Visual filtering in time and space among persons with Down syndrome.

BACKGROUND: Individuals with Down syndrome (DS) appear to perform at a level that is commensurate with developmental expectations on simple tasks of selective attention. In this study, we examine how their selective attention is impacted by target changes that unfold over both time and space. This increased complexity reflects an attempt at greater ecological validity in an experimental task, as a steppingstone for better understanding attention among persons with DS in real-world environments. METHODS: A modified flanker task was used to assess visual temporal and spatial filtering among persons with DS (n = 14) and typically developing individuals (n = 14) matched on non-verbal mental age (mental age = 8.5 years). Experimental conditions included varying the stimulus onset asynchronies between the onset of the target and flankers, the distances between the target and flankers, and the similarity of the target and flankers. RESULTS: Both the participants with DS and the typically developing participants showed slower reaction times and lower accuracy rates when the flankers appeared closer in time and/or space to the target. CONCLUSION: No group differences were found on a broad level, but the findings suggest that dynamic stimuli may be processed differently by those with DS. Implications of the findings are discussed in relation to the developmental approach to intellectual disability originally articulated by Ed Zigler.

Choices, challenges, and constraints: a pragmatic examination of the limits of mental age matching in empirical research.

The work of Ed Zigler spans decades of research all singularly dedicated to using science to improve the lives of children facing different challenges. The focus of this article is on one of Zigler's numerous lines of work: advocating for the practice of mental age (MA) matching in empirical research, wherein groups of individuals are matched on the basis of developmental level, rather than chronological age. While MA matching practices represented a paradigm shift that provided the seeds from which the developmental approach to developmental disability sprouted, it is not without its own limits. Here, we examine and test the underlying assumption of linearity inherent in MA matching using three commonly used IQ measures. Results provide practical constraints of using MA matching, a solution which we hope refines future clinical and empirical practices, furthering Zigler's legacy of continued commitment to compassionate, meaningful, and rigorous science in the service of children.

Sexual function after vaginal erbium laser: the results of a large, multicentric, prospective study.

The aim of this multicentric, prospective study was to evaluate the effects of vaginal erbium laser (VEL-SMOOTH®) on sexual function in postmenopausal women suffering from the genitourinary syndrome of menopause (GSM). This study was performed on an outpatient basis without anesthesia or drug use before or after the intervention, using an erbium laser (XS Fotona Smooth®, Fotona, Ljubljana, Slovenia) in 1081 postmenopausal women (age 54.3 ± 3.9 years) treated with up to three laser applications every 30 days. Patients were assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). No adverse events were recorded during the study. The FSDS-R scores (n = 554), from basal values of 25.5 ± 3.5, were 11.5 ± 3.0, 10.5 ± 3.5 and 11.5 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Individual FSFI domain scores (n = 569) significantly (p < 0.001) increased after VEL-SMOOTH® treatment and remained significantly higher up to the 24th week after the end of treatment. The total scores, from basal values of 15.5 ± 1.5, were 27.5 ± 2.5, 27.6 ± 2.7and 27.0 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Albeit not randomized, this large, prospective study shows that VEL-SMOOTH® treatment may improve sexual function in postmenopausal women suffering from GSM.

The H3+ ionosphere of Uranus: decades-long cooling and local-time morphology.

The upper atmosphere of Uranus has been observed to be slowly cooling between 1993 and 2011. New analysis of near-infrared observations of emission from H3+ obtained between 2012 and 2018 reveals that this cooling trend has continued, showing that the upper atmosphere has cooled for 27 years, longer than the length of a nominal season of 21 years. The new observations have offered greater spatial resolution and higher sensitivity than previous ones, enabling the characterization of the H3+ intensity as a function of local time. These profiles peak between 13 and 15 h local time, later than models suggest. The NASA Infrared Telescope Facility iSHELL instrument also provides the detection of a bright H3+ signal on 16 October 2016, rotating into view from the dawn sector. This feature is consistent with an auroral signal, but is the only of its kind present in this comprehensive dataset. This article is part of a discussion meeting issue 'Advances in hydrogen molecular ions: H3+, H5+ and beyond'.

The role of arsenic in the hydrolysis and DNA metalation processes in an arsenous acid-platinum(ii) anticancer complex.

Platinum(ii)-based molecules are the most commonly used anticancer drugs in the chemotherapeutic treatment of tumours but possess serious side effects and some cancer types exhibit resistance with respect to these compounds (e.g. cisplatin). For these reasons, the research of new compounds that can bypass this limitation is in continuous development. Recently, mixed Pt(ii)-As(iii) systems have been synthesized and tested as potential anticancer agents. The mechanism of action of these kinds of drugs is unclear. Since in other platinum(ii) containing drugs, hydrolysis plays an important role in the activation of the compound before it reaches DNA, we have explored the aquation process using density functional theory (DFT), focusing our attention on the arsenoplatin complex, [Pt(µ-NHC(CH3)O)2ClAs(OH)2]. As DNA is believed to be the cellular target for Pt anticancer drugs, the metalation mechanism of DNA purine bases has been also investigated. Also for this new drug it appears that guanine is the preferred site with respect to adenine as with other platinum-containing compounds. A comparison with cisplatin is performed in order to highlight the contribution of arsenic in the anticancer activity of this new proposed anticancer agent.

Halogen atom effect on the photophysical properties of substituted aza-BODIPY derivatives.

The influence of halogen atom substitution (Br and I), in different amounts and positions in an aza-BODIPY skeleton, on the photophysical properties of some aza-BODIPY derivatives has been investigated by using density functional theory and its time-dependent extension. The heavy atom effect on excitation energies, singlet-triplet energy gaps and spin-orbit matrix elements has been considered. The maximum absorption within the therapeutic window has been confirmed for all the aza-BODIPY derivatives. The feasible intersystem spin crossing pathways for the population of the lowest triplet state, that will depend on the values of the spin-orbit matrix elements, the energy gap as well as the orbital composition of the involved states have been found to most likely involve the S1 and T1 or T2 states. The outcomes of computations support the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy.

Mechanistic investigation of trimethylamine-N-oxide reduction catalysed by biomimetic molybdenum enzyme models.

In this paper, we report a theoretical investigation of the reduction reaction mechanism of Me3NO using molybdenum containing systems that are functional and structural analogues of trimethylamine N-oxide reductase mononuclear molybdenum enzyme. The reactivity of the monooxomolybdenum(IV) benzenedithiolato complex and its derivatives to carbamoyl (t-BuNHCO) and acylamino (t-BuCONH) substituents on the benzene rings in both cis and trans arrangements was explored. The calculated energy profiles describing the steps of two mechanisms of attack considered viable (named cis- and trans-attack) by the Me3NO substrate at cis and trans positions with respect to the oxo ligand show that the attack on cis is energetically more favourable than the attack on trans. Along the pathway for the cis-attack the first step of the reaction, that is rate-determining for all the studied compounds, is the approach of the substrate to the Mo centre in cis to the oxo ligand that causes a distortion of the initial square-pyramidal geometry of the complex. The reaction steps involved in the trans position attack were also explored. Calculations confirm that, as previously suggested, the introduction of ligands able to form intramolecular NH···S hydrogen bonds accelerates the reduction of the Me3NO substrate and contributes to the tuning of the reactivity of molybdoenzyme models.

[Ethical dilemmas about disclosure of errors in medicine]. / Dilemas éticos acerca de la revelación de errores médicos a los pacientes.

Since the publication of the Institute of Medicine’s report “To Err is Human: Building a Safer Health System” awareness of the importance of medical errors has increased. These are a major cause of morbidity and mortality and recent studies suggest that they can be the third leading cause of death in the United States. Difficulties have been identified by health personnel to prevent, detect and disclose to patients the occurrence of a medical error, an also to report them to the appropriate authorities. Although human error cannot be eliminated, it is possible to design safety systems to mitigate their frequency and consequences. Our goal is to provide an update on the major concepts related to medical errors, a review of Chilean legislation on the subject, and a bioethical analysis on the principles involved, along with a management proposal. We propose mandatory reporting of errors to the health institution where they occur, to serve as a measure of personal and team learning, and to disclose the error to patients, depending on their own preferences.

Neurocognitive and familial moderators of psychiatric risk in velocardiofacial (22q11.2 deletion) syndrome: a longitudinal study.

BACKGROUND: Although risk for psychosis in velocardiofacial (22q11.2 deletion) syndrome (VCFS) is well established, the cognitive and familial factors that moderate that risk are poorly understood. METHOD: A total of 75 youth with VCFS were assessed at three time points, at 3-year intervals. Time 1 (T1) psychiatric risk was assessed with the Behavior Assessment System for Children (BASC). Data reduction of BASC scores yielded avoidance-anxiety and dysregulation factors. Time 2 (T2) neuropsychological and family function and time 3 (T3) prodromal/overt psychosis were assessed. Poisson regression models tested associations between T3 positive prodromal symptoms/overt psychosis and T1 psychiatric risk, T2 cognitive and familial factors, and their interactions. RESULTS: T1 avoidance-anxiety ratings predicted T3 prodromal/overt psychosis. T2 verbal learning scores moderated this association, such that individuals with low avoidance-anxiety scores and stronger verbal learning skills were the least likely to demonstrate prodromal/overt psychosis at T3. Low scores on a T2 visual vigilance task also predicted T3 prodromal/overt psychosis, independently of the effect of T1 avoidance-anxiety scores. T1 dysregulation scores did not predict T3 prodromal/overt psychosis in a linear manner. Instead, the association between dysregulation and prodromal/overt psychosis was amplified by T2 levels of family organization, such that individuals with low dysregulation scores and low family organization scores were the most likely to exhibit T3 prodromal/overt psychosis. CONCLUSIONS: Significant moderators of psychiatric risk in VCFS include verbal learning skills as well as levels of family organization, carrying implications for early identification and preventative treatment of youth with VCFS at highest risk for psychosis.

The working mechanism of the ß-carbonic anhydrase degrading carbonyl sulphide (COSase): a theoretical study.

In order to give insights into the working mechanism of the novel characterized enzyme carbonyl sulphide hydrolase (COSase), which efficiently converts COS into H2S and CO2, we have performed a detailed theoretical investigation using the framework of density functional theory (using B3LYP and M06 exchange-correlation functionals) by the cluster model approach. In the final part of the reaction the metal ion is unable to form a pentacoordinated species. The B3LYP-D3 and M06 potential energy surfaces have a very similar shape. The elucidation of the catalytic reduction of COS is important in view of its role in environmental chemistry.

Insight into the promiscuous activity of human carbonic anhydrase against the cyanic acid substrate from a combined QM and QM/MM investigation.

The promiscuous activity of human carbonic anhydrase (hCAII) against a non-physiological cyanic acid substrate has been investigated by using a combined QM and QM/MM level of theory. Results show that the hCAII is able to hydrate the cyanic acid by a reaction mechanism similar to that of the CO2 native substrate. The energy barrier for the nucleophilic attack is found to be 15.6 and 4.3 kcal mol(-1) at QM and QM/MM levels, respectively. This result underlines the importance of taking into account the surrounding residues around the active site in the presence of the substrate having small molecular sizes. The carbamate is strongly stabilized with respect to the bicarbonate of the native substrate indicating a more difficult release of the reaction product.

[Analysis of the main ethical conflicts in the 2008 declaration of Helsinki and the proposed changes in the new version]. / Análisis de los principales conflictos éticos entre la Declaración de Helsinki 2008 y su propuesta de cambio.

The Declaration of Helsinki (DoH) of the World Medical Association is the basis of the rules governing research on human beings. The latest version (enacted in Korea, 2008) has been a source of ethical discussions, particularly regarding the use of placebos, the measures to assure the access of study subjects to interventions identified as beneficial once the study has ended, and the need of a better protection of potentially vulnerable groups. These issues led to draft a revised version, that was approved in 2013. In this paper, we present an ethical analysis of the main changes contained in the DoH, including the proposed changes in the new version, referring, when appropriate, to relevant Chilean laws governing research on human subjects. In our opinion, the 2008 DoH contains significant imprecisions on some of these issues, making a new version of the declaration necessary to fully protect subjects participating in biomedical research, as stated by the new version approved in 2013.

[Adjuvant chemoradiotherapy in advanced gastric cancer: experience in 168 patients]. / Radioquimioterapia adyuvante en cáncer gástrico completamente resecado: experiencia del Instituto Nacional del Cáncer de Chile.

BACKGROUND: Gastric cancer is one of the most lethal tumors in the Chilean population. AIM: To report the results of adjuvant chemoradiotherapy in advanced gastric cancer. MATERIAL AND METHODS: Review of medical records of patients with locoregionally advanced gastric cancer, subjected to a curative resection and treated with adjuvant chemoradiotherapy. The treatment was based on the INT 0116/SWOG protocol, which includes 5-fuorouracil as a single agent. Patients were followed for a median of 58 months. RESULTS: the records of 168 patients (99 men) treated between 2004 and 2011, were reviewed. Median survival was 41 months. Median lapses between surgery and onset of chemo and radiotherapy were 12 and 17 weeks, respectively. Overall three and five years survival was 53 and 41%, respectively. On multivariate analysis the factors associated with a lower survival were an antral location of the tumor, presence of signet ring cells and more than 15 involved lymph nodes. CONCLUSIONS: Three and five years survival of gastric cancer patients subjected to adjuvant chemoradiotherapy was 53 and 41% respectively. These results are similar to those reported elsewhere.

[Radiation therapy in the treatment of brain-stem tumors in children]. / Tumores de tronco cerebral en niños tratados con radioterapia.

INTRODUCTION: Due to their location, tumors of the trunk (TT) present a high surgical risk and the diagnosis is usually made by imaging. In Chile, these cases are treated according to the PINDA Program (national treatment guide for pediatric tumors). All patients receive radiotherapy (RT) after diagnosis. The aim of this study is to evaluate the treatment results for TT at the National Cancer Institute (NCI) between 1993 and 2011. PATIENTS AND METHOD: A retrospective review of patients diagnosed with TT at NCI was conducted. Patient population, symptoms, treatment received and overall survival are described. Prognostic factors were analyzed. RESULTS: From November 1993 to December 2011, 70 children were referred for possible RT, 68 of them actually received it. The median age at diagnosis was 7 years old. In June 2012, out of 70 patients, 60 were deceased, all due to disease progression. The median survival of patients who received RT (68 patients) was 8.5 months from the end of treatment; the survival rates at 1, 2 and 3 years was 31.5 %, 14.3 % and 12.8% respectively. Univariate analysis showed that survival was affected by the MRN high resolution imaging (p = 0.07) and by the diffuse tumor pattern (p = 0.025). Multivariate analysis showed survival is affected by the MRN high resolution imaging (p = 0.011) and a higher dose of RT protector (p = 0.015). CONCLUSIONS: The poor results obtained in the treatment of TT with RT at the INC are similar to those reported by other centers. Further explorations regarding other treatment options based on combined therapy using RT are needed.

Compositional homogeneity in the fragmented comet 73P/Schwassmann-Wachmann 3.

The remarkable compositional diversity of volatile ices within comets can plausibly be attributed to several factors, including differences in the chemical, thermal and radiation environments in comet-forming regions, chemical evolution during their long storage in reservoirs far from the Sun, and thermal processing by the Sun after removal from these reservoirs. To determine the relevance of these factors, measurements of the chemistry as a function of depth in cometary nuclei are critical. Fragmenting comets expose formerly buried material, but observational constraints have in the past limited the ability to assess the importance of formative conditions and the effects of evolutionary processes on measured composition. Here we report the chemical composition of two distinct fragments of 73P/Schwassmann-Wachmann 3. The fragments are remarkably similar in composition, in marked contrast to the chemical diversity within the overall comet population and contrary to the expectation that short-period comets should show strong compositional variation with depth in the nucleus owing to evolutionary processing from numerous close passages to the Sun. Comet 73P/Schwassmann-Wachmann 3 is also depleted in the most volatile ices compared to other comets, suggesting that the depleted carbon-chain chemistry seen in some comets from the Kuiper belt reservoir is primordial and not evolutionary.

Fertility and endocrine outcome after robot-assisted laparoscopic myomectomy (RALM).

INTRODUCTION: Laparoscopic myomectomy has recently gained wide acceptance but this procedure remains technically highly demanding and concerns have been raised about the increased blood loss and an higher risk of postoperative uterine rupture of the pregnant uterus. OBJECTIVE: The aim of the present study is to evaluate the fertility and endocrine outcome in women underwent robot-assisted laparoscopic myomectomy (RALM). METHODS: Data from 48 RALM performed in our department between the years 2007 and 2011 have been collected. Conception rate, abortion rate, incidence of feto-maternal morbidity or severe pregnancy and labor-related complications were reported; FSH and AMH levels and ultrasound valuation of AFC has been made before and 6 months after operation. Number of cesarean sections and vaginal deliveries were described. RESULTS: The average age of the patients was 35 years and median Body Mass Index was 23 kg/m(2) (range 18-35 kg/m(2)). Seven women (13%) became pregnant after RALM with eight pregnancies. One pregnancy is actually on going; there were six deliveries with caesarian section and one spontaneous delivery. No spontaneous abortions. No uterine ruptures occurred. No significant modification of ovarian function was found after myomectomy. CONCLUSION: RALM seems to have a favorable impact on the reproductive outcome of young patients with no impact on the ovarian function.

Polycystic ovary syndrome: brain-derived neurotrophic factor (BDNF) plasma and follicular fluid levels.

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age. Features of PCOS are hyperandrogenism, chronic anovulation and polycystic ovaries on ultrasonography. Follicle development is a complex and carefully orchestrated phenomenon, involving gonadotropins and a rapidly expanding list of other intraovarian regulators, such as brain-derived neurotrophic factor (BDNF). The aim of this study is to evaluate BDNF in plasma and in follicular fluid in women affected by PCOS and in normal menstruating women. In PCOS patients the BDNF levels in plasma and in follicular fluid are higher than values obtained in healthy controls. Therefore we can hypothsize that high levels of luteinizing hormone, probably increase the secretion of BDNF in PCOS patients.

Evaluation of brain-derived neurotrophic factor in menstrual blood and its identification in human endometrium.

The presence of high-affinity brain-derived neurotrophic factor receptor Trk B in mouse and in human fetal oocytes, together with the presence of neurotrophins in human follicular fluid suggests a paracrine role for brain-derived neurotrophic factor (BDNF) in female biology. This study aims to evaluate if BDNF is present and quantitatively determined in human menstrual blood and endometrium. Twenty-one women were studied and subdivided in two groups: A, 11 fertile women (27 ± 2 days cycle length) and B, 10 anovulatory women and/or women with inadequate luteal phase (36 ± 2 days cycle length). In fertile women menstrual BDNF levels was higher than plasma (679.3 ± 92.2 vs 301.9 ± 46.7 pg/ml p <0.001). Similarly, in Group B, BDNF in menstrual blood was higher than plasma (386.1 ± 85.2 vs 166.8 ± 24.1 pg/ml p < 0.001). Moreover, both menstrual and plasma BDNF concentrations in Group A were significantly higher respect to Group B (679.3 ± 92.2 vs 386.1 ± 85.2 pg/ml p < 0.001; 301.9 ± 46.7 vs 166.8 ± 24.1 pg/ml p < 0.001). Immunohistochemistry evidence of BDNF in endometrium, during follicular and luteal phase, was also shown. The detection of BDNF in the human menstrual blood and endometrium further supports the role of this neurotrophin in female reproductive function.

Immunocytochemical localization of lysosomal beta-galactosidase in rat liver.

beta-galactosidase is a ubiquitous lysosomal hydrolase that specifically cleaves terminal beta-galactosyl residues from glycoproteins, glycosaminoglycans, oligosaccharides, and glycolipids. To study the intracellular distribution of this enzyme, we prepared a specific polyclonal antibody to lysosomal beta-galactosidase by immunizing rabbits with a highly purified preparation of beta-galactosidase from rat liver. Using this antibody we employed an immunocytochemical technique (protein A coupled to horseradish peroxidase and diaminobenzidine cytochemistry) and showed that beta-galactosidase is present in all hepatocytes of the rat liver. All types of lysosomes, the rough endoplasmic reticulum, and the specialized region of smooth endoplasmic reticulum known as GERL showed immunoreactivity. This in situ distribution suggests that these organelles are involved in the biosynthesis and intracellular sorting of this lysosomal enzyme.

Psychological responses after abortion.

A review of methodologically sound studies of the psychological responses of U.S. women after they obtained legal, nonrestrictive abortions indicates that distress is generally greatest before the abortion and that the incidence of severe negative responses is low. Factors associated with increased risk of negative response are consistent with those reported in research on other stressful life events.