Currently there are no effective therapies available for the excruciating neuropathic pain that develops after spinal cord injuries (SCI). As such, a great deal of effort is being put into the investigation of novel therapeutic targets that can alleviate this pain. One such target is acrolein, a highly reactive aldehyde produced as a byproduct of oxidative stress and inflammation that is capable of activating the transient receptor potential ankyrin 1 (TRPA1) cation channel, known to be involved in the transmission and propagation of chronic neuropathic pain. One anti-acrolein agent, hydralazine, has already been shown to reduce neuropathic pain behaviors and offer neuroprotection after SCI. This study investigates another acrolein scavenger, phenelzine, for its possible role of alleviating sensory hypersensitivity through acrolein suppression. The results show that phenelzine is indeed capable of attenuating neuropathic pain behaviors in acute, delayed, and chronic administration schedules after injury in a rat model of SCI. Additionally, upon the comparison of hydralazine to phenelzine, both acrolein scavengers displayed a dose-dependent response in the reduction of acrolein in vivo. Finally, phenelzine proved capable of providing locomotor function recovery and neuroprotection of spinal cord tissue when administered immediately after injury for two weeks. These results indicate that phenelzine may be an effective treatment for neuropathic pain after SCI and likely a viable alternative to hydralazine.

Background The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking. Objective The objective of our study was to identify symptoms prognostic of COVID-19 infection severity. Methods We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value. Results Fatigue (95% CI 0.141 to 0.334, P<.001), expectoration (95% CI 0.107 to 0.305, P<.001) and stuffed nose (95% CI –0.499 to –0.082, P=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance. Conclusions Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.

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BACKGROUND The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking. OBJECTIVE The objective of our study was to identify symptoms prognostic of COVID-19 infection severity. METHODS We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value. RESULTS Fatigue (95% CI 0.141 to 0.334, <i>P</i>&lt;.001), expectoration (95% CI 0.107 to 0.305, <i>P</i>&lt;.001) and stuffed nose (95% CI –0.499 to –0.082, <i>P</i>=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance. CONCLUSIONS Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.

Purpose. The pathological role of axial stress in intervertebral disc degeneration (IDD) is controversial, and there was no quantified study until now. Here, we tried to clarify the correlation between IDD or low back pain (LBP) and axial stress at different duration and magnitude in vitro and in vivo. Method. In vitro, the gene expression of aggrecan, matrix metalloproteinase-3 (MMP3), calcitonin gene-related peptide (CGRP), and substance P (SP) was measured when nucleus pulposus cells (NPCs) were compressed under gradual severity. In vivo, a measurable Ilizarov-type compression apparatus was established for single coccygeal (Co) intervertebral disc (IVD) compression of Co7-8 in mouse. Gradient stress was placed at 0.4 Mpa (mild), 0.8 Mpa (moderate), and 1.2 Mpa (severe) for three days to investigate the effect of the magnitude of axial stress. Additionally, mild compression with 3, 7, and 14 days was used to determine the effect of the duration of axial stress. Subsequently, we evaluated the severity of IDD and LBP by radiological X-ray film; histological examination with H&E staining; immunohistochemical analysis with collagen II, aggrecan, and CGRP staining; and western blot analysis with collagen II, aggrecan, MMP-3, and interleukin-1β (IL-1β). Results. When NPCs suffered gradual increased mechanical stress, the cells exhibited gradual downregulated expression of extracellular matrix (ECM)-related gene of aggrecan, upregulated expression of IDD-related gene of MMP3, and LBP-related gene of CGRP and SP. In the meantime, with different magnitudes of axial stress, the IVD showed progressively severe IDD and LBP, with gradual narrowing intervertebral height, destruction of IVD anatomy, decreased ECM, and increased catabolic factors and proalgesic peptides. Conclusion. Axial compression is one of the critical pathological factors to cause IDD and LBP, and there was a strong positive correlation depended on the duration and magnitude of compression.