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Long-term neurological complaints after SARS-CoV-2 infection occur in 4-66% of children and adolescents. Controlled studies on the integrity of the peripheral nerve system are scarce. Therefore, we examined the somatosensory function in children and adolescents after SARS-CoV-2 infection in a case-control study compared with age-matched individuals.

Discrimination of cues predicting non-nociceptive/nociceptive stimuli is essential for predicting whether a non-painful or painful stimulus will be administered and for eliciting placebo/nocebo (pain reduction/pain enhancement) effects. Dysfunction of the neural system involved in placebo effects has been implicated in the pathology of chronic pain, while female sex is one of the important risk factors for development of chronic pain in young adults. The dorsolateral prefrontal cortex (dl-PFC) is suggested to be involved in placebo effects and is sensitive to sex and age. In this study, to examine the neural mechanisms by which sex and age alter placebo and nocebo effects, we analyzed cerebral hemodynamic activities in the dl-PFC in different sex and age groups during a differential conditioning task. During the training session, two different sounds were followed by low- and high-intensity electrical shocks. In the following recording session, electrical shocks, the intensity of which was mismatched to the sounds, were occasionally administered to elicit placebo and nocebo effects. In young female participants, both placebo effects and hemodynamic responses to the conditioned sounds in the right dl-PFC were significantly lower than those in elderly female participants, while there were no age differences in male participants. The hemodynamic responses to the sound paired with the safe stimulus in the right dl-PFC were significantly correlated with placebo effects, except in the young female group. These results suggest that blunted placebo effects in the young female participants are ascribed to blunted responses to the sound associated with the safe stimulus in the right dl-PFC, and that sex- and age-related factors may alter the responsiveness of the right dl-PFC to associative cues predicting a safe stimulus.

Lactic acidosis is a well-known complication of metformin accumulation in diabetic patients with kidney failure. However, it is not usual to raise the diagnosis of metformin-associated lactic acidosis when patients have normal kidney function. The causes of metformin-induced high lactate include the accumulation of normal doses of metformin in chronic kidney disease, an overdose of this drug without kidney failure, or an increase in lactate production due to the inhibition of liver gluconeogenesis. . We report the case of a 61-year-old diabetic man who was brought to the emergency room in a comatose state. His family reported abdominal pain with diarrhea in the last two days. He was found to have severe lactic acidosis with normal serum creatinine. He was on a regular dose of metformin, and his family denied any other medical history or any alcohol abuse. He showed no signs of infection, his liver enzymes were slightly elevated, and he had severe anemia. His hemodynamics deteriorated quickly within hours, and an abdominal computed tomography scan revealed no abnormalities. He underwent a laparotomy that ruled out mesenteric ischemia and revealed an abnormal liver. The liver biopsy later confirmed the diagnosis of cirrhosis.

Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa with unknown etiology. Suggested predisposing factors for the development of OLP include genetic factors, viral infections, psychological stress, trauma, drug intake, and some systemic diseases. This serial case aimed to evaluate the psychological stress in triggering various types of OLP and its management. . Six patients, four females and two males with an age range from 23 to 57 years, came to an oral medicine clinic with chief complaints of chronic pain and burning sensations in the oral cavity. All cases showed typical clinical features of OLP on the oral mucosa, including reticular, plaque-like, erosive, and ulcerative lesions. An incisional biopsy was performed in some cases and the histopathology features confirmed the diagnosis of OLP with no signs of dysplasia/malignancy. According to the Depression, Anxiety, Stress Scale (DASS)-21, the patients had different levels of depression ranging from mild to severe; 3 patients were considered to have moderate anxiety and others had severe anxiety; and 5 patients experienced mild stress and 1 patient had moderate stress. The patients were given corticosteroids, supportive therapy, and psychological counseling. All patients experienced significant improvement of the lesions after treatment.

Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.

High-impact temporomandibular disorder (TMD) pain may involve brain mechanisms related to maladaptive central pain modulation. We investigated brain responses to stimulation of trigeminal sites not typically associated with TMD pain by applying noxious dentoalveolar pressure to high- and low-impact TMD pain cases and pain-free controls during functional magnetic resonance imaging (fMRI). Fifty female participants were recruited and assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and Graded Chronic Pain Scale: controls (n = 17), low-impact (n = 17) and high-impact TMD (n = 16). Multimodal whole-brain MRI was acquired following the Human Connectome Project Lifespan protocol, including stimulus-evoked fMRI scans during which painful dentoalveolar pressure was applied to the buccal gingiva of participants. Group analyses were performed using non-parametric permutation tests for parcellated cortical and subcortical neuroimaging data. There were no significant between-group differences for brain activations/deactivations evoked by the noxious dentoalveolar pressure. For individual group mean activations/deactivations, a gradient in the number of parcels surviving thresholding was found according to the TMD pain grade, with the highest number seen in the high-impact group. Among the brain regions activated in chronic TMD pain groups were those previously implicated in sensory-discriminative and motivational-affective pain processing. These results suggest that dentoalveolar pressure pain evokes abnormal brain responses to sensory processing of noxious stimuli in high-impact TMD pain participants, which supports the presence of maladaptive brain plasticity in chronic TMD pain.

Dexamethasone can be used to prevent nausea and vomiting after surgery, but there is concern that it may induced perineal irritation. The aim of this study was to investigate the attenuation effect of dilution and slow injection on dexamethasone-induced perineal irritation. In this prospective, randomized, double-blind study, a total of 400 patients were enrolled and allocated into four groups: Group I, receiving 2 mL dexamethasone (5 mg/mL), Group II, receiving 5 mL dexamethasone (2 mg/mL), Group III, receiving 10 mL dexamethasone (1 mg/mL), and Group IV receiving 20 mL dexamethasone (0.5 mg/mL). Dexamethasone was diluted with 5% glucose. The injection time of dexamethasone was less than 2 s in Group I, while it was 30 s in Groups II, III, and IV. The incidence, onset, duration, and severity of perineal irritation were recorded. The incidence of dexamethasone-induced perineal irritation was 49, 33, 17, and 15% in Groups I, II, III, and IV, respectively. Group IV had less severity than Group I in mild and moderate perineal irritation ( < 0.008). The onset and duration of perineal irritation of Groups II, III, and IV were significantly improved compared to Group I ( < 0.001). Dexamethasone-induced perineal irritation can be alleviated by dilution of dexamethasone to 0.5 mg/mL with 5% glucose combined with prolonged injection time of 30 s.

Long-COVID is a syndrome characterized by debilitating symptoms that persist over 3 months after infection with the SARS-CoV-2 virus. It affects 15 to 33% of COVID-19 recovered patients and has no dedicated treatment. First, we found that β-caryophyllene and pregnenolone have a significant synergistic effect in the resolution of LPS-induced sepsis and inflammation in mice. Then we combined these two compounds with seven others and designed a unique dietary supplement formulation to alleviate long COVID inflammatory and neurological disorders. We performed a one-arm open-labeled study at a single site with 51 eligible patients from 18 states. Each participant recorded the severity level of 12 symptoms (including fatigue, weakness, cardiac and neurological symptoms, shortness of breath, gastrointestinal disorders, ageusia or anosmia, anxiety, joint pain, rash, cough, and insomnia) at baseline, 2- and 4-week time points. On average, all the symptoms were significantly milder after 2 weeks, with further improvement after 4 weeks. Importantly, each symptom was significantly attenuated in 72 to 84% of the participants. There were no significant adverse effects. Our data indicate that the use of this nutraceutical product is a safe and significantly efficient option to reduce multiple symptoms of long COVID.

Chronic constipation is common in children and often requires prolonged laxative treatment. Preliminary studies suggest that the probiotic () may be useful in treating constipation in children, but these preliminary results need to be replicated. The objective of this study was to assess the efficacy of in infants and young children with chronic functional constipation.

To investigate the effect of traditional Chinese manual therapy (TCMT) in alleviating pain and dysfunction in patients with lumbar disc herniation (LDH).