Rejected

How much scientific evidence is there to show that stem cell therapy is sufficient in preclinical and clinical studies of spinal cord injury before it is translated into clinical practice? This is a complicated problem. A single, small-sample clinical trial is difficult to answer, and accurate insights into this question can only be given by systematically evaluating all the existing evidence.

Irritable bowel syndrome (IBS) is a biopsychosocial model based on the malfunction of "brain-intestinal linking".

Prolapse is a common condition seen in women and its therapeutical management consists first and foremost of surgery. Postoperative pain is one of the most common side effects seen after surgery. The objective of this study was to identify risk factors for postoperative pain after cystocele repair with mesh.

Psychedelic serotonergic agonists such as psilocybin have recently been shown to produce sustained benefit in refractory depression, end of life anxiety and addiction when administered in hallucinogenic doses and coupled with psychotherapy. While it has been suggested that similar high dose protocols may help chronic pain conditions, there are few published clinical trials of psychedelics for pain. The use of these agents in sub-psychedelic doses for chronic pain management has received even less attention. This case series details the experiences of three individuals who have used low dose psilocybin to manage chronic neuropathic pain. While the nature and etiology of each patient's pain varies, they share a common experience, including inefficacy of current therapeutics and decreased quality of life. Through self-administration of psilocybin, these patients have achieved robust pain relief with decreased reliance on traditional analgesic medications. Despite varying preparations and uncertain potencies, the analgesic effects for all three patients occurred at doses without a psychedelic experience and with minimal cognitive or somatic adverse effects. Furthermore, the efficacy of pain relief, and in some cases the duration of the effect, were magnified when coupled with functional exercise. Additionally, in one case, repeated dosing appeared to produce increased relief, suggesting a possible long-term plasticity mediated effect. These commonalities highlight psilocybin's therapeutic potential in the treatment of chronic pain that warrants further investigation.

To describe clinical presentations of intracranial sinusitis complications in childhood, their pitfalls and imaging findings.

Type 2 diabetes mellitus (T2DM) is a global health problem for many reasons including the comorbidities, such as diabetic neuropathy (DPN), which is the most common. It has been suggested that aerobic training can improve metabolic health in individuals with T2DM. Still, the effect of aerobic training on DPN signs and its relationship with serum levels of tumor necrosis tumor alpha (TNF-α), an essential molecule in T2DM development, is unknown. We evaluated the effect of two intensities of aerobic training in adult male C57BL/6 mice divided into six groups: sedentary control (CTRL), control with low-intensity training (CTRL-LI), control with moderate-intensity training (CTRL-MI), T2DM sedentary (T2DM), T2DM with low-intensity training (T2DM-LI), and T2DM with moderate-intensity training (T2DM-MI). We induced the T2DM model by combining a hypercaloric diet and low doses of streptozotocin. We measured serum TNF-α levels and correlated them with peripheral sensitization and the cardinal signs of T2DM in mice. Moderate intensity aerobic training decreased the symptoms of DPN and improved metabolic health in T2DM. Interestingly, decreased TNF-α serum levels correlated with reduced peripheral thermal sensitivity and mechanical sensitivity by aerobic training. Moderate intensity aerobic training counteracts the development and symptoms of DPN and improve metabolic health in T2DM. Decreased TNF-α correlates with reduced peripheral thermal sensitivity and mechanical sensitivity by aerobic training.

Central nervous system (CNS) disorders, such as psychiatric disorders, neurodegeneration, chronic pain, stroke, brain tumor, spinal cord injury, and many other CNS diseases, would hugely benefit from specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to the brain is challenging due to their low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit peptides' clinical application and explain the interest in alternative routes of peptide administration, particularly nose-to-brain (N-to-B) delivery, which allows protein and peptide drugs to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure; the olfactory and trigeminal nerves provide a unique pathway to the brain and the external environment. This review highlights the intranasal delivery of drugs, focusing on peptide delivery, illustrating various clinical applications, nasal delivery devices, and the scope and limitations of this approach.

Modic type 1 changes (MC1) are vertebral bone marrow lesions and associate with low back pain. Increased serum C-reactive protein (CRP) has inconsistently been associated with MC1. We aimed to provide evidence for a role of CRP in the tissue pathophysiology of MC1 bone marrow. From thirteen MC1 patients undergoing spinal fusion at MC1 levels, vertebral bone marrow aspirates from MC1 and intra-patient control bone marrow were taken. Bone marrow CRP, IL-1, and IL-6 were measured with enzyme-linked immunosorbent assays; lactate dehydrogenase (LDH) was measured with a colorimetric assay. CRP, IL-1, and IL-6 were compared between MC1 and control bone marrow. Bone marrow CRP was correlated with blood CRP and with bone marrow IL-1, IL-6, and LDH. CRP expression by marrow cells was measured with PCR. Increased CRP in MC1 bone marrow (mean difference: +0.22 mg CRP/g protein, 95% CI [-0.04, 0.47], p=0.088) correlated with blood CRP (r=0.69, p=0.018), with bone marrow IL-1β (ρ=0.52, p=0.029) and IL-6 (ρ=0.51, p=0.031). Marrow cells did not express CRP. Increased LDH in MC1 bone marrow (143.1%, 95% CI [110.7%, 175.4%], p=0.014) indicated necrosis. A blood CRP threshold of 3.2 mg/L detected with 100% accuracy increased CRP in MC1 bone marrow. In conclusion, the association of CRP with inflammatory and necrotic changes in MC1 bone marrow provides evidence for a pathophysiological role of CRP in MC1 bone marrow. This article is protected by copyright. All rights reserved.

A chronic Achilles tendon rupture is a tendon rupture occurring more than 4-6 weeks after a traumatic injury. Haglund's deformity, caused by bony abnormalities in the ankle (mostly due to osteophyte or bone spur), can cause chronic inflammation and degeneration of the Achilles tendon, eventually leading to rupture. This presents a challenge for clinicians who provide tendon repair procedures. We present a 69-year-old woman who had difficulty moving her left leg and had a deformity on the left leg compared to her right leg after falling nine months before but with pain starting three months before the accident. There was a seven-centimeter gap in the calcaneus with a positive Thompson test. The Haglund's deformity on the left calcaneus was visible on the ankle X-ray. The patient had a chronic total rupture of the left Achilles tendon, which was treated with a flexor hallucis longus (FHL) tendon transfer and resection of the deformity. One week after surgery, the patient's ability to walk and the shape of the left leg improved. This case report describes a chronic left Achilles tendon condition that was successfully repaired through tendon repair surgery using FHL tendon transfer and removal of Haglund's deformity.

Hyperinflammation is frequently associated with the chronic pain of autoimmune disease and the acute death of coronavirus disease (COVID-19) via a severe cytokine cascade. CIGB-258 (Jusvinza), an altered peptide ligand with 3 kDa from heat shock protein 60 (HSP60), inhibits the systemic inflammation and cytokine storm, but the precise mechanism is still unknown. The protective effect of CIGB-258 against inflammatory stress of -ε-carboxymethyllysine (CML) was tested to provide mechanistic insight. CIGB-258 was treated to high-density lipoproteins (HDL) and injected into zebrafish and its embryo to test a putative anti-inflammatory activity under presence of CML. Treatment of CML (final 200 μM) caused remarkable glycation of HDL with severe aggregation of HDL particles to produce dysfunctional HDL, which is associated with a decrease in apolipoprotein A-I stability and lowered paraoxonase activity. Degradation of HDL by ferrous ions was attenuated by a co-treatment with CIGB-258 with a red-shift of the Trp fluorescence in HDL. A microinjection of CML (500 ng) into zebrafish embryos resulted in the highest embryo death rate, only 18% of survivability with developmental defects. However, co-injection of CIGB-258 (final 1 ng) caused the remarkable elevation of survivability around 58%, as well as normal developmental speed. An intraperitoneal injection of CML (final 250 μg) into adult zebrafish resulted acute paralysis, sudden death, and laying down on the bottom of the cage with no swimming ability via neurotoxicity and inflammation. However, a co-injection of CIGB-258 (1 μg) resulted in faster recovery of the swimming ability and higher survivability than CML alone injection. The CML alone group showed 49% survivability, while the CIGB-258 group showed 97% survivability ( < 0.001) with a remarkable decrease in hepatic inflammation up to 50%. A comparison of efficacy with CIGB-258, Infliximab (Remsima), and Tocilizumab (Actemra) showed that the CIGB-258 group exhibited faster recovery and swimming ability with higher survivability than those of the Infliximab group. The CIGB-258 group and Tocilizumab group showed the highest survivability, the lowest plasma total cholesterol and triglyceride level, and the infiltration of inflammatory cells, such as neutrophils in hepatic tissue. CIGB-258 ameliorated the acute neurotoxicity, paralysis, hyperinflammation, and death induced by CML, resulting in higher survivability in zebrafish and its embryos by enhancing the HDL structure and functionality.