Natural compounds as inhibitors of transthyretin amyloidosis and neuroprotective agents: analysis of structural data for future drug design

Natural compounds, such as plant and fruit extracts have shown neuroprotective effect against neurodegenerative diseases. It has been reported that several natural compounds binding to transthyretin (TTR) can be useful in amyloidosis prevention. TTR is a transporter protein that under physiological condition carries thyroxine (T4) and retinol in plasma and in cerebrospinal fluid (CSF); it also has a neuroprotective role against Alzheimer’s disease (AD). However, TTR also is an amyloidogenic protein responsible for familial amyloid polyneuropathy (FAP) and familial amyloid cardiomyopathy (FAC). The TTR amyloidogenic potential is speeded up by several point mutations. One therapeutic strategy against TTR amyloidosis is the stabilisation of the native tetramer by natural compounds and small molecules. In this review, we examine the natural products that, starting from 2012 to present, have been studied as a stabiliser of TTR tetramer. In particular, we discussed the chemical and structural features which will be helpful for future drug design of new TTR stabilisers

Interprofessional clinical placement involving speech pathology and counselling psychology

This paper examines the interprofessional learning of a speech pathology and counselling psychology student in an interprofessional placement within an institution of the Department of Corrective Services in Perth, Western Australia. The institution is a pre-release centre that promotes rehabilitation and community reintegration in which up to six women are able to have their children, aged 0–4 years of age, live with them. The students provided a program to the mothers to facilitate development of a healthy mother–child relationship and the children’s communication development. This paper utilised qualitative descriptive analysis to explore two examples of student learning and found perceived growth in the students’ clinical skills, their understanding of the other profession and the concept of interprofessional collaboration. While students experience growth in a range of placements, the journey described in this paper is unusual in both the nature of the student collaboration and the placement itself. The research highlights the importance of joint clinical placements in the development of interprofessional collaborative relationships

Interprofessional clinical placement involving speech pathology and counselling psychology

This paper examines the interprofessional learning of a speech pathology and counselling psychology student in an interprofessional placement within an institution of the Department of Corrective Services in Perth, Western Australia. The institution is a pre-release centre that promotes rehabilitation and community reintegration in which up to six women are able to have their children, aged 0–4 years of age, live with them. The students provided a program to the mothers to facilitate development of a healthy mother–child relationship and the children’s communication development. This paper utilised qualitative descriptive analysis to explore two examples of student learning and found perceived growth in the students’ clinical skills, their understanding of the other profession and the concept of interprofessional collaboration. While students experience growth in a range of placements, the journey described in this paper is unusual in both the nature of the student collaboration and the placement itself. The research highlights the importance of joint clinical placements in the development of interprofessional collaborative relationships

Amount of therapy matters in very early aphasia rehabilitation after stroke: A clinical prognostic model

Background and Aim The effects of very early aphasia therapy on recovery are equivocal. This article examines predictors of very early aphasia recovery through statistical modeling. Methods This study involved a secondary analysis of merged data from two randomized, single-blind trials conducted in Australian acute and subacute hospitals. Study 1 (n = 59) compared daily therapy to usual ward care for up to 4 weeks poststroke in patients with moderate to severe aphasia. Study 2 (n = 20) compared daily group therapy to daily individual therapy for 20 1-hour sessions over 5 weeks, in patients with mild to severe aphasia. The primary outcome measure was the Western Aphasia Battery Aphasia Quotient (AQ) at therapy completion. This analysis used regression modeling to examine the effects of age, baseline AQ and baseline modified Rankin Scale (mRS), average therapy amount, therapy intensity, and number of therapy sessions on aphasia recovery. Results Baseline AQ (p = 0.047), average therapy amount (p = 0.030), and baseline mRS (p = 0.043) were significant predictors in the final regression model, which explained 30% (p < 0.001) of variance in aphasia recovery. Conclusion The amount of very early aphasia therapy could significantly affect communication outcomes at 4 to 5 weeks poststroke. Further studies should include amount of therapy provided to enhance reliability of prognostic modeling in aphasia recovery. © 2013 by Thieme Medical Publishers, Inc

The positive side of the Alzheimer's disease amyloid cross-interactions: The case of the Aβ 1-42 peptide with tau, TTR, CysC, and ApoA1

Alzheimer's disease (AD) represents a progressive amyloidogenic disorder whose advancement is widely recognized to be connected to amyloid-β peptides and Tau aggregation. However, several other processes likely contribute to the development of AD and some of them might be related to protein-protein interactions. Amyloid aggregates usually contain not only single type of amyloid protein, but also other type of proteins and this phenomenon can be rationally explained by the process of protein cross-seeding and co-assembly. Amyloid cross-interaction is ubiquitous in amyloid fibril formation and so a better knowledge of the amyloid interactome could help to further understand the mechanisms of amyloid related diseases. In this review, we discuss about the cross-interactions of amyloid-β peptides, and in particular Aβ1-42, with other amyloids, which have been presented either as integrated part of Aβ neurotoxicity process (such as Tau) or conversely with a preventive role in AD pathogenesis by directly binding to Aβ (such as transthyretin, cystatin C and apolipoprotein A1). Particularly, we will focus on all the possible therapeutic strategies aiming to rescue the Aβ toxicity by taking inspiration from these protein-protein interactions

Antioxidant quercetin 3-O-glycosylated plant flavonols contribute to Transthyretin stabilization

Plants are rich in secondary metabolites, which are often useful as a relevant source of nutraceuticals. Quercetin (QUE) is a flavonol aglycone able to bind Transthyretin (TTR), a plasma protein that under pathological conditions can lose its native structure leading to fibrils formation and amyloid diseases onset. Here, the dual nature of five quercetin 3-O-glycosylated flavonol derivatives, isolated from different plant species, such as possible binders of TTR and antioxidants, was investigated. The crystal structure of 3-O-β-D-galactopyranoside in complex with TTR was solved, suggesting that not only quercetin but also its metabolites can contribute to stabilizing the TTR tetramer

Assessment of Cardiovascular Function in Childhood Leukemia Survivors: The Role of the Right Heart

Childhood acute lymphoblastic leukemia (ALL) survivors who underwent chemotherapy with anthracyclines have an increased cardiovascular risk. The aim of the study was to evaluate left and right cardiac chamber performances and vascular endothelial function in childhood ALL survivors. Fifty-four ALL survivors and 37 healthy controls were enrolled. All patients underwent auxological evaluation, blood pressure measurements, biochemical parameters of endothelial dysfunction, flow-mediated dilatation (FMD) of the brachial artery, mean common carotid intima-media thickness (c-IMT), antero-posterior diameter of the infra-renal abdominal aorta (APAO), and echocardiographic assessment. The ALL subjects had significantly lower FMD (p = 0.0041), higher left (p = 0.0057) and right (p = 0.0021) echocardiographic/Doppler Tei index (the non-invasive index for combined systolic and diastolic ventricular function) as compared to controls. Tricuspid annular plane excursion (TAPSE) was 16.9 +/- 1.2 mm vs. 24.5 +/- 3.7 mm, p &lt; 0.0001. Cumulative anthracycline doses were related to TAPSE (p &lt; 0.001). The ALL survivors treated with anthracyclines demonstrated systo/diastolic alterations of the right ventricle and reduced endothelial function compared with healthy controls. The early recognition of subclinical cardiac and vascular impairment during follow up is of utmost importance for the cardiologist to implement strategies preventing overt cardiovascular disease considering the growing number of young adults cured after childhood ALL

The development of aboriginal brain injury coordinator positions: A culturally secure rehabilitation service initiative as part of a clinical trial

Brain injury, resulting from stroke and traumatic brain injury, is a common occurrence in Australia, with Aboriginal people affected at a significant rate and impact felt by individuals, families and communities. Access to brain injury rehabilitation services for Aboriginal people is reported to be often limited, with very little support outside the hospital environment. Our research involving Aboriginal brain injury survivors and their families to date has revealed that people often manage ‘on their own’ following such events. Following recommendations from survivors and their families, the Healing Right Way clinical trial, currently underway in Western Australia, has created the role of Aboriginal Brain Injury Coordinator (ABIC) to assist in navigating information and services, particularly after discharge from hospital. Eight positions for this role have been instigated across metropolitan and rural regions in the state. Healing Right Way’s aim is to enhance rehabilitation services and improve quality of life for Aboriginal Australians after brain injury. The ABIC’s role is to provide education, support, liaison and advocacy services to participants and their families over a six-month period, commencing soon after the participant’s stroke or injury has occurred. This paper outlines the development of this role, the partnerships involved, experiences to date and identifies some facilitators and barriers encountered that may impact the role’s ongoing sustainability. Details of components of the planned full Process Evaluation of Healing Right Way related to the ABIC role and the partnerships surrounding it are also provided. In combination with the trial’s ultimate results, this detail will assist in future service planning and provide a model of culturally secure care for stroke and brain injury services that can also inform other sub-acute and primary care models

Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage?

<p>Abstract</p> <p>Background</p> <p>Hashimoto's thyroiditis is the most important cause of hypothyroidism. It is a systemic disease that can even affect the cardiovascular system, by accelerating the atherosclerotic process. Aim of this study was to examine whether autoimmune thyroiditis has an effect on the intima-media thickness of the common carotid artery (IMT-CCT), independently of the thyroid function and well-known cardiovascular risk factors. Hashimoto's thyroiditis is a systemic disease. The aim is to examine whether autoimmune thyroiditis and adiposity can effect carotid IMT independently of thyroid hormones and cardiovascular risk factors.</p> <p>Methods</p> <p>A total of 104 obese women (BMI ≥ 25.0 kg/m^-2), with FT3 and FT4 serum levels in the normal range and TSH levels < 4.5 μU/ml, were investigated. None of these patients was taking any kind of drug influencing thyroid function. Measurements were made of the IMT-CCT, BMI, waist circumference, blood pressure levels, as well as fasting TSH, FT3, FT4, anti-thyroid antibodies, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol serum concentrations.</p> <p>Results</p> <p>Of the 104 women, 30 (28.8%) were affected by autoimmune thyroiditis. Significantly higher values of IMT-CCT (p < 0.05), TSH (p < 0.05), and triglycerides (p < 0.05) were obtained, and significantly lower values of FT4 (p < 0.05), in patients with Hashimoto's thyroiditis as compared to those with a normal thyroid function. When examining the whole group together, at multiple regression analysis Hashimoto's thyroiditis maintained a positive association with the IMT (p < 0.001), independently of age, hypertension, BMI, and the fasting serum levels of TSH, FT3, FT4, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol levels.</p> <p>Conclusions</p> <p>The present study shows that Hashimoto's thyroiditis is associated to an increased IMT only in overweight and obese, independently of the thyroid function, BMI and cardiovascular risk factors. These results suggest that Hashimoto's thyroiditis is a marker of evolution of the atherosclerosis if combined to adiposity.</p