Background To identify the prevalence and also the full spectrum of symptoms/complaints of children and adolescents who are suffering from long COVID. Furthermore, we investigated the risk factors of long COVID in children and adolescents. Methods All consecutive children and adolescents who were referred to the hospitals anywhere in Fars province, Iran, from 19 February 2020 until 20 November 2020 were included. All patients had a confirmed diagnosis of COVID-19. In a phone call to patients/parents, at least 3 months after their discharge from the hospital, we obtained their current status and information if their parents agreed to participate. Results In total, 58 children and adolescents fulfilled the inclusion criteria. Twenty-six (44•8%) children/adolescents reported symptoms/complaints of long COVID. These symptoms included fatigue in 12 (21%), shortness of breath in 7 (12%), exercise intolerance in 7 (12%), weakness in 6 (10%), and walking intolerance in 5 (9%) individuals. Older age, muscle pain on admission, and intensive care unit admission were significantly associated with long COVID. Conclusions Long COVID is a frequent condition in children and adolescents. The scientific community should investigate and explore the pathophysiology of long COVID to ensure that these patients receive appropriate treatments for their condition.

We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease-2019 (COVID-19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18-55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post-COVID "brain fog" by the patients.In this large population-based study, we report that chronic post-COVID "brain fog" has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).

Stroke imposes a long-term neurological disability with limited effective treatments available for neuronal recovery. Transplantation of neural stem cells (NSCs) is reported to improve functional outcomes in the animal models of brain ischemia. However, the use of cell therapy is accompanied by adverse effects, so research is growing to use cell-free extracts such as extracellular vesicles (EVs) for targeting brain diseases. In the current study, male Wistar albino rats (20 months old) were subjected to middle cerebral artery occlusion (MCAO). Then, EVs (30 μg) were injected at 2 hours after stroke onset via an intracerebroventricular (ICV) route. Measurements were done at day 7 post-MCAO. EVs administration reduced lesion volume and steadily improved spontaneous locomotor activity.EVs administration also reduced microgliosis (ionized calcium-binding adaptor molecule 1 (Iba1) + cells) and apoptotic (terminal-deoxynucleotidyl transferase mediated nick end labelling [TUNEL]) positive cells and increased neuronal survival (neuronal nuclear (NeuN) + cells) in the ischemic boundary zone (IBZ). However, it had no effect on neurogenesis within the sub-ventricular zone (SVZ) but decreased cellular migration toward the IBZ (doublecortin (DCX) + cells). The results of this study showed neuroprotective and restorative mechanisms of NSC-EVs administration, which may offer new avenues for therapeutic intervention of brain ischemia. Significance of the study: Based on our results, EVs administration can effectively reduce microglial density and neuronal apoptosis, thereby steadily improves functional recovery after MCAO. These findings provide the beneficial effect of NSC-EVs as a new biological treatment for stroke. K E Y W O R D S extracellular vesicle (EV), ischemic boundary zone (IBZ), middle cerebral artery occlusion (MCAO), neural stem cell (NSC), neurogenesis

Spinal cord injury (SCI) is a devastating clinical problem that can lead to permanent motor dysfunction. Fingolimod (FTY720) is a sphingosine structural analogue, and recently, its therapeutic benefits in SCI have been reported. The present study aimed to evaluate the therapeutic efficacy of fingolimod‐incorporated poly lactic‐co‐glycolic acid (PLGA) nanoparticles (nanofingolimod) delivered locally together with neural stem/progenitor cells (NS/PCs) transplantation in a mouse model of contusive acute SCI. Fingolimod was encapsulated in PLGA nanoparticles by the emulsion–evaporation method. Mouse NS/PCs were harvested and cultured from embryonic Day 14 (E14) ganglionic eminences. Induction of SCI was followed by the intrathecal delivery of nanofingolimod with and without intralesional transplantation of PuraMatrix‐encapsulated NS/PCs. Functional recovery, injury size and the fate of the transplanted cells were evaluated after 28 days. The nanofingolimod particles represented spherical morphology. The entrapment efficiency determined by UV–visible spectroscopy was approximately 90%, and the drug content of fingolimod loaded nanoparticles was 13%. About 68% of encapsulated fingolimod was slowly released within 10 days. Local delivery of nanofingolimod in combination with NS/PCs transplantation led to a stronger improvement in neurological functions and minimized tissue damage. Furthermore, co‐administration of nanofingolimod and NS/PCs not only increased the survival of transplanted cells but also promoted their fate towards more oligodendrocytic phenotype. Our data suggest that local release of nanofingolimod in combination with three‐dimensional (3D) transplantation of NS/PCs in the acute phase of SCI could be a promising approach to restore the damaged tissues and improve neurological functions.

To have therapeutic promise of neural stem/precursor cells (NS/PCs) an appropriate scaffold is mostly essential. This study was conducted to fabricate collagen (Col)/chitosan-functionalized graphene oxide (CSGO) nanocomposite hydrogel and evaluated it as scaffold for NS/PCs. Graphene oxide was first functionalized with chitosan and the obtained CSGO was then added to Col solution and the solution underwent hydrogel formation. GO sheets were exfoliated after CS functionalization and the CSGO was homogenously dispersed in Col hydrogel. CSGO addition resulted in hydrogels with higher porosity and smaller Col fibers. Furthermore, CSGO increased the gelation time and water absorption capacity while the degradation was decreased. Cell studies demonstrated higher viability of NS/PCs on Col/CSGO hydrogel comparing with Col and poly-l-lysine as control (Cnt). NS/PCs were also penetrated into the Col/CSGO hydrogel and showed more cell spreading, neurite outgrowth and inter-cell connections in comparison with Col hydrogel. In addition, the cells traveled longer distance on Col/CSGO hydrogels than on Col and Cnt, indicating excellent migration capacity of NS/PCs on Col/CSGO hydrogel. Our results indicate the potential Col/CSGO hydrogels as an appropriate scaffold for NS/PCs.

Vitamin C (VC) is an essential supplement that plays an important role in cellular processes and functions and has been applied for therapeutic purposes for many years. Recently, the bene cial effects of VC on peripheral nerve regeneration have been gained lots of attention. In this study, electrospun polycaprolactone (PCL)/polyglycerol sebacate (PGS) bers incorporated with different concentrations of VC (5, 10, and 15 wt.%) were developed for peripheral nerve tissue engineering. The morphology of the bers was investigated using scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), tensile analysis (Young's modulus, ultimate tensile strength (UTS), and elongation at break), release pro le of VC from the PCL/PGS bers, in vitro degradation, water uptake behavior, and contact angle measurements were also studied. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and SEM were utilized to evaluate the attachment and viability of pheochromocytoma cells (PC12) on the scaffolds. The results showed that all scaffolds had a uniform diameter and mean diameter deceased from 1.24 to 0.88 µm followed by increasing VC. Young's modulus and UTS enhanced with increasing in VC percentage. Contact angle analysis showed that VC increased the surface hydrophilicity of PCL/PGS bers from 31.4º to 13.6º. MTT assays demonstrated that PCL/PGS containing 5 wt.% VC have a greater viability rate among other scaffolds. Our outcome indicated possible applicability of VC containing scaffolds for nerve tissue engineering.

The aim of this systematic review was to provide the required information regarding different aspects of the relationship between epilepsy/antiseizure medications and non‐alcoholic drinks. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement were followed. MEDLINE and Scopus from the inception until 7 August 2021 were systematically searched. These key words were used: “epilepsy” OR “seizure” OR “antiepileptic” OR “antiseizure” OR “anticonvulsant” AND “coffee” OR “tea” OR “soda” OR “juice” OR “drink” OR “cola” OR “diet” (35 key word combinations). The primary search yielded 21 458 publications (PubMed, n = 4778; Scopus, n = 16 680). Only 50 studies met all the inclusion criteria and were included in the current systematic review. In total, 17 articles investigated various non‐alcoholic drinks in human studies, 11 studies were case reports/series, and 22 articles were animal/in vitro studies. None of the studies provided a class 1 of evidence. There is limited evidence suggesting that certain drinks (eg, caffeinated energy drinks) might trigger seizures. Patients with epilepsy should avoid excessive consumption of certain fruit juices (eg, grapefruit, lime, pomegranate, kinnow, and star fruit) and caffeinated drinks. However, daily coffee and tea intake can be part of a healthy balanced diet, and their consumption does not need to be stopped in patients with epilepsy. Coffee/tea consumption is not harmful if consumed at levels of 200 mg (caffeine) in one sitting (about 2½ cups of coffee) or 400 mg daily (about five cups of coffee).

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