Application of science-based restoration planning to a desert river system.
Persistence of many desert river species is threatened by a suite of impacts linked to water infrastructure projects that provide human water security where water is scarce. Many desert rivers have undergone regime shifts from spatially and temporally dynamic ecosystems to more stable systems dominated by homogenous physical habitat. Restoration of desert river systems could aid in biodiversity conservation, but poses formidable challenges due to multiple threats and the infeasibility of recovery to pre-development conditions. The challenges faced in restoring desert rivers can be addressed by incorporating scientific recommendations into restoration planning efforts at multiple stages, as demonstrated here through an example restoration project. In particular, use of a watershed-scale planning process can identify data gaps and irreversible constraints, which aid in developing achievable restoration goals and objectives. Site-prioritization focuses limited the resources for restoration on areas with the greatest potential to improve populations of target organisms. Investment in research to understand causes of degradation, coupled with adoption of a guiding vision is critical for identifying feasible restoration actions that can enhance river processes. Setting monitoring as a project goal, developing hypotheses for expected outcomes, and implementing restoration as an experimental design will facilitate adaptive management and learning from project implementation. Involvement of scientists and managers during all planning stages is critical for developing process-based restoration actions and an implementation plan to maximize learning. The planning process developed here provides a roadmap for use of scientific recommendations in future efforts to recover dynamic processes in imperiled riverine ecosystems.


Bridging the information divide: health information sharing in home care.
As in many health sectors, in home care there have been significant investments made in electronic health information systems (EHIS) and accompanying standardized assessment instruments. While the potential of these systems to enhance the quality of care has been recognized, it has yet to be fully realized in Canadian home care settings. Data on EHIS barriers and facilitators were collected using a survey (n = 22).The results were discussed at a workshop (n = 30) and a "world café" session was held to consider strategies and interventions for improving health information exchange, with a focus on home care rehabilitation.


The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila.
Mutations in PTEN-induced kinase 1 (pink1) or parkin cause autosomal-recessive and some sporadic forms of Parkinson's disease. pink1 acts upstream of parkin in a common genetic pathway to regulate mitochondrial integrity in Drosophila. Mitochondrial morphology is maintained by a dynamic balance between the opposing actions of mitochondrial fusion, controlled by Mitofusin (mfn) and Optic atrophy 1 (opa1), and mitochondrial fission, controlled by drp1. Here, we explore interactions between pink1/parkin and the mitochondrial fusion/fission machinery. Muscle-specific knockdown of the fly homologue of Mfn (Marf) or opa1, or overexpression of drp1, results in significant mitochondrial fragmentation. Mfn-knockdown flies also display altered cristae morphology. Interestingly, knockdown of Mfn or opa1 or overexpression of drp1, rescues the phenotypes of muscle degeneration, cell death, and mitochondrial abnormalities in pink1 or parkin mutants. In the male germline, we also observe genetic interactions between pink1 and the testes-specific mfn homologue fuzzy onion, and between pink1 and drp1. Our data suggest that the pink1/parkin pathway promotes mitochondrial fission and/or inhibits fusion by negatively regulating mfn and opa1 function, and/or positively regulating drp1. However, pink1 and parkin mutant flies show distinct mitochondrial phenotypes from drp1 mutant flies, and flies carrying a heterozygous mutation in drp1 enhance the pink1-null phenotype, resulting in lethality. These results suggest that pink1 and parkin are likely not core components of the drp1-mediated mitochondrial fission machinery. Modification of fusion and fission may represent a novel therapeutic strategy for Parkinson's disease.


Plasmapheresis for the treatment of repeated early pregnancy wastage associated with anti-P.
It has been proposed that the blood group antibody, anti-P, produced by p or Pk individuals may cause abortion early in pregnancy. The authors have studied and successfully treated a Pk woman with anti-P who had 13 consecutive first-trimester miscarriages. Anti-P was implicated as the cause of repeated pregnancy loss after extensive clinical, endocrinologic, immunologic, and chromosomal evaluations. To remove P blood group antibodies, plasmapheresis was begun at five weeks' gestation during the 14th pregnancy with one plasma volume exchange two to three times per week. This therapy resulted in a reduction in the titer of anti-P, and the patient was delivered of a viable female infant after 33 weeks' gestation. The management and outcome indicate that habitual abortion presumably due to anti-P can be successfully treated with plasmapheresis. This case provides additional evidence that anti-P is responsible for abortions in p or Pk women, and that these abortions are immunologically mediated.


Evaluating the Rotation Correction of the Main Thoracic Curve in Severe Adolescent Idiopathic Scoliosis: Bending and Traction vs. Fulcrum - A Preliminary Report.
BACKGROUND Flexibility evaluation methods were only used to assess the changes of coronal Cobb angle in patients with adolescent idiopathic scoliosis (AIS). Little attention was attached to the vertebral rotation in these methods. MATERIAL AND METHODS 21 patients with severe adolescent idiopathic scoliosis were enrolled in this study. Coronal flexibility and rotation correction were compared on the supine bending, traction and fulcrum bending radiographs. The apical vertebral body rib ratio (AVB-R), and Perdriolle rotation angles were used to measure the rotation of the main thoracic curve. Statistical analysis was performed with one-way Analysis of Variance(ANOVA). Correlations between postoperative AVB-R and AVB-R in supine bending, traction and fulcrum bending radiographs were assessed utilizing the Linear Regression. RESULTS There were trends towards increased coronal flexibility in fulcrum bending versus traction versus supine bending, but there were no significant differences due to the limited sample size. And all were significantly lower than postoperative correction. The correction of AVB-R at traction and supine bending radiographs were significantly better than fulcrum bending, however, all were significantly lower than postoperative correction. Correction of Perdriolle rotation angle at traction radiograph was best among these methods. A univariant linear regression analysis showed a strong linear correlation between the postoperative AVB-R and the AVB-R in the traction radiograph. CONCLUSIONS As to patients with severe AIS, the coronal plane flexibility evaluated at the fulcrum bending radiograph is superior to that at the traction radiograph. This may be explained by the measurement errors induced by the better derotation capacity at the traction radiograph. Rotation correction evaluated at the traction radiograph proves better than the fulcrum bending radiographs, showing a linear correlation with the postoperative correction.


Characterization of soybean Bradyrhizobium strains adapted to the Brazilian savannas.
Brazilian soils are originally free from soybean bradyrhizobia and the first inoculants were brought to the country in this century, but a search for adapted strains started immediately and still continues. A strain selection program was established at Embrapa based on the reisolation of strains after a long period of adaptation to the soils followed by a search for variant genotypes with higher N(2) fixation capacity and competitiveness. A second approach of this program consists of searching for variant colonies of a single strain with higher N(2) fixation rates and competitiveness, following a short period of adaptation to the soil. In this study, using both approaches, strains belonging to three serogroups, CB 1809, 532C and SEMIA 5020, were obtained. In general, the variant strains showed differences in colony morphology (mucoidy) but produced similar protein and lipopolysaccharide profiles. Within serogroup CB 1809, containing variants obtained via the second approach, a low level of DNA polymorphism was detected relative to the parental genotype by ERIC and REP-PCR. However, within the two other serogroups, containing variant strains obtained via the first approach, a high level of polymorphism in ERIC and REP-PCR fingerprints was observed relative to the putative serologically related parental genotypes. These results show that a great variability can be detected following adaptation of Bradyrhizobium strains to the soil, although other potential explanations for the DNA polymorphisms observed are discussed. Some of the variant strains obtained by both methodologies were found to have higher rates of N(2) fixation and almost all were more competitive than the parental genotypes, suggesting that it is possible to select variant strains which can contribute to an improved plant N nutrition status.


Effect of Kombucha, a fermented black tea in attenuating oxidative stress mediated tissue damage in alloxan induced diabetic rats.
Diabetic complications associated with increased oxidative stress can be suppressed by antioxidants. In the present study we investigated the antidiabetic and antioxidant effects of Kombucha (KT), a fermented black tea, in comparison to that of unfermented black tea (BT), in ALX-induced diabetic rats. ALX exposure lowered the body weight and plasma insulin by about 28.12% and 61.34% respectively and elevated blood glucose level and glycated Hb by about 3.79 and 3.73 folds respectively. The oxidative stress related parameters like lipid peroxidation end products (increased by 3.38, 1.7, 1.65, 1.94 folds respectively), protein carbonyl content (increased by 2.5, 2.35, 1.8, 3.26 folds respectively), glutathione content (decreased by 59.8%, 47.27%, 53.69%, 74.03% respectively), antioxidant enzyme activities were also altered in the pancreatic, hepatic, renal and cardiac tissues of diabetic animals. Results showed significant antidiabetic potential of the fermented beverage (150 mg lyophilized extract/kg bw for 14 days) as it effectively restored ALX-induced pathophysiological changes. Moreover, it could ameliorate DNA fragmentation and caspase-3 activation in the pancreatic tissue of diabetic rats. Although unfermented black tea is effective in the above pathophysiology, KT was found to be more efficient. This might be due to the formation of some antioxidant molecules during fermentation period.


Benefit of Asian pigmented rice bioactive compound and its implication in breast cancer: a systematic review.
Background: Utilizing the bioactive compounds found in pigmented rice might significantly reduce the risk of breast cancer. This study aims to systematically review existing literature on the benefit of Asian pigmented rice bioactive compounds and their implication in breast cancer. Methods: Searches of the literature were conducted in two databases (Scopus and PubMed) for a systematic review. The keywords resulted in a total of 407 articles, consisting of 103 PubMed and 304 Scopus articles. 32 manuscripts were excluded because the article was over 10 years old. After excluding book chapters and non-English languages, we had 278 potential articles to be reviewed. After checking and screening the title and abstract and eliminating duplicate articles, then 66 articles were obtained. After the selection and elimination of the full-text manuscripts, finally 10 of them which met the inclusion criteria. Result: The included studies in this review were entirely based in Asia. The year of publication ranged from 2013 to 2020. Half of included studies used black rice extract, two used red jasmine rice extracts, and three used Korean rice extracts (black, red, dark purple and brown rice). All studies were conducted in vitro and three studies were compared with in vivo tests on female mice. The pigmented rice is mainly black, red, and dark purple rice, and contains a variety of peonidin-3-glucoside, cyanidin-3-glucoside, γ-oryzanol, γ-tocotrienol, proanthocyanidin, cinnamic acid, and anthocyanins that may act as pro-apoptotic, anti-proliferative, and anti-metastasis of the breast cancer cells. Conclusion: Pigmented rice is a beneficial food which possessed bioactive compounds that may have significant potential concerning a breast cancer.


Sex differences in anthropometric and cephalometric characteristics in the severity of obstructive sleep apnea syndrome.
Craniofacial anatomic abnormalities related to structural narrowing of the upper airway have been reported in patients with obstructive sleep apnea syndrome (OSAS). The purpose of this study was to test whether there are sex differences in the relative contributions of specific anthropometric and cephalometric measurements of OSAS severity. The subjects were Taiwanese patients who visited the Ear, Nose, and Throat Department of National Taiwan University Hospital with complaints of snoring or sleep apnea. The anthropometric, cephalometric, and overnight polysomnographic records of 109 subjects were evaluated. There are obvious sex differences in the craniofacial skeletal characteristics that contribute to OSAS severity. Male patients with the following risk factors are likely to have more severe type OSAS: increased neck size, inferiorly positioned hyoid bone, and greater anterior lower facial height. The risk factors related to the severity of OSAS in female patients include smaller posterior facial height and anteriorly positioned hyoid bone. To evaluate OSAS severity, different anthropometric and cephalometric measurements should be used for men and women. The craniofacial skeletal characteristics that contribute to OSAS severity were in the anterior lower portion of the profile in men and in the posterior portion of the profile in women.


Bone geometry and strength measurements in aging mice with the oim mutation.
Mice with the naturally occurring oim mutation allows investigation of bone pathobiology in the setting of one mutation: a G deletion in the murine Cola-2 gene (exon 52) encoding the proalpha2(I) C-propeptide. As a result, normal sized mRNA is transcribed, but no secreted protein has been identified in oim/oim fibroblasts or osteoblasts. Here we report longitudinal changes in body mass, bone geometry, and bone structural properties of femurs tested in torsion from wild type (+/+) mice and mice homozygous (oim/oim) and heterozygous (+/oim) for the oim mutation. Femurs from mice 3 months, 6 months, 12 months, and >18 months of age were dissected and X-ray films were taken in anterioposterior and mediolateral views to estimate the geometric properties. The metaphyseal ends of femurs were potted in polymethylemethacrylate and mounted on a torsional test fixture designed to convert axial tensile deformation to a torsional load using an INSTRON model 4204 materials tester. Compared with +/+ samples, peak torque at failure was reduced in oim/oim mice. Also, the geometric distribution of midshaft bone for oim/oim mice in terms of cortical area and polar moment was significantly reduced. However, the impact of the mutation on bone distribution was relatively minor for +/oim mice. Consistent with a type III classification in human OI patients, the presence of two nonfunctional alleles in homozygous oim mice significantly reduced body mass compared with age-matched wild type mice. However, no statistical difference in body mass was detected between +/oim and +/+ mice. The absence of a gross phenotypic difference between +/oim and +/+ mice demonstrates a milder phenotype in +/oim mice.


Detection and differentiation of Cryptosporidium hominis and Cryptosporidium parvum by dual TaqMan assays.
Rapid identification of the two major species of Cryptosporidium associated with human infections, Cryptosporidium hominis and Cryptosporidium parvum, is important for investigating outbreaks of cryptosporidiosis. This study reports the development and validation of a real-time PCR TaqMan procedure for detection of Cryptosporidium species and identification of C. hominis and C. parvum in stool specimens. This procedure comprised a generic TaqMan assay targeting the 18S rRNA for sensitive detection of Cryptosporidium species, as well as two other TaqMan assays for identification of C. hominis and C. parvum. The generic Cryptosporidium species assay can be duplexed with the C. parvum-specific assay. The generic Cryptosporidium species assay was able to detect ten Cryptosporidium species and did not cross-react with a panel of ten other protozoan parasites. The generic Cryptosporidium species assay could detect 1-10 oocysts in a 300 microl stool specimen, whilst each of the species-specific TaqMan assays had detection sensitivities that were approximately tenfold higher. The 18S rRNA assay was found to detect Cryptosporidium species in 49/55 DNA extracts from stool specimens containing either C. hominis or C. parvum. The C. hominis TaqMan assay correctly identified C. hominis in 24/31 validation panel specimens containing this species. The C. parvum-specific assay correctly identified C. parvum in 21/24 validation panel specimens containing this species. This real-time PCR procedure was used to detect and identify C. hominis and C. parvum in stool specimens from outbreak investigations in the USA and Botswana, resulting in identification of C. hominis and/or C. parvum in 66/67 stool specimens shown to be positive for these species using other techniques. From the outbreak specimens tested, the TaqMan procedure was found to have a specificity of 94%. This TaqMan PCR procedure should be a valuable tool for the laboratory diagnosis of cryptosporidiosis caused by C. hominis and C. parvum during outbreak investigations.


Cytotoxic effects of stem bark extracts and pure compounds from Margaritaria discoidea on human ovarian cancer cell lines.
Margaritaria discoidea (Baill.) G. L. Webster (Euphorbiaceae) is a well-known medicinal plant in Africa used for the treatment of various diseases. So far, no cytotoxic effects of plant extracts on cancer cell lines have been reported. To evaluate the cytotoxicity against human ovarian cancer cells of extracts of M. discoidea and characterize the major bioactive compounds. Both organic and aqueous extracts of this plant were obtained by maceration. The sulforhodamine B cell proliferation assay was used for evaluation of their cytotoxic activities and the potential bioactive compounds were characterized by gas chromatography-mass spectrometry. The organic extract of M. discoidea showed stronger cytotoxicity than the aqueous extract with IC50 values of 14.4±3.0, 14.2±1.2 and 34.7±0.5µg/ml on OVCAR-8, A2780 and cisplatin-resistant A2780cis ovarian cancer cells, respectively. The organic extract was further subjected to bioassay-guided fractionation by partitioning with n-hexane, ethyl acetate, and n-butanol in water. The ethyl acetate fraction was the most potent on the three ovarian cancer cell lines. A GC-MS analysis of trimethylsilyl derivatives of this fraction indicated the presence of phenolic compounds such as gallic acid and the alkaloid securinine. The IC50 values of these two compounds were determined to be in the range of 3-16µM, which indicated that they could contribute to the cytotoxic activity of the extract of M. discoidea. This study has evaluated the cytotoxicity of stem bark extracts of M. discoidea against ovarian cancer cells and provided a basis of further development of this plant for the treatment of ovarian cancer.


The enigma of microtubules and their self-organizing behavior in the cytoskeleton.
The cytoskeleton of eukaryotic cells contains networks of protein polymers called microtubules which structurally and functionally organize their interiors. Both in vivo and in vitro microtubules exhibit a fascinating and yet poorly understood array of important functions involving complex self-organization phenomena which are very sensitive to physiological and laboratory conditions, respectively. In this paper we discuss the main physical characteristics of microtubules focusing our attention on four particular aspects: (a) the dynamics of their assembly and disassembly processes (b) the types and the range of existence of ordered dipolar phases and (c) modes of energy transfer and (d) information processing capabilities.


Cognitive estimation of speed, movement and time across the lifespan.
We investigated the role of age and gender in cognitive estimation abilities. Participants completed two online tasks, where different categories of estimation were assessed (speed estimation by time and distance, and auditory estimation). Data from a total of 18886 participants (9911 females) with ages between 18 and 65 years old were gathered. Results showed variations in the estimation capacity as a function of age, with a slow but progressive decline. Estimates of duration and sound seemed to be more affected by age than estimates of speed and movement. Overall, male participants showed a better performance on both auditory and visual estimation tasks compared to females.


Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury.
Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings.


Histologic characterization of the involuting bursa of Fabricius in single-comb white Leghorn chickens.
Bursas from specific-pathogen-free white leghorn chickens of both sexes were examined at several intervals from hatching to 28 weeks of age. No histologic alterations other than scattered atrophic or cystic follicles were observed through 20 weeks. Obvious involution, first noted at 24 weeks, was in early stages in females and quite advanced in males. Involution was essentially complete by 26 weeks, and only cicatrized vestiges of bursas were present at 28 weeks of age. Gross manifestations included bursal atrophy, variable yellowish discoloration of the mucosa, and matting or total loss of identity of the mucosal plicae. Histologic characteristics of involution are summarized by the following approximate sequence: atrophy and exfoliation of plica epithelium; subepithelial stromal fibrosis; fusion and ultimate collapse of plicae; liquefactive necrosis of first medullary then cortical elements of follicles, which seemed to progress from basal to apical portions of the plicae; progressive proliferation of stromal connective tissue and infiltration of macrophages into areas occupied by necrotic follicles; and, finally, complete fibrous organization of luminal debris, leaving a firm nodule formed by a contracted muscularis surrounding the cicatrized remains of the mucosa.


The state of health in Indonesia's provinces, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.
Analysing trends and levels of the burden of disease at the national level can mask inequalities in health-related progress in lower administrative units such as provinces and districts. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to analyse health patterns in Indonesia at the provincial level between 1990 and 2019. Long-term analyses of disease burden provide insights on Indonesia's advance to universal health coverage and its ability to meet the United Nations Sustainable Development Goals by 2030. We analysed GBD 2019 estimated cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy at birth, healthy life expectancy, and risk factors for 286 causes of death, 369 causes of non-fatal health loss, and 87 risk factors by year, age, and sex for Indonesia and its 34 provinces from 1990 to 2019. To generate estimates for Indonesia at the national level, we used 138 location-years of data to estimate Indonesia-specific demographic indicators, 317 location-years of data for Indonesia-specific causes of death, 689 location-years of data for Indonesia-specific non-fatal outcomes, 250 location-years of data for Indonesia-specific risk factors, and 1641 location-years of data for Indonesia-specific covariates. For subnational estimates, we used the following source counts: 138 location-years of data to estimate Indonesia-specific demographic indicators; 5848 location-years of data for Indonesia-specific causes of death; 1534 location-years of data for Indonesia-specific non-fatal outcomes; 650 location-years of data for Indonesia-specific risk factors; and 16 016 location-years of data for Indonesia-specific covariates. We generated our GBD 2019 estimates for Indonesia by including 1 915 207 total source metadata rows, and we used 821 total citations. Life expectancy for males across Indonesia increased from 62·5 years (95% uncertainty interval 61·3-63·7) to 69·4 years (67·2-71·6) between 1990 and 2019, a positive change of 6·9 years. For females during the same period, life expectancy increased from 65·7 years (64·5-66·8) to 73·5 years (71·6-75·6), an increase of 7·8 years. There were large disparities in health outcomes among provinces. In 2019, Bali had the highest life expectancy at birth for males (74·4 years, 70·90-77·9) and North Kalimantan had the highest life expectancy at birth for females (77·7 years, 74·7-81·2), whereas Papua had the lowest life expectancy at birth for males (64·5 years, 60·9-68·2) and North Maluku had the lowest life expectancy at birth for females (64·0 years, 60·7-67·3). The difference in life expectancy for males between the highest-ranked and lowest-ranked provinces was 9·9 years and the difference in life expectacy for females between the highest-ranked and lowest-ranked provinces was 13·7 years. Age-standardised death, YLL, and YLD rates also varied widely among the provinces in 2019. High systolic blood pressure, tobacco, dietary risks, high fasting plasma glucose, and high BMI were the five leading risks contributing to health loss measured as DALYs in 2019. Our findings highlight that Indonesia faces a double burden of communicable and non-communicable diseases that varies across provinces. From 1990 to 2019, Indonesia witnessed a decline in the infectious disease burden, although communicable diseases such as tuberculosis, diarrhoeal diseases, and lower respiratory infections have remained a main source of DALYs in Indonesia. During that same period, however, all-ages death and disability rates from non-communicable diseases and exposure to their risk factors accounted for larger shares of health loss. The differences in health outcomes between the highest-performing and lowest-performing provinces have also widened since 1990. Our findings support a comprehensive process to revisit current health policies, examine the root causes of variation in the burden of disease among provinces, and strengthen programmes and policies aimed at reducing disparities across the country. The Bill & Melinda Gates Foundation and the Government of Indonesia. For the Bahasa Indonesia translation of the abstract see Supplementary Materials section.


Genes and elite athletes: a roadmap for future research.
There is compelling evidence that genetic factors influence several phenotype traits related to physical performance and training response as well as to elite athletic status. Previous case-control studies showed that ∼20 genetic variants seem to be associated with elite endurance athletic status. The present review aims to introduce novel methodological approaches in the field of sports genetics research, which can be applied in the near future to analyse the genotype profile associated with elite athletic status. These include genotype-phenotype association studies using gene expression analysis, analysis of post-transcriptional factors, particularly microRNAs, genome-wide scan linkage or genome-wide association studies, and novel algorithm approaches, such as 'genotype scores'. Several gaps in the current body of knowledge have been identified including, among others: small sample size of most athletic cohorts, lack of corroboration with replication cohorts of different ethnic backgrounds (particularly, made up of non-Caucasian athletes), the need of research accounting for the potential role of epigenetics in elite athletic performance, and also the need for future models that take into account the association between athletic status and complex gene-gene and gene-environment interactions. Some recommendations are provided to minimize research limitations in the field of sport genetics.


Outcome analysis and cost comparison between externalized pyeloureteral and standard stents in 470 consecutive open pyeloplasties.
Despite the widespread use of ureteral stents for pyeloplasty by pediatric urologists there is ongoing controversy regarding the most advantageous type of transanastomotic drainage. We compared patients who underwent placement of an externalized pyeloureteral Salle intraoperative pyeloplasty stent (Cook Urological, Spencer, Indiana) to those who had a standard Double-J ureteral stent placed to assess the benefits, drawbacks and costs of each modality during open pyeloplasty. Our study sample comprised 470 age matched children who underwent primary open pyeloplasty in an 11-year period. A total of 242 patients (51.5%) underwent Double-J ureteral stent insertion and 228 (48.5%) underwent placement of a Salle intraoperative pyeloplasty stent at surgery. Operative time, hospital stay, overall complication and success rates, type of complications and hospital costs were compared between the 2 groups. Median age was 18 months and median followup was 39 months. Mean hospital stay was 3.0 and 3.1 days in children with a Double-J ureteral and a Salle intraoperative pyeloplasty stent, respectively (p = 0.7). The overall complication rate was 9.9% (24 of 242 patients) for the Double-J ureteral stent vs 8.3% (19 of 228) for the Salle intraoperative pyeloplasty stent (p = 0.6). Complications in patients with a Double-J ureteral stent consisted of urinoma in 3, return visits due to bladder spasms in 7 or catheter obstruction in 6 and readmission due to pyelonephritis in 5. Complications in children with a Salle intraoperative pyeloplasty stent involved urinoma in 1, prolonged drainage through the Penrose drain in 5 and readmission due to pyelonephritis in 1. Recurrent ureteropelvic junction obstruction developed in 12 cases per group. The success rate was 95.0% (230 of 242 cases) and 94.7% (216 of 228) for the Double-J ureteral and the Salle intraoperative pyeloplasty stent, respectively (p = 0.2). Hospital charges, including the surgical procedure, postoperative hospitalization and cystoscopy or a clinical visit for catheter removal, in patients with a Double-J ureteral and a Salle intraoperative pyeloplasty stent were $9,825 and $9,260, respectively. The 2 ureteral stents are equivalent in regard to overall complication and success rates after pyeloplasty. However, Salle intraoperative pyeloplasty stent insertion was associated with a Canadian $565 cost decrease per patient and most importantly the preclusion of a second general anesthesia for catheter removal.


Activation of the cholinergic antiinflammatory pathway reduces ricin-induced mortality and organ failure in mice.
Exposure to ricin, either by accident through ingestion of castor oil plant seeds or intentionally through its use as a bioweapon, invariably leads to multiple organ damage and death. Currently there is only a vaccine in advanced development to ricin, but no other antidote. Ricin causes systemic inflammation with increased proinflammatory cytokine release and subsequent multiple organ failure, particularly kidney and liver dysfunction. Activation of the cholinergic antiinflammatory pathway, specifically through the alpha7 nicotinic acetylcholine receptor (either indirectly through vagus nerve stimulation or directly through nicotine treatment) reduces proinflammatory gene expression. This activation also increases release of proinflammatory chemokines and cytokines, and has proven effective in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against ricin toxicity in mice. Male Balb/c mice exposed to ricin had increased serum levels of the inflammatory cytokine tumor necrosis factor-alpha and markers of both kidney (blood urea nitrogen, creatine) and liver (alanine tranaminase) dysfunction, with a subsequent increase in mortality. Nicotine administration 2 h after ricin injection significantly delayed and reduced ricin-induced mortality, an effect coupled with reduced serum levels of tumor necrosis factor-alpha and markers of kidney and liver dysfunction. Both the kidney and liver had markedly increased cellular oxidative stress following ricin exposure, an effect attenuated by nicotine administration. In conclusion, these data demonstrate that in cases of ricin poisoning, activation of the cholinergic antiinflammatory pathway may prove beneficial by reducing organ damage, delaying mortality, and allowing for a greater chance of survival.


A Pilot Assessment of Ethnic Differences in Cosmetic Outcomes following Breast Conservation Therapy.
One of the primary benefits of breast conserving therapy (BCT) is the potential ability to preserve the aesthetic appearance of the breast. However, current literature and clinical experience suggest that the aesthetic benefits of BCT may not be equally shared among ethnic groups. This is a pilot study that uses novel techniques to evaluate the cosmetic outcomes of African American and white women following BCT. A total of 21 participants (10 African American and 11 white) completed the study. Cosmetic outcomes following BCT were evaluated by a multidisciplinary team using both quantitative and qualitative measures, including 3-dimensional photographic analysis and a pilot questionnaire. Preliminary measures were taken to evaluate the validity of the questionnaire. There were no statistically significant differences in objective measures of breast symmetry between African American patients and white patients (P > 0.05 in all cases). However, all raters reported the African American patients to have worse breast symmetry and appearance when compared with white patients. Interrater reliability was found to be fair with regard to the nipple complex questions [intraclass correlation (ICC), 0.56], good with regard to the breast mound questions (ICC, 0.66), and poor with regard to the scar appearance questions (ICC = 0.32). Although generalizing the results of this study is limited by the small sample size, it seems that there is a difference in the perception of cosmetic outcomes between white and African American patients. The novel techniques of cosmetic evaluation used in this study show promise toward identifying variables that can affect cosmetic outcome following BCT.


H-2 histocompatibility region: influence on the murine glucocorticoid receptor and its response.
The influence of the H-2 histocompatibility complex on glucocorticoid receptor levels, and the biochemical response of glucocorticoid action measured as the degree of inhibition of prostaglandin production, has been studied in the mouse thymus and lung. The B10A (H-2a) strain of mice has significantly higher glucocorticoid receptor levels and a significantly greater biochemical response to glucocorticoid than the B10 (H-2b) strain, which differs from B10A within the H-2 complex only. Thus, the anti-inflammatory hormone response of glucocorticoids is correlated to hormone receptor level, both of which are influenced by the H-2 locus.


[The condition and trends of morbidity of diseases of urogenital system in adult population of Moscow].
The article presents the results of studying state and trends of incidence of adult urban population in the city of Moscow by the classes of diseases of the genitourinary system. The purpose of study was to analyze urogenital morbidity of population of metropolis as compared with similar indices of the Central Federal Okrug and the Russian Federation in 2014-2018. The corresponding official statistical data of the Minzdrav of Russia and research publications were studied. It was established that permanent monitoring of dynamics of urological morbidity can be considered as important methodological and informational and analytical base for planning medical care of population, that makes it possible to develop in practice the basis of development and implementation of integrated system of measures of development of community-based and hospital care, which must be taken into account by the administration of medical organizations and health care management at various levels.


Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients.
Assessment of fluid responsiveness relies on dynamic echocardiographic parameters that have not yet been compared in large cohorts. To determine the diagnostic accuracy of dynamic parameters used to predict fluid responsiveness in ventilated patients with a circulatory failure of any cause. In this multicenter prospective study, respiratory variations of superior vena cava diameter (∆SVC) measured using transesophageal echocardiography, of inferior vena cava diameter (∆IVC) measured using transthoracic echocardiography, of the maximal Doppler velocity in left ventricular outflow tract (∆VmaxAo) measured using either approach, and pulse pressure variations (∆PP) were recorded with the patient in the semirecumbent position. In each patient, a passive leg raise was performed and an increase of aortic velocity time integral greater than or equal to 10% defined fluid responsiveness. Among 540 patients (379 men; age, 65 ± 13 yr; Simplified Acute Physiological Score II, 59 ± 18; Sequential Organ Failure Assessment, 10 ± 3), 229 exhibited fluid responsiveness (42%). ∆PP, ∆VmaxAo, ∆SVC, and ∆IVC could be measured in 78.5%, 78.0%, 99.6%, and 78.1% of cases, respectively. ∆SVC greater than or equal to 21%, ∆VmaxAo greater than or equal to 10%, and ∆IVC greater than or equal to 8% had a sensitivity of 61% (95% confidence interval, 57-66%), 79% (75-83%), and 55% (50-59%), respectively, and a specificity of 84% (81-87%), 64% (59-69%), and 70% (66-75%), respectively. The area under the receiver operating characteristic curve of ∆SVC was significantly greater than that of ∆IVC (P = 0.02) and ∆PP (P = 0.01). ∆VmaxAo had the best sensitivity and ∆SVC the best specificity in predicting fluid responsiveness. ∆SVC had a greater diagnostic accuracy than ∆IVC and ∆PP, but its measurement requires transesophageal echocardiography.


Bis-isonicotinoyl linkers containing polyaromatic scaffolds: synthesis, structure and spectroscopic properties.
In this study, a new series of extended linkers containing different polyaromatic chromophores (biphenyl, naphthalene, anthracene, fluorene, 9,9-dimethylfluorene and fluorenone) functionalized with isonicotinoyl moieties have been synthesized by Pd-catalyzed cross-coupling reactions involving isonicotinamide and the appropriate aromatic dibromide. The optimized protocol led to the isolation of the target molecules in good yield and with high purity. These were characterized by 1H NMR, FTIR, MS, and elemental analysis and their solid state structures were solved by single-crystal X-ray diffraction analysis. Electronic absorption and emission spectra were collected both in solution (DMF) and in the solid state. TDDFT calculations were carried out to investigate the effect of the isonicotinoyl moieties on the spectral features of the central chromophores. Although in solution only the linker containing a fluorenone scaffold shows a weak fluorescence, all the isolated linkers turned out to be fluorescent in the solid state, thus paving the way for their use for the fabrication of fluorescent MOFs.


An autoimmunized mouse model recapitulates key features in the pathogenesis of Sjögren's syndrome.
The pathogenesis of Sjögren's syndrome (SS) is poorly understood. To evaluate an autoimmunization-induced experimental SS model, we firstly observed the phenotype of lymphocyte infiltration in the enlarged submandibular gland (SG). Furthermore, significant activation of caspase-3 and a high ratio of Bax-to-Bcl-2 were detected, indicating the inflammatory apoptosis associated with developmental foci. Meanwhile, the dysregulated cytokines, such as tumor necrosis factor α, IL-1β and IL-6 mRNA expression, were found to be over-expressed. A progressive decrease of aquaporin 5 and its subcellular translocation from apical to basal membrane in SG was found to be associated with the abnormally expressed M3 muscarinic acetylcholine receptor. This pattern was found to be similar to that seen in human SS and possibly contributed to the saliva secretion deficiency. Thus, this autoimmunization-induced model recapitulates the key features of human SS and may have potential for studying the pathogenesis of human SS.


Clinical relative biological effectiveness of low-energy x-rays emitted by miniature x-ray devices.
Several groups are developing ultra-miniature x-ray machines for clinical use in radiation therapy. Current systems are for interstitial radiosurgery and for intravascular insertion for irradiation to prevent re-stenosis. Typical generating voltages are low, in the 20 to 40 kV range. It is well established that the biological effectiveness of such low-energy photons is large compared with higher-energy gamma rays, because of the dominance of photoelectric absorption at low energies. We have used microdosimetric analyses to estimate RBEs for such devices, both at low doses and clinically relevant doses, relative to radiations from 60Co, 192Ir, 125I and 90Sr/90Y. The RBEs at clinically relevant doses and dose rates for these low-energy x-ray sources are considerably above unity, both relative to 60Co and to 192Ir photons, and also relative to 125I and 90Sr/90Y brachytherapy sources. As a function of depth, the overall effect of the change in dose and the change in beam spectrum results in beams whose biologically weighted dose (dose x RBE) decreases with depth somewhat more slowly than does the physical dose. The estimated clinically relevant RBEs are sufficiently large that they should be taken into account during the treatment design stage.


Correlates of immune activation marker changes in human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women who use illicit drugs.
The majority of natural history studies of human immunodeficiency virus (HIV) infection have immune and viral parameters in men. Data demonstrating that women have lower HIV-1 RNA levels than men at the same CD4 cell counts have raised the question of immunologic differences in HIV-seropositive women. This study describes levels and changes in phenotypic markers of immune maturity, function, and activation in the CD4 and CD8 cell subsets in HIV-seropositive and high-risk HIV-seronegative women. Our primary hypothesis was that activation levels would be significantly higher among illicit drug users. However, results showed that HIV-1 RNA level was the strongest predictor of marker level and that both HIV-1 RNA level and CD4 cell count were independently associated with CD4 activation, but illicit drug use was not. In summary, this study demonstrated that immune activation was a significant pathogenic feature in women and that activation was driven by HIV infection and not illicit drug use.


Usefulness of the indocyanine green fluorescence endoscope in endonasal transsphenoidal surgery.
To avoid disorientation during endoscopic endonasal transsphenoidal surgery (ETSS), the confirmation of anatomical landmarks is essential. Neuronavigation systems can be pointed at exact sites, but their spatial resolution power is too low for the detection of vessels that cannot be seen on MR images. On Doppler ultrasonography the shape of concealed arteries and veins cannot be visualized. To address these problems, the authors evaluated the clinical usefulness of the indocyanine green (ICG) endoscope. The authors included 38 patients with pituitary adenomas (n = 26), tuberculum sellae meningiomas (n = 4), craniopharyngiomas (n = 3), chordomas (n = 2), Rathke's cleft cyst (n = 1), dermoid cyst (n = 1), or fibrous dysplasia (n = 1). After opening the sphenoid sinus and placing the ICG endoscope, the authors injected 12.5 mg of ICG into a peripheral vein as a bolus and observed the internal carotid arteries (ICAs), cavernous sinus, intercavernous sinus, and pituitary. The ICA was clearly identified by a strong fluorescence signal through the dura mater and the covering thin bone. The intercavernous and cavernous sinuses were visualized a few seconds later. In patients with tuberculum sellae meningiomas, the abnormal tumor arteries in the dura were seen and the vague outline of the attachment was identified. At the final inspection after tumor removal, perforators to the brain, optic nerves, chiasm, and pituitary stalk were visualized. ICG fluorescence signals from the hypophyseal arteries were strong enough to see and spread to the area of perfusion with the passage of time. The ICA and the patent cavernous sinus were detected with the ICG endoscope in real time and at high resolution. The ICG endoscope is very useful during ETSS. The authors suggest that the real-time observation of the blood supply to the optic nerves and pituitary helps to predict the preservation of their function.


Normalization of plasma insulin profiles in diabetic subjects with programmed insulin delivery.
Normalization of plasma glucose concentration with subcutaneous injections of insulin has been difficult. With intravenous insulin delivery, normalization of plasma glucose concentration in adult-onset diabetic patients has been achieved when their plasma insulin concentration was normalized. In juvenile-onset diabetic subjects totally lacking endogenous insulin, the effect of normalization of the plasma insulin concentration has not yet been reported. In the present studies, the plasma insulin profile was normalized in four brittle, insulin-dependent diabetic subjects throughout three meals (breakfast, lunch, and supper). Plasma free insulin concentration was assayed after precipitation of endogenous insulin antibodies with polyethylene glycol. Acute meal-related increases in plasma free insulin concentration were achieved with a programmable intravenous insulin delivery system. When plasma insulin profiles were normalized in insulin-dependent diabetic subjects lacking endogenous insulin secretion, an improvement in meal-related glucose excursions was observed. However, complete normalization of plasma glucose concentration was not achieved, suggesting that factors other than plasma insulin concentration modulate carbohydrate homeostasis in brittle diabetes. These factors may include portal vein hypoinsulinemia during peripheral vein insulin infusion, stress hormone concentrations, and tissue insulin resistance.


Whose Approval Matters Most? Examining Discrepancies in Self- and Other- Perceptions of Drinking.
Research demonstrates that perceptions of others' attitudes toward drinking behaviors (injunctive norms) are strong predictors of alcohol consumption and problems. Personalized normative feedback (PNF) aims to reduce the discrepancy between one's perception of others' attitudes toward drinking and others' actual attitudes toward drinking. An implicit assumption of PNF is that self and (perceived) other attitudes toward drinking are aligned (thus, shifting one's perceptions of others' attitudes shifts one's own attitudes). However, there is minimal research on the extent to which alignment (or discrepancy) in self-other attitudes toward drinking is associated with alcohol-related outcomes. College students (N = 1,494; Mage = 20.11, 61.0% female, 66.4% White) who endorsed past-month heavy episodic drinking reported injunctive norms toward drinking on weekends, drinking daily, drinking to black out, and drinking and driving. Participants reported their perceptions of attitudes toward these drinking behaviors for three reference groups: close friends, typical university-affiliated peers, and parents. Outcomes included weekly drinking, alcohol problems, and alcohol-related risk. Response surface analyses indicated that alignment in approval (versus alignment in disapproval) of drinking demonstrated a linear association with alcohol-related outcomes. Discrepancies in self-peer and self-parent attitudes were associated with alcohol-related outcomes and one's own attitudes (versus one's ratings of others' attitudes) of drinking were more strongly associated with outcomes. Results provide evidence of how self-other discrepancies in attitudes toward drinking are associated with alcohol-related outcomes. Future work is needed to test whether self-other discrepancies in attitudes toward drinking impacts response to norms-based interventions.


The implementation of guidelines and prognosis among patients with acute coronary syndromes is influenced by physicians' perception of antecedent physical and cognitive status.
Physicians' perception of antecedent physical/cognitive status may account for the suboptimal implementation of acute coronary syndrome (ACS) guidelines. In an ACS survey of all cardiac wards, physicians' perception of antecedent physical/cognitive status was prospectively recorded and categorized as either normal, mildly impaired or significantly impaired. We examined the impact of antecedent status on the use of evidence-based medications and procedures and on mortality. Of the 2,021 patients, 1,025 (51%) had ST elevation. Impaired antecedent physical/cognitive status was diagnosed in 417 patients (20.6%), more commonly among non-ST-elevation patients (26.2 vs. 15.2%). Patients with impaired physical/cognitive status, with or without ST elevation, had significantly worse baseline demographic and clinical characteristics. They less often received aspirin, clopidogrel, platelet glycoprotein IIb/IIIa receptor antagonists, statins and beta-adrenergic blockers, and significantly less often underwent in-hospital catheterization and revascularization. Reperfusion treatment was given significantly less frequently to ST elevation patients with impaired status (63.0% for normal vs. 50.8% and 33.3% for mildly and significantly impaired status, respectively; p = 0.001). After adjustment for differences in baseline characteristics, impaired antecedent status remained independently associated with lower use of these therapies and higher mortality rates. ACS guideline implementation is significantly influenced by physicians' perception of antecedent physical/cognitive status, and thus is a crucial parameter for understanding ACS management and outcomes.


Control of iron deficiency anemia in low- and middle-income countries.
Despite worldwide economic and scientific development, more than a quarter of the world's population remains anemic, and about half of this burden is a result of iron deficiency anemia (IDA). IDA is most prevalent among preschool children and women. Among women, iron supplementation improves physical and cognitive performance, work productivity, and well-being, and iron during pregnancy improves maternal, neonatal, infant, and even long-term child outcomes. Among children, iron may improve cognitive, psychomotor, and physical development, but the evidence for this is more limited. Strategies to control IDA include daily and intermittent iron supplementation, home fortification with micronutrient powders, fortification of staple foods and condiments, and activities to improve food security and dietary diversity. The safety of routine iron supplementation in settings where infectious diseases, particularly malaria, are endemic remains uncertain. The World Health Organization is revising global guidelines for controlling IDA. Implementation of anemia control programs in developing countries requires careful baseline epidemiologic evaluation, selection of appropriate interventions that suit the population, and ongoing monitoring to ensure safety and effectiveness. This review provides an overview and an approach for the implementation of public health interventions for controlling IDA in low- and middle-income countries, with an emphasis on current evidence-based recommendations.


[Rectal cancer: situation where a referral center is needed].
One of the objectives of the French strategic plan for cancer 2009-2013 is to structure the need for referral surgery, particularly for low rectal carcinoma. However, low rectal cancer is not the only situation in the field of rectal surgery where expert unit are needed for the referral of appropriate patients. We developed the multidisciplinary strategies for low rectal cancer, advanced rectal cancer, recurrent rectal cancer and peritoneal carcinomatosis. Optimal management of these difficult situations can give a chance of long term survival while a non-optimal management could jeopardise the future of patients by changing a potentially curable disease into an incurable one.


Fate and effects of triclosan in subtropical river biofilms.
Triclosan (TCS, 5-chloro-2-(2,4-dichlorophenoxy) phenol) is a broad-spectrum antimicrobial compound. Owing to its wide use, TCS has been frequently detected in river systems, especially in the (sub-)tropics. However, little information on its interaction with river biofilm in the (sub)tropics is currently available. In the present study, subtropical river biofilms were chronically exposed to TCS for 14 d at concentrations of 0.1-100 μg/L in artificial river water, which was followed by a 7 d recovery period. The results show that 100 μg/L TCS inhibited the growth of river biofilms and the no-observed-effect concentration (NOEC) of TCS on river biofilms was 10 μg/L. The affected biofilms did not completely recover within the 7 d of recovery period due to the adsorbed TCS which was not removed together with dissolved TCS. Exposure to TCS caused significant changes in prokaryotic species composition of river biofilms but no significant effects on eukaryotic species composition. In particular, the relative abundance of several TCS-tolerant bacterial species (e.g., Pseudoxanthomonas mexicana, Sphingopyxis alaskensis and Sphingomonas wittichii) in river biofilms increased following exposure to 10 and 100 μg/L TCS. River biofilm efficiently removed TCS from the liquid phase and the pH values of the aquatic system significantly affected the removal efficiency of TCS (from 36% at pH 6.5 to 60% at pH 8.5). No degradation products were detected in the liquid phase after 5 days of exposure, possibly due to strong adsorption of the hydrophobic degradation products to river biofilms and through biodegradation by bacteria utilizing TCS and its degradation products as source of carbon and energy for growth, such as Methyloversalitis universalis and Methylobacterium aquaticum.


Findings from the Families on Track Intervention Pilot Trial for Children with Fetal Alcohol Spectrum Disorders and Their Families.
Individuals with fetal alcohol spectrum disorders (FASD) are at high risk for costly, debilitating mental health problems and secondary conditions, such as school disruption, trouble with the law, and substance use. The study objective was to pilot a multicomponent intervention designed to prevent secondary conditions in children with FASD and improve family adaptation. Thirty children with FASD or prenatal alcohol exposure (PAE) (ages 4 to 8) and their primary caregivers were enrolled. Families were randomized to either the Families on Track Integrated Preventive Intervention or an active control of neuropsychological assessment and personalized community referrals. The 30-week intervention integrates scientifically validated bimonthly, in-home parent behavioral consultation, and weekly child skills groups. Outcomes measured at baseline and follow-up postintervention included intervention satisfaction, child emotional and behavioral functioning, child self-esteem, caregiver knowledge of FASD and advocacy, caregiver attitudes, use of targeted parenting practices, perceived family needs met, social support, and self-care. Data analysis emphasized calculation of effect sizes and was supplemented with analysis of variance techniques. Analyses indicated that families participating in the intervention reported high program satisfaction. Relative to comparison group outcomes, the intervention was associated with medium-to-large effects for child emotion regulation, self-esteem, and anxiety. Medium-sized improvements in disruptive behavior were observed for both groups. Medium and large effects were seen for important caregiver outcomes: knowledge of FASD and advocacy, attributions of behavior, use of antecedent strategies, parenting efficacy, family needs met, social support, and self-care. This pilot study yielded promising findings from the multicomponent Families on Track Integrated Preventive Intervention for child and caregiver outcomes. An important next step is to complete a randomized control trial of the Families on Track Program with a larger sample fully representative of this underserved clinical population with built-in study of implementation parameters.


Jugulotympanic paragangliomas treated with Gamma Knife radiosurgery: a single-center review of 58 cases.
Jugulotympanic paragangliomas (JTPs) are rare benign tumors whose surgical treatment is usually associated with partial resection of the lesion, high morbidity, and even death. Gamma Knife radiosurgery (GKRS) has been reported as a useful treatment option. The goal of this retrospective study is to analyze the role of GKRS in tumor volume control and clinical outcomes of these patients. A total of 75 patients with JTPs were treated with GKRS at the authors' center from 1995 to 2012. The authors analyzed those treated during this period to allow for a minimal observation time of 2 years. The MR images and clinical reports of these patients were reviewed to assess clinical and volumetric outcomes of the tumors. The radiological and clinical assessments, along with a group of prognostic factors measured, were analyzed using descriptive methods. The time to volumetric and clinical progression was analyzed using the Kaplan-Meier method. Prognostic factors were identified using log-rank statistics and multivariate Cox regression models. The mean follow-up was 86.4 months. The authors observed volumetric tumor control in 94.8% of cases. In 67.2% of cases, tumor volume decreased by a mean of 40.1% from the original size. Of patients with previous tinnitus, 54% reported complete recovery. Improvement of other symptoms was observed in 34.5% of cases. Overall, clinical control was achieved in 91.4% of cases. Previous embolization and familial history of paraganglioma were selected as significant prognostic factors for volumetric response to GKRS treatment in the univariate analysis. In multivariate analysis, no factors were significantly correlated with progression-free survival. No patient died of side effects related to GKRS treatment or tumor progression. Gamma Knife radiosurgery is an effective, safe, and efficient therapeutic option for the treatment of these tumors as a first-line treatment or in conjunction with traditional surgery, endovascular treatment, or conventional fractionated radiotherapy.


The association of MHC class I proteins with the 2B4 receptor inhibits self-killing of human NK cells.
The killing activity of NK cells is carried out by several activating NK receptors, which includes NKp46, NKp44, NKp30, NKp80, NKG2D, and 2B4. The ligands of these receptors are either self-derived, pathogen-derived, stress-induced ligands or tumor ligands. Importantly, none of these killer ligands are expressed on NK cells and thus self-killing of NK cells is prevented. A notable exception with this regard, is the ligand of the 2B4 receptor. This unusual receptor can exert both activating and inhibiting signals; however, in human NK cells, it serves mainly as an activating receptor. The ligand of 2B4 is CD48 and in contrast to the ligands of all the other NK activating receptors, CD48 is also present on NK cells. Thus, NK cells might be at risk for self-killing that is mediated via the 2B4-CD48 interaction. In this study, we identify a novel mechanism that prevents this self-killing as we show that the association of the MHC class I proteins with the 2B4 receptor, both present on NK cells, results in the attenuation of the 2B4-mediated self-killing of NK cells.


Acid Hydrolysis for the Extraction of Archaeal Core Lipids and HPLC-MS Analysis.
Lipid membranes are essential cellular elements as they provide cellular integrity and selective permeability under a broad range of environmental settings upon cell growth. In particular, Archaea are commonly recognized for their tolerance to extreme conditions, which is now widely accepted to stem from the unique structure of their lipids. While enhancing the stability of the archaeal cell membrane, the exceptional properties of archaeal lipids also hinder their extraction using regular procedures initially developed for bacterial and eukaryotic lipids. The protocol described here circumvents these issues by directly hydrolyzing the polar head group(s) of archaeal lipids and extracting the resulting core lipids. Although leading to a loss of information on the nature of polar heads, this procedure allows the quantitative extraction of core lipids for most types of archaeal cells in an efficient, reproducible, and rapid manner.


[Hormonal aspects of cathepsin D regulation in seminal follicles].
Androgen-dependent regulation of cathepsin D activity was studied in rat seminal follicles. Cathepsin D, isolated from the follicles by means of ammonium sulfate fractionation, chromatography on Hb-Sepharose and Sephadex G-200, was similar to the enzyme from other tissues in molecular mass, Km for hemoglobin, pH optimum of activity, thermolability. Concentration of androgens in tissues affected the properties of purified cathepsin D: the enzyme activity, its sensitivity to thermoinactivation and to chymotryptic hydrolysis were increased as well as the pH optimum was expanded after orchidectomy. Testosterone restored the initial enzyme properties altered after castration.


Staged ESWL monotherapy of complete renal staghorn calculi.
A retrospective study was done on 64 patients who received staged extracorporeal shock wave lithotripsy (ESWL) monotherapy for complete renal staghorn calculi. We used laboratory-proven stone components and a regular postoperative follow-up for a minimum of 6 months. There were 46 women and 18 men. The ages ranged from 19 to 75 years (mean 48.5 years). The number of ESWL sessions ranged from 1 to 4, with a mean of 2.1 sessions. The mean cumulative hospital stay was 13.3 days (range: 6-26 days). Successful treatments were defined as debulking over 90% of the stone burden and residual fragments of less than 3 mm in the longest diameter without obstruction 6 months post-treatment. A success rate of 86% was achieved in patients who had normal or minimal hydrocalycosis and only a 14.3% success rate for the patients with moderate to severe hydrocalycosis (p less than 0.005). Five of the patients with radiant calcium oxalate monohydrate had an unfavorable outcome. The best results were observed in the patient group of magnesium ammonium phosphate/apatite with normal to minimal hydrocalycosis (94.4% successful). The stone-free rate in this series was 51.6% at 6 months posttreatment. Being the least invasive, staged ESWL monotherapy is one of the better alternatives for the treatment of complete renal staghorn calculi in a select patient group.


Distribution and projections of nerves with enkephalin-like immunoreactivity in the guinea-pig small intestine.
Whole mounts of guinea-pig small intestine were used to examine the distribution of neurons with enkephalin-like immunoreactivity and the effects of microsurgical lesions on these neurons. The enkephalin neurons are intrinsic to the intestine. Cell bodies are found in the myenteric ganglia; processes are in the myenteric plexus, circular muscle (including deep muscular plexus) and submucosa, but not in the mucosa. The cell bodies have one prominent process and several short processes, the latter occasionally are seen to give rise in turn to fine, faint processes. The prominent processes provide fibres to the circular muscle and deep muscular plexus beneath and just anal (up to about 2 mm) to the cell bodies. Fibres in the submucous ganglia come from the overlying myenteric plexus. Orally-directed processes (possibly dendrites) of myenteric cell bodies provide the varicose fibres in the myenteric ganglia. These processes are 3.5-4 mm long. The enkephalin neurons represent a population of enteric neurons, with a distinct distribution and projections, which does not correspond to any of the other populations of enteric neurons that have been studied.


Late effects of jejunoileal bypass operations on hepatic inflammation, fibrosis and lipid content.
Patients more than six years following jejunoileal bypass operations for morbid obesity underwent liver biopsy for evaluation of hepatic histology and determination of hepatic lipid content. The amount of hepatic inflammation and fibrosis present was quantitated and compared to that present in liver biopsy specimens obtained at the time of performance of the jejunoileal bypass operation. Hepatic lipid content was compared to that present in the livers of six normal-weight patients with no liver disease, and with liver specimens from twenty morbidly obese patients undergoing gastroplasty operations. Since their jejunoileal bypass operations, hepatic fibrosis has increased in 87% of the patients and hepatic inflammation in 52%. Fibrotic liver disease is currently present in 50% of the patients compared to 10% at the time of performance of the jejunoileal bypass operations. Patients with jejunoileal bypass operations were found to have nine times more hepatic triglyceride than was found in patients with normal livers, and twice as much as identified in obese patients. These results suggest that some patients with jejunoileal bypass operations have severe liver histologic disease associated with increased hepatic triglyceride content. Patients with jejunoileal bypass operations should have periodic histologic evaluation of their liver.


Glycoprotein metabolism in inflammatory and neoplastic diseases of the human colon.
Carbohydrate compositions of the membrane and cytoplasmic fractions of human normal and cancerous colonic mucosa were compared in patients with blood groups O and B. The total sugar content in both fractions was reduced in the cancer tissues to about one-third of that in the normal colonic mucosa. The sugars that are associated with mucinous glycoproteins such as fucose and N-acetylgalactosamine were reduced significantly, while sugars that are primarily associated with "serum-type" glycoproteins were relatively unchanged or reduced to a lesser extent. The activities of glycoprotein:glycosyltransferases were variable, some showing so significant change, others beinb significnatly reduced in cancerous tissues. A polypeptidyl:N-acetylgalactosaminyltransferase (an enzyme that catalyzes the transfer of the first sugar to hydroxyamino acids of the protein core of mucinous glycoproteins), a sialyltransferase (involved in the addition of sialic acid to mucinous glycoproteins), and a galactoxyltransferase (thought to be responsible for blood group B antigenicity) were reduced in the cancerous colonic tissue. In contrast, the activities of these glycosyltransferases were unchanged in the colonic mucosa of patients with granulomatosis or ulcerative colitis. Glycosidase activities in the normal, cancerous, and inflammatory tissues were the same. These results suggest that in colonic cancer tissues the synthesis of one type of oligosaccharide chain may be greatly affected, while another family of oligosaccharides may remain relatively unaffected.


Cartilaginous symphysis pubis cysts: report of two cases, technique for removal, and review of the literature.
Cartilaginous symphysis pubis cysts are rare. There are 7 cases previously reported in the literature. Patients are commonly asymptomatic or may present with a slow-growing, painless vulvar mass, voiding difficulty, and/or dyspareunia. Two cases were managed at our center over 5 years. We present these 2 cases, a surgical technique for removal, a summary of all reported cases, and some perspectives on the pathophysiologic mechanisms for the origin of this lesion.


Local Symmetry Effects in Actinide 4f X-ray Absorption in Oxides.
A systematic X-ray absorption study at actinide N6,7 (4f → 6d transitions) edges was performed for light-actinide oxides including data obtained for the first time for NpO2, PuO2, and UO3. The measurements were supported by ab initio calculations based on local-density-approximation with added 5f-5f Coulomb interaction (LDA+U). Improved energy resolution compared to common experiments at actinide L(2,3) (2p → 6d transitions) edges allowed us to resolve the major structures of the unoccupied 6d density of states (DOS) and estimate the crystal-field splittings in the 6d shell directly from the spectra of light-actinide dioxides. The measurements demonstrated an enhanced sensitivity of the N(6,7) spectral shape to changes in the compound crystal structure. For nonstoichiometric NpO(2-x), the filling of the entire band gap with Np 6d states was observed thus supporting a phase coexistence of Np metal and stoichiometric NpO2 which is in agreement with the tentative Np-O phase diagram.


Yersinia remodels epigenetic histone modifications in human macrophages.
Various pathogens systematically reprogram gene expression in macrophages, but the underlying mechanisms are largely unknown. We investigated whether the enteropathogen Yersinia enterocolitica alters chromatin states to reprogram gene expression in primary human macrophages. Genome-wide chromatin immunoprecipitation (ChIP) seq analyses showed that pathogen-associated molecular patterns (PAMPs) induced up- or down-regulation of histone modifications (HMod) at approximately 14500 loci in promoters and enhancers. Effectors of Y. enterocolitica reorganized about half of these dynamic HMod, with the effector YopP being responsible for about half of these modulatory activities. The reorganized HMod were associated with genes involved in immune response and metabolism. Remarkably, the altered HMod also associated with 61% of all 534 known Rho GTPase pathway genes, revealing a new level in Rho GTPase regulation and a new aspect of bacterial pathogenicity. Changes in HMod were associated to varying degrees with corresponding gene expression, e. g. depending on chromatin localization and cooperation of the HMod. In summary, infection with Y. enterocolitica remodels HMod in human macrophages to modulate key gene expression programs of the innate immune response.


Morphology and function of the tongue and hyoid apparatus in Varanus (Varanidae, Lacertilia).
The morphology and function of the tongue and hyoid apparatus in Varanus were examined by anatomical and experimental techniques. Morphological features unique to Varanus include a highly protrusible tongue that has lost a roughened dorsal surface, an exceptionally strong and mobile hyobranchial apparatus, a well-defined joint between the ceratohyal and anterior process, and a series of distinct muscles inserting at the anterior hyobranchial region. Varanus is also unusual among lizards in a number of feeding behaviors; it ingests prey entirely by inertial feeding, as the tongue does not participate in food transport. Further specializations include an increased reliance on hyobranchial movements in drinking and pharyngeal packing and compression. The long, narrow tongue is most likely related to the mechanics of tongue protrusion; the increased amount, strength, and complexity of hyobranchial movement is related to the fact that the hyobranchium in Varanus replaces the tongue in many functions. Previous hypotheses for the origin of these adaptations are discussed, and the difficulties of attributing these specializations to any specific scenario of adaptation or constraint are emphasized.


What constitutes a good healthcare experience for unintended pregnancy? A qualitative study among young people in California.
Little is known about young people's experiences accessing healthcare for unintended pregnancy in the USA. To address this gap, we conducted in-depth interviews with 25 young people in California who had experienced at least one unintended pregnancy at or before 25 years of age. Participants were asked about their interactions with healthcare providers during the pregnancy, their thoughts on the determinants of their perceived quality of care, and the ways in which their healthcare experience could have been improved. Thematic analysis was used to organise information within and across interview transcripts. Two important determinants of participants' satisfaction with their healthcare experience were identified during analysis: (1) receiving comprehensive information about their pregnancy options and what to expect from each, and (2) having an empathetic, non-judgemental provider. Regarding abortion, participants described an unmet need for accurate information and frequent stigmatising experiences with dismissive and judgemental care providers. These findings highlight the importance of providing comprehensive, non-judgemental pregnancy options counselling to all pregnant people, regardless of age and desired pregnancy outcome; and reinforce the need for providers to consider ways in which their own bias may influence the quality of care they provide.


High-Efficiency Bifacial Dye-Sensitized Solar Cells for Application under Indoor Light Conditions.
High-efficiency, stable bifacial dye-sensitized solar cells (DSSCs) are prepared for application under indoor light conditions. A 3-methoxypropionitrile solvent and cobalt redox couples are utilized to prepare the electrolytes. To obtain the best cell performance, the components of the DSSCs, including electrolytes, photoanodes, and counter electrodes (CEs), are regulated. The experimental results indicate that an electrolyte comprising a Co (II/III) ratio of 0.11/0.025 M, 1.2 M 4-tert-butylpyridine, Y123 dye, a CE with the platinum (Pt) layer thickness of 0.16 nm, and a photoanode with titanium dioxide (TiO2) layer thickness of 10 μm (6 μm main layer and 4 μm scattering layer) are the best conditions under which to achieve a high power conversion efficiency. It is also found that the best cells have high recombination resistance at the photoelectrode/electrolyte interface and low charge transfer resistance at the counter electrode/electrolyte interface, which contributes to, respectively, the high current density and open-circuit voltage of the corresponding cells. This DSSC can achieve efficiencies of 22.66%, 23.48%, and 24.52%, respectively, under T5 light illumination of 201.8, 607.8, and 999.6 lx. For fabrication of bifacial DSSCs with a semitransparent property, photoanodes without the TiO2 scattering layer, as well as an ultrathin Pt film, are utilized. The thicknesses of the TiO2 main layer and Pt film are reregulated. This shows that a Pt film with 0.55 nm thickness has both high transmittance (76.01%) and catalytic activity. By using an 8 μm TiO2 main layer, optimal cell efficiencies of 20.65% and 17.31% can be achieved, respectively, for the front-side and back-side illuminations of 200 lx T5 light. The cells are highly stable during a long-term performance test at both 35 and 50 °C.


The antinociceptive effect of tramadol-venlafaxine combination on the paw withdrawal threshold in a rat model of neuropathic pain.
The combination of venlafaxine and tramadol was compared with the single use of these agents to investigate the antinociceptive effect on paw withdrawal latency (PWL) to paw pressure in rats with neuropathic pain. Rats were divided into 4 groups: group 1 received saline (0.2 ml i.p.); group 2 received venlafaxine (22 mg/kg i.p.); group 3 received tramadol (20 mg/kg i.p.); and group 4 received venlafaxine + tramadol. No statistically significant changes were observed in the saline and venlafaxine groups with respect to PWL in the lesioned paw. However, tramadol produced a significant antinociceptive effect on the lesioned paw at 30 min compared with the saline and venlafaxine groups. A more potent antinociceptive effect was observed in the tramadol + venlafaxine group, beginning at 60 min and lasting for 1 h. The combination of venlafaxine + tramadol was more effective in increasing the pain threshold in this animal model of neuropathic pain than either of these drugs administered alone.


Indexes of body cell mass: nitrogen versus potassium.
In vivo neutron activation has provided investigators with a powerful tool for research on body composition. Total-body nitrogen (TBN), total-body potassium (TBK), and total-body water (TBW) were measured in 133 normal subjects. TBN, measured by neutron activation, is a measure of total-body protein, an index of body cell mass. TBK, also measured by a nuclear reaction, is an index of body cell mass as well as lean body mass. The mass and protein content of two compartments, muscle and nonmuscle lean tissue, were determined from the combined TBN-TBK data by compartmental analysis. In this study, nitrogen was separated into the actively metabolizing body cell mass component and the slowly metabolizing structural component. The TBK, which is 95% intracellular, was found to be more closely related to the actively metabolizing nitrogen than to TBN. The relationship of body cell mass, a concept originally proposed by Moore, to lean body mass, is shown through the relationship of TBN and TBK. The clinical significance of this study, is that TBK is the more sensitive and reliable indicator of changes in body cell mass. Maximum information on body composition, however, is obtained by the measurement of both TBK and TBN.


Hyperplastic polyps in hereditary nonpolyposis colorectal cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, in particular hMLH1, hMSH2, and hMSH6. Dysfunction of MMR genes leads to loss of MMR protein expression and to microsatellite instability (MSI). MSI is also detected in 10-20% of sporadic colorectal cancers. Hyperplastic polyps (HP) may serve as precursor for these MSI+ sporadic colorectal cancers. The aim of this study was to examine whether hyperplastic polyps are also possible premalignant lesions in HNPCC. All HPs resected from (suspected) mismatch repair gene mutation carriers were retrieved from a screening program database. Clinical information on patient age at colonoscopy and location of the HP was collected. MLH1, MSH2, and MLH6 protein expression was evaluated using immunohistochemistry. A total of 90 HPs were resected from 21 men and 19 women. The mean patient age at resection was 45.7 yr (44.7 yr in men and 46.6 yr in women). In all patients, 19 (21%) HPs were resected from the proximal colon, 23 (26%) from the distal colon, and 48 (53%) from the rectum. None of the HPs demonstrated loss of MMR protein expression. Mismatch repair dysfunction in HPs of HNPCC patients is apparently very rare. It seems unlikely that HPs in HNPCC patients are precursors for (MSI+) cancers in these patients.


Cancer symptom burden negatively affects health-related quality of life in patients undergoing prehabilitation prior to liver resection: results from a 12-week randomized controlled trial.
Cancer symptoms negatively affect health-related quality of life (HRQoL) in patients with cancer awaiting liver resection. Prehabilitation maintained HRQoL after surgery. Future studies should test whether relieving cancer symptoms can improve HRQoL.


Membrane attack complex of complement. Evidence for its dimeric structure based on hybrid formation.
Molecular hybridization experiments provided new evidence for the dimeric nature of the membrane attack complex (MAC) of complement. Monomeric C5b-6, which constitutes the first intermediate complex in MAC formation, was prepared in two differentially labeled forms: biotin-125I-C5b-6 and 131I-C5b-6. Using a mixture of the differentially labeled C5b-6, the MAC was assembled on phospholipid vesicles upon addition of C7, C8, and C9. The assembled MAC containing biotin-125I and 131I was extracted from the vesicles with deoxycholate, purified, and exposed to avidin-Sepharose. Biotin-mediated binding of the MAC to avidin-Sepharose not only effected binding of 125I, but also of 131I, indicating that both radiolabels resided in the same molecular entity. When equimolar amounts of differentially labeled C5b-6 were available for MAC formation, 50% of MAC formed contained one molecule of each form. Theoretical analysis of the experimental data clearly favored the dimer structure over the structure of a higher oligomer. In contrast, fluid phase SC5b-9 was clearly monomeric on the basis of the same analysis. The electron microscopic appearance of the biotinated MAC hybrid closely resembled that of the characteristic membrane lesions of complement lysed cells. An avidin-ferritin conjugate attached itself to the ring-shaped portion of the biotinated MAC and not to its perpendicular structures, suggesting that C5b-6 is an integral part of the ring structure of the MAC.


Meeting targets or saving lives: maternal health policy and Millennium Development Goal 5 in Nicaragua.
In support of maternal health, disease-specific and target-oriented global policy initiatives, such as in Millennium Development Goal 5, have led to a prioritisation of narrow indicators at the expense of more comprehensive approaches. In line with global policy, Nicaragua has made skilled attendants and institutionalised delivery central to its efforts to achieving MDG5 on maternal health. Drawing on ethnographic fieldwork in Nicaragua, involving participant observation and interviews with hospital and community health workers, and women and their families, this paper critically discusses how target-oriented maternal health strategies were manifested in local realities. It shows that Nicaragua's brigadistas (community health workers) and parteras (traditional birth attendants) have been driven to narrowing their own roles to identifying pregnant women and advocating that they have an institutional delivery as one their most important tasks, making them agents of MDG 5 target achievement. This has engendered fear among brigadistas and parteras of being held individually responsible in the event of a maternal death, creating dissatisfaction with their role and reducing their motivation. While intended to improve maternal health, the pressure to reach targets has unintended negative implications for the relationship between women, the local volunteers and the formal health system, which needs to be addressed.


Effects of Artemisia Princeps Supplementation on Bone Metabolism in Ovariectomized Rats.
The aim of this study was to investigate the effects of Artemisia princeps (AP) extract on bone metabolism and its potential role in the prevention of osteoporosis in ovariectomized rats. Twenty-six female Sprague-Dawley rats were divided into five groups and treated as follows: sham-operated control group (SHAM); ovariectomized control group (OVX), ovariectomized group treated by gavage with 10 mg/kg/day alendronate (ALEN); ovariectomized group treated by gavage with 100 mg/kg/day Artemisia princeps (AP100); ovariectomized group treated by gavage with 300 mg/kg/day Artemisia princeps (AP300). Treatment of ovariectomized rats with AP extracts for 15 weeks prevented the reduction in bone thickness and trabecular bone mineral density caused by urinary Ca and Cr excretion, and also prevented the increase in bone turnover by maintaining the serum Ca/P ratio. As a result, the microarchitecture of the trabecular bone and cortical bone after ovariectomy was markedly improved by administration of AP extracts. In conclusion, AP prevented bone loss and osteoclast activity associated with high bone turnover in ovariectomized rats by controlling the serum Ca/P ratio and through anti-inflammatory and anti-oxidant properties. Our data implicate AP as a promising therapeutic option for the improvement of postmenopausal osteoporosis.


Social calls in humpback whale mother-calf groups off Sainte Marie breeding ground (Madagascar, Indian Ocean).
Humpback whales (Megaptera novaeangliae) use vocalizations during diverse social interactions or activities such as foraging or mating. Unlike songs produced only by males, social calls are produced by all types of individuals (adult males and females, juveniles and calves). Several studies have described social calls in the humpback whale's breeding and the feeding grounds and from different geographic areas. We aimed to investigate for the first time the vocal repertoire of humpback whale mother-calf groups during the breeding season off Sainte Marie island, Madagascar, South Western Indian Ocean using data collected in 2013, 2014, 2016, and 2017. We recorded social calls using Acousonde tags deployed on the mother or the calf in mother-calf groups. A total of 21 deployments were analyzed. We visually and aurally identified 30 social call types and classified them into five categories: low, medium, high-frequency sounds, amplitude-modulated sounds, and pulsed sounds. The aural-visual classifications have been validated using random forest (RF) analyses. Low-frequency sounds constituted 46% of all social calls, mid-frequency 35%, and high frequency 10%. Amplitude-modulated sounds constituted 8% of all vocalizations, and pulsed sounds constituted 1%. While some social call types seemed specific to our study area, others presented similarities with social calls described in other geographic areas, on breeding and foraging grounds, and during migrating routes. Among the call types described in this study, nine call types were also found in humpback whale songs recorded in the same region. The 30 call types highlight the diversity of the social calls recorded in mother-calf groups and thus the importance of acoustic interactions in the relationships between the mother and her calf and between the mother-calf pair and escorts.


Ultrathin and Flat Layer Black Phosphorus Fabricated by Reactive Oxygen and Water Rinse.
Ultrathin black phosphorus (BP) is one of the promising two-dimensional (2D) materials for future optoelectronic devices. Its chemical instability in ambient conditions and lack of a bottom-up approach for its synthesis necessitate efficient etching methods that generate BP films of designed thickness with stable and high-quality surfaces. Herein, reporting a photochemical etching method, we demonstrate a controlled layer-by-layer thinning of thick BP films down to a few layers or a single layer and confirm their Raman and photoluminescence characteristics. Ozone molecules generated by O2 photolysis oxidize BP, forming P2O5-like oxides. When the resulting phosphorus oxides are removed by water, the surface of BP with preset thickness is highly flat and self-protective by surface oxygen functional groups. This method provides a fabrication strategy of BP and possibly other 2D semiconductors with band gaps tuned by their thickness.


Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels.
The field of tissue engineering is severely limited by a lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent non-specific cell adhesion, thus providing a "blank slate", which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to the widespread effects of PDGF in the body and a half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on two-dimensional modified surfaces, migration in three-dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea micropocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized fibroblast growth factor-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels compared with the presentation of each factor alone. When a co-culture of endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared with soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering.


Branch retinal artery occlusion in a young woman with Ménière's disease.
An unusual case of a 32-year-old woman with branch retinal artery occlusion is presented. The patient was affected by Ménière's disease and had a history of occasional migraine headaches. A thorough clinical and laboratory investigation showed a high cholesterol level. Retinal arterial obstruction is rare in young people and it is difficult to establish the precise cause. The presumed multifactorial etiologic factors are discussed.


The mechanism of substrate activation of pyruvate decarboxylase: a first approach.
The sigmoidal shape of the curve for v[S], characteristic of pyruvate decarboxylase, indicates that the catalytic activity of this enzyme is regulated by the substrate. The enzyme, which is inactive in the absence of its substrate, is activated not only by 2-oxo acids but also by 2-oxo acid amides, which cannot act as a substrate of the enzyme. Whilst the dissociation constant of the enzyme-activator complex depends on the electrophilic nature of the carbonyl group, the catalytic activity reached at saturation concentrations of the activator species is independent of the structure of the activator molecules. The mechanism of activation which proceeds via two reversible steps could be evaluated exactly by stopped-flow techniques. The kinetic parameters of the activation and deactivation reaction were estimated and the validity of the equations derived which describe the activation kinetics could be proved by comparing them with the measured data. Using glyoxylic acid as an irreversibly binding active-site marker, it could be shown that addition of the substrate to the enzyme-bound thiamin diphosphate is the step of the catalytic mechanism whose rate is controlled by the substrate (activator) molecule.


Assessment of bile fluorescence patterns in a tropical fish, Nile tilapia (Oreochromis niloticus) exposed to naphthalene, phenanthrene, pyrene and chrysene using fixed wavelength fluorescence and synchronous fluorescence spectrometry.
Bile fluorescence patterns in Nile tilapia, a potential fish for biomonitoring tropical water pollution were assessed following exposure to selected polycyclic aromatic hydrocarbons (PAHs): naphthalene, phenanthrene, pyrene and chrysene. Non-normalized fixed wavelength fluorescence signals in the fish exposed to these PAHs reflected dose and/or time response relationships of their metabolism. Normalizing signals to biliverdin introduced deviations to these response patterns. The optimal wavelength pairs (excitation/emission) for synchronous fluorescence scanning measurements of bile metabolites of naphthalene, phenanthrene, pyrene and chrysene were identified as 284/326, 252/357, 340/382 and 273/382 respectively. This study supports the use of bile fluorescence in Nile tilapia by fixed wavelength fluorescence and synchronous fluorescence spectrometry with non-normalized data as a simple method for screening bioavailability of these PAHs.


Experiences of structural vulnerability among exotic dancers in Baltimore, Maryland: Co-occurring social and economic antecedents of HIV/STI risk.
Women who grow up in economic scarcity often face limited opportunities for upward mobility, as a result of challenges securing stable housing, quality education, and steady employment. Chronic instability may limit the capacity of women to protect themselves against HIV/STI-related harm when engaging in sexual activity or drug use. Characterizing the structural contexts that facilitate HIV/STI risk among women are critical to effective design and implementation of drug and sexual harm reduction interventions. Semi-structured in-depth interviews were completed with 25 female exotic dancers working in Baltimore City and County exotic dance clubs July 2014-May 2015. Using thematic analysis, interviews were examined to understand the nature of structural vulnerability experienced by dancers during their early lives through the initial months of exotic dancing, including an examination of the roles of drug use and social relationships in engagement of sexual risk behavior. Dancers depicted early experiences of social and economic disadvantage, which accumulated through early adulthood. Substance use emerged as an important subject for the majority of women, operating cyclically as both precursor to and product of accumulating social and economic hardship. Dancers revealed social strategies that buffered the effects of structural vulnerability and minimized exposure to workplace-related drug and sexual harms. This study provides insight on an understudied group of at-risk women with a unique demographic profile. Findings illustrate how the effects of structural vulnerability, substance abuse, social strategies, and opportunities for economic gain through sexual services in the workplace converge to produce varying levels of HIV/STI risk among exotic dancers.


Acceleration-based joint stability parameters for total knee arthroplasty that correspond with patient-reported instability.
There is no universally accepted definition of human joint stability, particularly in nonperiodic general activities of daily living. Instability has proven to be a difficult parameter to define and quantify, since both spatial and temporal measures need to be considered to fully characterize joint stability. In this preliminary study, acceleration-based parameters were proposed to characterize the joint stability. Several time-statistical parameters of acceleration and jerk were defined as potential stability measures, since anomalous acceleration or jerk could be a symptom of poor control or stability. An inertial measurement unit attached at the level of the tibial tubercle of controls and patients following total knee arthroplasty was used to determine linear acceleration of the knee joint during several activities of daily living. The resulting accelerations and jerks were compared with patient-reported instability as determined through a standard questionnaire. Several parameters based on accelerations and jerks in the anterior/posterior direction during the step-up/step-down activity were significantly different between patients and controls and correlated with patient reports of instability in that activity. The range of the positive to negative peak acceleration and infinity norm of acceleration, in the anterior/posterior direction during the step-up/step-down activity, proved to be the best indicators of instability. As time derivatives of displacement, these acceleration-based parameters represent spatial and temporal information and are an important step forward in developing a definition and objective quantification of human joint stability that can complement the subjective patient report.