Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Microvascular stabilization via blood-brain barrier regulation prevents seizure activity.

Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, the tight junction protein claudin-5 is the most enriched in brain endothelial cells and regulates size-selectivity at the BBB. Additionally, disruption of claudin-5 expression has been implicated in numerous disorders including schizophrenia, depression and traumatic brain injury, yet its role in epilepsy has not been fully deciphered. Here we report that claudin-5 protein levels are significantly diminished in surgically resected brain tissue from patients with treatment-resistant epilepsy. Concomitantly, dynamic contrast-enhanced MRI in these patients showed widespread BBB disruption. We show that targeted disruption of claudin-5 in the hippocampus or genetic heterozygosity of claudin-5 in mice exacerbates kainic acid-induced seizures and BBB disruption. Additionally, inducible knockdown of claudin-5 in mice leads to spontaneous recurrent seizures, severe neuroinflammation, and mortality. Finally, we identify that RepSox, a regulator of claudin-5 expression, can prevent seizure activity in experimental epilepsy. Altogether, we propose that BBB stabilizing drugs could represent a new generation of agents to prevent seizure activity in epilepsy patients.

Harnessing artificial intelligence in cardiac rehabilitation, a systematic review.

Aim: This systematic review aims to evaluate the current body of research surrounding the efficacy of artificial intelligence (AI) in cardiac rehabilitation. Presently, AI can be incorporated into personal devices such as smart watches and smartphones, in diagnostic and home monitoring devices, as well as in certain inpatient care settings. Materials & methods: The PRISMA guidelines were followed in this review. Inclusion and exclusion criteria were set using the Population, Intervention, Comparison and Outcomes (PICO) tool. Results: Eight studies meeting the inclusion criteria were found. Conclusion: Incorporation of AI into healthcare, cardiac rehabilitation delivery, and monitoring holds great potential for early detection of cardiac events, allowing for home-based monitoring, and improved clinician decision making.

Lay abstract Artificial intelligence (AI) involves the use of technologies capable of making decisions based on data provided. AI can be used in healthcare to provide actionable data for a clinician by analyzing patterns in patient data to predict outcomes and guide treatment. Cardiovascular disease is the leading cause of death worldwide. Cardiac rehabilitation is a therapy proven to reduce mortality and morbidity from cardiovascular disease. This study outlines three cases of AI based healthcare tools in cardiac rehabilitation. This includes the provision of personalized, home-based cardiac rehabilitation, the early detection of cardiac events through smart watch monitoring and by providing clinician decision making support in cardiac failure rehabilitation.

Decreased CSF1R Signaling and the Accumulation of Reticular Pseudo-Drusen?

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by dominant-acting mutations in the gene colony-stimulating factor 1 receptor (CSF1R). It is an ultra-rare leukoencephalopathy that involves demyelination of white matter and early-onset dementia. It has been well validated that mutations in the kinase region of the gene cause decreased signaling of the receptor via its two cognate ligands interleukin-34 (IL-34) and colony-stimulating factor-1 (CSF-1). In this article, we report a thorough analysis of retinal integrity in a 48-year-old genetically diagnosed ALSP patient. We show that although the optic nerve, optic chiasm, and optic tracts are relatively preserved, the patient has visual field deficits likely due to optic radiation and/or cortical atrophy. Intriguingly, we report the appearance of inner retinal vascular leakage and the appearance of reticular pseudo-drusen (RPD)-like deposits. We propose that the early stages of RPD accumulation may be associated with an attenuated CSF-1 receptor signaling axis. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:666-671.].

Repatriation of human remains following death in international travellers.

BACKGROUND: Death during international travel and the repatriation of human remains to one's home country is a distressing and expensive process. Much organization is required involving close liaison between various agencies. METHODS: A review of the literature was conducted using the PubMed database. Search terms included: 'repatriation of remains', 'death', 'abroad', 'tourism', 'travel', 'travellers', 'travelling' and 'repatriation'. Additional articles were obtained from grey literature sources and reference lists. RESULTS: The local national embassy, travel insurance broker and tour operator are important sources of information to facilitate the repatriation of the deceased traveller. Formal identification of the deceased's remains is required and a funeral director must be appointed. Following this, the coroner in the country or jurisdiction receiving the repatriated remains will require a number of documents prior to providing clearance for burial. Costs involved in repatriating remains must be borne by the family of the deceased although travel insurance may help defray some of the costs. If the death is secondary to an infectious disease, cremation at the site of death is preferred. No standardized procedure is in place to deal with the remains of a migrant's body at present and these remains are often not repatriated to their country of origin. CONCLUSIONS: Repatriation of human remains is a difficult task which is emotionally challenging for the bereaving family and friends. As a travel medicine practitioner, it is prudent to discuss all eventualities, including the risk of death, during the pre-travel consultation. Awareness of the procedures involved in this process may ease the burden on the grieving family at a difficult time.

Stem cell tourism--a web-based analysis of clinical services available to international travellers.

BACKGROUND: Stem cell therapies are advertised through online resources which describe a range of treatments with diverse clinical indications. Stem cell tourists may not be aware of the information they should seek when consulting these clinics, or of the potential risks involved. The aim of this study was to characterise the therapies offered by online stem cell clinics. METHODS: A web based search utilising five search terms was employed. The first twenty pages of each search result were screened against 340 variables. RESULTS: 224 out of 1091 websites advertised stem cell clinics. 68 eligible sites covering 21 countries were evaluated. The top five clinical indications for stem cell therapy were multiple sclerosis, anti-ageing, Parkinson's disease, stroke and spinal cord injury. Adult, autologous stem cells were the most commonly utilised stem cell, and these were frequently sourced from bone marrow and adipose tissue and administered intravenously. Thirty-four per cent of sites mentioned the number of patients treated while one quarter of clinics provided outcome data. Twenty-nine per cent of clinics had an internationally recognised accreditation. Fifteen per cent of clinics stated that their therapies posed no risk. Eighty-eight per cent of clinics claimed treatment effectiveness, with 16% describing their curative potential. Over 40% of sites did not specify the number or duration of treatments. Fifty-three per cent of clinics requested access to patients' medical records, and 12% recommended patients discuss the proposed therapy with their doctor. No clinic recommended that travellers consult a travel medicine specialist or receive vaccinations prior to their intended travel. One quarter of sites discussed contraindications to treatment, with 41% of sites detailing follow up patient care. CONCLUSIONS: There is potential for stem cell tourists to receive misleading or deficient information from online stem cell clinics. Both the stem cell tourist and travel medicine practitioner should be educated on the potential risks associated with stem cell clinical services advertised online.