A left basal ganglia case of dynamic aphasia or impairment of extra-language cognitive processes?

We report the case of OTM who presented with dynamic aphasia following a stroke that occurred in the left basal ganglia. He showed drastically reduced spontaneous speech in the context of well preserved naming, repetition and comprehension skills. OTM was particularly impaired in generating words, sentences and phrases when cued by a stimulus allowing many response options. By contrast, when a single response was strongly suggested by a stimulus, he could generate verbal responses adequately. OTM's non-verbal response generation abilities varied across tasks. He performed in the normal range in a motor movement generation test and he produced as many figures as controls when tested on a figural fluency task. He showed, however, many perseverations on this test. Moreover in a random number generation task he produced more responses that were part of ascending and descending series of numbers. The patient's impairments are interpreted as a consequence of two deficits. The first of these consists of an inability to generate verbal responses particularly in situations of high competition and involves the function of left frontal regions. The second deficit is one of impaired novel thought generation as evidenced by perseverations. This second deficit has been proposed to be a function of basal ganglia damage.     

Effect of dialect on phonological analysis

It is important to understand a child’s language background, to ensure appropriate assessment, diagnosis and treatment of speech sound disorders. Singapore is home to various cultures and languages, and local speech norms are needed to provide an accurate reference for assessing phonological disorders in the local population. This study aims to establish normative data and better understand the English phonological development of English–Mandarin bilingual preschoolers in Singapore, aged 3; 6–4; 5 years. The Articulation and Phonology subtests of the Diagnostic Evaluation of Articulation and Phonology – UK were used to collect speech data from 146 preschoolers. Responses were scored against two standards – British Standard English (BSE) and Singapore English (SGE), in terms of speech sound accuracy, and the frequency and type of error patterns present. The effect of language dominance on the children’s English phonological abilities was explored. Results showed that the preschoolers’ speech sound accuracy increased significantly when scored against SGE versus BSE targets. The number of children identified to be using several error patterns was reduced when SGE targets were used instead of BSE targets. English-dominant children scored significantly higher than their Mandarin-dominant peers on measures of speech sound accuracy. The identification of error patterns also differed between the two groups. These results show that it is important to take dialectal variation and language dominance into account in assessment, to determine if speech characteristics are due to a speech sound disorder or just normal dialectal variations.     

Depth of emotional experience and outcome

Abstract

The relationship between theme-related depth of experiencing (EXP) and outcome was explored in experiential therapy with depressed clients. The study sought to investigate whether depth of EXP predicts outcome, whether change in depth of EXP over therapy predicts outcome, and how these factors compare with the therapeutic alliance as predictors of outcome. The sample consisted of 35 clients, each of whom received 16 to 20 weeks of therapy. Themes that had emerged across therapy were identified. Depth of EXP was measured in relation to themes in one early session and in three sessions sampled from blocks across the last half of therapy. Analyses revealed that EXP on core themes in the last half of therapy was a significant predictor of reduced symptom distress and increased self-esteem. EXP did not correlate significantly with changes on the Inventory of Interpersonal Problems. EXP on core themes also accounted for outcome variance over and above that accounted for by early EXP and alliance.     

Characterization of human H1N1 influenza virus variants selected in vitro with zanamivir in the presence of sialic acid-containing molecules

Understanding the molecular mechanisms of influenza virus resistance to neuraminidase inhibitors is a main concern for their clinical use. In an attempt to reproduce in vivo selective conditions where influenza virus resistance to neuraminidase inhibitors can occur the zanamivir selection of an A/H1N1 influenza virus strain was carried out in Madin-Darby canine kidney cells performed in the presence or absence of sialic acid-containing inhibitor analogues that act as virus decoy receptors. The zanamivir-selected variants passaged in the presence of sialic acid-containing molecules resembling the human-like virus receptor lost the ability to bind red blood cells. Furthermore, whereas all zanamivir-selected variants exhibited a robust reduction in susceptibility to zanamivir in plaque assays only those obtained after extensive passages acquired a powerful neuraminidase enzyme resistance to zanamivir and oseltamivir. Evidence that balanced neuraminidase and hemagglutinin activities mediated by mutations induced during selection could play a role in the decrease of virus replication susceptibility to zanamivir is reported.     

Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population

BackgroundIt is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19.ObjectivesThis observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders.MethodsThis multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed.Results1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28–0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03–0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02–1.17).ConclusionIBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.     

Functions of vasopressin and oxytocin in bone mass regulation

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr^−/− mice have osteopenia, and Avpr1α^−/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr^−/−:Avpr1α^−/− double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α^−/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling.Over the past decade, we have described direct actions of anterior and posterior pituitary hormones on the skeleton (1–8). We have shown that these actions are exerted via G protein-coupled receptors resident on both osteoblasts and osteoclasts. We also find that the skeleton is highly sensitive to the action of posterior pituitary hormones; for example, mice haploinsufficient in oxytocin (Oxt) have osteopenic bones, but lactation is normal; lactation is impaired only in Oxt^−/− mice (2). Likewise, Tshr haploinsufficient mice are completely euthyroid with normal thyroid follicles but display significant osteopenia (4). The exquisite sensitivity of the skeleton to pituitary hormones comes as no surprise, considering that the pituitary gland and the skeleton are both evolutionarily more primitive than target endocrine organs (7).Apart from the known actions of growth hormone on the skeleton, Tsh, Fsh, Acth, Oxt, and vasopressin (Avp) have all been shown to regulate the formation and/or function of both osteoblasts and osteoclasts and thus to control bone remodeling in vivo (2–4, 6–8). The two neurohypophyseal hormones Oxt and Avp have opposing functions (2, 3). Oxt stimulates and Avp inhibits osteoblast formation. Consequently, the genetic deletion of the Oxt receptor (Oxtr) and Avp receptor 1α (Avpr1α) yields opposing phenotypes, notably osteopenia in Oxtr^−/− mice and high bone mass in Avpr1α^−/− mice (2, 3). These findings may explain the rapid recovery of bone loss at weaning when plasma Oxt levels are high (9) and also the profound loss of bone noted in chronic hyponatremic states, such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which serum Avp levels are elevated (3).We find high levels of Oxtr expression on both osteoclasts and osteoblasts (2, 10), in addition to their abundant expression in breast and uterine tissue, where they regulate lactation and parturition, respectively (11). Avpr1αs, in contrast, are distributed more ubiquitously, whereas Avpr2s are localized mainly in the kidney, where they regulate free water excretion (12). Osteoblasts express both Avpr1α and Avrpr2 (3). The only other known isoform, Avpr1β, is expressed predominantly in the pancreas and pituitary; it regulates ACTH secretion from pituitary corticotrophs (13). Sequence alignment shows that the binding sites of the Oxtr and Avprs are highly conserved, with specific amino acids within the predicted binding pocket providing ligand selectivity (14–16). The respective ligands Oxt and Avp also are homologous nonapeptides, differing in only two amino acids, and are known to interact with the other’s receptor with different affinities (17).To our knowledge, osteoblasts and osteoclasts are the only cells in which Oxtr, Avpr1α, and Avpr2 are coexpressed. We also have shown that osteoblastic Oxtrs undergo internalization and nuclear translocation upon binding to Oxt and that this action is independent of cytosolic Erk phosphorylation (18). Avpr1α activation by Avp also activates Erk phosphorylation within minutes (3). The homology between the ligands and their respective receptors and converging downstream signals suggest that Avp and Oxtr may share receptors with opposing or convergent signals. Here, we have explored these interactions in the regulation of osteoblastic bone formation by using mice lacking one or both receptors, chemical inhibitors, and physiological models of high bone turnover.     

Estimated intermediate risk endometrial cancer: debate and new perspectives on therapy individualization and prognosis establishment starting from a peculiar case

The adequate treatment for stage IB endometrial cancer (EC) with G1-G2 grading (intermediate risk patients) is still debated. FIGO guidelines recommend adjuvant radio-therapy in order to avoid recurrences, despite it has been demonstrated that this does not improve the overall survival. Recently, other than the conventional risk-factor (histology, stage and grading), lymph-vascular involvement, tumor size and neoplasia molecular patterns has been proposed with intent to establish the most appropriated EC oncologic treatment and prognosis. We report an interesting case of a patient affected by an early stage EC (estimated intermediate low risk), treated by the adequate surgical staging and subsequent adjuvant radio-therapy that showed, in a follow up period, a very poor prognosis, similarly to patients affected by high risk cancer. Even if the classical validated risk factors remain the “cornerstone” in risk assessment, adjuvant treatments and follow up planning after surgery, the molecular investigation of estimated intermediate risk EC could represent a “keystone” to solve and avoid the “oncologic dilemma” of cases in which the observed prognosis results very different from the expected one. Only a detailed molecular evaluation of these cases could allow a more specific treatment targeting, leading to an individualized therapy and low recurrence-risk. The importance of recurrence-risk reduction is linked to difficulties in both their early detection and appropriate management. The delay in diagnosis as well as the performance of not adequate treatment can potentially make the prognosis of these cases worst that the one detected in case of uterine sarcoma or mixed müllerian tumors.