Modifiable factors for migraine prophylaxis: A mendelian randomization analysis.

Objective: To examine the causal effect of potentially modifiable risk factors contributing to migraine pathogenesis. Methods: We performed Mendelian randomization analyses and acquired data from United Kingdom Biobank, FinnGen Biobank, and the MRC IEU OpenGWAS data infrastructure. An inverse-variance weighted (IVW) model was used to examine the relationship between 51 potentially modifiable risk factors and migraine in 3215 participants with migraine without aura (MwoA), 3541 participants with migraine with aura (MwA), and 176,107 controls. We adopted a Bonferroni-corrected threshold of p = 9.8 × 10-4 (.05 divided by 51 exposures) as a sign of significant effect, and a p < .05 was considered as the sign of a suggestive association. Results: More years of schooling significantly correlated with lower odds of MwoA pathogenesis (OR .57 [95%CI .44 to .75], p < .0001). More vitamin B12 intake (OR .49 [95%CI .24 to .99], p = .046) and lower level of stress [OR 8.17 (95%CI 1.5 to 44.36), p = .015] or anxiety disorder (OR 1.92 × 109 [95%CI 8.76 to 4.23*1017], p = .029) were suggestive to be correlated lower odds of MwoA pathogenesis. More coffee intake (OR .39 [95%CI .22 to .7], p = .001), lower level of eicosapentaenoic acid status (OR 2.54 [95%CI 1.03 to 6.26], p = .043), and more light physical activity (OR .09 [95%CI .01 to .94], p = .046) were suggestive to be associated with lower odds of MwA. Conclusion: The years of schooling, light physical activity, vitamin B12 intake, and coffee intake were the protective factors for migraine; stress, anxiety, and eicosapentaenoic acid status were harmful factors. Interventions could be developed based on modifying these factors for migraine prophylaxis.

Matching adjusted indirect comparison of acupuncture versus fremanezumab in the preventive treatment of episodic migraine.

OBJECTIVE: Acupuncture and fremanezumab are second-line treatments for migraine prophylaxis. We aimed to compare acupuncture with fremanezumab in the preventive treatment of episodic migraine by using a matching-adjusted indirect comparison analysis (MAIC). METHODS: We acquired participant-level data from an acupuncture trial recruiting 302 participants and summary-level data from a fremanezumab trial recruiting 875 participants (290 participants received monthly fremanezumab [MF] and 291 received single-dose fremanezumab [SF]). The primary outcome was the mean reduction in monthly headache days. The secondary outcomes were the mean reduction in monthly moderate-to-severe headache days, days with acute medication, and the adverse events rate. RESULTS: Before matching, the acupuncture arm had significantly lower BMI, fewer headache days with at least moderate severity, and fewer days with acute medication. After matching, the baseline variables were comparable between groups. The three arms had no difference in the change of monthly migraine days (MF vs. acupuncture: mean difference 0.3, 95%CI -0.5 to 1.1, p-value = 0.473; SF vs. acupuncture: mean difference 0.5, 95%CI -0.3 to 1.3, p-value = 0.214). The results were similar in the analyses of secondary outcomes sensitivity analyses. Thirty-six (25%) participants in the acupuncture arm reported adverse events, versus 192(66%) participants in the MF arm and 193 (66%) in the SF arm. CONCLUSION: The preventive treatment effect of acupuncture is equivalent to fremanezumab, and it presented with a lower adverse event rate, which indicates that acupuncture can be an alternative to fremanezumab.

Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene.

Malignant hyperthermia (MH) is an autosomal dominant genetic condition of the skeletal muscle triggered by inhaled general anesthetic agents or succinylcholine and associated with a hypermetabolic state and skeletal muscle rigidity. Tachycardia, increased carbon dioxide production, hypercarbia, hyperthermia, acidosis, hyperkalemia, cardiac arrhythmias, muscle rigidity, and rhabdomyolysis are common symptoms of MH. As the progression of the syndrome could be rapid or less evident, even experienced physicians have difficulty in diagnosing MH, which can lead to delays in treatment and increased mortality. We report a rare case of a 36-year-old man, who underwent open reduction and internal fixation of the left clavicle after inhaled anesthetics. The patient developed dyspnea, hypotension, unremitting hyperthermia, tachycardia, and elevated serum myoglobin, and finally died of pyemia and disseminated intravascular coagulation. We reviewed the process of disease development, summarized the steps of diagnosis, and improved genetic testing. Exome sequencing revealed a new mutation c.8519G>A (p.arg2840 GLN) in the RYR1 gene that could be associated with MH. The gene mutation was also found in his daughter's genetic test. This case emphasized the importance of the awareness of MH and its atypical clinical symptoms. The presence of dyspnea, hypotension, unremitting hyperthermia, tachycardia, and raised myoglobin in serum might further strengthen the clinical diagnosis of suspected MH.

Efficacy and Safety of Dahuang Zhechong Pill in Silicosis: A Randomized Controlled Trial.

BACKGROUND: There is no effective therapy for silicosis, and Dahuang Zhechong pill (DHZCP), an ancient Chinese medicine prescription, may have a therapeutic effect on silicosis. This study aims to verify the efficacy and safety of DHZCP in silicosis. METHODS: This is a randomized controlled clinical trial done at Panzhihua Second People's Hospital (Panzhihua City, Sichuan Province, China). Participants diagnosed with silicosis were recruited and randomized to the conventional treatment group (CG) or DHZCP combined with the conventional treatment group (DG). Forced vital capacity % predicted (FVC%), diffusing capacity of the lung for carbon monoxide % predicted (DLCO%), six-minute walk distance (6MWD), peripheral oxygen (SpO2), King's Brief Interstitial Lung Disease Questionnaire (K-BILD), and safety outcomes were measured at baseline and 9 weeks. RESULTS: Fifty-six participants (28 in each group) completed the study, and 53 of them (26 in DG and 27 in CG) completed pulmonary function. At 9 weeks, compared with no DHZCP, DHZCP treatment was associated with significant improvements in FVC% (mean ± SD, 95%CI) (8.2 ± 3.9, 0.3 to 16.0), DLCO% (8.6 ± 3.5, 1.5 to 15.7), SpO2 (3.8 ± 0.7, 2.3 to 5.2), and K-BILD total score (6.0 ± 2.3, 1.4 to 10.7). And, there were no statistical differences of safety outcomes between the two groups. Eight patients accepting DHZCP developed mild diarrhea during the first week, which subsequently resolved on its own. CONCLUSION: DHZCP could improve the pulmonary function, the quality of life, and the exercise capacity of silicosis patients.

Dahuang Zhechong Pills Suppress Silicosis Fibrosis Progression via p38 MAPK/TGF-ß1/Smad Pathway In Vitro.

BACKGROUND: Dahuang Zhechong pills (DHZCP) is a classic Chinese medicinal prescription in "Treatise on Cold Pathogenic and Miscellaneous Diseases (Shanghan Zabing Lun)," and it has the function of tonifying blood, nourishing Yin, and removing blood stasis. Previous studies have shown that DHZCP could alleviate SiO2 induced pulmonary fibrosis in mice. This study aims to further explore the preventive and therapeutic effects of DHZCP against silicosis fibrosis and the underlying mechanisms in vitro. METHODS: We used the experimental model of SiO2-induced MH-S cells to evaluate the therapeutic potential of DHZCP. MH-S cells induced by SiO2 were intervened with the drug-containing serum of DHZCP, and the effects of drug-containing serum of DHZCP on the MH-S cells were detected by CCK8, ELISA, flow cytometry, western blot, and immunofluorescence. RESULTS: DHZCP improved cell viability by reducing apoptosis. It also decreased the levels of TNF-α, IL-1ß, IL-6 in the supernatant of MH-S cells induced by SiO2, inhibited the expression of p38 MAPK, blocked the activation of NF-κB, and controlled the upstream inflammatory response by multiple targeting. Concomitantly, we observed upregulation of Smad7 and a marked decline in TGF-ß1, α-SMA, Smad2, Smad3 expression in MH-S cells treated with DHZCP. CONCLUSION: To sum up, we conclude that DHZCP protects against SiO2-induced silicosis by reducing the persistent irritation of inflammation, regulating the p38 MAPK/TGF-ß1/Smad pathway.

A robust electrode configuration for bioimpedance measurement of respiration.

Electrode configuration is an important issue in the continuous measurement of respiration using impedance pneumography (IP). The robust configuration is usually confirmed by comparing the amplitude of the IP signals acquired with different electrode configurations, while the relative change in waveform and the effects of body posture and respiratory pattern are ignored. In this study, the IP signals and respiratory volume are simultaneously acquired from 8 healthy subjects in supine, left lying, right lying and prone postures, and the subjects are asked to perform four respiratory patterns including free breathing, thoracic breathing, abdominal breathing and apnea. The IP signals are acquired with four different chest electrode configurations, and the volume are measured using pneumotachograph (PNT). Differences in correlation and absolute deviation between the IP-derived and PNT-derived respiratory volume are assessed. The influences of noise, respiratory pattern and body posture on the IP signals of different configurations have significant difference (p < 0.05). The robust electrode configuration is found on the axillary midline, which is suitable for long term respiration monitoring.

[Role of prone position mechanical ventilation in patients with acute respiratory distress syndrome originating from pulmonary disease and extra-pulmonary disease].

OBJECTIVE: To assess the effect of mechanical ventilation on prone position for the treatment of acute respiratory distress syndrome (ARDS) originating from pulmonary disease and extra-pulmonary disease. METHODS: From January 2001 to February 2004 in intensive care unit (ICU), 42 patients with ARDS were divided into pulmonary disease group and extra-pulmonary disease group. All the patients were mechanically ventilated on prone position. Arterial blood gases, respiratory rate (RR), fraction of inspired oxygen (FiO(2)), pulmonary compliance (C), tidal volume (V(T)), airway resistance (Raw) were measured before prone position and 2 hours and 4 hours after prone position. Lung-CT was measured in supine position and prone position. RESULTS: When patients were turned to prone position, SaO(2) and RR were decreased markedly in two groups. V(T) was increased in extra-pulmonary disease groups compared with pulmonary disease group at the same time. Oxygen index, hemoglobin oxygen saturation and Raw were increased markedly when patients were turned to prone position, and oxygen index of pulmonary disease group was higher than that of extra-pulmonary disease group at the same time. No change was found in blood pH and partial pressure of carbon dioxide in artery (PaCO(2)), but oxygenation was improved markedly in two groups. The effective rate of improved oxygenation was 65% in pulmonary disease group and 68% in extrapulmonary disease group, but no significant difference was found. Lung CT revealed that when the patients were in prone position, the degree of lung infiltration in the dorsal part of lung decreased while that in the ventral part increased. CONCLUSION: Oxygenation is improved markedly in prone position in two groups. Mechanical ventilation on prone position was an effective method in the treatment of ARDS patients.