Anxiety in children with Williams syndrome : association with negative reactivity, self-regulation, and sensory modulation.

Williams syndrome (WS) is a neurodevelopmental disorder caused by a submicroscopic deletion of approximately 25 genes on chromosome 7q11.23 (Hillier et al., 2003). This genotype is associated with a characteristic set of phenotypic features including mild to moderate intellectual disability, a distinctive cognitive profile, facial dysmorphology, common personality traits, cardiovascular problems, and connective tissue disorders (Morris, 2010). In addition, behavioral difficulties such as anxiety symptoms (e.g., Leyfer, Woodruff-Borden, & Mervis, 2009), negative reactivity (e.g., Davies, Udwin, & Howlin, 1998), problems with self-regulation (e.g., Woodruff-Borden, Kistler, Henderson, Crawford, & Mervis, 2010), and sensory modulation difficulties (e.g., John & Mervis, 2010) are common. While anxiety as a behavioral concern for individuals with WS is well-documented, little is known about why these individuals are at an increased risk for this type of problem. Several features of the WS behavioral phenotype have been associated with child anxiety in the general population, specifically negative reactivity (e.g., Lonigan, Phillips, & Hooe, 2003), self-regulation problems (e.g., Eisenberg et al., 2001), and sensory modulation difficulties (e.g., Ben-Sasson, Cermak, Orsmond, Tager-Flusberg, Kadlec, & Carter, 2008). The purpose of this dissertation was to explore the relations of negative reactivity (NR), difficulties with self-regulation (SR), and sensory modulation difficulties (SM) to the increased prevalence of anxiety symptoms in children with WS. Study hypotheses are: (1) The shared variance between NR, SR, and SM will be adequately represented by a single underlying ‘behavioral phenotype’ factor. (2) This factor will share a significant relation with anxiety symptoms in children with WS. Participants were 115 children with WS aged 6 – 10 years. Primary caregivers completed four measures: (1) Children’s Behavior Questionnaire (Rothbart, Ahadi, Hershey, & Fisher, 2001). NR was measured using the Negative Affectivity factor score. (2) Short Sensory Profile (McIntosh, Miller, Shyu, & Dunn, 1999). SM was measured using the Total Sensory Modulation score. (3) Behavior Rating Inventory of Executive Functioning (Gioia, Isquith, Guy, & Kenworthy, 2000). SR was measured using the Behavioral Regulation Index T-score. (4) Child Behavior Checklist 6 – 18 (Achenbach & Rescorla, 2001). Anxiety symptoms were measured using the DSM-IV Anxiety Problems T-score. Exploratory factor analysis and regression analysis were conducted to test the study hypotheses. The results supported both hypotheses: The WS behavioral phenotype features of negative reactivity, difficulties with sensory modulation, and difficulties with self-regulation were adequately represented by one underlying factor; and this factor explained a substantial portion of the variance in anxiety symptoms for children with WS aged 6 – 10 years. Implications for future research and treatment of anxiety in children with WS are discussed

The Mixed State of a π\pi-Striped Superconductor

A model of an anti-phase modulated d-wave superconductor has been proposed to describe the decoupling between Cu-O planes in 1/8 doped La$_{2-x}$Ba$_{x}$CuO$_{4}$. Unlike a uniform d-wave superconductor, this model exhibits an extended Fermi surface. Within Bogoliubov-de Gennes theory, we study the mixed state of this model and compare it to the case of a uniform d-wave superconductor. We find a periodic structure of the low-energy density of states, with a period that is proportional to $B$, corresponding to Landau levels that are a coherent mixture of particles and holes. These results are also discussed in the context of experiments which observe quantum oscillations in the cuprates, and are compared to those for models in which the Fermi surface is reconstructed due to translational symmetry breaking in the non-superconducting state and to a model of a Fermi-arc metal

Quantum Oscillations in a π\pi-Striped Superconductor

Within Bogoliubov-de Gennes theory, a semiclassical approximation is used to study quantum oscillations and to determine the Fermi surface area associated with these oscillations in a model of a $\pi$-striped superconductor, where the d-wave superconducting order parameter oscillates spatially with period 8 and zero average value. This system has a non-zero density of particle-hole states at the Fermi energy, which form Landau-like levels in the presence of a magnetic field, B. The Fermi surface is reconstructed via Andreev-Bragg scattering, and the semiclassical motion is along these Fermi surface sections as well as between them via magnetic breakdown. Within the approximation, oscillations periodic in 1/B are found in both the positions and widths of the lowest Landau levels. The area corresponding to these quantum oscillations for intermediate pairing interaction strength is similar to that reported for experimental measurements in the cuprates. A comparison is made of this theory to data for quantum oscillations in the specific heat measured by Riggs et al.Comment: 18 pages and 34 figure

Topographical localisation of glucidic residues and their variations in the canine zona pellucida during folliculogenesis.

In the present ultrastructural study, horseradish peroxidase-labelled lectins, in conjunction with antiperoxidase antibody and protein A-gold, were used to characterise and localise the oligosaccharide sequences of zona pellucida glycoproteins at different stages of follicular development in the canine ovary. Deacetylation and sialidase digestion were also performed before lectin cytochemistry. The zona pellucida of oocytes present in unilaminar primary follicles reacts with WGA- and RCA-I-lectins. The zona pellucida of oocytes present in bilaminar and trilaminar secondary follicles displays positivity to WGA, RCA-I, Con-A, UEA-I, and sialidase/SBA. This labelling pattern persists in the zona pellucida of oocytes present in antral tertiary follicles with the exception of WGA and RCA-I reactive sites which are differently distributed throughout the zona pellucida. The topographical distribution of these carbohydrates is not uniform throughout the zona pellucida, indicating the regionalization of oligosaccharide chains within three concentric bands of the zona matrix: an inner surface close to the oocyte plasma membrane, an intermediate portion and an outer layer in contact with the follicular cells. Our results demonstrated variations in the presence and distribution of the carbohydrate residues in the canine zona pellucida during different stages of follicular growth. We also observed the presence of vesicles in both the ooplasm and granulosa cells, showing a similar lectin binding pattern to that of the zona pellucida

Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting

Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumours that originate from cells of neural crest (NC) origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage. Therapeutic resistance, post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell (CSC)-like subpopulations, which through their self-renewing capacity, intermittent and slow cell cycles, drug-resistant and reversibly adaptive plastic phenotypes, represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs. In this review, dedicated to NB CSCs and the prospects for their therapeutic eradication, we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction, specification, epithelial to mesenchymal transition and migratory behaviour, in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB. We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs, before providing a comprehensive review of the salient molecules, signalling pathways, mechanisms, tumour microenvironmental and therapeutic conditions involved in promoting, selecting and maintaining NB CSC subpopulations, and that underpin their therapy-resistant, self-renewing metastatic behaviour. Finally, we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance, post-therapeutic relapse and metastatic progression

Clinical Efficacy of the GnRH Agonist (Deslorelin) in Dogs Affected by Benign Prostatic Hyperplasia and Evaluation of Prostatic Blood Flow by Doppler Ultrasound.

In six German Shepherds dogs, GnRH agonist implants (Deslorelin) were inserted subcutaneously one month after histological confirmation of benign prostatic hyperplasia (BPH). Prostatic volume (PV), characteristics of ejaculate, serum testosterone concentrations and Doppler parameters of prostatic and subcapsular arteries were detected at different time intervals, for 6 month. The prostatic volume showed a significantly reduction starting at day 37. The decrease in sperm concentration, motility and increase in morphological abnormal sperm were observed from day 22 to day 37, when it was no longer possible to obtain the ejaculate. The values of peak systolic velocity and end-diastolic velocity in prostatic and subcapsular arteries showed from day 11 a gradual decrease, significant at day 22 until day 37 and reaching the lowest values at day 52 until the end of observation. The power Doppler pixel intensity of both arteries showed a gradual decrease from day 5 until day 52. In particular, a significant decrease was observed for both arteries from day 11. Testosterone serum concentration decreased to undetectable levels by day 11 until the end of the observations. All these Doppler parameters and testosterone values were positively correlated with the prostatic volume. Furthermore, testosterone values were positively correlated with peak systolic velocity, end diastolic velocity and pixel numbers. The use of implants containing GnRH analogues, even in asymptomatic subjects, is effective for the control of BPH and the application of Doppler exam of prostatic blood flow represent an non-invasive tool for monitoring the response of medical treatment

Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer

Hypoxia-induced alternative splicing is a potent driving force in tumour pathogenesis and progression. In this review, we update currents concepts of hypoxia-induced alternative splicing and how it influences tumour biology. Following brief descriptions of tumour-associated hypoxia and the pre-mRNA splicing process, we review the many ways hypoxia regulates alternative splicing and how hypoxia-induced alternative splicing impacts each individual hallmark of cancer. Hypoxia-induced alternative splicing integrates chemical and cellular tumour microenvironments, underpins continuous adaptation of the tumour cellular microenvironment responsible for metastatic progression and plays clear roles in oncogene activation and autonomous tumour growth, tumor suppressor inactivation, tumour cell immortalization, angiogenesis, tumour cell evasion of programmed cell death and the anti-tumour immune response, a tumour-promoting inflammatory response, adaptive metabolic re-programming, epithelial to mesenchymal transition, invasion and genetic instability, all of which combine to promote metastatic disease. The impressive number of hypoxia-induced alternative spliced protein isoforms that characterize tumour progression, classifies hypoxia-induced alternative splicing as the 11th hallmark of cancer, and offers a fertile source of potential diagnostic/prognostic markers and therapeutic targets

Legitimacy in REDD+ governance in Indonesia

This paper addresses the question of legitimacy in REDD+ governance in Indonesia. It develops a legitimacy framework that builds on elements of Scharpf (J Eur Pub Policy 4(1):18–36, 1997) input and output legitimacy concept and the political economy lens described by Brockhaus and Angelsen (Analysing REDD+: Challenges and choices, CIFOR, Bogor, 2012). Using data collected through key informant interviews and focus groups, we identify and explore stakeholder perceptions of legitimacy. The analysis reveals a complex interplay between input and output legitimacy, finding that state, non-state and hybrid actors perceive output legitimacy (i.e. project outcomes) as highly dependent on the level of input legitimacy achieved during the governance process. Non-state actors perceive proxies for input legitimacy, such as participation and inclusion of local people, as goals in themselves. In the main, they perceive inclusion to be integral to the empowerment of local people. They perceive output legitimacy as less important because of the intangibility of REDD+ outcomes at this stage in the process. The findings also highlight the challenges associated with measuring the legitimacy of REDD+ governance in Indonesia

Concurrent RAS and RAS/BRAF V600E Variants in Colorectal Cancer: More Frequent Than Expected? A Case Report

The assessment of RAS and BRAF mutational status is one of the main steps in the diagnostic and therapeutic algorithm of metastatic colorectal cancer (mCRC). Multiple mutations in the BRAF and RAS pathway are described as a rare event, with concurrent variants in KRAS and BRAF genes observed in approximately 0.05% of mCRC cases. Here, we report data from a case series affected by high-risk stage III and stage IV CRC and tested for RAS and BRAF mutation, treated at our Medical Oncology Unit. The analysis of KRAS, NRAS (codons 12, 13, 59, 61, 117, 146), and BRAF (codon 600) hotspot variants was performed in 161 CRC tumors from August 2018 to September 2021 and revealed three (1.8%) patients showing mutations in both KRAS and BRAF (V600E), including two cases with earlier CRC and one with metastatic disease. We also identified one patient (0.6%) with a mutation in both KRAS and NRAS genes and another one (0.6%) with a double KRAS mutation. Notably, the latter was characterized by aggressive behavior and poor clinical outcome. The mutational status, pathological features, and clinical history of these five CRC cases are described. Overall, this study case series adds evidence to the limited available literature concerning both the epidemiological and clinical aspects of CRC cases characterized by the presence of concurrent RAS/BRAF variants. Future multicentric studies will be required to increase the sample size and provide additional value to results observed so far in order to improve clinical management of this subgroup of CRC patients