Rejected

Peripheral neuropathies constitute a group of disorders affecting the peripheral nervous system. Neuropathies have multiple causes such as infections (i.e., COVID-19), diabetes, and nutritional (low vitamin levels), among others. Many micronutrients, such as vitamins (A, C, D, E, B6, B12, and folate), certain minerals (Fe, Mg, Zn, Se, and Cu), and ω-3 fatty acids have immunomodulatory effects. Therefore, they may play an instrumental role in the treatment of COVID-19 infection. However, many COVID-19 patients can undergo neuropathy. In this context, there is a wealth of information on a variety of first-, second-, and third-line treatment options. This review focuses on the application of nutraceutical strategies in order to improve the symptomatology of neuropathy and neuropathic pain in patients that suffered from COVID-19. Our aim is to provide an alternative vision to traditional medical-pharmacological treatment through nutraceuticals.

To examine current evidence of the relationship between sleep and pain from the neonatal period through adolescence. This review serves as a critical review of the literature and of the needs for future research on pediatric sleep and pain.

SARS-CoV-2 infection (COVID-19) affects the respiratory system but is not limited to it. The gastrointestinal symptoms are polymorphic, including diarrhea, vomiting, abdominal pain, and even acute pancreatitis (AP). Pregnant women are more vulnerable to SARS-CoV-2 infection and have a higher risk of severe outcomes of COVID-19.

Therapeutic drugs of chronic neuralgia have a high risk of addiction, making it crucial to identify novel drugs for chronic neuralgia. This study aimed to explore the therapeutic effect of paeoniflorin on chronic sciatica via inhibiting Schwann cell apoptosis. 28 SD rats were randomly divided into four groups, including the sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and paeoniflorin group. The therapeutic effect and mechanism of paeoniflorin were evaluated via rat and cell experiments. Mechanical, hot, or cold hyperalgesia was induced in the rats after CCI operation, while paeoniflorin relieved chronic neuralgia. Besides, paeoniflorin decreased the levels of IL1, IL6, TNF-α, CRP, and LPS and increased the level of IL10 in serum. As for the sciatic nerve, the number of inflammatory cells was decreased, and Schwann cells were present after paeoniflorin treatment, and paeoniflorin promoted the recovery of nerve structure. In cell experiments, LPS induced Schwann cell apoptosis via the TLR4/NF-kB pathway. And paeoniflorin attenuated LPS-induced Schwann cell apoptosis by decreasing the levels of TLR4, p-NF-kB, caspase3, cleaved-caspase3, and cleaved-caspase7. Overall, these results suggest that paeoniflorin alleviates chronic sciatica by decreasing inflammatory factor levels and promotes the repair of damaged nerves by reducing Schwann cell apoptosis.

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people's lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.

For decades, carbonic anhydrase (CA) inhibitors, most notably the acetazolamide-bearing 1,3,4-thiadiazole moiety, have been exploited at high altitudes to alleviate acute mountain sickness, a syndrome of symptomatic sensitivity to the altitude characterized by nausea, lethargy, headache, anorexia, and inadequate sleep. Therefore, inhibition of CA may be a promising therapeutic strategy for high-altitude disorders. In this study, co-crystallized inhibitors with 1,3,4-thiadiazole, 1,3-benzothiazole, and 1,2,5-oxadiazole scaffolds were employed for pharmacophore-based virtual screening of the ZINC database, followed by molecular docking and molecular dynamics simulation studies against CA to find possible ligands that may emerge as promising inhibitors. Compared to the co-crystal ligands of PDB-1YDB, 6BCC, and 6IC2, ZINC12336992, ZINC24751284, and ZINC58324738 had the highest docking scores of -9.0, -9.0, and -8.9 kcal/mol, respectively. A molecular dynamics (MD) simulation analysis of 100 ns was conducted to verify the interactions of the top-scoring molecules with CA. The system's backbone revealed minor fluctuations, indicating that the CA-ligand complex was stable during the simulation period. Simulated trajectories were used for the MM-GBSA analysis, showing free binding energies of -16.00 ± 0.19, -21.04 ± 0.17, and -19.70 ± 0.18 kcal/mol, respectively. In addition, study of the frontier molecular orbitals of these compounds by DFT-based optimization at the level of B3LYP and the 6-311G(d,p) basis set showed negative values of the HOMO and LUMO, indicating that the ligands are energetically stable, which is essential for forming a stable ligand-protein complex. These molecules may prove to be a promising therapy for high-altitude disorders, necessitating further investigations.

Abdominal pain is the most distressing symptom of chronic pancreatitis (CP), and current treatments show limited benefit. Pain phenotypes may be more useful than diagnostic categories when planning treatments, and the presence or absence of constant pain in CP may be a useful prognostic indicator.

Pseudomelanosis duodeni is a rare finding usually described as a black/brown speckled or tattooed appearance of the intestinal mucosa. Although an incidental finding, it has been associated with different medications and chronic medical conditions such as diabetes mellitus and chronic renal failure. We describe an elderly male who presented with epigastric pain and melena. Endoscopy showed pseudomelanosis duodeni related to intravenous (IV) iron transfusion. To our knowledge, this is the first report of pseudomelanosis duodeni related to IV iron use. In spite of its benign nature, the diagnosis of pseudomelanosis duodeni is essential to rule out other serious medical conditions that mimic its physical findings.

The primary purpose of the current study was to determine the value of the shunt surgery and/or prophylactic antiepileptic therapy, in patients after mild traumatic brain injury (mTBI) with ventricular dilatation (VD) and incipient cognitive impairment, in the prevention of cognitive deterioration and probably in the development of dementia. Based on the following criteria: a) mTBI b) VD detected in CT scan during admission, and c) the presence of one of the following: i) dizziness, ii) headache, and iii) seizures, admitted to the Emergency Department between January 2010 and January 2020, we enrolled 127 of 947 eligible subjects. The subjects were divided into five groups: Group A (control group): only VD illustration in CT scan, Group B: incipient dementia, who had a more insidious onset presenting with cognitive dysfunctions at indefinite ages, Group C: shunt system (SH)/antiepileptic drugs (AEDs) presenting with cognitive dysfunction and urinary incontinence or gait disturbances or both, that were treated as idiopathic normal-pressure hydrocephalus (iNPH) with the surgical placement of an SH and AED therapy (standard AED phenytoin (1000 mg loading dose followed by 300 mg) daily), and Group D: AED, presenting with cognitive dysfunctions at indefinite ages and one or two episodes of seizures in the past, treated with AED from the very first moment of initiation with a standard AED phenytoin (1000 mg loading dose followed by 300 mg) daily. Overall, improvement in daily activities was achieved in 14.1% (18 of 127 patients), recording a significantly higher performance in group D (5.5%) rather than in groups A (1.5%), B (3.1%), and C (3.9%), (p < 0.05). We concluded that changes in VD (ΔVD) were associated with improvement in mRS (ΔmRS ≥ 1) – daily activities and mental status. ΔVD was also independently associated with reduced daily activities during the long-term follow-up. Interestingly, therapeutic shunting and AED in patients with a history of epilepsies may have a positive impact on the development of mental status impairment. This is a novel observation that has to be confirmed by more extensive multicenter studies in the future.

Lumbar spinal stenosis, a narrowing of the spinal canal around the spinal neurovascular structures, is a common etiology for lower back and leg pain in older people. Sciatica, a frequent symptom of lumbar spinal stenosis, typically presents with sharp and/or aching pain that originates in the buttock, extends to the thigh, and radiates into the foot and toes; in addition, it can be accompanied by weakness of the associated lower extremity. In individuals with sciatica-related persistent symptoms or functional limitations or both, spinal decompression surgery may be necessary. A cerebrospinal fluid leak is a potential complication of lumbar spinal stenosis surgery; it is frequently–yet not always–accompanied by a postural headache. The cerebrospinal fluid leak can result from an intraoperative tear or postoperatively. Albeit a more common adverse event after body contouring surgery, seroma–a postoperative serous fluid collection that is usually detectable as a palpable or visible fluid wave on clinical examination–has also been observed as a complication following lumbar spinal stenosis surgery. A man who experienced an intra-operative accidental dural tear during lumbar spinal stenosis surgery is described. A large cerebrospinal fluid leak that involved both the laminectomy bed and the subcutaneous tissue of his back subsequently developed; the leak eventually presented as duro-cutaneous fistulas without headache. His doctors misinterpreted the cerebrospinal fluid leak as a seroma; this may have occurred since not only did the color of the persistent and continuously dripping fluid varied from being clear to slightly tinged pink, but also the patient never had a headache or any other symptoms associated with a cerebrospinal fluid leak. When his lower back was appropriately evaluated with magnetic resonance imaging, the diagnosis of a large cerebrospinal fluid leak was established. In conclusion, lumbar spinal stenosis back surgery can be associated with postoperative complications, including cerebrospinal fluid leak and–less frequently–seroma. However, following lumbar spinal stenosis surgery, the absence of a headache does not exclude the possibility of a cerebrospinal fluid leak. Also, the presence of fluid leaking from the surgical site after lumbar spinal stenosis back surgery should not only prompt the clinician to entertain the possibility of a surgery-associated cerebrospinal fluid leak but also to obtain additional diagnostic studies–such as magnetic resonance imaging–to establish the diagnosis.