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'.

Menopausia y terapia hormonal de la menopausia. Las recomendaciones 2018 de la Unidad de Endocrinología Ginecológica de Clínica Alemana de Santiago -Sociedad Italiana de la Menopausia y la Sociedad Chilena de Endocrinología Ginecológica / Menopause and menopausal hormone therapy. The 2018 recommendations of the Gynecological Endocrinology Unit of Clínica Alemana de Santiago -Italian Society of Menopause and the Chilean Society of Gynecological Endocrinology

ABSTRACT In the last decade, the risk benefits ratio of MHT has been evaluated mainly in terms of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these Recommendations is to provide a simple and updated reference on postmenopausal MHT. The term MHT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential (Seq) when progestogen is added to ERT for 10-14 days a month, or continuous combined (CC) when progestogen is administered continuously every day along with a fixed amount of estrogen. MHT also includes Tibolone and the Tissue Selective Estrogen Complex (TSEC).

Brief Report: Social Functioning Predicts Externalizing Problem Behaviors in Autism Spectrum Disorder.

Individuals with ASD often display externalizing behaviors, which have been associated with lower quality of life in adulthood. Social difficulties have been hypothesized to underlie externalizing problems among individuals with ASD (Klin and Volkmar in Asperger Syndrome, 340-366, 2000), but this has never been tested empirically. We examined whether socialization abilities predicted externalizing problems assessed by parent report in a group of 29 individuals with ASD (age range 7-16 years) and 29 TD individuals matched for IQ, age, and gender. Socialization scores accounted for 50% of the variance in externalizing behaviors among individuals with ASD, but not in TD children. These findings have implications for intervention, and suggest that targeting social difficulties might provide a better means to addressing externalizing problems.

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.

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.

Dilemas éticos acerca de la revelación de errores médicos a los pacientes

Since the publication of the Institute of Medicines 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.

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.

Synthesis and characterization of a family of M(2+) complexes supported by a trianionic ONO(3-) pincer-type ligand: towards the stabilization of high-spin square-planar complexes.

High-spin square-planar molecular compounds are rare. In an effort to access this unique combination of geometry and spin state, we report the synthesis of a series of M(II) compounds stabilized by a trianionic pincer-type ligand, highlighting the formation of a high-spin square-planar Co(II) complex. Low-temperature, variable-frequency EPR measurements reveal that the ground electronic state of the Co(II) analogue is a highly anisotropic Kramers doublet (effective g values 7.35, 2.51, 1.48). This doublet can be identified with the lowest doublet of a quartet, S = 3/2 spin state that exhibits a very large ZFS, D ≥ 50 cm(-1). The observation of an effective g value considerably greater than the largest spin-only value 6, demonstrates that the orbital angular moment is essentially unquenched along one spatial direction. Density Functional Theory (DFT) and time-dependent DFT calculations reveal the electronic configurations of the ground and excited orbital states. A qualitative crystal field description of the geff tensor shows that it originates from the spin-orbit coupling acting on states obtained through the transfer of a ß electron from the doubly occupied xy to the singly-occupied {xz/yz} orbitals.

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.

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.

A high-spin square-planar Fe(ii) complex stabilized by a trianionic pincer-type ligand and conclusive evidence for retention of geometry and spin state in solution.

Square-planar high-spin Fe(ii) molecular compounds are rare and the only three non-macrocyclic or sterically-driven examples reported share a common FeO4 core. Using an easily modifiable pincer-type ligand, the successful synthesis of the first compound of this type that breaks the FeO4 motif was achieved. In addition, we present the first evidence that geometry and spin state persist in solution. Extensive characterization includes the first high-field EPR and variable field/temperature Mössbauer spectra for this class of compounds. Analysis of the spectroscopic data indicates this complex exhibits a large and positive zero-field splitting tensor. Furthermore, the unusually small ΔEQ value determined for this compound is rationalized on the basis of DFT calculations.

[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.

[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.

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.

[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.