Rejected

The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent episodes of manic/hypomanic or depressive symptoms and euthymic periods, with some patients suffering a gradual deterioration of illness and consequent cognitive deficits during the late stage. Migraine is a disease generally without abnormal medical examinations, neurological examinations or laboratory studies, and the diagnosis is made based on the retrospective demonstration of headache features and groupings of disease-associated symptoms. The epidemiology of comorbid BD and migraine is high and it is obligatory to find effective treatments to improve the prognosis. Recent investigations demonstrated that the close relationship between BD and migraine significantly increased the rapid cycling rates of both BD and migraine in patients. Although the detailed mechanism is complex and largely unclear in comorbid BD and migrain, genetic factors, neurotransmitters, altered signaling pathways, disturbances of inflammatory cytokines, and mitochondrial dysfunction are risk factors of BD and migraine. Particularly these two diseases share some overlapping mechanisms according to previous studies. To this end, we call for further investigations of the potential mechanisms, and more efforts are underway to improve the treatment of people with comorbid BD and migraine. In this review, we provide an overview of the potential mechanisms in patients with BD or migraine and we further discuss the treatment strategies for comorbid BD and migraine and it is obligatory to find effective treatments to improve the prognosis. This work will provide insights for us to know more about the mechanisms of comorbid BD and migraine, provides new therapeutic targets for the treatment and give clinicians some guidance for more appropriate and beneficial treatment.

COVID-19 is typically associated with fever and severe respiratory symptoms including dry cough and dyspnea. However, COVID-19 may also affect both central and peripheral nervous systems. To date, the incidence rate of spinal cord involvement in COVID-19 is not known and the pathogenesis is still not fully understood. We report here two female patients admitted to Assiut University Hospitals/Egypt during the period from first of July to August 10, 2020. Both presented with a positive SARS-CoV-2 polymerase chain reaction (PCR) nasopharyngeal swab, elevated serum d-dimer and ferritin levels, and bilateral ground glass appearance in a CT chest scan. The first was a 60-year-old female with acute onset of flaccid paraplegia 10 days after flu-like symptoms, in whom MRI revealed transverse myelitis. The second was a 21-year-old female with symptoms of acute quadriplegia, fever, headache, and anosmia in whom an MRI scan revealed long cervico-thoracic myelopathy. Anterior spinal artery occlusion and possibly transverse myelitis were considered as differential diagnosis of long segment myelopathy.

While young adults with chronic low back pain (CLBP) exhibit impaired lumbar proprioception, it remains unclear if the same phenomenon is observed in middle-aged adults with CLBP. This study aimed to investigate whether young or middle-aged adults with CLBP displayed different proprioception ability as compared to age-matched asymptomatic controls. Sixty-four young adults with [median age:34 [interquartile range (IQR): 29-37] years] and without [median age:29 (IQR; 23-34) years] CLBP, and 87 middle-aged adults with [median age:53 (IQR: 49-58) years] and without [median age: 54 (IQR: 45-64) years] CLBP underwent postural sway tests on a force-plate with (unstable surface) and without a foam (stable surface), while bilateral L5/S1 multifidi and triceps-surae were vibrated separately. An individual's proprioception reweighting ability was estimated by relative proprioceptive reweighting (RPW). Higher RPW values indicate less reliance on lumbar multifidus proprioceptive signals for balance. Participants also underwent lumbar repositioning tests in sitting to determine repositioning errors in reproducing target lumbar flexion/extension positions. Young adults with CLBP demonstrated significantly higher median RPW values than age-matched asymptomatic controls for maintaining standing balance [stable surface: CLBP: 0.9 (IQR: 0.7-0.9), asymptomatic: 0.7 (IQR: 0.6-0.8), < 0.05; unstable surface: CLBP: 0.6 (IQR: 0.4-0.8), asymptomatic: 0.5 (IQR: 0.3-0.7), < 0.05]. No significant differences in repositioning error were noted between young or middle-aged adults with and without CLBP ( > 0.05). RPW values were unrelated to repositioning errors in all groups ( > 0.05). Young adults with CLBP, and middle-aged adults with and without CLBP had inferior proprioceptive reweighting capability. This finding may indicate potential age-related deterioration in central and peripheral processing of lumbar proprioceptive signals. Future studies should use advanced imaging and/or electroencephalogram to determine mechanisms underlying changes in proprioceptive reweighting in middle-aged adults.

We aimed to assess the level of patient's satisfaction and associated factors regarding postoperative pain management.

The purpose of this study was to evaluate matrix metalloproteinases (MMP) -2 and MMP-3 in serum, and keratinocyte-derived chemoattractant (KC), interleukin 8 (IL-8) and monocyte chemoattractant 1 (MCP-1) in synovial fluid (SF) as stifle osteoarthritis (OA) biomarkers in dogs. Dogs with naturally occurring cranial cruciate ligament (CrCL) rupture (OA group) and healthy controls were recruited. Stifles with CrCL deficiency were surgically stabilized. Serum, SF, and synovial biopsy samples were collected from the OA group preoperatively, whereas samples were collected once from control dogs. A blinded veterinary pathologist graded synovial biopsies. Serum and SF analyses were performed using xMAP technology. General linear regression was used for statistical comparisons of serum biomarkers, and mixed linear regression for SF biomarkers and temporal concentration changes. The overall discriminative ability was quantified using area under curve (AUC). Spearman's correlation coefficient was used to assess correlations between synovial histology grades and the biomarkers. Samples from 62 dogs in the OA group and 50 controls were included. The MMP-2 and MMP-3 concentrations between the OA and control groups were not significantly different, and both with an AUC indicating a poor discriminative ability. All three SF biomarker concentrations were significantly different between the OA group and controls (P <0.05). The MCP-1 was the only biomarker showing an acceptable discriminative performance with an AUC of 0.91 (95% confidence interval: 0.83-0.98). The sum of the inflammatory infiltrate score was significantly correlated with all three SF biomarkers (P <0.01). Summed synovial stroma, and all scores combined were significantly correlated with IL-8 and MCP-1 concentrations (P <0.003), and the summed synoviocyte scores were significantly correlated with MCP-1 concentrations (P <0.001). Correlations between MCP-1 concentrations and synovial histopathologic grading and its discriminative ability suggest its potential as a synovitis biomarker in canine stifle OA associated with CrCL rupture.

Diminished ovarian reserve (DOR) is the weakening of ovarian oocyte production and quality. It will further become premature ovarian failure without timely cure. However, disease pathology and diagnostic markers are still incompletely understood. Liu-Wei-Di-Huang (LWDH) pill, a traditional Chinese medicine formula, is commonly used in the treatment of DOR in China. To explore the mechanism of the effect of LWDH on in vitro fertilization (IVF) outcomes in patients with DOR, a pseudotargeted metabolomics study combined with multivariate data processing strategy was carried out. A liquid chromatography tandem mass spectrometry-based metabolomics approach was applied to characterize metabolic biomarker candidates. Multiple pattern recognition was used to determine groups and confirm important variables. A total of 21 potential biomarkers were characterized, and related metabolic pathways were identified. The study displayed that the established pseudotargeted metabolomics strategy is a powerful approach for investigating the mechanism of DOR and LWDH. In addition, the approach may highlight biomarkers and metabolic pathways and can capture subtle metabolite changes from headache, which may lead to an improved mechanism understanding of DOR diseases and LWDH treatment.

A case is presented of a woman with a history of daily persistent head pressure and dizziness who developed a cytotoxic lesion of the splenium of the corpus callosum after an acute withdrawal of chronic acetazolamide treatment and then, in quick succession, a CSF pressure/volume drop with a lumbar puncture. This is the first documentation that rapid alterations of CSF pressure/volume may trigger cytotoxic lesions in the central nervous system.

COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.

The high prevalence of chronic pain and difficulties in pain management in older people are challenging for healthcare providers globally. Patient satisfaction regarding pain management is one of the measures to assess efficacy of pain control as well as healthcare services. Thus, our study aimed to evaluate the older patients' satisfaction with pain management and its associated factors in Vietnam.