Dominique Bauby is an autobiographical account of Mr. Bauby's experiences in the locked-in state after he suffered a brain stem stroke at age 43. Each resident was given a copy of this paperback to read over 4 weeks. Interns (PGY-1) were on a 4-week oncology ward rotation, and all junior and senior residents (PGY-2 and PGY-3) were on elective rotations during this period. Residents were instructed to mark their favorite passages of the book, to be prepared to read aloud such passages in small-group sessions, and to explain why they chose the specific passage. Attendance was mandatory, and residents were asked to complete a questionnaire at the end of the small-group discussion. Eighteen PGY-ls and 30 PGY-2/3s completed the curriculum. Seventeen of 18 PGY-ls read the entire book, and all 30 PGY-2/3s read the book from cover to cover. Only 3 of 18 PGY-1 residents felt that the task of reading this book interfered with their work. More than 90% of the residents felt that reading the book clearly improved their attitudes toward the care of the terminally ill patient. Lessons learned from the book included all the humanistic qualities important in caring for the terminally ill and severely disabled. Well-chosen narratives of literature can be a powerful tool to learn attitudes and humanistic qualities in the care of the terminally ill.


Stage-specific transcription of germline IgH C gamma and C alpha regions during human B cell differentiation.
Previous studies have suggested that transcription of germline heavy chain constant region (CH) genes in murine B cells may determine the potential of their different CH regions to undergo isotype switch recombination. We have examined the transcriptional activity across the immunoglobulin heavy chain (IgH) locus in human B lineage cells. Transcription of germline C gamma and C alpha was observed in every surface IgM+ or surface IgM+/IgD+ B cell stage cell line and malignancy. In contrast, such transcription could not be detected in pre-B cells and only low levels of C alpha but not C gamma transcription were evident in IgM-secreting plasmablast cells. Transcriptional activity of germline IgH C epsilon was singularly absent at all stages of B cell development. Our results suggest that germline transcription of the C gamma and C alpha regions may be a constitutive feature of the human B cell differentiation program. Because this transcriptional activity is limited primarily to the B cell stage and occurs prior to the actual isotype switch, the induction of C gamma and C alpha transcription may represent preparation of the downstream IgH chromatin for potential switch recombination.


Chemical diversity and defence metabolism: how plants cope with pathogens and ozone pollution.
Chemical defences represent a main trait of the plant innate immune system. Besides regulating the relationship between plants and their ecosystems, phytochemicals are involved both in resistance against pathogens and in tolerance towards abiotic stresses, such as atmospheric pollution. Plant defence metabolites arise from the main secondary metabolic routes, the phenylpropanoid, the isoprenoid and the alkaloid pathways. In plants, antibiotic compounds can be both preformed (phytoanticipins) and inducible (phytoalexins), the former including saponins, cyanogenic glycosides and glucosinolates. Chronic exposure to tropospheric ozone (O(3)) stimulates the carbon fluxes from the primary to the secondary metabolic pathways to a great extent, inducing a shift of the available resources in favour of the synthesis of secondary products. In some cases, the plant defence responses against pathogens and environmental pollutants may overlap, leading to the unspecific synthesis of similar molecules, such as phenylpropanoids. Exposure to ozone can also modify the pattern of biogenic volatile organic compounds (BVOC), emitted from plant in response to herbivore feeding, thus altering the tritrophic interaction among plant, phytophagy and their natural enemies. Finally, the synthesis of ethylene and polyamines can be regulated by ozone at level of S-adenosylmethionine (SAM), the biosynthetic precursor of both classes of hormones, which can, therefore, mutually inhibit their own biosynthesis with consequence on plant phenotype.


Benzene metabolism in rodents at doses relevant to human exposure from urban air.
Benzene is both an environmental pollutant and a component of cigarette smoke, gasoline, and automotive emissions. Although occupational exposure to benzene has been shown to cause blood disorders and cancer in humans, the potential health effects resulting from exposure to low levels of benzene are not known. The goals of this project were to determine how well benzene is metabolized and to assess its binding to macromolecules in rodents at doses more closely mimicking human environmental exposure. To determine whether genotoxic metabolites of benzene are produced at environmental exposure levels. various doses of 14C-benzene were given intraperitoneally to male B6C3F1 mice at doses from 5 ng/kg to 500 mg/kg body weight. Samples of urine, plasma, liver, and bone marrow were taken at selected times up to 48 hours after exposure. Individual benzene metabolites in the samples were measured by accelerator mass spectrometry (AMS*). Metabolites were quantified by determining the area under the curve (AUC) for 24 to 48 hours. The major metabolites found in urine were an unidentified radiolabeled metabolite. phenyl sulfate, phenyl glucuronide. and muconic acid (an indicator of muconaldehyde formation). The major metabolites found in plasma, liver, and bone marrow samples were muconic acid and hydroquinone. Only liver showed a dose response for hydroquinone and muconic acid. The kinetics of both DNA and protein adduct formation were assessed over 48 hours at a 14C-benzene dose of 5 microg/kg body weight. A dose-response study was then conducted using 14C-benzene doses from 5 ng/kg to 500 mg/kg body weight in B6C3F1 mice. Adduct levels were determined by AMS in liver and bone marrow. DNA and protein adducts in liver reached maximum levels 30 minutes after benzene administration, whereas those in bone marrow reached maximum levels after six hours. Both protein and DNA adduct AUCs were greater in bone marrow than in liver. Dose-response assessments at both 1 and 12 hours showed that DNA and protein adducts in liver and bone marrow were dose dependent over doses spanning eight orders of magnitude. Consistent with the benzene metabolism data, these data show that reactive forms of benzene were present in liver and bone marrow after exposure to human-relevant benzene levels. Thus, at low doses, benzene was absorbed and metabolized into reactive intermediates capable of binding to DNA and protein. The relation between benzene metabolism and macromolecular binding was examined by comparing benzene macromolecular adduct formation among strains of male mice (B6C3F1, DBA/2, and C57BL/6) and male rats. These animals have been reported to have different metabolic capacities for benzene and also different tumorigenic and cytotoxic responses to benzene exposure. We hypothesized that differences in the capacity to metabolize benzene affect macromolecular adduct formation and that the amount of macromolecular damage is related to benzene's ability to cause cancer and other blood disorders. 14C-benzene was administered intraperitoneally to all rodents (5 microg/kg body weight) and adduct levels were determined by AMS at selected time points up to 48 hours after exposure. AUCs for protein and DNA adducts in bone marrow, the primary target organ for benzene toxicity, decreased in the following order: B6C3F1, DBA/2, C57BL/6, and rats. Similarly, adduct AUCs in liver were greater in B6C3F1 mice than in rats although the trend was less clear for the DBA/2 and C57BL/6 mouse strains. The results of this work are consistent with previously published work showing that the ability to metabolize benzene follows a similar pattern with these animals and is consistent with the tumorigenicity of benzene in mice and rats. Thus, our data suggest that benzene toxicity is related to the ability to produce macromolecular adducts. Preliminary studies were conducted to assess adduct dosimetry after low-dose inhalation of benzene. Inhalation methods were developed to administer a nominal body burden of 5 microg benzene/kg body weight. Then, 14C-benzene was administered to B6C3F1 mice and rats by both intraperitoneal (IP) administration and by inhalation, and DNA and protein adducts in liver and bone marrow were analyzed by AMS. AUCs for adduct levels were greater after IP benzene administration than after inhalation of benzene. Adduct levels were greater in DNA from B6C3F1 mouse bone marrow than in DNA from liver regardless of exposure route. Collectively, these data show that the internally reactive dose was greater when benzene exposure was by IP administration. In summary, the results suggest that benzene is metabolized to reactive forms capable of binding both protein and DNA in target and nontarget organs of rats and mice at doses encountered by humans through environmental exposure. Macromolecular binding was dose-dependent at low doses of benzene and reflected benzene toxicity, based on its carcinogenicity and ability to cause other blood-related disorders. These data are consistent with macromolecular adducts being indicative of benzene exposure and benzene toxicity although much more research is needed to validate this point. Additionally, benzene metabolism varies among species and among strains within a species of rodent. Thus data are needed in humans to understand how to use the rodent data in risk assessment and ultimately to determine whether macromolecular adducts are a useful indicator of exposure and a useful predictor of risk.


Large Retinectomies for Retinal Detachment Complicated by Proliferative Vitreoretinopathy: Anatomical and Functional Outcome of Silicone Oil versus Perfluoropropane Gas.
To assess the anatomic and functional outcomes of eyes undergoing vitrectomy and large retinectomy for the management of retinal detachment (RD) complicated by advanced proliferative vitreoretinopathy (PVR). A total of 66 eyes of 63 patients with RD complicated by PVR were treated with vitrectomy and 180° or more retinectomy and silicone oil (n=46) or perfluoropropane gas (n=20) were used as intraocular tamponades. Retinal reattachment was achieved in 89.39% (59 eyes) of the cases. The mean follow-up was 33.7 months (range 12-76 months). In gas-filled eyes, the final anatomic success rate was 85% (17 eyes) and in silicone oil-filled eyes was 91.3% (42 eyes) (p=0.46). After the initial retinectomy, the total anatomic success rate was 80.3% (53/66 eyes), 70% in gas-filled eyes (14/20 eyes) and 84.79% in silicone oil-filled eyes (39/46 eyes) (p=0.19). Visual acuity (VA) improved in 37 (56.06%) eyes, remained the same in 19 (28.78%) eyes and became worse in 10 (15.15%) cases. Best corrected VA was ≥20/200 in 22 eyes 33.33%. The final VA was associated with the preoperative VA (r=0.68), the preoperative status of the macula influence significantly the final visual acuity (p<0.0001) and there is statistically significant difference in the final visual acuity between eyes with and without anatomic success (p<0.05). The large circumferential retinectomies can be beneficial in eyes with RD complicated by advanced PVR. No significant difference was found in anatomic success rate, and rate of complications between eyes with silicone oil tamponade and long acting gas undergoing large retinectomy. Regarding the final BCVA, slight difference was found in favor of gas-filled eyes.


Blocked herpes simplex virus type 2-specific DNA synthesis in simian virus 40-transformed hamster cells permissive for herpes simplex virus type 1.
Simian virus 40-transformed hamster cells (LL-1) permissive to herpes simplex virus type 1 (HSV-1) were shown to be relatively nonpermissive to HSV-2. When LL-1 cells were infected with HSV-2, there was a 3- to 4-log reduction in infectious viral progeny at 24 h postinfection as compared with HSV-1 under identical cultured conditions. HSV-2 could be carried in the LL-1 cell line for up to 12 passages without any appreciable cytopathology. Various early functions of the replicative cycle of HSV-2 appeared to be normal. Experiments demonstrated that early enzyme activity, HSV-2 thymidine kinase, and DNA polymerase appeared at permissive levels in extracts of HSV-2-infected LL-1 cells. However, DNA analysis of HSV-2 infected LL-1 cells demonstrated a block in HSV-2-specific DNA synthesis, although HSV-2 was capable of inhibiting DNA synthesis in LL-1 cells. Furthermore, indirect immunofluorescence studies indicate that late HSV-2 structural protein synthesis was inhibited in infected LL-1 cells. Thus, the inability of HSV-2 to replicate in LL-1 cells is due to a block at or before HSV-specific DNA synthesis, resulting in a reduction of the structural protein synthesis required for viral maturation.


Home-based Palliative Intervention to Improve Quality of Life in Children with Cancer: A Randomized Controlled Trial.
Over the past few years, an integrated approach of palliative care (PC) to chronic and/or life-threatening conditions care has been widely used. Home-based PC (HBPC) service is developed to meet the needs of patients at home; however, it has not been used widely. This study is aimed at determining the benefits of integrated HBPC for the quality of life (QoL) and symptoms intensity in Indonesian children with malignancies. A randomized controlled trial was carried out to compare the quality of life between patients who were given PC (a three-month home visit) and those who did not receive PC (control group). Each group was constituted of thirty children with cancer and aged 2-18 years old and were consulted by a palliative team. The participants were randomly allocated to two groups. In the first and twelfth weeks of the intervention, all patients were assessed using the Pediatric Quality of Life Inventory (PedsQLTM) questionnaire cancer module 3.0 (report by proxy or self-report). Symptoms intensity (pain, anorexia, sleep disturbance) were scored by using Edmonton Symptoms Assessment Scale (ESAS). The mean score and each dimension score of both groups were compared and analyzed using bivariate analysis. In total, fifty participants were included in the study. A significant difference was found between the two groups in terms of the mean total score in control group 62.39 and intervention group 81.63 (p<0.001). The QoL was improved in the intervention group, while it was declined in the control group as the disease progressed. The main improvements were in the pain and nausea aspects (p<0.001), followed by procedural anxiety (p=0.002), treatment anxiety (p=0.002), and worry (p=0.014). Palliative intervention significantly reduced sleep disturbances (p=0.003) and anorexia (p<0.001). Home-based PC improved several aspects of QoL and caused better symptom management in children with malignancies. An early intervention concurrent with the underlying treatment can improve QoL in these children.


TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens.
Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase involved in key processes during mitosis. Human PLK1 has been shown to be overexpressed in various human cancers, and elevated levels of PLK1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. TAK-960 [4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl) benzamide] is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). Consistent with PLK1 inhibition, TAK-960 treatment caused accumulation of G(2)-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3) in vitro and in vivo. TAK-960 inhibited proliferation of multiple cancer cell lines, with mean EC(50) values ranging from 8.4 to 46.9 nmol/L, but not in nondividing normal cells (EC(50) >1,000 nmol/L). The mutation status of TP53 or KRAS and MDR1 expression did not correlate with the potency of TAK-960 in the cell lines tested. In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 has entered clinical evaluation in patients with advanced cancers.


Thiol-reactive lanthanide chelates for phasing protein X-ray diffraction data.
Lanthanides can contribute a large anomalous component to X-ray scattering when present and ordered in a target crystal. This large anomalous signal is a useful source of phase information in X-ray crystallographic studies of biological macromolecules. Thiol-reactive lanthanide chelates were tested as a means of incorporation of lanthanides into protein crystals. Two compounds, each capable of being loaded with a lanthanide of choice, were synthesized: diethylenetriaminepentaacetic 3-(2-pyridyldithio)propionyl hydrazide (DTPA-PDPH) and 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic 3-(2-pyridyldithio)propionyl hydrazide (DOTA-PDPH). A cysteine mutant of the 34 kDa phosphate-binding protein (PBP-A197C) from Escherichia coli was used as a test case. PBP-A197C was labeled with DTPA-PDPH loaded with dysprosium. Characteristics of DTPA-PDPH enabled spectroscopic monitoring of the labeling reaction. Complete labeling of PBP-A197C was confirmed by mass spectrometry and SDS-PAGE analysis. Labeled PBP-A197C (PBP-A197C-DTPA-Dy) crystallized identically to unlabeled protein. X-ray diffraction data were collected from PBP-A197C-DTPA-Dy crystals in-house with a Cu Kalpha rotating-anode source and with a tuneable synchrotron source (ALS 5.0.2). Synchrotron data were collected at energies corresponding to the Dy L(III) edge f" peak and a high-energy remote. Each data set was treated as an independent SAD experiment. A large anomalous signal was present in the data collected in-house and at the synchrotron. The Dy site was easily located in anomalous difference Patterson maps calculated from each of the data sets. In each case, SAD phasing resulted in high-quality electron-density maps, as evidenced by the success of automated model building. The generality of the method was analyzed with several other test proteins. Labeling of some of these proteins with thiol-reactive lanthanide chelates was deleterious to protein solubility or crystallization. In two of the cases the lanthanide chelate was disordered in the crystals. These results suggest that this method may not be well suited for high-throughput crystallography. However, for difficult cases requiring a large anomalous signal, thiol-reactive lanthanide chelates may prove to be a valuable tool.


High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.
In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria. We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.


Interleukin-17 receptor D constitutes an alternative receptor for interleukin-17A important in psoriasis-like skin inflammation.
T helper 17 (TH17) cells and interleukin-17A (IL-17A) produced by them are critical in autoinflammatory diseases, such as psoriasis. IL-17A has been shown to signal through IL-17 receptor A/IL-17 receptor C (IL-17RA/IL-17RC) complex to drive inflammatory responses. However, in a psoriasis model, we found that Il17rc deficiency did not completely ameliorate the disease, suggesting another receptor. In search for another IL-17A-interacting receptor, we found that IL-17RD directly bound IL-17A but not IL-17F or IL-17A/F heterodimer and formed a heterodimer with IL-17RA. IL-17A-, but not IL-17F- or IL-17A/F-, mediated gene expression was defective in Il17rd-deficient keratinocytes. Il17rd deficiency in nonhemopoietic cells attenuated imiquimod-induced psoriasis-like skin inflammation. Although IL-17RC and IL-17RD differentially activated IL-17A-dependent signaling and gene expression, their compound mutation led to complete deficits in keratinocytes. IL-23 was found induced by IL-17A in keratinocytes, dependent on both IL-17RC and IL-17RD, suggesting feed-forward regulation of IL-23/IL-17 axis in psoriasis. Together, IL-17RD constitutes a second functional receptor for IL-17A and, together with IL-17RC, mediates the proinflammatory gene expression downstream of IL-17A.


Light and plant development: the discovery of phototropins by Winslow R. Briggs (1928-2019).
The American biologist Winslow Russel Briggs (1928-2019) was a global leader in plant physiology, genetics and photobiology. In this contribution, we try to share our knowledge of the remarkable career of this outstanding scientist. After earning his PhD at Harvard (Cambridge, Massachusetts), he started his independent research program at Stanford University (California). Among many major contributions was his elegant experiment that conclusively demonstrated the role of auxin transport in the phototropic bending response of grass coleoptiles. During subsequent years as Professor of biology at Harvard University, Briggs focused on phytochrome and photomorphogenesis. In 1973, he re-located to Stanford to become Director of the Department of Plant Biology, Carnegie Institution for Science, and faculty member in the Biology Department at Stanford University. After his retirement (1993), he continued his research on "light and plant development" as an emeritus at Carnegie until the day of his death on February 11, 2019. Through his long research career, Briggs stayed at the cutting edge by re-inventing himself from a plant physiologist, to biochemist, geneticist, and molecular biologist. He made numerous discoveries, including the LOV-domain photoreceptor phototropin. Winslow Briggs, who was also a naturalist and gifted pianist, inspired and promoted the work of generations of young scientists - as mentor, colleague and friend.


A partnership development process assessment scale for public health nurses in Japan.
The objective of this study was to develop and test a Partnership Development Process Assessment (PDPA) scale for content and construct validity and internal consistency reliability. This is needed to document and evaluate community health partnership development processes between public health nurses and community-based organizations in Japan. The study was conducted in three phases. Ten semi-structured interviews were conducted to generate items for a new scale. Thirty items were generated and reviewed by an expert panel for content validity and item refinement. A national postal survey of public health nurses was conducted to determine the scale's internal structure, evaluate its reliability, and explore its construct and criterion validity. Validity and reliability testing of the PDPA scale using a content validity index and analysis of correlations with an existing scale were performed. Twenty-six items were selected and grouped into four factors: activities to share roles to manage community health issues, platform activities to support partnerships, activities to evaluate partnership practices, and activities to share information regarding community health issues. After factor analysis, 23 items were retained. The PDPA scale is a valid and reliable instrument for public health nurses to assess partnership development activities.


Laboratory mating trials indicate incipient speciation by sexual selection among populations of the cichlid fish Pseudotropheus zebra from Lake Malawi.
It has been suggested that sexual selection may have played a major role in the rapid evolution of hundreds of species of cichlid fishes in Lake Malawi. We report the results of a laboratory test of assortative mating among Lake Malawi cichlid fishes from five closely related geographical populations differing in male courtship colour. Paternity of clutches was tested using microsatellite DNA typing of offspring. Out of 1955 offspring typed, 1296 (66.3%) were sired by the male from the same population as the female, which is more than three times the rate expected if females do not differentiate among males of the different populations (20%). This result indicates that mate preferences of geographical races are strongly differentiated, consistent with the races representing incipient geographical species diverging under sexual selection exerted by female preferences for different male courtship colours.


Effectiveness of Gratitude Therapy in Diabetes Management: A Qualitative Study.
The present study involves a Qualitative research design. The study intends to assess the effectiveness of interventions on the diabetic participants. In the present study, four participants screened with high perceived stress, moderate depression, poor sense of gratitude, were selected. The study consisted of three successive phases such as baseline assessment, intervention, and follow-up. Pre-test and Post-test design were adopted. Qualitative data were expressed as percentages, and Schwartz and Blanchard's technique was administered. Participants have shown improvement in positive dimension scores and there is reduction in negative dimension scores. Blood glucose level readings are also marked before, during, and after the intervention. Participants are found to control their blood glucose level, but the change in the glucose level is not clinically significant.


Research on the application of Thelephora ganbajun exopolysaccharides in antioxidant, anti-inflammatory and spot-fading cosmetics.
Thelephora ganbajun exopolysaccharides (TGEP) with a "coral-like" branched chain structure (main chain diameter ~ 80 nm) were prepared by liquid fermentation and fractionated by ion-exchange chromatography. The main fraction (TGEP-2) with the highest in vitro antioxidant capacity was composed of Glc, Man, Gal, GalA, GlcA, Ara, Rha, GlcN, Fuc and Rib in a molar ratio of 465.43:420.43:219.14:188.43:37:35.14:31.43:19.43:11.14:1, with a molecular weight of 1.879 × 104 Da. The sequence of monosaccharide residue release revealed that Gal, Glc and Ara residues were more distributed in the side-branch chains and at their ends, whereas Man and GalA residues were more distributed in the main chains. TGEP-2 contained linear residues (mainly →4)-Glcp-(1 → and →4)-Manp-(1→), branch residues (→3,6)-Glcp-(1→, →4,6)-Glcp-(1 → and →3,6)-Galp-(1→) and terminal residues (Galp-(1→, Manp-(1 → and Glcp-(1→). TGEP-2 consisted of α- and β-glycosidically linked pyranosides, with a triple helical conformation and many long branches. Zebrafish oxidative stress and inflammation models found that TGEP-2 had antioxidant and anti-inflammatory activities. The zebrafish skin black spot assay showed that TGEP-2 inhibited melanin formation. Therefore, extracellular polysaccharides of T. ganbajun have strong application potential in anti-oxidant, anti-inflammatory and skin spot-fading functions cosmetics.


Evaluation of n-alkanes and their carbon isotope enrichments (δ(13)C) as diet composition markers.
Plant cuticular n-alkanes have been successfully used as markers to estimate diet composition and intake of grazing herbivores. However, additional markers may be required under grazing conditions in botanically diverse vegetation. This study was conducted to describe the n-alkane profiles and the carbon isotope enrichment of n-alkanes of common plant species from the Mid Rift Valley rangelands of Ethiopia, and evaluate their potential use as nutritional markers. A total of 23 plant species were collected and analysed for long-chain n-alkanes ranging from heptacosane to hexatriacontane (C(27) to C(36)), as well as their carbon isotopic ratio ((13)C/(12)C). The analysis was conducted by gas chromatography/combustion isotope ratio mass spectrometry following saponification, extraction and purification. The isotopic composition of the n-alkanes is reported in the delta notation (δ(13)C) relative to the Vienna Pee Dee Belemnite standard. The dominant n-alkanes in the species were C(31) (mean ± s.d., 283 ± 246 mg/kg dry matter) and C(33) (149 ± 98 mg/kg dry matter). The carbon isotopic enrichment of the n-alkanes ranged from -19.37‰ to -37.40‰. Principal component analysis was used to examine interspecies differences based on n-alkane profiles and the carbon isotopic enrichments of individual n-alkanes. Large variability among the pasture species was observed. The first three principal components explained most of the interspecies variances. Comparison of the principal component scores using orthogonal procrustes rotation indicated that about 0.84 of the interspecies variances explained by the two types of data sets were independent of each other, suggesting that the use of a combination of the two markers can improve diet composition estimations. It was concluded that, while the n-alkane profile of the pasture species remains a useful marker for use in the study region, the δ(13)C values of n-alkanes can provide additional information in discriminating diet components of grazing animals.


A model for the autosensitization autoantibody production associated with xenogeneic thymic RNA.
Normal C57BL/6 bone marrow cells cultured for 3 weeks with xenogeneic thymic RNA and syngeneic C57BL/6 antigens (immunoglobulin G or red blood cells) produced anti-immunoglobulin antibody or anti-mouse red blood cell antibody (hemolysin). Addition of both xenogeneic thymic RNA and autoantigens to bone marrow cultures was necessary to elicit autosensitization. Syngeneic thymic RNA would not substitute for xenogeneic RNA. Normal recipients inoculated with syngeneic kidney or spinal cord homogenates and xenogeneic thymic RNA developed albuminuria or motor neuropathies within 10 days. Histologic examination of tissues from these animals revealed immunoglobulin deposits on glomerular or tubular basement membranes or on myelin sheaths. These changes were not observed in tissues from control animals inoculated with only the organ homogenates. Normal mice injected with syngeneic bone marrow cells, which had been autosensitized in vitro against kidney or spinal cord homogenates, also developed albuminuria or motor neuropathies, respectively. These abnormalities were observed only if bone marrow cells had been cultured with both xenogeneic thymic RNA and autoantigens. Histologic examination of tissues from these mice also revealed immunoglobulin deposits in kidney or spinal cord tissues. These results demonstrate that xenogeneic thymic RNA can play important roles in the formation of autoantibodies.


Highly Potent Non-Carboxylic Acid Autotaxin Inhibitors Reduce Melanoma Metastasis and Chemotherapeutic Resistance of Breast Cancer Stem Cells.
Autotaxin (ATX, aka. ENPP2) is the main source of the lipid mediator lysophosphatidic acid (LPA) in biological fluids. This study reports on inhibitors of ATX derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provide a comprehensive structure-activity relationship of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. The three most potent analogues (3a, IC50 ∼ 32 nM; 3b, IC50 ∼ 9 nM; and 14, IC50 ∼ 35 nM) inhibit ATX-dependent invasion of A2058 human melanoma cells in vitro. Two of the most potent compounds, 3b and 3f (IC50 ∼ 84 nM), lack inhibitory action on ENPP6 and ENPP7 but possess weak antagonist action specific to the LPA1 G protein-coupled receptor. In particular, compound 3b potently reduced in vitro chemotherapeutic resistance of 4T1 breast cancer stem-like cells to paclitaxel and significantly reduced B16 melanoma metastasis in vivo.


Effect of different segmentation algorithms on metabolic tumor volume measured on 18F-FDG PET/CT of cervical primary squamous cell carcinoma.
It is known that fluorine-18 fluorodeoxyglucose PET/computed tomography (CT) segmentation algorithms have an impact on the metabolic tumor volume (MTV). This leads to some uncertainties in PET/CT guidance of tumor radiotherapy. The aim of this study was to investigate the effect of segmentation algorithms on the PET/CT-based MTV and their correlations with the gross tumor volumes (GTVs) of cervical primary squamous cell carcinoma. Fifty-five patients with International Federation of Gynecology and Obstetrics stage Ia∼IIb and histologically proven cervical squamous cell carcinoma were enrolled. A fluorine-18 fluorodeoxyglucose PET/CT scan was performed before definitive surgery. GTV was measured on surgical specimens. MTVs were estimated on PET/CT scans using different segmentation algorithms, including a fixed percentage of the maximum standardized uptake value (20∼60% SUVmax) threshold and iterative adaptive algorithm. We divided all patients into four different groups according to the SUVmax within target volume. The comparisons of absolute values and percentage differences between MTVs by segmentation and GTV were performed in different SUVmax subgroups. The optimal threshold percentage was determined from MTV20%∼MTV60%, and was correlated with SUVmax. The correlation of MTViterative adaptive with GTV was also investigated. MTV50% and MTV60% were similar to GTV in the SUVmax up to 5 (P>0.05). MTV30%∼MTV60% were similar to GTV (P>0.05) in the 5<SUVmax≤10 group. MTV20%∼MTV60% were similar to GTV (P>0.05) in the 10<SUVmax≤15 group. MTV20% and MTV30% were similar to GTV (P>0.05) in the SUVmax of at least 15 group. MTViterative adaptive was similar to GTV in both total and different SUVmax groups (P>0.05). Significant differences were observed among the fixed percentage method and the optimal threshold percentage was inversely correlated with SUVmax. The iterative adaptive segmentation algorithm led to the highest accuracy (6.66±50.83%). A significantly positive correlation was also observed between MTViterative adaptive and GTV (Pearson's correlation r=0.87, P<0.0001). MTViterative adaptive is independent of SUVmax, more accurate, and correlated with GTV. Iterative adaptive algorithm segmentation may be more suitable than the fixed percentage threshold method to estimate the tumor volume of cervical primary squamous cell carcinoma.


[Epidemiology--the same procedure as every year?].
The seasonal flu strikes every year with many different faces. Beside a common flu, influenza claims every year a high number of victims especially among the elderly. Despite an active surveillance of the flu activity and circulating viruses on a national and international level, the factors which determine the spread of the influenza virus remain unclear. Regarding the thread of a new pandemic, both, basic research and surveillance of influenza has been intensified to get a more detailed view on the activity and transmissibility of the influenza virus. This article describes the influenza surveillance schemes in Austria, Germany and especially Switzerland highlighting the differences between the three countries. In addition, the new mortality surveillance method used in Switzerland is presented.


USF binds to the APB alpha sequence in the promoter of the amyloid beta-protein precursor gene.
The APB alpha domain in the amyloid beta-protein precursor (APP) promoter contains a nuclear factor binding domain with the core recognition sequence TCAGCT-GAC. Proteins in nuclear extracts from brain and numerous cell lines bind to this domain and it contributes approximately 10-30% to the basal APP promoter activity. Included in this domain is the CANNTG motif, which is recognized by basic helix-loop-helix transcription factors. The same motif is also present in the CDEI element of the yeast centromere and in the adenovirus major late promoter (AdMLP). Here we present evidence based on thermostability, relative binding affinity, eletrophoretic mobility and antibody recognition that the cellular proteins that bind to the APB alpha and CDEI motifs are USF. However, the relative binding affinity for the motifs is different. The affinity of USF for AdMLP is approximately 20-fold higher than for the APB alpha sequence and 5-fold higher than for the CDEI sequence. Mutational analysis suggested that the primary determinant for USF binding affinity resides within the octamer CAGCTGAC, which is composed of the E-box consensus sequence CANNTG followed by the dinucleotide AC. The human homolog of the mouse CDEI binding protein did not bind to either the CDEI sequence or APB alpha.


Efficiency of transcatheter closure of atrial septal defects in small and symptomatic children.
We report the multicentric French experience with transcatheter closure in children weighing 15 kilograms or less, with the aim of assessing the efficacy of the procedure in this age group. We included all children weighing 15 kilograms or less, and seen between January, 1997, and June, 2004, who had successful transcatheter closure of an interatrial communication within the oval fossa. Transcatheter closure was performed in 35 patients weighing 15 kilograms or less, of whom 14 were male and 21 female. The procedures were undertaken in 8 different centres, the patients having a median age of 3 years, with a range from zero to 6.2 years, and a mean weight of 13 kilograms, with a range from 3.6 to 15 kilograms. All the patients were symptomatic, with associated cardiac malformations present in 4 cases, and extracardiac anomalies in 4 patients, including Down's syndrome in 3, and Adams Oliver syndrome in the other case. In 1 patient, emergency cardiac surgery was needed 24 h after the procedure to correct a previously undiagnosed divided right atrium. No other complication occurred. After a median follow-up of 2 years, with a range from 0.5 to 5.2 years, all the patients are asymptomatic, except for one long-standing patient with bronchodysplasia. In 1 other patient, a small residual bidirectional shunt was detected by echocardiography. No patient presented significant arrhythmia. In the patients followed-up for more than 12 months, we found a significant gain in weight gain. Transcatheter closure of an interatrial communication within the oval fossa is efficient in children weighing 15 kilograms or less, and can be proposed as a first line of treatment in symptomatic patients. Children with retarded growth tend to have complete recovery within one year of closure.


The role of gender in providing expert advice on cyber conflict and artificial intelligence for military personnel.
This article draws upon original qualitative interview data with Norwegian male and female cyberengineer cadets at the Norwegian Cyber Defense Academy, who could in the future be working with AI-enabled systems in a variety of positions throughout the Norwegian military. The interviews explored how these cadets feel they as cyberengineers will be perceived in their future positions in the military, what challenges they feel they may face, and how gender may play a role in this. Different cyberengineers expressed concern about being able to communicate the cyber domain to their non-technology specialist colleagues due to the increasing complexity of new technologies. Gender appeared to be playing a role in this concern as the women interviewed expressed specific concerns that they feel as women, that they do not fit the stereotype of who is a cyberengineer, while some of the men felt that as cyberengineers they were seen as embodying a nerd masculinity, and that these gendered perceptions has implications for how they feel others perceive their competence levels. The findings from this article highlights gendered hierarchies in the military and the need for military institutions to focus on developing communication skills among those working with cyber operations. As the role of cyber is expected to grow in military operations, cyberengineers will need to find ways of communicating effectively with non-specialists-especially as complex AI-enabled systems are introduced. Finally, this paper argues the need for military institutions to take gender into account for this training and need for gender-sensitive policies.


Anatomical congruence of metabolic and electromagnetic activation signals during a self-paced motor task: a combined PET-MEG study.
We have investigated the degree of spatial correlation between the cerebral blood flow variations measured by positron emission tomography (PET) and the electromagnetic sources as measured by magnetoencephalography (MEG) in five subjects while performing a self-paced right index finger tapping task. Data were processed independently for each technique using both single-case and intersubject analysis. PET and MEG were coregistered with anatomical magnetic resonance images for each subject. Both extension and flexion motor-related fields were extracted from the MEG signal. Using the single dipole model we identified the motor evoked field 1 (MEF1) in all subjects and the motor field (MF) in three subjects. Individual and intersubject averaged PET data showed consistent contralateral primary sensorimotor (PSM) hand area and bilateral supplementary motor area activation. MEG individual and intersubject averaged results demonstrated that both MEF1 and MF dipoles were localized within the PSM PET activated area. Individual PSM mass center to dipole distance was 12 and 15.3 mm on average for the MEF1 and the MF component, respectively. For the same components, the intersubject averaged analysis shows distances between the PET Z-score maximum and the dipole locations of 6.3 and 15.0 mm, respectively. These results show that PET and MEG MEF1 activation signals spatially coincide within instrumental, registration, and modeling errors.


Magnesium: its role in nutrition and carcinogenesis.
Magnesium (Mg2+) plays a key role in many essential cellular processes such as intermediary metabolism, DNA replication and repair, transporting potassium and calcium ions, cell proliferation together with signalling transduction. Dietary sources rich in magnesium are whole and unrefined grains, seeds, cocoa, nuts, almonds and green leafy vegetables. Hard water is also considered to be an important source of magnesium beneficial to human health. The daily dietary intake of magnesium is however frequently found to be below that recommended in Western countries. Indeed, it is recognised that magnesium deficiency may lead to many disorders of the human body, where for instance magnesium depletion is believed to play an important role in the aetiology of the following; cardiovascular disease (including thrombosis, atherosclerosis, ishaemic heart disease, myocardial infarction, hypertension, arrhythmias and congestive heart failure in human), as well as diabetes mellitus, gastrointestinal (GI) tract disease, liver cirrhosis and diseases of the thyroid and parathyroid glands. Insufficient dietary intake of magnesium may also significantly affect the development and exacerbation ofADHD (Attention Deficit- Hyperactivity Disorder) symptoms in children. The known links between magnesium and carcinogenesis still remain unclear and complex, with conflicting results being reported from many experimental, epidemiological and clinical studies; further knowledge is thus required. Mg2+ ions are enzyme cofactors involved in DNA repair mechanisms that maintain genomic stability and fidelity. Any magnesium deficiencies could thereby cause a dysfunction of these systems to occur leading to DNA mutations. Magnesium deficiency may also be associated with inflammation and increased levels of free radicals where both inflammatory mediators and free radicals so arising could cause oxidative DNA damage and therefore tumour formation. The presented review article now provides a summary discussion of the various research performed concerning the impact that low magnesium intake has on tumour incidence; this includes impairment of magnesium homeostasis frequently observed in tumour cells, the influence of magnesium depletion on the progression of existing tumours and the occurrence of hypo-magnesaemia when patients are treated with certain anticancer drugs.


A minority of final stacks yields superior amplitude in single-particle cryo-EM.
Cryogenic electron microscopy (cryo-EM) is widely used to determine near-atomic resolution structures of biological macromolecules. Due to the low signal-to-noise ratio, cryo-EM relies on averaging many images. However, a crucial question in the field of cryo-EM remains unanswered: how close can we get to the minimum number of particles required to reach a specific resolution in practice? The absence of an answer to this question has impeded progress in understanding sample behavior and the performance of sample preparation methods. To address this issue, we develop an iterative particle sorting and/or sieving method called CryoSieve. Extensive experiments demonstrate that CryoSieve outperforms other cryo-EM particle sorting algorithms, revealing that most particles are unnecessary in final stacks. The minority of particles remaining in the final stacks yield superior high-resolution amplitude in reconstructed density maps. For some datasets, the size of the finest subset approaches the theoretical limit.


Superficial nephrons in BALB/c and C57BL/6 mice facilitate in vivo multiphoton microscopy of the kidney.
Multiphoton microscopy (MPM) offers a unique approach for addressing both the function and structure of an organ in near-real time in the live animal. The method however is limited by the tissue-specific penetration depth of the excitation laser. In the kidney, structures in the range of 100 µm from the surface are accessible for MPM. This limitation of MPM aggravates the investigation of the function of structures located deeper in the renal cortex, like the glomerulus and the juxtaglomerular apparatus. In view of the relevance of gene-targeted mice for investigating the function of these structures, we aimed to identify a mouse strain with a high percentage of superficially located glomeruli. The mean distance of the 30 most superficial glomeruli from the kidney surface was determined in 10 commonly used mouse strains. The mean depth of glomeruli was 118.4±3.4, 123.0±2.7, 133.7±3.0, 132.3±2.6, 141.0±4.0, 145.3±4.3, 148.9±4.2, 151.6±2.7, 167.7±3.9, and 207.8±3.2 µm in kidney sections from 4-week-old C3H/HeN, BALB/cAnN, SJL/J, C57BL/6N, DBA/2N, CD1 (CRI), 129S2/SvPas, CB6F1, FVB/N and NMRI (Han) mice, respectively (n = 5 animals from each strain). The mean distance from the kidney surface of the most superficial glomeruli was significantly lower in the strains C3H/HeN Crl, BALB/cAnN, DBA/2NCrl, and C57BL/6N when compared to a peer group consisting of all the other strains (p<.0001). In 10-week-old mice, the most superficial glomeruli were located deeper in the cortex when compared to 4-week-old animals, with BALB/cAnN and C57BL/6N being the strains with the highest percentage of superficial glomeruli (25% percentile 116.7 and 121.9 µm, respectively). In summary, due to significantly more superficial glomeruli compared to other commonly used strains, BALB/cAnN and C57BL/6N mice appear to be particularly suitable for the investigation of glomerular function using MPM.


Global perspectives of the impact of the COVID-19 pandemic on learning science in higher education.
The COVID-19 pandemic required higher education institutions to rapidly transition to Emergency Remote Instruction (ERI) with little preparation. Discussions are now underway globally to learn the lessons of COVID-19 and to use this knowledge to shape the future of learning science in higher education. In this study, we examined the experiences of instructors and students to ERI in three universities across three continents-America, Europe, and Australia. We measured the instructional strategies used by instructors including assessment types, and interaction opportunities during and outside class schedules. We also measured the learning challenges experienced by students including planning, distractions, technology, learning resources, their views on educational quality and what characterized quality interactions during ERI. Our findings suggest that most instructional strategies used by instructors changed little during ERI, although the nature of instructor and student interactions during class relied more heavily on technology. Students reported significant learning challenges which included distractions from their physical and social media environments and access to technology. Both instructors and students reported that interactions with each other and their peers were concerningly low, albeit similar to pre COVID-19 pandemic levels. There were differences in the perceptions of instructors and students on whether instructor-student interactions were better or worse online. Common among all universities, there was a large proportion of students reporting mental health and work-related stress. Lessons to be learned from the COVID-19 pandemic include ensuring more support for instructors to implement effective and equitable pedagogies and an increased recognition of the importance of practicals, and the social, interactive and hands-on aspects of learning science in higher education. We predict that the incorporation of active learning pedagogies and strategies which increase student engagement and foster a sense of belonging will be ongoing global challenges for learning science in a post COVID-19 campus.


Clinical presentation of psoriasis.
Psoriasis is a chronic, inflammatory disease affecting 1-3% of the world's population. Joints can be affected in up to 30% of patients. About one third of patients have either severe or moderate (involving more than 10% of body surface area) disease. Patients affected with extensive psoriasis have an impaired quality of life. Psoriasis has a large spectrum of clinical features and evolution, so no complete agreement on the classification of the clinical variants exists. Plaque psoriasis is the commonest form (more than 80% of affected patients). The course of plaque psoriasis varies. Spontaneous resolution is possible, but rarely occurs. Plaques tend to remain static or slowly enlarge. Flexural (inverse, intertriginous) psoriasis manifests with lesions thinner than those of plaque form with no or minimal scaling, and is localized in the skin folds. Guttate (eruptive) psoriasis has frequently a sudden onset and frequently appears abruptly after a bacterial or viral febrile episode of inflammation of the upper ways. Pustular and erythrodermic psoriasis are the most severe clinical variants. In the diffuse pustular form recurrent episodes of fever occur, followed by new outbreaks of pustules. Erythrodermic psoriasis corresponds to the generalized form of the disease. The entire skin is bright red and is covered by superficial scales. Fatigue, myalgia, shortness of breath, fever and chills may also occur. In sebopsoriasis (seborrheic dermatitis + psoriasis) the lesions tend to occur at the same sites as seborrheic dermatitis; greasy scales predominate, but silvery scales can be found in some areas. Nail psoriasis shows various features: nail pits; oil spots; subungual hyperkeratosis; onycholysis. Rare forms include psoriasis circinata, lip psoriasis and oral psoriasis. Differential diagnosis includes many other dermatological conditions.


Functional Outcome of Surgical Stabilisation of Acetabular Fractures.
Approach to the management of displaced acetabular fractures has evolved from conservative to operative management after the work of Judet and Letournel. Various surgical methods have been explored and described by authors to address this type of fracture, leading to improved clinical outcome. This study aimed to evaluate functional outcome of surgically treated displaced acetabular fractures in the Malaysian context. We analysed 43 patients with isolated acetabular fractures who were treated operatively with a minimum of three years follow-up. Anthropometric data, Judet-Letournel fracture pattern, surgical approach and complications were recorded. Post-operative Matta radiological outcome were evaluated for joint congruency and hip functional outcome was evaluated using Merle d'Aubgine-Postel and Harris Hip Score (HHS). All statistical analyses were analysed using SPSS version 24.0. The most frequent elementary fracture type was posterior wall (30.2%) while associated type was both columns (23.3%). Mean functional outcome of Merle d'Aubigné-Postel was 15.77 and HHS was 86.6. Thirty-three (76.7%) patients achieved satisfactory functional outcome, 19 (44.1%) patients achieved anatomic reduction (<2 mm step-off) based on Matta classification while 24 (55.8%) did not achieve the desired outcome. Fracture pattern exhibited strong association with post-operative Matta radiological outcome (p-value 0.001). However both fracture pattern and Matta radiological outcome did not exhibit association with the functional outcome group. The mean time for surgical interventions was 10.8 days and there was no significant association with final functional outcome score. Fracture pattern is a strong contributing factor towards post-operative Matta radiological outcome. However, achieving the perfect anatomical reduction is not of utmost important factor to predict the good functional outcome.


Testicular cancer: an oncological success story.
Testicular cancer has become a model for a curable neoplasm. Our studies with cisplatin combination chemotherapy allow us to conclude that: (a) short-duration intensive induction therapy with the most active agents in optimal dosage is more important than maintenance therapy; (b) modest dose escalation increases toxicity without improving therapeutic efficacy; (c) it is possible to develop curative salvage therapy for refractory germ cell tumors; and (d) preclinical models predicting synergism, such as vinblastine + bleomycin or cisplatin + etoposide have clinical relevance. Finally, testicular cancer has also become a model for new drug development. Cisplatin was approved by the Food and Drug Administration for testis and ovarian cancer, and etoposide and ifosfamide were approved for refractory germ cell tumors. The success of these studies confirms the importance of the continued search for new investigational drugs in all solid tumors.


Oxidative stress and redox regulation on in vitro development of mammalian embryos.
Many factors affect development of mammalian preimplantation embryos in vitro. It is well known that in vitro development of bovine embryos is highly affected by culture condition including energy source, growth factors, pH or gas environment. Many efforts have been made towards the suitable environments which can successfully support embryo development in vitro. For a rapid growth and differentiation, embryo requires energy by utilizing ATP, NADPH with oxygen molecules. These energy substrates are produced from the electron transport chain in the mitochondria. In addition to energy production, reactive oxygen species (ROS) are also generated as by-product of such energy production system. ROS production is sensitively controlled by the balance of oxidizing and reducing status and affected by several antioxidant enzymes such as superoxide dismutase (SOD), Catalase, glutathione peroxidase (GPx) or low molecular weight thiols such as glutathione (GSH). Imbalance of oxidation and reduction causes production of excess ROS, which causes the developmental arrest, physical DNA damage, apoptosis induction or lipid peroxidation. Environmental oxygen condition during embryo culture also highly affects embryo development as well as intracellular redox balance. Several studies have revealed that regulation of intra- and extra- cellular reducing environment by reducing excess ROS by using antioxidants, reducing oxygen concentration are effective for improving embryo development. Also, recent studies have demonstrated the difference in gene expression affected by oxidative stress. This review briefly summarizes the effects of ROS and the role of redox balance on preimplantation embryos for improving the efficiency of in vitro production of mammalian embryos.


Association of the Protective Dietary Pattern for Blood Pressure with Elevated Blood Pressure and Hypertension among Chinese Children and Adolescents Aged 6-17 Years Old: Data from China Nutrition and Health Surveillance (2015-2017).
Studies focused on the association between dietary patterns and elevated blood pressure (BP) and hypertension (HTN) among children and adolescents remain insufficient. This study aimed to explore a dietary pattern that could be helpful for the prevention of abnormal BP and to investigate the association between this dietary pattern and elevated BP and HTN among Chinese children and adolescents. A total of 52,080 Chinese children and adolescents aged 6~17 years old from the China Nutrition and Health Surveillance (CNHS) 2015-2017 were included in the current study. The reduced rank regression (RRR) method was applied to derive a dietary pattern that is associated with BP. Multivariable logistic regression was used to assess the association between dietary pattern (DP) and elevated BP and HTN. The Dietary Approach to Stop Hypertension (DASH) score was also calculated for each participant as a comparative method to validate the dietary pattern derived with the RRR method. A protective dietary pattern (PDP) for BP among Chinese children and adolescents was derived, which was characterized by high intakes of dairy products, mushrooms/edible fungi, fresh vegetables, fresh fruits, fresh eggs, aquatic products, mixed legumes, soybeans and related products, offal, dried fruits, and coarse cereals, with low intakes of refined grains. After multiple adjustments, there were significant inverse associations between PDP scores and the odds of elevated BP and HTN (elevated BP: Q5 vs. Q1, OR = 0.849, 95%CI = 0.755-0.931, P-trend < 0.05; HTN: Q5 vs. Q1, OR = 0.795, 95%CI = 0.694-0.911, P-trend < 0.05). The DASH diet was also observed to have protective effects on elevated BP in model I (Q5 vs. Q1, OR = 0.899, 95%CI = 0.828-0.975, P-trend < 0.05), but was not observed to have protective effects on HTN (HTN: Q5 vs. Q1, OR = 0.958, 95%CI = 0.876-1.048, P-trend > 0.05). The current study suggested that greater adherence to the PDP for BP among Chinese children and adolescents might be associated with lower odds of elevated BP and HTN.


Postoperative complications after reconstructive surgery for cloacal malformations: a systematic review.
The repair of cloacal malformations is most often performed using a posterior sagittal anorecto-vagino-urethroplasty (PSARVUP) or total urogenital mobilization (TUM) with or without laparotomy. The aim of this study was to systematically review the frequency and type of postoperative complication seen after cloacal repair as reported in the literature. A systematic literature search was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA). Eight records were eligible for this study which were qualitatively analyzed according to the Rangel score. Overall complication rates reported in included studies ranged from 0 to 57 %. After meta-analysis of data, postoperative complications were seen in 99 of 327 patients (30 %). The most common reported complications were recurrent or persistent fistula (n = 29, 10 %) and rectal prolapse (n = 27, 10 %). In the PSARVUP group, the complication rate was 40 % and in the TUM group 30 % (p = 0.205). This systematic review shows that postoperative complications after cloacal repair are seen in 30 % of the patients. The complication rates after PSARVUP and TUM were not significantly different. Standardization in reporting of surgical complications would inform further development of surgical approaches. Other techniques aiming to lower postoperative complication rates may also deserve consideration.


"Small places close to home": toward a health and human rights strategy for the US.
Much of the discussion about "health as a human right" has centered on global health initiatives, largely ignoring the application of human rights principles to the significant socioeconomic and racial health disparities in the United States. Given the persistent gaps in insurance coverage and access to quality preventive care in the US, the health and human rights movement has primarily focused its efforts on achieving universal health care coverage. However, this focus has left unaddressed how a human rights strategy might also address the social determinants of health. As Americans' health continues to worsen-the US Institute of Medicine recently reported that the US now fares worse in nine areas of health than 16 peer high-income democracies--a broader social determinants approach is warranted. This article explores the application of international human rights principles, including a "right to health" to the US context, and analyzes how existing domestic law may be used to advance health as a human right for America's most vulnerable populations. It demonstrates that an effective health and human rights strategy must build partnerships among health care providers, public health professionals, and lawyers to identify rights violations, hold officials and systems accountable, and mobilize communities to advocate for systems and policy change.


Severe Persistent Hyponatremia: A Rare Presentation of Biliary Fluid Loss.
Hypotonic hyponatremia is caused by a serum sodium level of <135 mEq/L in the setting of excess solute loss accompanied by free water retention because of antidiuretic hormone release, subsequent to decreased effective arterial blood volume. Acute hyponatremia can have various neurological manifestations, including drowsiness, lethargy, coma, seizures, respiratory depression, and even death. In this article, we present a case of a 41-year-old man who presented with hyponatremia as a result of sodium containing biliary fluid loss and resultant renal free water retention in response to increased antidiuretic hormone secretion. He underwent placement of a cholecystostomy tube for acalculous cholecystitis and was found to be persistently hyponatremic despite repletion with sodium-containing fluids. Once the cholecystostomy tube was removed, the patient's sodium levels improved, and his symptoms resolved. Our case highlights choleuresis as an unusual but significant cause of hyponatremia in patients who have external biliary drainage.


Hybrid submental flaps for reconstruction in the head and neck: part pedicled, part free.
Evaluate feasibility and success of elongating only the venous pedicle of the submental flap to increase the superior arc of rotation for the "hybrid" flap allowing coverage of more distal defects. Retrospective evaluation of all submental flaps undergoing pedicle-lengthening procedure at a single institution. Medical records were reviewed for all patients undergoing reconstruction with submental flaps between 2002 and 2012. Information regarding demographics, etiology, location, size, and extent of defects, type of submental flap harvested, operative time, and outcomes were recorded. Special note was made of vascular pedicle length and any pedicle vessel manipulation to increase the superior arc of rotation. Nine patients (67% male) with a mean age of 61 years (range, 25-83 years) underwent hybrid submental flap procedures. Eight surgical defects resulted from cancer ablation and one from trauma. Five flaps were musculocutaneous, and four were osseomusculocutaneous. The divided pedicle vein was anastomosed to the external jugular vein (n = 6), retromandibular vein (n = 1), common facial vein (n = 1), and internal jugular vein (n = 1). Pedicle vessel elongation averaged 5 cm. Skin paddle size averaged 71 cm(2) (range, 48-99 cm(2)). All donor sites were closed primarily with no further surgery required. One flap experienced venous thrombosis and was successfully salvaged. Overall flap survival was 100%. No local or regional cancer recurrence was detected in the cancer patients with a mean follow-up of 20 months (range, 3-87 months). The hybrid submental flap safely extends the arc of rotation 5 cm, allowing coverage of defects in the forehead, temporal-parietal, and occipital regions.


[Isolated compression of the motor branch of the ulnar nerve].
This paper reports four cases of isolated compression of the deep branch of the ulnar nerve, and reviews the various etiologies (tumor, malformation and microtraumatism). The authors stress the importance of the electric examination, particularly conduction velocity in the palm in localizing the nerve lesion. Surgical exploration in these cases revealed a Giant cell tumor, two synovial cysts, and an abnormal fibrous band stretching between the flexor digiti quinti brevis and the opponens digiti quinti. Postoperative courses were uncomplicated and every patient recuperated quickly and completely. Early surgical exploration in such cases is mandatory.


Alternative geometries of DNA looping: an analysis using the SfiI endonuclease.
Many processes are governed by proteins that bind to separate sites in DNA and loop out the intervening DNA, but the geometries of the loops have seldom been determined. The SfiI endonuclease cleaves DNA after interacting with two recognition sites, and is a favourable system for the analysis of DNA looping. A gel-shift assay was used here to examine the binding of SfiI to a series of linear DNA molecules containing two SfiI sites separated by 109-170 base-pairs. The complexes in which SfiI trapped a loop by binding to two sites in the same DNA were separated from the complexes containing SfiI bound to separate DNA molecules. Step-wise changes in the inter-site spacing generated two forms of the looped complex with different electrophoretic mobilities. The yields of each looped complex and the complexes from intermolecular synapses all varied cyclically with the inter-site spacing, with similar periodicities ( approximately 10.5 base-pairs) but with different phases. One looped complex predominated whenever the DNA between the sites needed to be underwound in order to produce the correct helical orientation of the binding sites. The other looped complex predominated whenever the intervening DNA needed to be overwound. We conclude that the former has trapped a right-handed loop with a negative node and the latter a left-handed loop with a positive node.


Effects of GSK2606414 on cell proliferation and endoplasmic reticulum stress‑associated gene expression in retinal pigment epithelial cells.
GSK2606414 is a novel, highly selective inhibitor of protein kinase R‑like endoplasmic reticulum kinase (PERK). GSK2606414 and its analogues have recently been demonstrated to delay tumor growth and prevent neurodegeneration. The present study investigated the effects of GSK2606414 on proliferation, apoptosis, and the expression of activating transcription factor 4 (ATF4), CCAAT/enhancer‑binding protein homologous protein (CHOP) and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under endoplasmic reticulum (ER) stress. ARPE‑19 human RPE cells were treated with 0.01‑50 µM GSK2606414, and ER stress was induced by thapsigargin (TG) treatment. Cell proliferation was assessed using the Cell Counting kit‑8 cell viability assay. Apoptosis was detected by Annexin‑V/propidium iodide double staining using flow cytometry. Western blot analysis was used to measure eukaryotic initiation factor 2α (eIF2α) phosphorylation levels. ATF4, CHOP and VEGF mRNA expression levels were assessed using reverse transcription‑quantitative polymerase chain reaction. GSK2606414 treatment inhibited RPE cell proliferation in a dose‑dependent manner, however it did not induce apoptosis. In addition, GSK2606414 treatment inhibited eIF2α phosphorylation and reduced CHOP and VEGF mRNA expression levels in RPE cells under TG‑induced ER stress. To the best of our knowledge, the present study is the first to demonstrate that GSK2606414 has a potential antiproliferative effect in RPE cells in vitro. This effect appeared to be achieved via inhibition of the PERK/ATF4/CHOP signaling pathway and suppression of VEGF expression levels.


[Superficial tongue blood volume and the tongue spectrophotometric determination on coronary heart disease with blood stasis syndrome].
The tongue bodies of coronary heart disease (CHD) patients with blood stasis syndrome were looking dull purple in different degree. The authors adopted two kinds of biophysics methods which are tongue spectrophotometer and DM-80-6 superficial tongue blood volume meter. 52 CHD patients with blood stasis syndrome, 50 normal individuals and 26 patients before and after the treatment according to promote blood circulation to remove the blood stasis, were examined. The results were as follows: The purple ray values of the tongue spectrum of the CHD patients with blood stasis syndrome were more than that of normal individuals. Statistics showed significant difference (P less than 0.01). So was the tongue blood volume (P less than 0.01). In the treatment group, the purple ray value of tongue spectrum reduced, and the red ray volume of tongue increased significantly, as well (P less than 0.01). The results suggested that both methods may be quantitative comparative parameters for diagnosis, differentiation of symptoms and signs, and evaluation of the therapeutic effectiveness.