Structure and Luminescent Properties of Glasses in the GeS2-Ga2S3-Sb2S3:Pr3+ System.
The physicochemical, optical, and luminescent properties and structures of glasses of the Ga2S3-GeS2-Sb2S3:Pr system have been studied in a wide range of concentrations of the main components in order to reveal their correlation with the composition. According to the calculations using the Judd-Ofelt theory, glasses with a high content of Sb2S3 should provide the highest luminescence efficiency of Pr3+ ions. However, this result is leveled by enhancing the concentration quenching effect, followed by an increase of the Sb2S3 content in the glasses. The introduction of Pr leads to a significant increase in the fraction of Sb-Sb, Sb-Ge, Ge-Ge bonds in glasses enriched with Sb2S3 and GeS2. In the cases of the glasses enriched with Ga2S3, this effect was not observed, apparently because Ga promotes the formation of three-coordinated sulfur atoms.


Patient awareness, knowledge and use of colchicine: an exploratory qualitative study in the Counties Manukau region, Auckland, New Zealand.
INTRODUCTION Treatment of gout, specifically with colchicine, varies globally. Colchicine can be fatal due to its narrow therapeutic index and potential for interactions. In New Zealand, cases of intentional and unintentional colchicine overdose have been documented. AIMS To explore patients' knowledge on the use of gout medicines, and in particular their awareness of the maximum dose of colchicine, the dangers of colchicine overdose, and their opinions on restricting colchicine dispensing. The study also investigates where patients receive gout information. METHODS Thirty people with gout presenting to their regular gout clinic in Auckland currently or previously taking colchicine were invited to participate in a 30-min semi-structured interview. Data were analysed using a general inductive thematic approach. FINDINGS Overall, participants had a lack of knowledge regarding colchicine and used variable doses during an acute gout attack. Participants were unsure of the maximum dose of colchicine and several took more than prescribed. The prophylactic use of colchicine and allopurinol varied from 3 weeks to 15 years. Mixed views were reported on restricting colchicine supply. Most participants received gout information from their general practitioner (GP). CONCLUSION Poor understanding of colchicine contributed to inappropriate use and highlights the need for targeted patient education. Considerable inter-patient variability exists in the use of colchicine for acute gout, suggesting the efficacy of low dose regimens be explored. The length of adjunctive colchicine use, as part of a prophylaxis regimen, needs to be regularly reviewed and tailored to each patient. Further research is required on limiting the amount of colchicine dispensed.


Modular surgical training for endoscopic extraperitoneal radical prostatectomy.
To develop a modular training scheme which enabled the use of individual steps of laparoscopic radical prostatectomy (RP) for teaching and training surgeons with varied experience, including residents with no experience in open RP, as in extending laparoscopic surgery to more complex operations like RP, the proper training of urologists is crucial. The technique of endoscopic extraperitoneal RP (EERP) was divided into 12 individual steps of differing complexity. The levels of difficulty were called "modules" and graded according to their requisite skills from module 1 (lowest level of difficulty) to module 5 (highest level). Based on this modular system we established a training programme whereby the trainee learns the procedure in a mentor-initiated schedule. During each training operation the trainee only performs the modules (steps) of the operation, which correspond with his or her actual skill level. The mentor performs all the other steps, with the trainee assisting. Four trainees with different surgical experience participated in the study. After a phase of assisting and camera holding during EERP, the trainees entered the modular training programme and required 32-43 procedures until they were considered to be competent. An analysis of the first 25-50 procedures done independently by the trainee showed mean operative times of 176-193 min and a transfusion rate of 1.3%. Complications during and after EERP requiring re-intervention were one each of recto-urethral fistula, haemorrhage, symptomatic lymphocele and anastomotic leak. The positive margin rate for pT2 disease was 12.2% and for pT3 tumours 37%. The modular concept for teaching EERP is an attractive concept, which overcomes many of the problems involved in complex laparoscopic procedures. Based on a highly standardized technique, this concept offers a short learning curve; it enables training on different sites in cooperation with a high-volume centre, and it makes it possible to start with this complex procedure as a beginner or with no experience in open RP.


Does GH replacement therapy in adult GH-deficient patients result in recurrence or increase in size of pituitary tumours?
Hypopituitary GH-deficient patients have an increased cardiovascular mortality and GH replacement in this population has resulted in considerable therapeutic benefit. GH replacement involves administration of a potentially mitogenic substance to patients with a previous or residual pituitary tumour. Our objective was to evaluate whether GH replacement results in an increase in the size of pituitary tumours. This was a non-randomised observational study on patients recruited from the endocrine clinic. All subjects had GH deficiency, proven on an insulin tolerance test and were divided into those who were or were not receiving long-term GH replacement. Comparison of change in pituitary size was made with interval radiological imaging of the pituitary. Seventy-five patients (40 men and 35 women) were in the study, 47 were on long-term GH replacement and there were 28 controls. The average length of treatment for the treated group was 3.6 patient years. Thirty-nine patients in the treated group had at least 2 years of GH treatment between imaging studies of the pituitary. Two patients in the treated group had an increase in pituitary size (non-functioning adenomas) and two in the control group (one functioning and one non-functioning adenoma adenoma). None of these four patients required further treatment. There was no statistically significant difference between the two groups. Using a representative cohort of hypopituitary patients attending an endocrine clinic, GH replacement was not associated with an increased pituitary tumour recurrence rate. Although the results are not conclusive, in the period of observation GH had little adverse effect but longer studies are required to be certain.


The requirement of integrins for breast epithelial proliferation.
Epithelial cells forming mammary gland ducts and alveoli require adhesion to the extracellular matrix for their function. Mammary epithelial cells need β1-integrins for normal cell cycle regulation. However, the role of β1-integrins in tumorigenesis has not been fully resolved. β1-integrin is necessary for tumour formation in transgenic mice expressing the Polyomavirus Middle T antigen, but it is dispensable in those overexpressing ErbB2. This suggests that some oncogenes can manage without β1-integrin to proliferate and form tumours, while others still require it. Here we have developed a model to test whether expression of an oncogene can surpass the need for β1-integrin to drive proliferation. We co-expressed the ErbB2 or Akt oncogenes with shRNA to target β1-integrin in mammary epithelial cells, and found that they show a differential dependence on β1-integrin for cell division. Moreover, we identified a key proliferative role of the Rac1-Pak axis downstream of β1-integrin signalling. Our data suggest that, in mammary epithelial cells, oncogenes with the ability to signal to Pak surpass the requirement of integrins for malignant transformation. This highlights the importance of using the correct combination therapy for breast cancer, depending on the oncogenes expressed in the tumour.


Updates on functions of ceramide in chemotherapy-induced cell death and in multidrug resistance.
The sphingolipid ceramide, a bioeffector lipid, is known to regulate anti-proliferative responses, such as apoptosis, growth arrest, differentiation and senescence in various human cancer cell lines. Previous studies have demonstrated that many anti-cancer agents cause elevation of endogenous ceramide levels generated via the de novo pathway and/or the hydrolysis of sphingomyelin, accompanied by apoptotic cell death in human cancer cells. It has also been shown that decreased levels of endogenous ceramide by over-expression of glucosylceramide synthase, which clears ceramide levels by incorporating it into glucosylceramide, results in the development of a multidrug resistant phenotype in cancer cells. These studies demonstrate that ceramide plays important roles in the response of cancer cells to chemotherapeutic drugs. The goal of this review is to provide an update on recent studies which shed new light into the roles of ceramide in chemotherapy-induced apoptosis and in multidrug resistance (MDR) in human cancer cells.


Mechanisms for CO oxidation on Fe(iii)-OH-Pt interface: a DFT study.
The full catalytic cycle that involves the oxidation of two CO molecules is investigated here by using periodic density functional calculations. To simulate the nature of Fe(OH)(x)/Pt nanoparticles, three possible structural models, i.e., Fe(OH)(x)/Pt(111), Fe(OH)(x)/Pt(332) and Fe(OH)(x)/Pt(322), are built. We demonstrate that Fe(iii)-OH-Pt stepped sites readily react with CO adsorbed nearby to directly yield CO(2) and simultaneously produce coordinatively unsaturated iron sites for O(2) activation. By contrast, the created interfacial vacancy on Fe(OH)(x)/Pt(111) prefers to adsorb CO rather than O(2), thus inhabiting the catalytic cycles of CO oxidation. We suggest that such structure sensitivity can be understood in terms of the bond strengths of Fe(iii)-OH.


Moods as ups and downs of the motivation pendulum: revisiting reinforcement sensitivity theory (RST) in bipolar disorder.
Motivation is a key neurobehavioral concept underlying adaptive responses to environmental incentives and threats. As such, dysregulation of motivational processes may be critical in the formation of abnormal behavioral patterns/tendencies. According to the long standing model of the Reinforcement Sensitivity Theory (RST), motivation behaviors are driven by three neurobehavioral systems mediating the sensitivity to punishment, reward or goal-conflict. Corresponding to current neurobehavioral theories in psychiatry, this theory links abnormal motivational drives to abnormal behavior; viewing depression and mania as two abnormal extremes of reward driven processes leading to either under or over approach tendencies, respectively. We revisit the RST framework in the context of bipolar disorder (BD) and challenge this concept by suggesting that dysregulated interactions of both punishment and reward related processes better account for the psychological and neural abnormalities observed in BD. We further present an integrative model positing that the three parallel motivation systems currently proposed by the RST model, can be viewed as subsystems in a large-scale neurobehavioral network of motivational decision making.


The regulatory role of human helper T-cell clones on antithyroid antibody production by peripheral B-cells.
The helper effects of thyroid antigen-specific T-cell clones (TCC) on antibody production by peripheral B-cells were studied and compared with similar effects of self major histocompatibility complex II (MHC-II)-reactive TCC as well as uncloned CD4+ cells. Ten TCC were derived from thyroid tissue or peripheral blood mononuclear cells (PBMC) in patients with Graves' disease. Uncloned CD4+ cells were also obtained from PBMC in patients with autoimmune thyroid disease. All TCC were CD3+/CD4+. B-Cells from patients with mainly high serum levels of microsomal antibodies (McAb) were cultured alone and with either TCC or uncloned CD4+ cells in the presence or absence of thyroid antigens [microsomal antigen/thyroid peroxidase (McAg/TPO) and thyroglobulin (Tg)] or pokeweed mitogen (PWM). Total immunoglobulin G (IgG) and specific thyroid antibodies were measured by enzyme-linked immunosorbent assay. Self MHC-II-reactive TCC induced B-cell production of total IgG and even McAb independent of antigens or PWM. Specific TCC required thyroid antigens to induce antibodies. The optimal McAg/TPO or Tg concentration was 10 ng/mL for total IgG production and 1 ng/mL McAg/TPO for McAb synthesis. The addition of PWM did not affect McAb production, but enhanced total IgG synthesis by B-cells under the influence of some specific TCC. Uncloned CD4+ cells induced both total IgG and McAb synthesis in the presence of PWM. With thyroid antigens, uncloned CD4+ cells induced total IgG synthesis at levels comparable to those of specific TCC, but induced smaller quantities of McAb in the presence of McAg/TPO. Our antigen-specific TCC could, therefore, stimulate specific B-cells to produce thyroid antibodies in vitro. Self MHC-II-reactive TCC could also induce specific antibodies by B-cells. Both self MHC-II-reactive CD4+ cells and antigen-specific CD4 cells may play an important role in the pathogenesis and/or perpetuation of autoimmune thyroid disease.


Mating patterns of a subdivided population of the andean oak (Quercus humboldtii Bonpl., Fagaceae).
Mating patterns play a critical role in the maintenance of genetic variation. We analyzed the mating system in a recently fragmented population of the Andean oak (Quercus humboldtii) using four microsatellite loci. Five fragments in northeastern Colombia, South America, were selected consisting of 30.4 trees on average. We sampled about 30 seeds from three target trees in each fragment and genotyped them with four microsatellite loci with a total of 40 alleles across loci. Progenies were analyzed under the mixed mating system model (MLTR program) and the TwoGener pollen pool structure analyses. The number of unshared pollen donors per family (Nu) was estimated using gametotypic counts with the program HAPLOTYPES. Low selfing (3%) is occurring at the population and fragment level. Biparental inbreeding is present (4.9%), but reduced, in the largest fragment. The average pollen neighborhood size (Nep = 5.1 to 6.1) appears comparable to other oak species in sparse landscapes. In contrast, Nu consists of 2 to 4 main donors, although up to 12 are possible, with the mode positively correlated with fragment size. The Andean oak appears to be a resilient species capable of tolerating population subdivision, provided landscapes include large fragments.


Social Determinants of Health: Addressing Unmet Needs in Nephrology.
There is ongoing recognition that a wide array of social, economic, and environmental factors influence individuals' opportunities to engage in health care and healthy behaviors. Despite spending $34 billion annually on the care of patients with end-stage renal disease, the American public and nephrology community remain remarkably complacent about addressing "upstream" factors that influence the prevention, progression, and treatment of chronic kidney diseases. Recently, a growing number of health plans and dialysis providers have begun to embrace population health management; accept greater accountability for health, health care, and health costs; and envision kidney health beyond their traditional roles in care delivery. This narrative offers a framework to evaluate social determinants of health and understand their link to chronic kidney diseases and provides recommendations for integrating social determinants into clinical care and delivery settings to assist vulnerable patients with broad social needs. Addressing unmet social needs with the same intention as treating hypertension, proteinuria, or anemia represents an important step toward making optimal health a palpable reality for all people who are at risk for or affected by chronic kidney diseases.


A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions.
The aim of this study was to investigate the capacity of an HPV16 E6/E7 synthetic overlapping long-peptide vaccine to stimulate the HPV16-specific T-cell response, to enhance the infiltration of HPV16-specific type 1 T cells into the lesions of patients with HPV16+ high-grade cervical squamous intraepithelial lesion (HSIL) and HPV clearance. This was a placebo-controlled randomized phase II study in patients with HPV16-positive HSIL. HPV16-specific T-cell responses were determined pre- and post-vaccination by ELISPOT, proliferation assay and cytokine assays in PBMC and HSIL-infiltrating lymphocytes, and delayed-type hypersensitivity skin tests. Motivational problems of this patient group to postpone treatment of their premalignant lesions affected the inclusion rates and caused the study to stop prematurely. Of the accrued patients, 4 received a placebo and 5 received 1-2 vaccinations. Side effects mainly were flu-like symptoms and injection site reactions. A strong HPV-specific IFNγ-associated T-cell response was detected by ELISPOT in all vaccinated patients. The outcome of the skin tests correlated well with the ELISPOT analysis. The cytokine profile associated with HPV16-specific proliferation varied from robust type 1 to dominant type 2 responses. No conclusions could be drawn on vaccine-enhanced T-cell infiltration of the lesion, and there was no HPV clearance at the time of LEEP excision. Thus, vaccination of HSIL patients results in increased HPV16-specific T-cell immunity. Further development of this type of treatment relies on the ability to motivate patients and in the reduction in the side effects.


Carbon monoxide--a regulator of vascular tone in hypoxia?
Carbon monoxide is a side product of enzymatic degradation of heme--a reaction catalyzed by heme oxygenase (HO). There are three independent molecular forms (isozymes) of heme oxygenase in man. Isoforms HO-2 and HO-3 are constitutive. More detailed studied isoform HO-2 is especially abundant in the human brain. In contrast to isoforms: HO-2 and HO-3, isoform HO-1 is an inducible species of heme oxygenase. Seen in other tissues, expression of HO-1 is also manifested in the endothelium and smooth muscle of blood vessels. Accumulated experimental data indicate more and more clearly on the possible role of endogenous carbon monoxide in cell cytoprotection, and shows it as a probable factor participating in modulation of the vascular tonus in hypoxia.


An emission based optical CO2 sensor fabricated on grating-like TiO2 substrates using HPTS.
TiO2 is a widely used material in various applications, including photo-catalysis, sensing, and dye-sensitized solar cells. In this work, we presented a stable and sensitive CO2 sensor working on principle of emission signals of the HPTS dye immobilized on TiO2 substrates whose effectiverefractive indicesin the parallel and perpendicular grating orientations evidenced earlier. The HPTS exhibited 8.4-fold enhanced emission signal on the offered substrates with respect to the previously reported intensities recorded for the polymeric supports. The emission peaks of the HPTS exhibited CO2 induced intensity quenching when excited at 466 nm. Calibration sensitivity of the offered composites has been tested exposing the sensor materials to varying concentrations of the CO2 between 0.0 and 100.0 % pCO2 and correlating the measured fluorescence intensity with the corresponding CO2 levels. The dye revealed enhanced CO2 induced response exhibiting the I0/100 values of 11.9, 13.3, 11.2 and 6.5. We also recorded bi-exponential excited state lifetimes for the HPTS on four different test materials both in the absence and presence of the CO2. The emission based variations were followed as the analytical signal due to higher CO2-induced relative signal changes than that of the lifetime based variations. Herein we used the ion pair form of the HPTS in a protective chemical microenvironment and obtained considerable long term stability extending to16 mounts which can be attributed to the presence of the 1-butyl-3-methylimidazolium tetrafluoroborate as an internal buffering system in the sensing composition as well as the inert and robust structure of the substrate. The extremely high optical response, advantage of excitation with blue LEDs and long-term stability observed on grating-like TiO2 surfaces make the proposed system a promising design for the quantification of CO2 for further applications.


Development of a Comprehensive Quality-of-Life Measure for Facial and Torso Acne.
Background Acne is a chronic skin disorder which generally presents in adolescence but continues into adulthood, and negatively affects both physical and psychosocial well-being. Presently, there are no validated acne-specific quality-of-life (QoL) measures that include dimensions for both facial and torso acne. The objective of this study was to develop a QoL instrument for both facial and torso acne (CompAQ) in accordance with recommended standards. A literature review and Delphi survey of patients and clinicians were used to develop the conceptual framework for outcomes perceived important to acne patients. An initial version of the measure was developed, CompAQ-v1, and pilot tested with patients via cognitive interviews. The Delphi survey generated 4 domains (physical, psychological, sociological, and treatment) and 54 items. These, along with a literature review and input from clinical experts, informed the development of the CompAQ-v1. Eleven cognitive interviews were conducted, resulting in the second version of the measure, CompAQ-v2. Psychometric validation resulted in the final 20-item CompAQ measure comprising 5 domains. An abbreviated 5-item measure was also developed (CompAQ-SF). CompAQ and CompAQ-SF are instruments intended to evaluate QoL in patients with acne on their face or torso. The former is a 21-item QoL intended for research, while the latter is intended for clinical practice.


Differential regulation of L-arginine transporters (cationic amino acid transporter-1 and -2) by peroxynitrite in rat mesangial cells.
It has become evident that increased nitric oxide (NO) generation may be associated with production of reactive oxygen species, such as peroxynitrite (ONOO-). Peroxynitrite has been postulated to be responsible for several of the cytotoxic effects previously ascribed to NO. Since cellular arginine uptake has been shown to modulate nitric oxide synthase activity, we were intrigued to study the effect of ONOO- on arginine traffic in renal mesangial cells. Arginine uptake, CAT-1 and CAT-2 mRNA expression by northern blotting analysis, and CAT-1 protein content using western blotting were determined in mesangial cells pre-treated with peroxynitrite (0.1 and 0.5 mM) for 2 h. Peroxynitrite induced a significant increase in arginine uptake and CAT-2 mRNA expression compared with untreated cells. In contrast, CAT-1 mRNA expression and protein abundance were diminished. In rat mesangial cells, peroxynitrite augments arginine uptake via augmentation of CAT-2 while decreasing CAT-1 expression.


Development of Selective Clk1 and -4 Inhibitors for Cellular Depletion of Cancer-Relevant Proteins.
In cancer cells, kinases of the Clk family control the supply of full-length, functional mRNAs coding for a variety of proteins essential to cell growth and survival. Thus, inhibition of Clks might become a novel anticancer strategy, leading to a selective depletion of cancer-relevant proteins after turnover. On the basis of a Weinreb amide hit compound, we designed and synthesized a diverse set of methoxybenzothiophene-2-carboxamides, of which the N-benzylated derivative showed enhanced Clk1 inhibitory activity. Introduction of a m-fluorine in the benzyl moiety eventually led to the discovery of compound 21b, a potent inhibitor of Clk1 and -4 (IC50 = 7 and 2.3 nM, respectively), exhibiting an unprecedented selectivity over Dyrk1A. 21b triggered the depletion of EGFR, HDAC1, and p70S6 kinase from the cancer cells, with potencies in line with the measured GI50 values. In contrast, the cellular effects of congener 21a, which inhibited Clk1 only weakly, were substantially lower.


Detection of N-acetylated forms of alpha-MSH and beta-endorphin in the intermediate pituitary of the holostean fishes, Lepisosteus spatula, Lepisosteus osseus, and Amia calva.
Acid extracts of the intermediate pituitaries of the gars, L. spatula and L. osseus, were fractionated by Sephadex G-50 column chromatography and analyzed by radioimmunoassay. This procedure revealed that immunoreactive forms of N-acetylated beta-endorphin- and alpha-MSH-sized material were present in equimolar amounts and represented the major end products of the POMC biosynthetic pathway in these species. Cation-exchange chromatography indicated that multiple N-acetylated forms of beta-endorphin were present in the intermediate pituitaries of the two species of gar, and that these forms differed in their net positive charge and in their apparent molecular weight. Reversed-phase HPLC analysis of the alpha-MSH-related material indicated that up to 90% of the total MSH in the pituitary of the gar was N-acetylated. Furthermore, the predominant form of alpha-MSH in both species of gar was N,O-diacetyl-ACTH(1-13)-NH2. Nearly identical results were obtained following the analysis of alpha-MSH-related peptides in the intermediate pituitary of the bowfin, A. calva. The pattern of posttranslational processing of POMC observed in the intermediate pituitaries of holostean fishes is very similar to the processing events observed in lungfishes, turtles, and mammals; hence, the processing of POMC has been remarkably conserved during vertebrate evolution.


Healing the heart: integrating complementary therapies and healing practices into the care of cardiovascular patients.
Complementary therapies and healing practices have been found to reduce stress, anxiety, and lifestyle patterns known to contribute to cardiovascular disease. Promising therapies include imagery and hypnosis, meditation, yoga, tai chi, prayer, music, exercise, diet, and use of dietary supplements. Many of these complementary approaches to healing have been within the domain of nursing for centuries and can readily be integrated into the care of patients with cardiovascular disease. While individual complimentary modalities hold considerable merit, it is critical that the philosophy underlying these therapies--caring, holism, and harmony--also be understood and honored.


MDCT findings in primary amyloidosis of the greater omentum and mesentery: a case report.
Imaging findings of amyloid infiltration of the greater omentum, mesentery, and retroperitoneal spaces have only extremely rarely been reported in the radiological literature. This report illustrates the MDCT findings fortuitously found in a 70-year-old male presenting with a known latent myeloma.Extra abdominal deposits-axilla and cardiophrenic angles-were first fortuitously found during thoracic MDCT. Secondary abdominal MDCT revealed the extensive abdominal spread that consisted of very diffuse but asymptomatic pseudo carcinomatous hazy omental, mesenteric and-in a minder proportion-retroperitoneal deposits; these remained isolated without calcification, lymphadenopathy, ascites, or any sign of associated bowel wall thickening. A specific definite histologic diagnosis was made without laparotomy through a biopsy in the right axilla.


Distal aortic reintervention after surgery for acute DeBakey type I or II aortic dissection: open versus endovascular repair.
Aortic dissection DeBakey type I and II may require distal reinterventions after initial proximal repair. We evaluated outcomes following open versus endovascular approaches to distal aortic pathologies after surgery for acute dissection. One hundred and forty-one consecutive patients underwent 152 distal reinterventions after previous type I or II dissection repair [63 (first quartile, 55; third quartile, 72) years old; initially 86% DeBakey type I; 54% hemiarch, 39% isolated ascending, 7% total arch replacement] at two tertiary centres in the USA and Europe over the last 14 years. Among them, 56 and 85 required reintervention for the aortic arch and the descending aorta, respectively. The median follow-up was 2.1 (first quartile, 0.8; third quartile, 5.8) years (439 patient-years). The median time between acute aortic dissection repair and descending aortic reintervention was longer in the open group (2.7 (first quartile, 0.8; third quartile, 6.7) vs 0.6 (first quartile, 0.1; third quartile, 3.5) years, P < 0.01). There was one irreversible spinal ischaemia in the open and one stroke in the endovascular group. Two patients in the open and none in the endovascular group required re-exploration for bleeding. Two open and 4 endovascular patients required more than 1 distal reintervention (6 vs 8%, P = 1). Descending aortic open-repair patients experienced higher in-hospital mortality (23 vs 0%, P < 0.01) and lower survival at 1 and 5 years (74 ± 8% vs 96 ± 3%, 65 ± 9% vs 92 ± 5%, P < 0.01, respectively). Endovascular intervention for descending aortic pathologies after DeBakey type I or II dissection surgical repair is associated with lower in-hospital mortality and better survival, and does not raise the likelihood of later reinterventions at the mid-term follow-up.


Post-metallic stent placement bleeding caused by stent-induced ulcers.
Placement of self-expandable metal stents (SEMS) is an effective mode of palliative treatment for patients with malignant gastrointestinal obstruction. Gastrointestinal mucosal bleeding complicates about 5% of placement of SEMS but is not well described. We report three cases of gastrointestinal bleeding post-SEMS placement and suggest that bleeding is caused by direct mucosal infringement by the sharp edges of the ends of the stents.


Endometrial thickness and uterine diameter not affected by ultralow doses of 17beta-estradiol in elderly women.
Our purpose was to monitor changes in endometrial thickness and uterine diameter during treatment with ultralow doses of estradiol, which might improve the serum lipid profile in elderly women. Ultrasonographic changes were monitored in 60 women with an intact uterus in a group of 70 healthy women who were previously evaluated for changes in serum lipid levels. Subjects were 60 years and older and were randomly assigned to receive parenteral 17beta-estradiol (7.5 microg/24 h), delivered by a vaginal ring (Estring; Pharmacia-Upjohn, Malmö, Sweden), or no treatment for 12 months. Estring treatment yielded minor increases in serum estrone sulfate and 17beta-estradiol levels within the normal postmenopausal range. The maximal endometrial thickness was 2.8 mm at baseline and 2.6 mm at 12 months. No significant changes within or between the study groups were found in endometrial thickness or uterine diameter. There were no significant interactions between age and baseline serum estrone sulfate or 17beta-estradiol levels. Ultralow doses of 17beta-estradiol, which might improve serum lipid levels, did not significantly change endometrial thickness or uterine diameter. This might indicate that there is a "therapeutic window" for systemic effects of ultralow doses of estradiol in elderly women without any apparent increase in endometrial thickness.


Hepadnaviral Lymphotropism and Its Relevance to HBV Persistence and Pathogenesis.
Since the discovery of hepatitis B virus (HBV) over five decades ago, there have been many independent studies showing presence of HBV genomes in cells of the immune system. However, the nature of HBV lymphotropism and its significance with respect to HBV biology, persistence and the pathogenesis of liver and extrahepatic disorders remains underappreciated. This is in contrast to studies of other viral pathogens in which the capability to infect immune cells is an area of active investigation. Indeed, in some viral infections, lymphotropism may be essential, and even a primary mechanism of viral persistence, and a major contributor to disease pathogenesis. Nevertheless, there are advances in understanding of HBV lymphotropism in recent years due to cumulative evidence showing that: (i) lymphoid cells are a reservoir of replicating HBV, (ii) are a site of HBV-host DNA integration and (iii) virus genomic diversification leading to pathogenic variants, and (iv) they play a role in HBV resistance to antiviral therapy and (v) likely contribute to reactivation of hepatitis B. Further support for HBV lymphotropic nature is provided by studies in a model infection with the closely related woodchuck hepatitis virus (WHV) naturally infecting susceptible marmots. This animal model faithfully reproduces many aspects of HBV biology, including its replication scheme, tissue tropism, and induction of both symptomatic and silent infections, immunological processes accompanying infection, and progressing liver disease culminating in hepatocellular carcinoma. The most robust evidence came from the ability of WHV to establish persistent infection of the immune system that may not engage the liver when small quantities of virus are experimentally administered or naturally transmitted into virus-naïve animals. Although the concept of HBV lymphotropism is not new, it remains controversial and not accepted by conventional HBV researchers. This review summarizes research advances on HBV and hepadnaviral lymphotropism including the role of immune cells infection in viral persistence and the pathogenesis of HBV-induced liver and extrahepatic diseases. Finally, we discuss the role of immune cells in HBV diagnosis and assessment of antiviral therapy efficacy.


A mutant of Escherichia coli citrate synthase that affects the allosteric equilibrium.
We describe a mutant of Escherichia coli citrate synthase, CS R319L, in which the arginine residue at position 319 of the sequence has been replaced by leucine. In this mutant, saturation by the substrate acetyl-CoA is changed from sigmoid (Hill parameter = 1.75 +/- 0.2) to hyperbolic (Hill parameter = 1.0 +/- 0.1) and dependence on the activator KCl is greatly reduced. Further mutations at this site and at position 343 (which model building predicts is close enough to allow a side-chain interaction with position 319) are also described. In the wild-type enzyme, the model suggests the possibility of a salt-bridge interaction between Arg-319 (located on the P helix in the small domain) and Glu-343 (in the Q helix in the same domain), but mutation of Glu-343 to Ala (CS E343A) produced a much smaller difference in the kinetic properties than the ARg-319 to Leu mutation did. Small changes in kinetic properties were also obtained with an Arg-319----Glu (CS R319E) mutation. In CS R319L, oxaloacetate, the first substrate to bind, induces an ultraviolet difference spectrum which is obtained with wild-type enzyme only in the presence of KCl. To account for these observations we postulate that wild-type E. coli citrate synthase exists in two conformational states, T and R, which are equilibrium; T state binds NADH, the allosteric inhibitor, while R state binds substrates and can be converted to another substrate-binding state, R', by KCl.(ABSTRACT TRUNCATED AT 250 WORDS)


Cleavage Stimulation Factor Subunit 2: Function Across Cancers and Potential Target for Chemotherapeutic Drugs.
The cleavage stimulation factor subunit complex is involved in the cleavage and polyadenylation of 3'-end pre-mRNAs that regulate mRNA formation and processing. However, cleavage stimulation factor subunit 2 (CSTF2) was found to play a more critical regulatory role across cancers. General cancer data sets from The Cancer Genome Atlas and Genotype-Tissue Expression project were thus downloaded for differential analysis, and the possible functions and mechanisms of CSTF2 in general cancer were analyzed using the Compartments database, cBioPortal database, Tumor Immune Single-cell Hub database, and Comparative Toxigenomics database using gene set enrichment analysis and R software. The results showed that CSTF2 could affect DNA repair and methylation in tumor cells. In addition, CSTF2 was associated with multiple tumor immune infiltrates in a wide range of cancers, and its high expression was associated with multiple immune checkpoints; therefore, it could serve as a potential target for many drug molecules. We also proved that CSTF2 promotes oral cell proliferation and migration. The high diagnostic efficacy of CSTF2 suggested that this gene may act as a new biomarker and personalized therapeutic target for a variety of tumors.


Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population.
Little is known the about the reproductive health of offspring after fertility treatment. In 2001-2005, the authors approached young Danish men attending a compulsory physical examination to determine their fitness for military service. A total of 1,925 men volunteered, delivered a semen sample, had a physical examination performed and a blood sample drawn, and responded to a questionnaire. Their mothers were questioned about whether they had received fertility treatment in order to conceive their sons. Forty-seven mothers reported having received fertility treatment to conceive the index subject. After control for confounders, men whose mothers had received fertility treatment to conceive them had a 46% lower sperm concentration (95% confidence interval (CI): -63, -20) and a 45% lower total sperm count (95% CI: -64, -16). They had a smaller testis size (-0.9 ml, 95% CI: -2.2, 0.4), fewer motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a lower serum testosterone level and free androgen index (results not statistically significant). These findings should be viewed in light of the increasing use of fertility treatments. Although the cause of these findings is unknown, they raise concern about possible late effects of fertility treatment. Larger-scale studies of children born after fertility treatment should be performed.


Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells.
Even though tremendous advances have been made in the treatment of cancers during the past decades, the success rate among patients with cancer is still dismal, largely because of problems associated with chemo/radioresistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in the tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small cell lung carcinoma H292 and H460 cells. Exposure of NO gradually altered the cell morphology toward mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype, indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. These effects of NO on stemness were reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO donor, S-nitroso-N-acetylpenicillamine. Importantly, inhibition of NO by the known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide strongly inhibited CSC-like aggressive cellular behavior and marker expression. Last, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1), which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation.


"Bright Band Sign" A Grayscale Ultrasound Finding in Hepatic Infarction.
Hepatic infarction is infrequent due to the dual blood supply of the liver and the compensatory relationship between the hepatic artery and portal vein. Most cases occur in liver transplants due to vascular complications. Grayscale sonography combined with color and spectral wave Doppler can assess for vessel patency and parenchymal abnormalities. Liver infarctions appear as hypoechoic nonvascular regions on conventional and Doppler sonography. Here, we describe a grayscale ultrasound feature within liver infarctions in 2 liver transplants and in 1 native liver due to iatrogenic complication. This feature is similar to those described recently in the literature within splenic infarcts.


Crystal structure analysis of a serine proteinase from Streptomyces fradiae at 0.16-nm resolution and molecular modeling of an acidic-amino-acid-specific proteinase.
We have determined the three-dimensional structure of a proteinase from Streptomyces fradiae ATCC 14544 (SFase-2) at 0.16-nm resolution. SFase-2, a typical serine proteinase, has broad substrate specificity. The characterization and crystallographic analysis of this enzyme have been reported previously [Kitadokoro, K., Tsuzuki, H., Nakamura, E., Sato, T. & Teraoka, H. (1994) Eur. J. Biochem. 220, 55-61]. In the present study, data were collected to approximately 0.16-nm resolution on a Rigaku R-AXIS IIC imaging plate detector system. Preliminary phases were obtained by molecular replacement methods with a search model derived from the previously determined structure of Streptomyces griseus protease A [Sielecki, A. R., Hendrickson, W. A., Broughton, C. G., Delbaere, L. T., Brayer, G. D. & James, M. N. (1979) J. Mol. Biol. 134, 781-804]. The starting model gave an initial crystallographic R factor of 0.443. Refinement with restrained least-squares converged at a final R factor of 0.182 for 16128 observed reflections. The final model includes 86 water molecules. The crystal structure showed that the enzyme consists of two domains, each of which is comprised of a beta barrel with six-stranded beta sheets and two alpha helices. The overall tertiary structure of SFase-2 is similar to the structures of other chymotrypsin-like proteinases from S. griseus, namely proteinase A and proteinase B. The essential residues of the catalytic triad are located on the cleft between the two domains. These two domains have different sequences, but possess similar three-dimensional structures, indicating that a gene duplication event has occurred to produce these two domains. We predicted the tertiary structure of an acidic-amino-acid-specific proteinase on the basis of the crystal structure of SFase-2, and compared the active-site conformations of these two enzymes. We found a characteristic histidine cluster of three histidine residues in the active site of the acidic-amino-acid-specific proteinase. The substrate recognition mechanism of SFase-2 may be mediated through the hydrophobic amino acid residues. However, in the acidic-amino-acid-specific proteinase, the positive charge of this histidine cluster would attract the negative charges of glutamic acid and aspartic acid.


The effect of the M1-selective telenzepine on esophageal acid exposure in healthy volunteers.
In order to study the effect of the new M1-selective antimuscarinic compound telenzepine on physiological esophageal acid exposure, ten healthy volunteers underwent a 24-hour esophageal pH-monitoring during a one week treatment with either tablets containing telenzepine 3 mg nightly or placebo in a double-blind cross-over trial. Side-effects were recorded, and stimulated salivary output was assessed. Using a cut-off pH less than 4, under telenzepine a significant reduction of reflux time and of maximum reflux duration was observed in supine position. Using a cut-off pH less than 2, reflux time was reduced during and after meals, number of refluxes was decreased during meals, and esophageal clearance was improved with telenzepine in supine position. Telenzepine reduced salivary output significantly on day 4 and on day 7. From the results it can be concluded that the drug is not contraindicated in peptic ulcer patients with heartburn. As telenzepine reduces gastroesophageal reflux time during and after meals and in supine position it may be tried as adjuvant treatment in esophageal reflux disease.


A qualitative evaluation of the Students of Service (SOS) program for sexual abstinence in Louisiana.
Abstinence-only programs for preventing teen pregnancy are the only options in some states but are the programs of choice in others. Effectiveness data, however, are lacking. The SOS Adolescent Family Life Program (SOS), an abstinence-only teen pregnancy prevention program, was implemented in south central Louisiana. Peer mentoring with an abstinence and life skills curriculum comprised the major components. SOS was implemented in the same grades in the same schools with new students each year for five years. During the final years of the program, qualitative evaluation was conducted with principals, teachers, peer mentors, and students. Use of peer mentors was reaffirmed as valuable; however, quality of peer mentoring was questioned and was a major issue for improvement. Other issues included: starting sexuality education in earlier grades, updating curricula and materials, offering more interactive classes, improving peer mentor training, and using teacher input to improve educational aspects of the program. Qualitative assessments provided valuable insights for future improvement in abstinence-only programs.


Cardiac amyloidosis: a challenging diagnosis.
Cardiovascular involvement of amyloidosis is present in 90% of cases, which is frequently associated with the primary form of the disease (AL amyloidosis). Clinical manifestations are represented by heart failure due to restrictive myocardiopathy and electrical impulse conduction abnormalities, which are clinically remarkable in up to 50% of the cases. The prognosis of patients with systemic amyloidosis is directly associated with the presence of cardiac involvement, such that survival does not usually exceed 4 months after the onset of heart failure signs and symptoms. The authors report a case of primary systemic amyloidosis, diagnosed only at autopsy, with severe cardiac involvement.


Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is cytopathological diagnosis possible?
Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor of the thyroid gland which occurs predominantly in children, adolescents, and young adults. It usually presents as a painless neck or thyroid mass and only exceptionally as a diffusely enlarged thyroid gland, without metastatic disease at diagnosis. We report on the case of 12-yr-old girl who had diffusely enlarged thyroid gland for about 1 yr and was initially treated for thyroiditis. Fine-needle aspiration biopsy (FNAB) was performed 8 mo after the first admission. Cytological examination of smears showed unusual morphological features. FNAB smears were cellular, with dissociated cells, naked oval nuclei, aggregates, and groups. Three main cell types were observed: spindle, epithelioid, and epithelial. These cells were uniform, cytologically bland, with few mitotic figures. The distinction between these cells was not always unequivocal. In the background of the smears abundant red extracellular material in the form of fine, dust-like granules and irregular patches were present. It was also observed in some aggregates and groups of tumor cells. Spindle and epithelioid cells were immunocytochemically diffusely pan-cytokeratin-positive. In the differential diagnosis, medullary thyroid carcinoma and SETTLE were suggested. The final histological diagnosis was SETTLE. In cases of SETTLE presented as a diffuse thyromegaly the correct diagnosis may be delayed because clinically and ultrasonographically thyroiditis is suspected. To avoid such a delay, FNAB should be used preoperatively. It can provide specific cytological diagnosis based on morphological features and certain immunocytochemical characteristics of the tumor.


Applying torque to the Escherichia coli flagellar motor using magnetic tweezers.
The bacterial flagellar motor of Escherichia coli is a nanoscale rotary engine essential for bacterial propulsion. Studies on the power output of single motors rely on the measurement of motor torque and rotation under external load. Here, we investigate the use of magnetic tweezers, which in principle allow the application and active control of a calibrated load torque, to study single flagellar motors in Escherichia coli. We manipulate the external load on the motor by adjusting the magnetic field experienced by a magnetic bead linked to the motor, and we probe the motor's response. A simple model describes the average motor speed over the entire range of applied fields. We extract the motor torque at stall and find it to be similar to the motor torque at drag-limited speed. In addition, use of the magnetic tweezers allows us to force motor rotation in both forward and backward directions. We monitor the motor's performance before and after periods of forced rotation and observe no destructive effects on the motor. Our experiments show how magnetic tweezers can provide active and fast control of the external load while also exposing remaining challenges in calibration. Through their non-invasive character and straightforward parallelization, magnetic tweezers provide an attractive platform to study nanoscale rotary motors at the single-motor level.


Towards understanding the sign preference in binary atmospheric nucleation.
The role of the ion sign in the binary H2SO4-H2O nucleation remains unclear despite significant progress in both theory and instrumentation achieved within the last decade. In order to advance the understanding of ion nucleation phenomena, a quantum-chemical study of binary sulfuric acid-water ionic clusters nucleating in the atmosphere has been carried out. We found a profound sign effect caused by the pronounced difference in the structure and properties of clusters formed over core ions of different sign. The sign preference is found to be controlled by two somewhat competing factors: hydration and sulfuric acid attachment. While hydration of cations is clearly favorable, the affinity of sulfuric acid, which largely controls the nucleation intensity, to negative ions is much higher than that to positive ions. The presence of a very large difference in the affinity of sulfuric acid between positive and negative ions suggests that nucleation of negative ions is likely favorable.


Targeted gene panel sequencing prenatally detects two novel mutations of DYNC2H1 in a fetus with increased biparietal diameter and polyhydramnios.
Genetic skeletal disorders (GSDs) are clinically and genetically heterogeneous with more than 350 genes accounting for the diversity of disease phenotypes. Prenatal diagnosis of these disorders has been challenging because of the limited but variable prenatal phenotypes, highlighting the need of a novel genetic approach. Short-rib polydactyly syndrome (SRPS) Type III is an autosomal recessive GSD characterized by extreme narrowness of the thorax, severely shortened tubular bones, polydactyly and multiple malformations. Cytogenetic and molecular analyses using GTG-banding, single nucleotide polymorphism array and a novel GSDs targeted gene panel sequencing were performed in a 24 weeks fetus with increased biparietal diameter (BPD), short limbs, narrow thorax and polyhydramnios. No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the fetus. Two novel compound heterozygous mutations c.2992C > T and c.12836G > C in the DYNC2H1 gene were identified by targeted genes panel sequencing. A literature review was performed to delineate the prenatal phenotype of SRPS Type III. This is the first report of prenatal diagnosis of DYNC2H1 mutations causing SRPS Type III in a fetus with increased BPD associated with polyhydramnios in China. Our findings expand the mutation spectrum of DYNC2H1 in this rare disease and demonstrate that targeted gene panel capture followed by next-generation sequencing (NGS) is an efficient and cost-effective method to perform a molecular prenatal diagnosis of a rare genetic skeletal disorder.


Weight at birth and subsequent risk of preeclampsia as an adult.
We examined the influence of maternal birth weight on the risk of the development of preeclampsia, a likely precursor to adult chronic disease. This hospital-based case-control study included 181 preeclampsia cases and 349 control subjects. Participants provided information about their birth weight and other covariates that included medical and reproductive history, prepregnancy weight, and adult height. Odds ratios and 95% CIs were estimated by logistic regression. The risk of preeclampsia decreased as maternal birth weight increased (P=.01). After an adjustment was made for confounders, data showed that women with a low birth weight (<2500 g) had a 2.3-fold increased risk of experiencing preeclampsia (95% CI, 1.0-5.3) as compared with women who weighed 2500 to 2999 g at birth. Conversely, women with a birth weight of >/=4000 g appeared to have a nonstatistically significant, but >50%, reduction in the risk of experiencing preeclampsia (95% CI, 0.2-1.2). This relationship differed for lean and overweight women (body mass index, <25 kg/m(2) vs >/=25 kg/m(2)). Among lean women, those who were low birth weight had a near doubling in risk of the development of preeclampsia (odds ratio, 1.9; 95% CI, 0.8-4.6), although this association did not reach statistical significance. However, among overweight women, those women who weighed <2500 g at birth had an almost 4-fold increased risk of experiencing preeclampsia (odds ratio, 3.8; 95% CI, 1.1-13.8). These results confirm two earlier reports and expand the literature by showing that women who are small at birth and who become overweight as adults are at particularly high risk of the development of preeclampsia.


Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir.
Telbivudine, a nucleoside analog inhibitor of the viral polymerase of hepatitis B virus (HBV), has been approved for the treatment of chronic HBV infection, along with the nucleoside inhibitors lamivudine and entecavir, and the nucleotide inhibitors adefovir and tenofovir. The resistance profiles of these agents were investigated via drug treatment of HepG2 cells stably transfected with wild-type or mutant HBV genomes bearing known resistance mutations. Telbivudine was not active against HBV strains bearing lamivudine mutations L180M/M204V/I but remained active against the M204V single mutant in vitro, potentially explaining the difference in resistance profiles between telbivudine and lamivudine. Against HBV genomes with known telbivudine-resistance mutations, M204I and L80I/M204I, telbivudine, lamivudine and entecavir lost 353- to >1000-fold activity whereas adefovir and tenofovir exhibited no more than 3-5-fold change. Conversely, against HBV cell lines expressing adefovir resistance mutations N236T and A181V, or the A194T mutant associated with resistance to tenofovir, telbivudine remained active as shown by respective fold-changes of 0.5 (N236T) and 1.0 (A181V and A194T). These in vitro results indicate that nucleoside and nucleotide drugs have different cross-resistance profiles. The addition of telbivudine to ongoing adefovir therapy could provide effective antiviral therapy to patients who develop adefovir resistance.


Cement augmentation versus extended dorsal instrumentation in the treatment of osteoporotic vertebral fractures: a biomechanical comparison.
Loosening of pedicle screws is a major complication of posterior spinal stabilisation, especially in the osteoporotic spine. Our aim was to evaluate the effect of cement augmentation compared with extended dorsal instrumentation on the stability of posterior spinal fixation. A total of 12 osteoporotic human cadaveric spines (T11-L3) were randomised by bone mineral density into two groups and instrumented with pedicle screws: group I (SHORT) separated T12 or L2 and group II (EXTENDED) specimen consisting of T11/12 to L2/3. Screws were augmented with cement unilaterally in each vertebra. Fatigue testing was performed using a cranial-caudal sinusoidal, cyclic (1.0 Hz) load with stepwise increasing peak force. Augmentation showed no significant increase in the mean cycles to failure and fatigue force (SHORT p = 0.067; EXTENDED p = 0.239). Extending the instrumentation resulted in a significantly increased number of cycles to failure and a significantly higher fatigue force compared with the SHORT instrumentation (EXTENDED non-augmented + 76%, p < 0.001; EXTENDED augmented + 87%, p < 0.001). The stabilising effect of cement augmentation of pedicle screws might not be as beneficial as expected from biomechanical pull-out tests. Lengthening the dorsal instrumentation results in a much higher increase of stability during fatigue testing in the osteoporotic spine compared with cement augmentation. Cite this article: Bone Joint J 2016;98-B:1099-1105.


The use of mixer torque rheometry to study the effect of formulation variables on the properties of wet granulations.
Mixer torque rheometry was used to investigate the rheological behavior of wet granulations with different concentrations of drug, binder, and water. An experimental design was employed to systematically study the effects of the three formulation variables on the torque profiles of the wet masses over time. Under comparable conditions, increasing binder and water concentrations tended to produce higher wet mass consistencies. Friability of the dried granules was measured as an indication of the strength of the granules. A reduced quadratic model in terms of each of the three variables was found to satisfactorily predict granule friability. Granule friability decreased with increases in the binder level and increased slightly with increasing drug concentration. An inverse relationship was seen between granule friability and the amount of water added to the formulation, especially at lower drug concentrations. Mixer torque rheometry is a useful method for studying the properties of wet granulations when minimal amounts of drug are available for the development of a wet granulated formulation.


Supporting the implementation of breast pathology recommendations: feasibility of a feedback mechanism to pathologists.
The aims of the study were to explore the feasibility, acceptability, impact and cost of a feedback program to pathologists reporting on breast specimens through a BreastScreen Service. The study was conducted at a single BreastScreen NSW Screening and Assessment Service. Pathology reports were audited against the ACN recommendations about pathology reporting [Australian Cancer Network Pathology Working Party. The Pathology Reporting of Breast Cancer: a guide for pathologists, surgeons and radiologists. Sydney: Australian Cancer Network, 1997] during two consecutive periods. Feedback was provided to pathologists at the completion of each audit. A comparison of completeness of pathology reports between audits was undertaken. The Screening and Assessment Service staff and participating pathologists were interviewed to assess acceptability and information about resource allocation. The study demonstrated that the feedback mechanism was acceptable to pathologists and staff at the BreastScreen Screening and Assessment Service, and that participation in the study resulted in some improvements in pathology reporting. The study demonstrated the feasibility of providing feedback to pathologists about their reporting of breast specimens. However, there were costs to the Service of participating. A way of managing these costs would need to be explored if the feedback mechanism was made a routine BreastScreen procedure.


BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies.
BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN. Antiviral immunity plays a crucial role in controlling BKV replication, and our increasing knowledge about host-virus interactions has led to the development of improved diagnostic tools and clinical management strategies. Currently, there are no effective antiviral agents for BKV infection, and the mainstay of managing reactivation is reduction of immunosuppression. Development of immune-based therapies to combat BKV may provide new and exciting opportunities for the successful treatment of BKV-associated complications.


[Iris shape change and risk of anterior chamber angle closure].
Potential obstruction of the anterior chamber angle by iris root is a key factor of the pathogenesis of angle-closure glaucoma. Development and adoption of ultrasound biomicroscopy and optical coherence tomography in clinical practice have significantly expanded the capabilities of studying the structures of the anterior eye segment in terms of angle closure risk factors through improving visualization depth and quality of examination, including different variants of iris structure and potential changes of its shape in mydriasis. The article reviews various studies dedicated to the progression of primary angle-closure glaucoma and its dependence on the biometric parameters of the eye and changes in pupil size.


LncRNA MAGI2-As3 Suppresses the Proliferation and Invasion of Cervical Cancer by Sponging MiR-15b.
Cervical cancer is the leading cause of cancer deaths among women, and more than 85% of cervical cancer deaths occur in low and middle-income countries. The purpose of this study is to investigate the functions of MAGI2-AS3 and miR-15b in cervical cancer. The mRNA levels of MAGI2-AS3, miR-15b, and CCNE1 were evaluated using RT-qPCR assay. Dual-luciferase reporter gene assay was used to confirm whether miR-15b binds to CCNE1. LncRNA MAGI2-AS3 was downregulated, while miR-15b was upregulated in cervical cancer. Cervical cancer patients with low expression of MAGI2-AS3 have a poor prognosis. Upregulation of MAGI2-AS3 inhibited proliferative and invasive abilities of HeLa cells via regulating the expression of miRNA-15b. MiR-15b inhibitor suppressed cell proliferation and invasion. CCNE1 was a direct target gene of miR-15b, which binds to the 3'-UTR of its mRNA. MiR-15b partially reversed the inhibitory effect of overexpression of MAGI2-AS3 on the proliferation and invasion of HeLa cells. MAGI2-AS3 mediated the expression of CCNE1 in HeLa cells. LncRNA MAGI2-AS3 inhibits the proliferation and invasion of cervical cancer cells via the miRNA-15/CCNE1 axis. Our results illustrates that MAGI2-AS3 can be used as a useful clinical predictor for early diagnosis and prognosis assessment of cervical cancer.


Association between triglyceride glucose index and arterial stiffness in Korean adults.
The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.


Regiospecific and highly stereoselective coupling of 6-(substituted-imidazol-1-yl)purines with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride. Sodium-salt glycosylation in binary solvent mixtures: improved synthesis of cladribine.
Glycosylation of 6-(substituted-imidazol-1-yl)purine sodium salts with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride proceeds with regiospecific formation of the N9 isomers. Base substrates with lipophilic substituents on the C6-linked imidazole moiety are more soluble in organic solvents, and the solubility is further increased with binary solvent mixtures. Selective solvation also diminishes the extent of anomerization of the chlorosugar. Stirred reaction mixtures of the modified-purine sodium salts generated in a polar solvent and cooled solutions of the protected 2-deoxysugar chloride in a nonpolar solvent give 2'-deoxynucleoside derivatives with N9 regiochemistry and enhanced beta/alpha configuration ratios. Application of the binary-solvent methodology with 2-chloro-6-(substituted-imidazol-1-yl)purine salts in cold acetonitrile and the chlorosugar in cold dichloromethane gives essentially quantitative yields of the N9 isomers of beta-anomeric 2'-deoxynucleoside intermediates. Direct ammonolysis (NH(3)/MeOH) of such intermediates or benzylation of the imidazole ring followed by milder ammonolysis of the imidazolium salt gives high yields of the clinical anticancer drug cladribine (2-chloro-2'-deoxyadenosine).


Modafinil reduces choice impulsivity while increasing motor activity in preadolescent rats treated prenatally with alcohol.
Rats exposed prenatally to alcohol show a reduction in the spontaneous activity of dopaminergic neurons of the ventral tegmental area (VTA), as well as greater impulsive behavior and motor activity, behavioral alterations that have been related to dopaminergic dysfunction. Modafinil (MOD) is a dopamine (DA) reuptake blocker prescribed to treat sleep disorders; however, in recent years it has been used for the treatment of ADHD with positive results. Also, studies in humans and rodents show beneficial effects on learning and attention; however, studies evaluating MOD effects on impulsivity are few and show contradictory results. The purpose of this work was to evaluate the effect of a daily dose of MOD (60 mg/kg i.g.) on cognitive (or choice) impulsivity and motor activity in male preadolescent rats exposed prenatally to alcohol or sucrose (isocaloric control). MOD reduced the impulsive responses in a delay discounting task (DDT) at the same time that increased the motor activity, in both healthy and prenatal alcohol treated rats; however, MOD reduced the response latency in DDT only in prenatal alcohol treated rats. This differential effect of DA activation on impulsivity and motor activity show that the MOD dose that improves the impulse control, does not necessarily decrease motor activity, and suggests a possible differential neural mechanism underlying the expression of these behaviors. On the other hand, the changes in the response latency, only in prenatal alcohol treated groups, suggest that decision-making in animals with a dopaminergic dysfunction is more susceptible to be affected by MOD action.


Vision-related quality-of-life assessment using NEI VFQ-25 in patients after Boston keratoprosthesis implantation.
The aim of this study was to determine the impact of Boston keratoprosthesis (KPro) implantation on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25). This is a prospective study of patients undergoing implantation of Boston KPro. The NEI VFQ-25 was used to assess vision-related quality of life preoperatively and postoperatively at 3 and 6 months and yearly thereafter. Baseline scores were compared with postoperative scores using paired t test. Stratified analysis was performed to compare results by visual acuity of the contralateral eye. Twenty-four patients were included. Mean baseline NEI VFQ-25 overall score was 44.6. At the first follow-up time point, mean overall score was 70.0, representing a statistically significant change from baseline (P < 0.001). Breakdown of subcategories within VFQ-25 showed significant improvement in general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, color vision, and peripheral vision (P < 0.05). This improvement was also observed when comparing baseline scores with postoperative scores at average follow-up of 16 months. Although a greater change in scores was observed in patients who had poor vision in the contralateral eye, patients with vision better than 20/200 in the nonsurgical eye showed statistically significant improvement in overall scores and subscale scores compared with baseline. The quality of life of patients who underwent KPro significantly improved postoperatively compared with their preoperative status. These results did not change when stratifying by visual acuity of the contralateral eye.


Intracellular parasitism, the driving force of evolution of Legionella pneumophila and the genus Legionella.
Legionella pneumophila is an intracellular pathogen that causes a severe pneumonia called Legionnaires' disease that is often fatal when not promptly diagnosed and treated. Legionella parasitize aquatic protozoa with which it co-evolved over an evolutionary long time. The close relationship between hosts and pathogens, their co-evolution, led to molecular interactions such as the exchange of genetic material through horizontal gene transfer (HGT). Genome sequencing of L. pneumophila and of the entire genus Legionella that comprises over 60 species revealed that Legionellae have co-opted genes and thus cellular functions from their eukaryotic hosts to a surprisingly high extent. Acquisition and loss of these eukaryotic-like genes and domains is an on-going process underlining the highly dynamic nature of the Legionella genomes. Although the large amount and diversity of HGT in Legionella seems to be unique in the prokaryotic world the analyses of more and more genomes from environmental organisms and symbionts of amoeba revealed that such genetic exchanges occur among all amoeba associated bacteria and also among the different microorganisms that infect amoeba. This dynamic reshuffling and gene-acquisition has led to the emergence of Legionella as human pathogen and may lead to the emergence of new human pathogens from the environment.


Osmotic Demyelination Syndrome in Hospitalized Patients With Cirrhosis: Analysis of the National Inpatient Sample (NIS).
Characterize prevalence of osmotic demyelination syndrome (ODS) in hospitalized patients with cirrhosis. ODS is a serious complication of rapid serum sodium correction. Patients with cirrhosis experience labile sodium levels related to portal hypertension and diuretic use, often with rapid correction-intentional or unintentional-during hospitalizations. We used validated International Classification of Diseases, Ninth Revision (ICD-9) codes to identify inpatients 18 years and older with cirrhosis from the 2009-2013 National Inpatient Sample, excluding those with liver transplantation during hospitalization. The primary outcome was ODS (ICD-9 341.8). Baveno IV defined decompensated cirrhosis (stages 3 and 4); Charlson Comorbidity Index identified severe comorbid illness (score >3). Logistic regression modeled factors associated with ODS. Of 547,544 adult inpatients with cirrhosis, 94 (0.02%) had ODS. Inpatients with versus without ODS were younger (54 vs. 57 y, P=0.0001), and more likely to have alcohol-related cirrhosis (58% vs. 33%, P<0.0001). ODS did not associate with decompensated cirrhosis (33% vs. 37%, P=0.43), specific complications (ascites 33% vs. 33%, P=0.97; hepatic encephalopathy 24% vs. 17%, P=0.06), or severe comorbid illness (12% vs. 16%, P=0.24). In both univariable and multivariable analysis, age [adjusted odds ratio (ORadj): 0.97, 95% confidence interval (CI): 0.95-0.99], female gender (ORadj: 1.53, 95% CI: 1.01-2.30), Hispanic race (ORadj: 0.41, 95% CI: 0.19-0.89), alcohol-related cirrhosis (ORadj: 2.65, 95% CI: 1.71-4.09), and congestive heart failure (ORadj: 0.37, 95% CI: 0.15-0.95) significantly associated with ODS. In hospitalized patients with cirrhosis, ODS is extremely rare, and associated with alcohol-related cirrhosis, younger age, and female gender. ODS is not associated with liver disease severity, specific complications including ascites, or comorbid disease.


A uniform genomic minor histocompatibility antigen typing methodology and database designed to facilitate clinical applications.
Minor Histocompatibility (H) antigen mismatches significantly influence the outcome of HLA-matched allogeneic stem cell transplantation. The molecular identification of human H antigens is increasing rapidly. In parallel, clinical application of minor H antigen typing has gained interest. So far, relevant and simple tools to analyze the minor H antigens in a quick and reliable way are lacking. We developed a uniform PCR with sequence-specific primers (PCR-SSP) for 10 different autosomal minor H antigens and H-Y. This genomic minor H antigen typing methodology allows easy incorporation in the routine HLA typing procedures. DNA from previously typed EBV-LCL was used to validate the methodology. To facilitate easy interpretation for clinical purposes, a minor H database named dbMinor (http://www.lumc.nl/dbminor) was developed. Input of the minor H antigen typing results subsequently provides all relevant information for a given patient/donor pair and additional information on the putative graft-versus-host, graft-versus-tumor and host-versus-graft reactivities. A simple, uniform and rapid methodology was developed enabling determination of minor H antigen genotypes of all currently identified minor H antigens. A dbMinor database was developed to interpret the genomic typing for its potential clinical relevance. The combination of the minor H antigen genomic typing methodology with the online dbMinor database and applications facilitates the clinical application of minor H antigens anti-tumor targets after stem cell transplantation.


Genotypic and phenotypic characterization of two Swedish isolates and two prototypic strains of Coxiella burnetii.
Two Swedish isolates of Coxiella burnetii and the two prototype strains of the species, Nine Mile and Priscilla, were characterized with regard to their multiplication and cytopathic effect on BGM cells and by PCR-based amplification of repetitive element DNA and the C. burnetii-specific plasmids QpH1 and QpRS. Moreover, 1330 bp of each 16S rRNA gene were sequence-determined. All four strains multiplied at virtually the same rate and displayed the same type of vacuoles in the BGM cells. Genetic homogeneity was observed inasmuch as the 16S rDNA sequences were identical and the strains showed identical PCR amplification patterns using primers specific to enterobacterial repetitive intragenic consensus DNA sequences. The two Swedish strains and the Priscilla strain also showed identical patterns after PCR amplification of repetitive extragenic palindromic DNA sequences, whereas the Nine Mile strain demonstrated a similar, but not identical pattern. Thus, the investigated strains demonstrated very similar phenotypic and genotypic characteristics. This finding is discussed in view of the very rare occurrence of domestic Q fever in Sweden.


Electropolymerized tricopolymer based on N-pyrrole derivatives as a primer coating for improving the performance of a drug-eluting stent.
The coating of medical implants by polymeric films aims at increasing their biocompatibility as well as providing a durable matrix for the controlled release of a drug. In many cases, the coating is divided into a primer layer, which bridges between the medical implant and the drug-eluting matrix. The primer coating must be very carefully designed in order to provide optimal interactions with the surface of the medical implant and the outer layer. Here we present a simple and versatile approach for designing the primer layer based on electropolymerization of a carefully chosen blend of three different pyrrole derivatives: N-methylpyrrole (N-me), N-(2-carboxyethyl)pyrrole (PPA), and the butyl ester of N-(2-carboxyethyl)pyrrole (BuOPy). The composition and physical properties of the primer layer were studied in detail by atomic force microscopy (AFM) and a nano scratch tester. The latter provides the in-depth analysis of the adhesion and viscoelasticity of the coating. AFM phase imaging reveals a uniform distribution of the three monomers forming rough morphology. This primer layer significantly improved the morphology, stability, and paclitaxel release profile of a paclitaxel-eluting matrix based on methyl and lauryl methacrylates.


Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy.
The presence of disseminated tumour cells (DTCs) in bone marrow is predictive of poor metastasis-free survival of patients with breast cancer with localized disease. DTCs persist in distant tissues despite systemic administration of adjuvant chemotherapy. Many assume that this is because the majority of DTCs are quiescent. Here, we challenge this notion and provide evidence that the microenvironment of DTCs protects them from chemotherapy, independent of cell cycle status. We show that chemoresistant DTCs occupy the perivascular niche (PVN) of distant tissues, where they are protected from therapy by vascular endothelium. Inhibiting integrin-mediated interactions between DTCs and the PVN, driven partly by endothelial-derived von Willebrand factor and vascular cell adhesion molecule 1, sensitizes DTCs to chemotherapy. Importantly, chemosensitization is achieved without inducing DTC proliferation or exacerbating chemotherapy-associated toxicities, and ultimately results in prevention of bone metastasis. This suggests that prefacing adjuvant therapy with integrin inhibitors is a viable clinical strategy to eradicate DTCs and prevent metastasis.


Moina hemanti sp. nov., a new species of the genus Moina s.l. (Branchiopoda: Anomopoda) from Pune, India.
We describe and figure Moina hemanti sp. nov. from ephemeral pools on the campus of Pune University, India. Although the pools flood during the monsoon, the moinid only appears irregularly and for a short period of time. In morphology, it is extremely close to Moina dumonti from Mexico and Cuba. This geographic gap remains unexplained for the time being, although more similar cases among cladocerans are on record. Molecular analysis has suggested that M. hemanti is relatively close to Moinodaphnia, and might form a genus in its own right, presumably together with M. dumonti. The latter, however, remains to be analyzed. Further candidates for this clade are Moina oryzae and M. rostrata, if the presence of an ocellus and/or a rostrum can be shown to be apomorphies.


Elucidating redox-level dispersion and local dielectric effects within electroactive molecular films.
The electron exchange between a redox-active molecular film and its underlying electrode can be cleanly tracked, in a frequency-resolved manner, through associated capacitive charging. If acquired data is treated with a classical (non quantum) model, mathematically equivalent to a Nernst distribution for one redox energy level, redox site coverage is both underestimated and environmentally variable. This physically unrealistic model fails to account for the energetic dispersion intrinsically related to the quantized characteristics of coupled redox and electrode states. If one maps this redox capacitive charging as a function of electrode potential one not only reproduces observations made by standard electroanalytical methods but additionally and directly resolves the spread of redox state energies the electrode is communicating with. In treating a population of surface-confined redox states as constituting a density of states, these analyses further resolve the effects of electrolyte dielectric on energetic spread in accordance with the electron-transfer models proposed by Marcus and others. These observations additionally underpin a directly (spectrally) resolved dispersion in electron-transfer kinetics.


Phyllosticta musarum Infection-Induced Defences Suppress Anthracnose Disease Caused by Colletotrichum musae in Banana Fruits cv 'Embul'.
Anthracnose development by Colletotrichum musae was observed to be significantly less in the fruits of the banana cultivar 'Embul' (Mysore, AAB) infected with Phyllosticta musarum than in fruits without such infections. Anthracnose disease originates from quiescent C. musae infections in the immature fruit. P. musarum incites minute, scattered spots, referred to as freckles, in the superficial tissues of immature banana peel which do not expand during maturation or ripening. P. musarum does not appear to have a direct suppressive effect on C. musae as conidia of C. musae germinate on both freckled and non-freckled fruit forming quiescent infections. Our investigations have shown that P. musarum infection induced several defence responses in fruit including the accumulation of five phytoalexins, upregulation of chitinase and β-1,3-glucanase, phenylalanine ammonia lyase (PAL) activity and cell wall lignification. (1)H and (13)C NMR spectral data of one purified phytoalexin compared closely with 4'-hydroxyanigorufone. Some of the P. musarum-induced defences that retained during ripening, restrict C. musae development at the ripe stage. This paper examines the potential of P. musarum-induced defences, in the control of anthracnose, the most destructive postharvest disease in banana.


Heterogeneity of transplantable melanomas differing in the rate of growth and cellular differentiation in relation to their cell transglutaminase activity.
Transglutaminase activity has been investigated by the fluorescent method in cells of two transplantable melanoma lines of the same origin but differing in rate of growth and the degree of differentiation. Transglutaminase activity within the cells under examination was not the same. In comparison with the original melanotic line, the amelanotic melanoma line, less differentiated and growing faster, was characterized by a greater heterogeneity of cells with regard to transglutaminase activity, and it also displayed greater activity of the enzyme.


Very Severe and Refractory Noninfectious Cystitis in Patients with Systemic Lupus Erythematosus: Potential Role of Rituximab Therapy.
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations, including, rarely, a form of interstitial cystitis (lupus cystitis, LC). LC can be asymptomatic and usually has discrete symptoms that improve with conventional therapies available for SLE and/or typical interstitial cystitis. A very severe and refractory form is rarely described. In this study, we present four patients with SLE and a very severe form of noninfectious cystitis refractory to the different forms of treatment described. The clinical descriptions of the cases, demographic factors, manifestations associated with SLE, and clinical and paraclinical manifestations related to cystitis, treatments, and outcomes are provided. A proposal for the pathogenesis of this condition is based on the common findings of these patients, including the fact that three were in SLE remission and all four receiving rituximab as induction and/or maintenance therapy.


Long-term chemiluminescence signal is produced in the course of luminol oxidation catalyzed by enhancer-independent peroxidase purified from Jatropha curcas leaves.
Isoenzyme c of horseradish peroxidase (HRP-C) is widely used in enzyme immunoassay combined with chemiluminescence (CL) detection. For this application, HRP-C activity measurement is usually based on luminol oxidation in the presence of hydrogen peroxide (H2O2). However, this catalysis reaction was enhancer dependent. In this study, we demonstrated that Jatropha curcas peroxidase (JcGP1) showed high efficiency in catalyzing luminol oxidation in the presence of H2O2. Compared with HRP-C, the JcGP1-induced reaction was enhancer independent, which made the enzyme-linked immunosorbent assay (ELISA) simpler. In addition, the JcGP1 catalyzed reaction showed a long-term stable CL signal. We optimized the conditions for JcGP1 catalysis and determined the favorable conditions as follows: 50 mM Tris buffer (pH 8.2) containing 10 mM H2 O2, 14 mM luminol and 0.75 M NaCl. The optimum catalysis temperature was 30°C. The detection limit of JcGP1 under optimum condition was 0.2 pM. Long-term stable CL signal combined with enhancer-independent property indicated that JcGP1 might be a valuable candidate peroxidase for clinical diagnosis and enzyme immunoassay with CL detection.


Sex pheromone signal and stability covary with fitness.
If sexual signals are costly, covariance between signal expression and fitness is expected. Signal-fitness covariance is important, because it can contribute to the maintenance of genetic variation in signals that are under natural or sexual selection. Chemical signals, such as female sex pheromones in moths, have traditionally been assumed to be species-recognition signals, but their relationship with fitness is unclear. Here, we test whether chemical, conspecific mate finding signals covary with fitness in the moth Heliothis subflexa. Additionally, as moth signals are synthesized de novo every night, the maintenance of the signal can be costly. Therefore, we also hypothesized that fitness covaries with signal stability (i.e. lack of temporal intra-individual variation). We measured among- and within-individual variation in pheromone characteristics as well as fecundity, fertility and lifespan in two independent groups that differed in the time in between two pheromone samples. In both groups, we found fitness to be correlated with pheromone amount, composition and stability, supporting both our hypotheses. This study is, to our knowledge, the first to report a correlation between fitness and sex pheromone composition in moths, supporting evidence of condition-dependence and highlighting how signal-fitness covariance may contribute to heritable variation in chemical signals both among and within individuals.


Conceptual and empirical advances in Neotropical biodiversity research.
The unparalleled biodiversity found in the American tropics (the Neotropics) has attracted the attention of naturalists for centuries. Despite major advances in recent years in our understanding of the origin and diversification of many Neotropical taxa and biotic regions, many questions remain to be answered. Additional biological and geological data are still needed, as well as methodological advances that are capable of bridging these research fields. In this review, aimed primarily at advanced students and early-career scientists, we introduce the concept of "trans-disciplinary biogeography," which refers to the integration of data from multiple areas of research in biology (e.g., community ecology, phylogeography, systematics, historical biogeography) and Earth and the physical sciences (e.g., geology, climatology, palaeontology), as a means to reconstruct the giant puzzle of Neotropical biodiversity and evolution in space and time. We caution against extrapolating results derived from the study of one or a few taxa to convey general scenarios of Neotropical evolution and landscape formation. We urge more coordination and integration of data and ideas among disciplines, transcending their traditional boundaries, as a basis for advancing tomorrow's ground-breaking research. Our review highlights the great opportunities for studying the Neotropical biota to understand the evolution of life.


Organization of the coelomic lining and a juxtaposed nerve plexus in the suckered tube feet of Parastichopus californicus (Echinodermata: Holothuroida).
The coelomic lining of the water-vascular canal in a suckered tube foot from the sea cucumber, Parastichopus californicus, is a pseudostratified myoepithelium consisting of flagellated adluminal cells and myofilament-bearing retractor cells. The bodies of adluminal cells flank the water-vascular canal and send basal processes between the underlying retractor cells to confront the podial connective tissue. Retractor cells have a contractile apparatus of unregistered thick and thin myofilaments. The contractile apparatus is confined to the medullary sarcoplasm and oriented parallel to the primary axis of a tube foot. The bodies and processes of retractor cells intermingle with the basal processes of adluminal cells at the basal lamina of the coelomic lining. A ganglionated nerve plexus in the podial connective tissue approximates the basal lamina. Neuronal connectives link the ganglia to one another and to the nerve plexus in deep sectors of the podial epidermis. External laminae enveloping the ganglia and connectives in the podial connective tissue are continuous with the basal lamina of the epidermis. The adventitial nerve plexus, since it merges with the epidermal nerve plexus, is a component of the ectoneural division of the echinoderm nervous system.


Everyday Acts of Resistance: Mexican, Undocumented Immigrant Children and Adolescents Navigating Oppression With Mentor Support.
Study aims were to examine oppression in education among Mexican immigrant youth with undocumented status and how mentors and other adults helped them resist oppression. Qualitative, narrative one-on-one interviews were conducted with 17 Mexican immigrant young adults with undocumented or DACA status in the U.S. Participants provided retrospective accounts from childhood through older adolescence. Analyses revealed critical junctures in which participants experienced oppression: (1) developmental milestones and school events, (2) college application process, (3) unforeseen life events, and (4) incidents of racial discrimination. Mentors and other adults helped participants to resist oppression through advocacy, social capital efforts, role modeling, and emotional, instrumental, and financial support. This study fills gaps in the literature on mentoring and immigrant youth who are undocumented.


Site-specific (13) С/(12) С isotope abundance ratios in dicarboxylic oxyacids as characteristics of their origin.
Recommendations of relevant international organizations controlling the quality of grape wines and beverages specify that only tartaric acids of grape origin can be introduced to achieve the required parameters. The development of methods for determining the origin of tartaric acid in grape wine is of great technological significance. Organic dicarboxylic oxyacids were extracted from wines as barium salts. Carbon dioxide, which included all the carbon atoms of the acids, was used to determine the carbon isotope ratios by Isotope Ratio Mass Spectrometry. The alkyl part of the oxyacids was burned at 560°C in the presence of air; BaCO3 containing the carboxyl carbon was left. This carbonate was used to measure the carbon isotope ratios in the carboxyl part of the acid. The carbon isotope ratios of the alkyl part of tartaric acid were found by isotope mass balance. The carbon isotope composition of carboxyl groups (δ(13) С values) in tartaric acid of grape (biogenic origin) had a higher (13) С content than the carbon in the alkyl part of the molecule. Tartaric acid produced by chemical synthesis (abiogenic origin) was noted to have a different (13) С/(12) С distribution: the carboxyl group of tartaric acid produced by chemical synthesis contained a smaller than or equal amount of (13) С to the alkyl part. This is the first determination of the site-specific distribution of the (13) С/(12) С isotopes in tartaric acids as evidence of their biogenic and abiogenic origins. The presented method for determining the origin of tartaric acid can be used for efficient control of the quality of grape wines and beverages.


Enantioselective synthesis of (+)-cortistatin a, a potent and selective inhibitor of endothelial cell proliferation.
This manuscript describes an enantioselective synthesis of the naturally occurring inhibitor of endothelial cell proliferation, cortistatin A. Key steps of the synthesis are a silicate-directed elimination/ring expansion reaction and a highly diastereoselective aza-Prins cyclization with a subsequent transannular etherification.


Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways.
Ornithine δ-aminotransferase (OAT, E.C. 22.214.171.124) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines. It is also involved in proline (Pro) synthesis. Deficiency in OAT causes gyrate atrophy, a rare but serious inherited disease, a further measure of the importance of this enzyme.


Assessing medication adherence self-efficacy among low-literacy patients: development of a pictographic visual analogue scale.
Health behavior interventions are often grounded in Social Cognitive Theory, but instruments used to assess self-efficacy rely on verbal skills and yield scores that are highly positively skewed. Based on a review of the research literature and qualitative research with key informants, a pictographic medication adherence self-efficacy scale was developed. Two studies were conducted to test the pictographic and color visual analogue scale for assessing self-efficacy for medication adherence. Study 1 (N = 81) demonstrated that the pictographic self-efficacy scale was internally consistent (alpha = 0.68), time stable (2-week test-re-test r = 0.63), and showed evidence for convergent and divergent construct validity. Study 2 (N = 64) further supported the reliability of the pictographic self-efficacy scale with additional data supporting its convergent, divergent and criterion-related validity, including associations with medication adherence and HIV viral load. Distributions of self-efficacy scores approximated normal. This newly developed pictographic scale may be useful in assessing medication adherence self-efficacy in lower-literacy populations.


Enhanced Passive RF-DC Converter Circuit Efficiency for Low RF Energy Harvesting.
For radio frequency energy transmission, the conversion efficiency of the receiver is decisive not only for reducing sending power, but also for enabling energy transmission over long and variable distances. In this contribution, we present a passive RF-DC converter for energy harvesting at ultra-low input power at 868 MHz. The novel converter consists of a reactive matching circuit and a combined voltage multiplier and rectifier. The stored energy in the input inductor and capacitance, during the negative wave, is conveyed to the output capacitance during the positive one. Although Dickson and Villard topologies have principally comparable efficiency for multi-stage voltage multipliers, the Dickson topology reaches a better efficiency within the novel ultra-low input power converter concept. At the output stage, a low-pass filter is introduced to reduce ripple at high frequencies in order to realize a stable DC signal. The proposed rectifier enables harvesting energy at even a low input power from -40 dBm for a resistive load of 50 kΩ. It realizes a significant improvement in comparison with state of the art solutions.


Enhancement of entomopathogenic nematode production in in-vitro liquid culture of Heterorhabditis bacteriophoraby fed-batch culture with glucose supplementation.
Nematode yield is a decisive factor for successful large-scale commercial production of entomopathogenic nematode. Various carbon sources were tested in in-vitro liquid culture to improve the yield of the entomopathogenic nematode Heterorhabditis bacteriophora. Canola oil was the optimal carbon source for nematode culture compared to carbohydrates when applied as a sole carbon source. However, when some of carbohydrates were applied together with canola oil, significant increases in nematode yield were observed. When 25 mg glucose ml(-1) was supplemented to 25 mg oil-based liquid culture medium ml(-1), the highest nematode yield, 3.62 x 10(5) infective juveniles, was achieved at 12 days, but nematode growth was suppressed at higher than 75 mg glucose ml(-1). A fed-batch culture process was introduced in nematode liquid culture consisting of two growth phases: bacteria and nematode. In the oil fed-batch culture, in which only glucose was initially added and oil was fed to the culture after the bacterial growth phase concurrent with nematode inoculation, nematode yield increased up to 4.25 x 10(5) infective juveniles ml(-1), while the batch culture resulted in 3.60 x 10(5) infective juveniles ml(-1). These results indicate that glucose is a superior carbon source for the bacteria, whereas canola oil is optimal for the nematode. The application of fed-batch culture provides significant enhancement of nematode yield in in-vitro liquid culture.