Parkinson's Disease Management through ICT

Parkinson's Disease (PD) is a neurodegenerative disorder that manifests with motor and non-motor symptoms. PD treatment is symptomatic and tries to alleviate the associated symptoms through an adjustment of the medication. As the disease is evolving and this evolution is patient specific, it could be very difficult to properly manage the disease.The current available technology (electronics, communication, computing, etc.), correctly combined with wearables, can be of great use for obtaining and processing useful information for both clinicians and patients allowing them to become actively involved in their condition.Parkinson's Disease Management through ICT: The REMPARK Approach presents the work done, main results and conclusions of the REMPARK project (2011 – 2015) funded by the European Union under contract FP7-ICT-2011-7-287677. REMPARK system was proposed and developed as a real Personal Health Device for the Remote and Autonomous Management of Parkinson’s Disease, composed of different levels of interaction with the patient, clinician and carers, and integrating a set of interconnected sub-systems: sensor, auditory cueing, Smartphone and server. The sensor subsystem, using embedded algorithmics, is able to detect the motor symptoms associated with PD in real time. This information, sent through the Smartphone to the REMPARK server, is used for an efficient management of the disease

Parkinson's Disease Management through ICT

Parkinson's Disease (PD) is a neurodegenerative disorder that manifests with motor and non-motor symptoms. PD treatment is symptomatic and tries to alleviate the associated symptoms through an adjustment of the medication. As the disease is evolving and this evolution is patient specific, it could be very difficult to properly manage the disease.The current available technology (electronics, communication, computing, etc.), correctly combined with wearables, can be of great use for obtaining and processing useful information for both clinicians and patients allowing them to become actively involved in their condition.Parkinson's Disease Management through ICT: The REMPARK Approach presents the work done, main results and conclusions of the REMPARK project (2011 – 2015) funded by the European Union under contract FP7-ICT-2011-7-287677. REMPARK system was proposed and developed as a real Personal Health Device for the Remote and Autonomous Management of Parkinson’s Disease, composed of different levels of interaction with the patient, clinician and carers, and integrating a set of interconnected sub-systems: sensor, auditory cueing, Smartphone and server. The sensor subsystem, using embedded algorithmics, is able to detect the motor symptoms associated with PD in real time. This information, sent through the Smartphone to the REMPARK server, is used for an efficient management of the disease

Digital innovation in Multiple Sclerosis Management

Due to innovation in technology, a new type of patient has been created, the e-patient, characterized by the use of electronic communication tools and commitment to participate in their own care. The extent to which the world of digital health has changed during the COVID-19 pandemic has been widely recognized. Remote medicine has become part of the new normal for patients and clinicians, introducing innovative care delivery models that are likely to endure even if the pendulum swings back to some degree in a post-COVID age. The development of digital applications and remote communication technologies for patients with multiple sclerosis has increased rapidly in recent years. For patients, eHealth apps have been shown to improve outcomes and increase access to care, disease information, and support. For HCPs, eHealth technology may facilitate the assessment of clinical disability, analysis of lab and imaging data, and remote monitoring of patient symptoms, adverse events, and outcomes. It may allow time optimization and more timely intervention than is possible with scheduled face-to-face visits. The way we measure the impact of MS on daily life has remained relatively unchanged for decades, and is heavily reliant on clinic visits that may only occur once or twice each year.These benefits are important because multiple sclerosis requires ongoing monitoring, assessment, and management.The aim of this Special Issue is to cover the state of knowledge and expertise in the field of eHealth technology applied to multiple sclerosis, from clinical evaluation to patient education

Parkinson's disease management through ICT: the REMPARK approach

Parkinson's Disease (PD) is a neurodegenerative disorder that manifests with motor and non-motor symptoms. PD treatment is symptomatic and tries to alleviate the associated symptoms through an adjustment of the medication. As the disease is evolving and this evolution is patient specific, it could be very difficult to properly manage the disease. The current available technology (electronics, communication, computing, etc.), correctly combined with wearables, can be of great use for obtaining and processing useful information for both clinicians and patients allowing them to become actively involved in their condition. Parkinson's Disease Management through ICT: The REMPARK Approach presents the work done, main results and conclusions of the REMPARK project (2011 - 2015) funded by the European Union under contract FP7-ICT-2011-7-287677. REMPARK system was proposed and developed as a real Personal Health Device for the Remote and Autonomous Management of Parkinson's Disease, composed of different levels of interaction with the patient, clinician and carers, and integrating a set of interconnected sub-systems: sensor, auditory cueing, Smartphone and server. The sensor subsystem, using embedded algorithmics, is able to detect the motor symptoms associated with PD in real time. This information, sent through the Smartphone to the REMPARK server, is used for an efficient management of the disease. Implementation of REMPARK will increase the independence and Quality of Life of patients; and improve their disease management, treatment and rehabilitation.Peer ReviewedPostprint (published version

Instilling reflective practice – The use of an online portfolio in innovative optometric education Accepted as: e‐poster Paper no. 098

At UCLAN we are breaking the mould and have developed a blended learning MSci optometry programme which is the first blended learning course in optometric education in the UK and the first to use a practice-based online portfolio. Optometry has traditionally been taught as a 3‐year undergraduate programme. Upon successful graduation, students are required to complete a year in practice and meet the General Optical Council's (GOC) “ability to” core competencies. However, a recent study by the GOC found that 76% of students felt unprepared for professional practice with insufficient clinical experience and in response, the GOC is currently undertaking an educational strategic review. To ensure the students receive high-quality clinical experience in the workplace, we have developed an online logbook and portfolio. Students log their experiences, learning points and reflections. The portfolio is closely monitored both by the student's mentor in practice and by academic staff. The content and reflections logged by the students then helps to drive the face to face teaching, small group discussions and clinical experiences provided by the university

Artificial Intelligence in Oncology Drug Discovery and Development

There exists a profound conflict at the heart of oncology drug development. The efficiency of the drug development process is falling, leading to higher costs per approved drug, at the same time personalised medicine is limiting the target market of each new medicine. Even as the global economic burden of cancer increases, the current paradigm in drug development is unsustainable. In this book, we discuss the development of techniques in machine learning for improving the efficiency of oncology drug development and delivering cost-effective precision treatment. We consider how to structure data for drug repurposing and target identification, how to improve clinical trials and how patients may view artificial intelligence

Regulatory post-translational modifications and protein-protein interactions involved in function and proteostasis of aromatic amino acid hydroxylases

The non-heme iron and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) dependent aromatic amino acid hydroxylases (AAAHs) family of enzymes include phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), and tryptophan hydroxylase 1 and 2 (TPH1 and TPH2). PAH catalyses the rate-limiting step in the catabolism of phenylalanine (L-Phe) that mainly takes place in the liver. TH catalyses the first and rate-limiting step in the biosynthesis of catecholamine neurotransmitters and hormones dopamine, norepinephrine and epinephrine in the brain and periphery. TPHs catalyse the first and rate-limiting step in the biosynthesis of serotonin in the peripheral (TPH1) and the central (TPH2) nervous systems. The AAAHs are of physiological and clinical importance. Dysfunctional PAH results in phenylketonuria (PKU), characterised by elevated levels of L-Phe in the blood, which can lead to brain damage. Catecholamine deficiency, due to dysfunctional TH, leads to motor dysfunction and neuropsychiatric disorders, such as TH deficiency (THD) and Parkinson’s disease. Reduced level of serotonin has been linked to anxiety disorder, depression, posttraumatic stress disorder and attention deficit hyperactivity disorder. Hence, the reactions catalysed by the AAAHs are important and tightly regulated. The aim of this thesis was to study the regulation of the AAAHs PAH and TH both in physiological and pathological states. We focused on regulatory mechanisms by selected post-translational modifications and protein-protein interactions and phosphorylation, investigating their role in the function, localisation and proteostasis of these enzymes using cellular and animal models. We investigated the role of DNAJC12, a type III member of the HSP40/DNAJ family, in the folding and degradation of wild-type (Wt) and mutant PAH. We observed a positive correlation between DNAJC12 and Wt and mutant PAH protein levels in the soluble cellular fractions. Detailed characterisations in liver lysates of the hyperphenylalaninemic Enu1 mouse (p.V106A-PAH mutation) revealed increased ubiquitination, instability, and aggregation of mutant PAH compared with Wt PAH. Furthermore, we showed that in the liver lysates, DNAJC12 interacts with both Wt and mono-ubiquitinated PAH; also, PAH mutation did not alter mRNA expression of DNAJC12. Our results support the role of DNAJC12 not only in proper folding but also in the processing of misfolded ubiquitinated PAH. We characterised a new custom-made Pah-R261Q knock-in mouse carrying mutation c.782G>A in the Pah gene. The homozygous Pah-R261Q mice exhibited reduced PAH activity and BH4 responsive hyperphenylalaninemia. Moreover, the mutant mice presented a reduced BH4 content in the liver, altered lipid metabolism, and increased oxidative stress, including increased mRNA expression of DNAJC12. Furthermore, the Pah-R261Q mice displayed large amyloid-like ubiquitinated PAH aggregates. The colocalisation of mutant PAH with selective autophagy markers indicated the involvement of the autophagic pathway in the clearance of mutant aggregates. These findings indicate a paradigm shift from a loss-of-function disorder to a toxic gain-of-function in PKU pathology. We next investigated the functional role of Ser31 phosphorylation in the regulation of TH in the cellular models. We observed that the perinuclear distribution of THpSer31 was concomitant with Golgi complex and synaptic vesicle marker in rat and human dopaminergic cells. The co-distribution of THpSer31 with vesicular monoamine transporter 2 (VMAT2) and α-synuclein (α-syn) in cells and their detection as co-immunoprecipitant in mouse brain lysate indicated an association of TH with vesicles. Furthermore, disruption of the microtubules caused accumulation of TH in the cell soma. Our study revealed that Ser31 phosphorylation regulates the subcellular localisation of TH by facilitating protein-protein interaction with VMAT2 and α-syn and enabling its transport toward axon terminals along microtubules. Finally, using SH-SY5Y cells, we sought to investigate the relationship between phosphorylation at different phosphosites and the nuclear distribution of TH, which was earlier proposed to be associated with Ser19 phosphorylation. We indeed observed that THpSer19 was predominantly nuclear, yet the phospho-null mutant of Ser19 (V5-TH-S19A) surprisingly accumulated significantly higher in the nuclear fraction when compared to Wt. Moreover, other phosphosites (Ser31 and Ser40) did not seem to influence the nuclear distribution of TH. When the phospho-null mutant of Thr8 (V5-TH-T8A) was expressed in SH-SY5Y cells, recombinant TH in the nuclear fraction was significantly reduced compared to Wt and the phospho-mimicking mutant V5-THT8E, indicating the potential role of Thr8 phosphorylation in the nuclear distribution of TH. In addition, inhibition of importin-β also reduced the amount of recombinant TH in the nucleus suggesting the involvement of the importin-β/RanGTP system in the nuclear localisation of TH in SH-SY5Y cells. To conclude, this study has brought new insights on the short-term regulation of AAAHs (PAH and TH) in physiological and pathological conditions by interacting with partners and by post-translational modifications, such as ubiquitination and phosphorylation (for TH), which ultimately affect their abundance, function and availability in different compartments of cells. Thus, this study has shed light on some of the molecular mechanisms involved in the proteostasis of AAAHs. Together, these findings open new research avenues to better understand disorders associated with the AAAHs.Doktorgradsavhandlin