Frontrunners in the Latest Stem Cell Technology

Attracting investor attention In January 2022, the company was recognized as one of the top 25 BioTech start-ups (1). Since its conception, it has attracted USS86.9 million (€80.8 million) in series A and B funding from private equity investors, including Leonard Green and Partners, XAnge, AQUITI Gestion, BNP Paribas Developpement, and Bpifrance, as well as Bristol Myers Squibb, Aquitaine Science Transfer, and the European Commission (1). First-in-human trial expected in 2024 TreeFrog's lead programme targets Parkinson's disease via the generation of three-dimensional (3D) neurospheres which contain mature dopaminergic neurons. In 2022, TreeFrog awarded several Stem Cell SpaceShot grants to leading academic institutions including the University of Sheffield, UK;MCR Laboratory of Molecular Biology, 13 Dec 2022).

Management of Parkinson's Disease during the COVID-19 Pandemic: Challenges and Opportunities

COVID-19 has wreaked havoc in the lives of people worldwide, but for people who are elderly and have comorbid chronic conditions, the pandemic has been particularly devastating. Despite the growing research on the effects of COVID-19 on people with Parkinson's disease (PD), the long-term effects are unknown. Research does not support a higher risk of contracting COVID-19 among people with PD;however, the indirect effects of the pandemic mitigation efforts on the lives of people with PD are significant. The interruption of routine medical care and physical therapy and exercise programs along with the indirect effects of social distancing and pervasive lock downs appear to have contributed to worsening of previously experienced PD-related symptoms and the development of new ones. This pandemic has challenged the entire healthcare delivery model and, for people with PD, the resultant repercussions on quality of life have been and continue to be particularly consequential. In this article, we will describe how COVID-19 has negatively impacted the lives of, and healthcare protocols for, people with PD, along with a discussion of the broad implications and possible solutions (e.g., virtual exercise classes, telemedicine).

The challenge of managing parkinson's disease patients during the COVID-19 pandemic

The 2019 novel coronavirus (nCoV) pandemic is rapidly developing across the globe and new information is emerging expeditiously and constantly, particularly in relation to neurological illnesses. Both central and peripheral nervous system involvement has been reported including headache, dizziness, hyposmia/anosmia, taste disturbances, seizures, stroke, alteration of the sensorium, and even acute hemorrhagic necrotizing leukoencephalopathy. Varying degrees of olfactory disturbances may pre-empt the diagnosis of COVID-19. Although no direct effect of 2019 nCoV has been reported yet on Parkinson's disease, there are enormous possible indirect effects and implications. We examine the potential effects and challenges posed by this pandemic to individuals with Parkinson's disease, particularly in the Indian context where telecommunication access or support group access may be lacking for these patients. Additionally, lockdown and social distancing may pose hurdles in the provision of optimum medical therapy, particularly if patients experience motor and non-motor deteriorations due to diverse reasons.

This Week in the Journal

Issue HighlightsIssue Highlights, February 23, 2023

Potential Neurological Outcomes in COVID-19 Patients: A Non-systematic Review of the Literature During the First Year of the COVID-19 Pandemic

Coronavirus emerged from Wuhan China, which has been a global challenge for healthcare authorities and individuals. Patients are presenting to clinicians with neurological symptoms caused by coronavirus disease-2019 (COVID-19) or with preexisting neurological conditions with fear of contracting the virus. This is a literature review of COVID-19 patients and patients with underlying neurological conditions affected by the pandemic encompassing December 2020 to March 2021. We searched multiple databases including PubMed, Google Scholar, EBSCO, Semantic Scholar, and Wiley Online for information on neurological manifestations of patients suffering from coronavirus. Clinical data and co-morbidities of the patients were examined. Headache, dizziness, hyposmia, and stroke symptoms were reported. According to recently published literature, some of the patients with coronavirus who have respiratory symptoms also develop neurological symptoms. Certain medical emergencies such as stroke require immediate treatment to ensure better clinical outcomes for the patients. Neurologists and clinicians need to recognize these acute symptoms in order to timely manage and treat the affected patients.

Post COVID-19 medical complications

The infection triggered by the SARS-CoV-2 virus resulted in the novel coronavirus infection (COVID-19), which was firstly identified in city of China, namely Wuhan. The main symptoms such as muscle fatigability, aches, and pain are associated with this condition. Thus, a high proportion of patients who recovered manifest a plethora of long-lasting symptoms. Although, many patients fully recover, health complications can delay a person's complete return to a regular lifestyle. Fatigue is experienced by a considerable percentage of individuals who have recovered from COVID-19 disease. Thus, the neurological symptoms of COVID-19 are frequent and debilitating enough to have piqued the interest of the scientific and general press for their brief and long effect on population health. The authors have searched articles from various search engines. The articles on coronavirus have been collected from PubMed and Scopus databases from Jan., 2019 to July, 2021. On the basis of their importance and uniqueness, articles were included in this review. The study aims on COVID-19 infection on survivors and complications to return to normal life and role of consulting sessions, physiotherapy and other medications after recovery. Some long-term researches are created to investigate the COVID-19's medical, psychological, and socio-economic complications. To resume normal life, COVID-19 survivors are required to take aid to consultations, physiotherapy, and dermatological care.

Assessing predictors of NEDA in RRMS patients initiating dimethyl fumarate in a real-world setting

IntroductionNo evidence of disease activity (NEDA) is a treatment goal when using disease modifying therapy for treating relapsing remitting multiple sclerosis (RRMS).1 However, predicting which patients may achieve NEDA is challenging.ObjectiveTo identify the baseline clinical and MRI features that predict NEDA in patients initiating dimethyl fumarate (DMF).Method: In our observational study, we retrospectively collected clinical and radiological data acquired for patients with RRMS initiating DMF. Demographics and clinical details at MS onset and at DMF initiation (baseline) were evaluated. We investigated the associations between all the baseline clinical and MRI findings and NEDA at 24 months using a combined multiple logistic regression.ResultsWe had a total of 670 patients in our cohort and only 339 (50%) achieved NEDA at 24 months. Lower EDSS (Log odds[95%CI]= -0.19[-0.30 to -0.03], p=0.01), lower number of new MRI lesions at baseline (Log odds[95%CI]= -0.14[-0.32 to -0.04], p=0.01) and lower number of relapses in the previous 12 months (Log odds[95%CI]= -0.39[-0.77 to -0.26], p=0.0001) significantly predicted NEDA at 24 months.ConclusionSignificant predictors for achieving NEDA were the number of relapses in the previous year, the number of new MRI lesions and the EDSS at DMF initiation. This could be useful in clinical practice to counsel patients regarding their potential response to DMF.

Is There a Moral Issue When Doctors Prescribe Placebos?

Medicine has made use of placebos, or sugar pills, with no medicinal value for several thousand years. Even clinical studies conducted today use placebos to compare the efficacy of investigative medications or treatments. For example, in the COVID-19 era, experimental investigations including hydroxychloroquine, steroids, or plasma from patients who have had COVID-19 and have antibodies that may be efficacious in treating COVID-19, have been compared with placebo or inert substances that certainly don't affect the course of the disease. Only in this fashion is it possible to determine the response to these and other substances. The use of placebos has raised an ethical question regarding giving patients an inert substance which has no known impact on the disease or condition being studied. Doctors or other medical investigators have a moral obligation to inform patients that they may be receiving either an active drug or a placebo. The patient cannot be told, however, which arm of a study they are in and whether they received the active drug or the placebo until the study has been completed. This article explains how placebos work and offers advice on the clinical use of placebos.

Completion of an advance care plan (ACP) with patients with advanced neurological conditions, the evidence

BackgroundAs a result of service development through COVID-19, a community based Speciality Doctor was recruited to write ACPs for patients with progressive advanced neurological conditions through domiciliary visits. This study seeks to understand how their ACP may benefit patients and their primary health care providers (PHCP).MethodsRetrospective cohort study, examining electronic hospital records 3 months pre-ACP/3 months post-ACP of 36 patientsOnline survey of patient’s named PHCPResults36 patients were reviewed, diagnoses included advanced Parkinson’s disease/Parkinson’s plus, secondary multiple sclerosis, NF1 and superficial siderosis. 2 of these patients were known to hospice services before ACP commencement.5 patients died since their ACP was made, all in their preferred place of care (home), with anticipatory medications, and without hospital or hospice input at end of life. Comparing 3 months pre to 3 months post ACP, ED attendances reduced from 35 to 9, and acute hospital inpatient stays reduced from 16 to 5 (136 to 21 bed days). 9 of 26 PHCPs surveyed replied. 89% (8) knew about the ACP but none had used it so far to make a clinical decision. 89% (8) felt confident of what an ACP is (8+/10 self scoring) with 33% (3) very confident to complete/review themselves. All responders felt happy for an ACP to be completed on behalf of them, concluding that it should be done by the ‘most appropriate’ ‘experienced clinician’ who ‘knows the patient best’.ConclusionsThis study demonstrates the benefit from ACP in terms of achieving PPOC and avoiding hospital admissions. For these 36 patients, there were potentially 11 acute hospital admissions avoided, with a reduction in 115 bed days.Data will be extended by a further 3 months by the time of the PCC. Future work gauging patient’s and carer’s opinion of ACP is planned.

Palliative care for patients with parkinson’s disease: a UK-based focus group study

BackgroundParkinson’s disease (PD) is a common life-limiting neurodegenerative condition. As far as we are aware, no study to date has looked holistically at how palliative and end of life care is delivered for patients with PD in the UK from the perspective of healthcare professionals. To address this knowledge gap, a focus group of experts in the fields of palliative care and Parkinson’s disease was held to determine the current landscape of care and areas where care could be improved.MethodsAn exploratory qualitative focus group took place online in December 2020 with twelve clinicians comprising physicians, nurses and a pharmacist from a range of speciality backgrounds and geographical areas. The focus group was recorded and transcribed verbatim. Analysis was conducted using an iterative approach based on inductive coding by two independent reviewers to categorise the data into themes and sub-themes.ResultsFour major themes were identified: i) Patient centred care - clinicians felt that lack of personalised care meant that assessment and management of symptoms was sub-optimal ii) Navigating advance care plans - clinicians expressed difficulty in initiating and engaging in ACP discussions, as well as facilitating patient adaptability iii) Uncertainty - uncertainty of both the clinician and the patient was felt to be a barrier to the delivery of quality care iv) Strengthening care across different settings – clinicians stressed the importance of strengthening support in community and primary care settings, with the role of a coordinating keyworker being advocatedConclusionMeaningful relationships between patients and healthcare professionals, as well as services and settings, are the foundation of providing high quality care. New ways of delivering care due to the COVID-19 pandemic have been continued, such as video consultations. This focus group provided a rich discussion and has been used as springboard to develop a Delphi study to develop gold standards in palliative care for patients with PD.

Does Olfactory Dysfunction Correlate with Disease Progression in Parkinson’s Disease? A Systematic Review of the Current Literature

Background. Loss of olfaction is a well-established early feature of Parkinson’s disease (PD). Although olfactory dysfunction has been widely described as a prodromal feature of PD in the literature, whether it can be considered a biomarker of PD progression is still a matter of debate. Objective. The aim of this work is to define the possible relationship between the progression of olfactory dysfunction and other putative clinical hallmarks of PD over time, through a systematic review of the current literature. Methods. We conducted a systematic review of the literature on PubMed from inception to March 2022. We included only longitudinal studies conducted on patients with diagnosis of idiopathic PD who underwent olfactory function testing at baseline and repeated it at least once during follow-up. Results. Among 5740 records identified through database searching, nine longitudinal studies met full criteria and underwent data extraction. Conclusions. Olfaction seemed to decrease over time, albeit with a degree of fluctuation. Moreover, smell detection ability seems to deteriorate more rapidly in the early phase of disease, indicating a possible association with disease progression. More studies are needed to better understand the role of olfaction as a biomarker of PD progression over time.

Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders

It has been found that soluble epoxide hydrolase (sEH;encoded by the EPHX2 gene) in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation, which, in turn, plays a part in the pathogenesis of neuropsychiatric disorders. Meanwhile, epoxy fatty acids such as epoxyeicosatrienoic acids (EETs), epoxyeicosatetraenoic acids (EEQs), and epoxyeicosapentaenoic acids (EDPs) have been found to exert neuroprotective effects in animal models of neuropsychiatric disorders through potent anti-inflammatory actions. Soluble expoxide hydrolase, an enzyme present in all living organisms, metabolizes epoxy fatty acids into the corresponding dihydroxy fatty acids, which are less active than the precursors. In this regard, preclinical findings using sEH inhibitors or Ephx2 knock-out (KO) mice have indicated that the inhibition or deficiency of sEH can have beneficial effects in several models of neuropsychiatric disorders. Thus, this review discusses the current findings of the role of sEH in neuropsychiatric disorders, including depression, autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease (PD), and stroke, as well as the potential mechanisms underlying the therapeutic effects of sEH inhibitors.

Multi-Scale Sparse Graph Convolutional Network For the Assessment of Parkinsonian Gait

Automated assessment of patients with Parkinson's disease (PD) is urgently required in clinical practice to improve the diagnostic efficiency and objectivity and to remotely monitor the motor disorder symptoms and general health of these patients, especially in view of the travel restrictions due to the recent coronavirus epidemic. Gait motor disorder is one of the critical manifestations of PD, and automated assessment of gait is vital to realize automated assessment of PD patients. To this end, we propose a novel two-stream spatial-temporal attention graph convolutional network (2s-ST-AGCN) for video assessment of PD gait motor disorder. Specifically, the skeleton sequence of human body is extracted from videos to construct spatial-temporal graphs of joints and bones, and a two-stream spatial-temporal graph convolutional network is then built to simultaneously model the static spatial information and dynamic temporal variations. The multi-scale spatial-temporal attention-aware mechanism is also designed to effectively extract the discriminative spatial-temporal features. The deep supervision strategy is then embedded to minimize classification errors, thereby guiding the weight update process of the hidden layer to promote significant discriminative features. Besides, two model-driven terms are integrated into this deep learning framework to strengthen multi-scale similarity in the deep supervision and realize sparsification of discriminative features. Extensive experiments on the clinical video dataset show that the proposed model exhibits good performance with an accuracy of 65.66% and an acceptable accuracy of 98.90%, which is much better than that of the existing sensor- and vision-based methods for Parkinsonian gait assessment. Thus, the proposed method is potentially useful for assessing PD gait motor disorder in clinical practice.

Dancing with paper

The exhibition also includes colour photographs of dancers taken at their homes by visual artist Sara Hibbert, and a film documentary about the project directed by Teale and Skapin. Hibbert says that, by cropping her colour photographs of dancers' hands and limbs, her final exhibited images “explore the notion of shared space, of presence becoming visible within the gaps, of collective timing and exchange”. The exhibition provides illuminating glimpses into the creative processes of dance and visual art.

Music Therapy Service Provision via Telehealth in Response to COVID-19 Restrictions: A Survey of Australian Practitioners and Consumers

Music Therapy and Telehealth Early exploratory studies of telehealth music therapy, aimed to increase access to services for those clients living in areas where there were no music therapy services (Baker & Krout, 2009;Fuller & McLeod, 2019;Lightstone et al., 2015;Tamplin et al., 2019) or who were unable to travel to onsite workplaces due to health reasons (Stegemöller et al., 2020). Telehealth music therapy was first reported with an autistic adolescent (Baker & Krout, 2009), and since then, exploratory studies have been undertaken in adults with spinal cord injury (Tamplin et al., 2019), with war veterans experiencing post-traumatic stress (Lightstone et al., 2015;Vaudreuil et al., 2020), in Parkinson's Disease (Stegemöller et al., 2020) and with children experiencing hearing loss and their families (Fuller & McLeod, 2019). When working with an autistic adolescent, a microanalysis of video footage found that there was very little difference in the level of engagement (confirming statements, disagreeing statements, discussions of musical elements, discussions of song structure, self-expression, the offering or extension of lyrics, eye contact, head nodding, smiling/laughing, and playing music) between the two contexts (Baker & Krout, 2009;2013). Research into online singing groups for people living with Parkinson's disease has demonstrated improvements in phonation duration, pitch range, vocal intensity, and maximum respiratory pressures, although as a feasibility pilot, this study was not powered to test statistical significance (Stegemöller et al., 2020).

Alterations in taste and smell associated with SARS-CoV-2: an exploratory study investigating food consumption and subsequent behavioural changes for those suffering from post-acute sequelae of COVID-19

Objective: To explore food consumption and subsequent behavioural changes amongst PASC suffers associated with alterations in taste and smell. Design: A qualitative study involving five focus groups. Setting: Birmingham and Leicester, England, United Kingdom. Participants: Forty-seven Post-Acute Sequelae of COVID-19 sufferers. Results: Shifts in taste and odour were very common with disgusting or unpleasant notes being perceived in many foods, including animal products rich in protein. Food consumption patterns varied affecting nutrition status, individuals weight, types of foods consumed, cooking habits, coping mechanisms, anxieties, family and social interactions. Individuals expressed the need to taste something or experience normal tastes and flavour. Low pH foods, highly processed foods which may contain large amounts of refined sugars as well as cold processed food were the preferred items for consumption. Conclusion: Olfactory dysfunction was related to the consumption of nutrients that require moderation and to the quality of life. Intervention at an early stage is necessary in order to help avoid such complications and thus, this work informs medical practitioners and health workers of the variety of food choices that are more acceptable for people suffering from altered tastes and odour perception.

Vaccine equity . . . and other stories

Using data on the daily number of motor vehicle collisions resulting in death or injury and adjusting for seasonality, a complicated analysis shows a small decrease when compared with England and Wales, where there is no minimum price for alcohol. Omega 3 fatty acids for depression in adults Although omega 3 polyunsaturated fatty acids are no longer thought to have any protective influence on cardiovascular disease, there have been suggestions that they might reduce the occurrence and severity of depressive disorders. Any beneficial effect of omega 3 polyunsaturated fatty acids is probably too small to be useful (Cochrane Database Syst Rev doi:10.1002/14651858.CD004692.pub5).

EDITORIAL

Assessment and prevention of frailty and sarcopenia are of particular importance during the COVID-19 pandemic. Since 2020, the pandemic has been a new risk factor for frailty and sarcopenia. Feeding problems are common among older patients who had a stroke, advanced dementia, neurologic degenerative diseases (parkinsonism), or sarcopenic dysphagia.3 Although careful hand feeding is implemented in some geriatric units, nasogastric tube feeding is common in Hong Kong, particularly in residential care homes. Rehabilitation has beneficial effects on motor and swallowing function, activities of daily living, and quality of life in patients with Parkinson disease.7,8 Pilates exercise seems to be useful to improve balance and motor function of patients with Parkinson disease.