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METHODS: We systematically searched for guideline recommendation on the day-to-day use of peripheral inflammatory markers such as NLR published in the English language between January 1, 2005, and October 2020. Any other evidence of system biology-based approach or recommendation was explored within the selected guidelines for this scoping review. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 4 authors to determine clinical scenarios explained/given, scientific evidence used, and recommendations presented in the context of system biology. RESULTS: The scoping review found 2,911 titles at the beginning of the search. Final review included with 15 guidelines. Stroke-related organizations wrote sixty-five percent of the guidelines while national ministries wrote a fewer number of guidelines. We were primarily interested in recommendations for acute management in AIS published in the English language. Fifteen eligible guidelines were identified from 15 different countries/regions. None of the guidelines recommended the routine use of peripheral markers of inflammation, such as NLR, among their acute assessment and management recommendations. None of the existing guidelines explored the system biology approach to one of the most complex diseases affecting the human brain, stroke. CONCLUSIONS: This systematic review has identified a significant evidence-practice gap in all existing national stroke guidelines published in English medium as of October 2020. These guidelines included the only current "living stroke guidelines," stroke guidelines from Australia with a real opportunity to modernize the living stroke guidelines with systems biology approach, and provide 2020 vision towards better stroke care globally. Investigation of complex disease such as stroke is best served through a systems biology approach. One of the easiest places to start is simple blood tests such as total white cell count and NLR. System

Hereditary cancer syndromes are inherited pathogenic genetic variants that significantly increase the risk of developing cancer. When individuals become aware of their increased probabil-ity of having cancer, the whole family is affected by this new reality and needs to adjust. However, adjustment to hereditary cancer syndromes has been mainly studied at an individual level, and research about familial adjustment remains dispersed and disorganized. To overcome this gap, this review aims to understand how families adjust to genetic testing and risk management, and to what extent the family’s adjustment influences the psychological response and risk management behav-iors of mutation carriers. We conducted searches on the PubMed/Med Line, PsycInfo, SCOPUS, and Google Scholar databases and used the Mixed Methods Appraisal Tool (MMAT-v2018) to assess the methodological quality of each selected study. Thirty studies met the inclusion criteria. Most results highlighted the interdependent nature of adjustment of pathogenic variant carriers and their fami-lies. The way carriers adjust to the syndrome is highly related to how family members react, partic-ularly partners and siblings dependent on prior family functioning. Couples who share their wor-ries and communicate openly about cancer risk present a better long-term adjustment than couples who use protective buffering (not talking about it to avoid disturbing the partner) or emotional distancing. Parents need help dealing with disclosing genetic information to their children. These findings reinforce the importance of adopting a family-centered approach in the context of genetic counseling and the necessity of involving family members in research.

Reports of different types of neurological manifestations of COVID-19 are rapidly increasing, including changes of posterior reversible leukoencephalopathy syndrome (PRES). Here we describe the first reported case of COVID-19 and PRES in Australia diagnosed on basis of MRI brain imaging and confirmed clinically by presence of confusion, delirium, headaches, also associated with hypertension and blood pressure variability and stable long-term kidney problems. He made full recovery as his blood pressure was controlled and clinical status was supported with appropriate supportive therapy. Although traditionally a rare condition, PRES is likely to be more common among patients with COVID-19 pathobiology there is Renin downregulation of ACE2 receptors, involvement of Renin-Angiotensin-Aldosterone system, endotheliitis, cytokine storm, and hyper-immune response. Thus we advocate clinical suspicion and early brain imaging with MRI brain among vulnerable patients with known co-morbidities, and diagnosed with COVID-19 given that hypertension and blood pressure variability are often exacerbated by acute SARS-CoV-2 immune reactions. Such acute hypertensive encephalopathy was able to be reversed with timely supportive therapy ensuring re-hydration and re-establishment of blood pressure control.

In this narrated review, we draw attention to the use of happiness as a novel outcome measure in clinical research studies regarding patients with stroke. Commonly used outcome measures in clinical trials in stroke rehabilitation include the modified Rankin Score (mRS), Functional Impairment Measures (FIM), Barthel Index and quality of life (QoL). Despite being a part of QoL, happiness is arguably a significant construct on its own. While QoL assesses perceptions of various extrinsic aspects of life, happiness may be used as a measure of subjective enjoyment of life after an illness. We review the literature discussing the use of happiness as a formal outcome measure in stroke care and subacute and long-term stroke rehabilitation. Ultimately we recommend the wider use of happiness as an outcome measure where appropriate in these settings.

Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS), encephalopathy, seizures, headaches, acute necrotizing encephalitis, cerebral microbleeds, posterior reversible leukoencephalopathy syndrome, hemophagocytic lymphohistiocytosis, peripheral neuropathy, cranial nerve palsies, transverse myelitis, and demyelinating disorders, are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain. This scoping review has focused on the pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. It also highlights the common biological processes shared between AIS and COVID-19 infection and the importance of the recognition that severe respiratory dysfunction and neurological impairments associated with COVID and chronic inflammation [post-COVID-19 neurological syndrome (PCNS)] may significantly impact recovery and ability to benefit from neurorehabilitation. This study provides a comprehensive review of the pathobiology of COVID-19 and ischemic stroke. It also affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception. This work is of fundamental significance to the neurorehabilitation community given the increasing number of COVID-related ischemic strokes, the current limited knowledge regarding the risk of reinfection, and recent reports of a PCNS. It further highlights the need for global collaboration and research into new pathobiology-based neurorehabilitation treatment strategies and more integrated evidence-based care.

Stroke is one of the leading causes of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of acute ischemic stroke (AIS), during the index event and the repair process. Research on neurovascular inflammation has created a renewed interest in the use of easily available biomarkers reflective of innate and adaptive immunological changes with potential diagnostic, prognostic, and therapeutic implications particularly in AIS. The current scoping review aimed to assess the significance the neutrophil to lymphocyte (NLR) in AIS and its related complications and explore their association with post-stroke recovery trajectory. The Arksey and O’Malley methodological framework was employed to review the published papers on the neutrophil–lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000–2020 were included in this scoping review. Fifty-three published papers were reviewed. This review’s key finding is that a canonical inflammatory response occurs in the hyperacute, acute, subacute, and chronic stages of stroke. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes) are associated with poorer outcomes during the acute interventions as well as the recovery trajectory. This scoping review’s findings highlights the utility of a systems biology-based approach in stroke care.

Ischemic Stroke precedes depression. Post-stroke depression (PSD) is a major driver for poor recovery, negative quality of life, poor rehabilitation outcomes and poor functional ability. In this systematic review, we analysed the inflammatory basis of post-stroke depression, which involves bioenergetic failure, deranged iron homeostasis (calcium influx, Na influx, potassium efflux etc), excitotoxicity, acidotoxicity, disruption of the blood brain barrier, cytokine-mediated cytotoxicity, reactive oxygen mediated toxicity, activation of cyclooxygenase pathway and generation of toxic products. This process subsequently results in cell death, maladapted, persistent neuro-inflammation and deranged neuronal networks in mood-related brain regions. Furthermore, an in-depth review likewise reveals that anatomic structures related to post-stroke depression may be localized to complex circuitries involving the cortical and subcortical regions.

Various health settings have advocated for involving patients and members of the public (PPI) in research as a means to increase quality and relevance of the produced knowledge. However, youth PPI has been an understudied area. This protocol paper describes a new project that aims to summarize what is known about PPI with young people in mental health research. In line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement guidelines we will identify and appraise suitable articles and extract and synthesize relevant information including at least two reviewers at each stage of the process. Results will be presented in two systematic reviews that will describe (a) how youth PPI has been conducted (Review1) and (b) what impact youth PPI had on the subsequent research and on stakeholders (Review2). To our knowledge, this is the first set of reviews that uses a critical appraisal tool, which is co-developed with children and young people. Findings from this project will provide valuable insights and set out the key steps to adopting adequate PPI methods when involving children and young people in mental health research.

An easily accessible guide for patients, caregivers, family members, and health care professionals presenting a state of the art overview of PUI.

Corona virus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) is recognized as a global pandemic by WHO 2020 with 5,934 936 infections, 367,166 deaths and affecting over 200 countries as of 30th May 2020. Acute Ischemic Stroke (AIS) in brain is also emerging as an important neurovascular/neurological complication of COVID-19, associated with extreme immune responses leading to dysregulated coagulation system and generalized thrombo-embolic status and increased risk of AIS especially among usually less vulnerable younger adults in this cohort. Thus, in early June 2020, we aimed to review the clinical data on all published cases of COVID-19 and concomitant AIS, with a view to understanding the pertinent clinical, laboratory and imaging features. The neutrophil-lymphocyte ratio (NLR) at time of hospital admission for COVID infection correlates positively with the duration of time before onset of clinical features of AIS. Higher NLR, C-Reactive protein, serum ferritin, D-dimer and fibrinogen levels are associated with poor prognosis of AIS in COVID-19 with 75% of patients dying or being severely disabled at present. Currently it is too early to comment on the long-term outcomes for survivors.

Coronaviruses (CoVs) are enveloped RNA viruses and have been shown to cause mild to severe respiratory infections in humans, with some severe cases inducing neurological manifestations. The lethality and Neurological effects of the Severe Acute Respiratory Syndrome (SARS-CoV), Middle-East Respiratory Syndrome (MERS-CoV), and recently the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) have been well documented though currently there is little literature regarding long term effects and the implications for neurorehabilitation. SARS-CoV-2 and MERS-CoV have been linked to the infection associated inflammatory cytokine storms and induced hypercoagulopathic states that affect the entire vascular system including that of the brain. This mini-review provides an overview of the commonalities among studies published on all three types of the coronavirus related to acute ischemic stroke (AIS). The aim was to elucidate the physiological mechanisms underpinning COVID-2 and to reflect the similarities with the chronic inflammation induced symptoms of AIS that are likely to prove a further challenge for neurorehabilitation clinicians post COVID. In terms of increased incidence of COVID and AIS, it is likely that in depth knowledge of increased thrombotic risk in this population will require appropriate anticoagulation treatment, and other therapeutic interventions as well as neurorehabilitation interventions. Lastly the risk of spreading the virus requires further balancing of the provision of neurorehabiliatation services useful to the patient.

The death, disability and economic cost of stroke are enormous. Indeed, among the 16 million people worldwide who suffer a stroke' annually, nearly six million die, and another five million are left permanently disabled making prevention of stroke one of the most important priorities in healthcare. Currently carotid artery stenosis (CS) or narrowing of the common carotid artery (CCA) or internal carotid artery (ICA) due to atherosclerotic plaque, accounts for 20-30% of all ischemic strokes. Atherosclerosis is now regarded as a chronic inflammatory disease in response to vascular compromise especially from hypertension. This has long been known to lead to inflammation and atherosclerotic plaque formation in the blood vessels. This mini-review aims to highlight the role of inflammation and neuro-immunological processes in carotid artery disease. Various cellular elements of inflammation and advanced imaging techniques have been identified as potential markers of plaque progression. Therapies related to decreasing and modulating immune-responsive inflammation in the carotid vessels have been shown to translate into decreased occurrence of acute neurologic events and improvement of clinical outcomes.

Background: There is a high prevalence of children and young people (CYP) experiencing mental health (MH) problems. Owing to accessibility, affordability, and scalability, an increasing number of digital health interventions (DHIs) have been developed and incorporated into MH treatment. Studies have shown the potential of DHIs to improve MH outcomes. However, the modes of delivery used to engage CYP in digital MH interventions may differ, with implications for the extent to which findings pertain to the level of engagement with the DHI. Knowledge of the various modalities could aid in the development of interventions that are acceptable and feasible. Objective: This review aimed to (1) identify modes of delivery used in CYP digital MH interventions, (2) explore influencing factors to usage and implementation, and (3) investigate ways in which the interventions have been evaluated and whether CYP engage in DHIs. Methods: A literature search was performed in the Cochrane Library, Excerpta Medica dataBASE (EMBASE), Medical Literature Analysis and Retrieval System Online (MEDLINE), and PsycINFO databases using 3 key concepts “child and adolescent mental health,” “digital intervention,” and “engagement.” Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed using rigorous inclusion criteria and screening by at least two reviewers. The selected articles were assessed for quality using the mixed methods appraisal tool, and data were extracted to address the review aims. Data aggregation and synthesis were conducted and presented as descriptive numerical summaries and a narrative synthesis, respectively.Results: This study identified 6 modes of delivery from 83 articles and 71 interventions for engaging CYP: (1) websites, (2) games and computer-assisted programs, (3) apps, (4) robots and digital devices, (5) virtual reality, and (6) mobile text messaging. Overall, 2 themes emerged highlighting intervention-specific and person-specific b

An easily accessible guide for patients, caregivers, family members, and health care professionals presenting a state of the art overview of PUI.

How one builds, checks, validates and interprets a model depends on its ‘purpose’. This is true even if the same model code is used for different purposes. This means that a model built for one purpose but then used for another needs to be re-justified for the new purpose and this will probably mean it also has to be re-checked, re-validated and maybe even re-built in a different way. Here we review some of the different purposes for a simulation model of complex social phenomena, focusing on seven in particular: prediction, explanation, description, theoretical exploration, illustration, analogy, and social interaction. The paper looks at some of the implications in terms of the ways in which the intended purpose might fail. This analysis motivates some of the ways in which these ‘dangers’ might be avoided or mitigated. It also looks at the ways that a confusion of modelling purposes can fatally weaken modelling projects, whilst giving a false sense of their quality. These distinctions clarify some previous debates as to the best modelling strategy (e.g. KISS and KIDS). The paper ends with a plea for modellers to be clear concerning which purpose they are justifying their model against.