Rejected

Postoperative cognitive dysfunction (POCD) affects a substantial number of aged individuals. Although advanced age has been regarded as the only independent risk factor for cognitive decline following anesthesia and surgery, the exact cellular and molecular mechanisms remain poorly understood. Histone deacetylase 3 (HDAC3), an epigenetic regulator of memory plays an important role in age-dependent disease. In this study, we investigated the role of HDAC3 in POCD using a laparotomy mouse model. The results showed that the level of HDAC3 in the dorsal hippocampus (DH) was elevated in aged mice compared with young mice. The surgery impaired the spatial-temporal memory in aged mice, as indicated in the object location memory (OLM) and temporal order memory (TOM) tests. Model mice also exhibited increased expression of HDAC3 protein and decreased levels of dendritic spine density and synaptic plasticity-related proteins in the DH. Selectively blocking HDAC3 in the DH of aged mice reversed spatial-temporal memory impairment induced by surgery and restored dendritic spine density and synaptic plasticity-related proteins in the DH. Overexpression of HDAC3 by adeno-associated virus in the DH of young mice mimicked the behavioral deficits induced by anesthesia and surgery. Our results indicated that HDAC3 negatively regulates spatial-temporal memory in aged mice after anesthesia and surgery. Targeting HDAC3 might represent a potential therapy to avoid POCD.

The increase of individuals with Osteoarthritis (OA) has generated an increase in public spending in the treatments, which are still not that effective. So, the purpose of this study was to analyze and compare four types of interventions: platelet-rich plasma (PRP), adipose-derived stem cells (ADSCs), ADSCs + PRP and the standard surgical video arthroscopy (All groups passed through standard arthroscopy before intervention). The evaluation was performed by applying the questionnaires Western Ontario McMaster Universities, Short Form Health Survey 36 and Visual Analog Pain Scale, also by analyzing the synovial fluid (inflammatory cytokines, enzymatic, colorimetric and viscosity analysis), this evaluation happened in two moments: before the surgical procedures and after 6 months of the interventions and also was made a comparison to standard arthroscopy. The questionnaires results showed a greater improvement in the scores of the domains analyzed in the ADSCs + PRP group, followed by the ADSCs and PRP group. In the evaluation of inflammatory cytokines, there was a significant reduction in the cytokine IL-1b only in the ADSCs + PRP group (46%) and ADSCs (31%), of IL-6 in the ADSCs + PRP group (72%), of IL-8 in the ADSCs + PRP group (50%) and ADSCs (31%), and TNF in the ADSCs + PRP group (46%). There was also a significant increase in the amount of total proteins (79%) in the control group and polymorphonuclear cells (47%) in the ADSCs + PRP group. Taking all the results into account, we infer that therapies with ADSCs + PRP and only ADSCs are safe and effective over 6 months for the improvement of pain, functional capacity and joint inflammation in volunteers with OA. It is also considered that the use of ADSCs + PRP, particularly, is a promising alternative to help manage this disease, due to the better results presented among the four propose interventions.

Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disease with diverse predisposing factors. We report a case of CVST caused by a thyroid storm induced by traumatic brain injury.

In 2013, the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration identified one high-quality Randomized Controlled Trial (RCT) investigating multimodal rehabilitation of recent-onset cervical radiculopathy. No high quality RCTs were identified to inform the management of persistent cervical radiculopathy. Therefore, updating this systematic review is warranted.

Hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) progressively affects patients' functionality and compromises health-related quality of life (HRQL). The aim of this study was to quantify the projected long-term treatment effects of inotersen versus placebo on HRQL measures.

Telemedicine during this pandemic acts as a lifeline for many non-COVID patients especially with chronic neurological diseases. The aim of present study was to evaluate cost effectiveness and level of satisfaction amongst patients from teleneurology outpatient department (OPD).

Osteoarthritis (OA) is the most frequent cause of disability in elderly people. In daily practice, the main objective of the physician is to reduce patient symptoms using treatments without adverse effects. However, the most prescribed treatment to manage OA symptoms remains nonsteroidal anti-inflammatory drugs which are associated with severe adverse effects. Therefore, we need a safe alternative to managing OA. One candidate is Rubus idaeus leaf extracts known to inhibit inflammatory responses.

Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.

The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer's disease and dementia, is reported to have a good safety profile in humans, and preclinical data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models.