Background
Periodontal disease may drive a systemic inflammatory response that triggers migraine; however, the association between periodontal disease and migraine has rarely been investigated in a ...community‐based setting.
Methods
This cross‐sectional study included 66,109 participants aged 30 to 70 years from Taiwan Biobank (TWB). A structured questionnaire was administered to participants, who were also subjected to whole‐genome single nucleotide polymorphism genotyping using the customized Axiom–TWB array. To identify subjects with periodontal disease and migraine, the computerized linkage of data obtained from TWB and the National Health Insurance Research Database was performed. Participants were evaluated for their genetic predisposition to migraine using a polygenic risk score. We examined and estimated the magnitude of associations between periodontal disease and migraine.
Results
In this study, 4618 (4618/66,109; 7%) participants with migraine and 61,491 (61,491/66,109; 83%) participants without migraine were included. Participants with migraine exhibited a higher prevalence of periodontal disease than participants without migraine (4324/4618; 94% vs. 56,036/61,491; 91%). A significant positive association was observed between periodontal disease and migraine, with an adjusted odds ratio (ORadj) of 1.40 (95% confidence interval CI = 1.24–1.59; p < 0.001). The association remained consistent even after excluding participants with other comorbidities (ORadj = 1.34; 95% CI = 1.16–1.55; p < 0.001). Moreover, the positive association between periodontal disease and migraine remained significant across the subgroups of age, sex, other comorbidities, and classified polygenic risk scores of migraine, with the ORadj ranging from 1.26 to 1.78.
Conclusions
A significant positive association was observed between periodontal disease and migraine. Future studies need to explore the biological mechanisms of how periodontal disease might affect migraine.
Objective
To investigate the distribution, clinical associations, and treatment responses for the most bothersome symptoms of migraine in a large sample of patients with migraine in Taiwan.
...Background
The most bothersome symptom is recently recommended as a co‐primary endpoint in clinical trials of acute treatment of migraine. However, most clinical trials and observational studies have been conducted in the United States and Europe, with photophobia representing the most common most bothersome symptom.
Methods
Patients who were newly diagnosed with migraine by headache specialists in Taipei Veterans General Hospital were recruited. All participants completed a questionnaire for headache profile, including the most bothersome symptom. Clinical associations of the most bothersome symptoms and response rates to previous acute treatments were analyzed.
Results
Among the recruited 1188 patients with migraine (female 79.4%, mean age 39.0 ± 12.1 years) in this cross‐sectional study, nausea (n = 729/1188, 61.4%) was the most common symptom that was most bothersome, followed by phonophobia (n = 280/1188, 23.6%), and photophobia (n = 122/1188, 10.3%). The frequency ranking was the same regardless of sex and age. Compared to migraine without aura, migraine with aura was associated with photophobia (adjusted odds ratio OR = 2.97, 95% confidence interval CI 1.76–5.0, p < 0.001). Chronic migraine was associated with phonophobia (adjusted OR = 1.51, 95% CI 1.13–2.01, p = 0.005), but there was a lower chance for nausea (adjusted OR = 0.68, 95% CI 0.53–0.88, p = 0.004), as the most bothersome symptom. Patients with different most‐bothersome symptoms responded similarly to previous acute treatments, with an overall response rate of 52.2% (n = 550/1053).
Conclusion
Patients with migraine in Taiwan reported a distinct ranking of the most bothersome symptom. However, the response rates of the most bothersome symptom and headache were similar, which supports the most bothersome symptom as an outcome measure for acute treatment of migraine. Further studies recruiting different populations are required to investigate regional differences in most bothersome symptoms.
Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in ...triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.
ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of ...morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS‐induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf‐2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration‐dependent improvement in LPS‐induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf‐2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS‐induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries.
Purpose of Review
Reversible cerebral vasoconstriction syndrome (RCVS) is a disorder with distinct features: recurrent thunderclap headaches with reversible vasoconstriction of intracranial arteries. ...Substantial studies regarding outcomes after RCVS were conducted, showing favorable functional outcomes in most patients despite the potentially life-threatening complications of RCVS, including ischemic stroke, intracranial hemorrhage, or convexity subarachnoid hemorrhage. However, patients may report headaches after the resolution of RCVS while relative studies were scarce.
Recent Findings
Two prospective studies from different cohorts consistently revealed that RCVS recurred in at least 5% of patients. Patients with prior migraine history and patients whose thunderclap headaches are elicited by sexual activity or exertion are at higher risk for RCVS recurrence. On the other hand, several retrospective studies and case reports reported that chronic headaches are common in RCVS patients after the resolution of acute bouts. The chronic headaches after RCVS are sometimes disabling in certain patients.
Summary
Headaches after RCVS are not uncommon but usually overseen. Medical attention and examinations are warranted in patient with RCVS who reported recurrence of thunderclap headaches or chronic headaches after RCVS.
Ischemic stroke is the most common type of cerebrovascular event and is responsible for approximately 85% of all strokes in Taiwan. Neurons contain high concentrations of polyamines, which are prone ...to various pathological states in the brain and are perturbed after cerebral ischemia. Acrolein, an α,β-unsaturated aldehyde, has been suggested as the primary culprit of neuronal damage in stroke patients. However, the mechanism by which acrolein induces neuronal damage during ischemic stroke is not clear.
Urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione (GSH) metabolite, plasma acrolein-protein conjugates (Acr-PC) and plasma GSH levels were analyzed to correlate disease severity and prognosis of stroke patients compared with control subjects. In vivo middle cerebral artery occlusion (MCAO) animal models and an in vitro oxygen glucose deprivation (OGD) stroke model were used to investigate the mechanisms of acrolein-induced neuronal damage.
A deregulated acrolein metabolism, including significantly increased plasma Acr-PC levels, decreased urinary 3-HPMA levels and decreased plasma GSH levels, was found in stroke patients compared to control subjects. We further observed that acrolein was produced during ischemia resulting in brain damage in in vivo MCAO animal model. The induction of acrolein in neuronal cells during OGD occurred due to the increased expression of spermidine/spermine N1-acetyltransferase (SSAT) by NF-kB pathway activation. In addition, acrolein elicited a vicious cycling of oxidative stress resulting in neurotoxicity. Finally, N-acetylcysteine effectively prevented OGD-induced neurotoxicity by scavenging acrolein.
Overall, our current results demonstrate that acrolein is a culprit of neuronal damage through GSH depletion in stroke patients. The mechanism underlying the role of acrolein in stroke-related neuronal damage occurs through SSAT-induced polyamine oxidation by NF-kB pathway activation. These results provide a novel mechanism of neurotoxicity in stroke patients, aid in the development of neutralizing or preventive measures, and further our understanding of neural protection.
Display omitted
•A deregulated acrolein metabolism is found in stroke patients.•Acrolein is produced resulting in brain damage in MCAO animal model.•Acrolein occurs through SSAT-induced polyamine oxidation by NF-kB pathway.•Acrolein elicits a vicious cycling of oxidative stress resulting in neurotoxicity.•N-acetylcysteine prevents OGD-induced neurotoxicity by scavenging acrolein.
Abstract
The coronavirus disease 2019 (COVID‐19) pandemic continues to have a substantial impact on the economies and livelihoods of all countries. Central and local government administrators are ...facing a critical issue of resource utilization efficiency due to their limited resources. This paper employs data envelopment analysis (DEA) and the concept of an assurance region (AR) to assess the relative efficiency of administrative divisions in Taiwan, whose effectiveness has been praised by other countries’ administrators and citizens, regarding COVID‐19 pandemic prevention and control. The input factors used were the cumulative number of deaths (an undesirable factor) and expenditures, and the output factors were the average number of unconfirmed citizens aged 65 and older, the average number of unconfirmed citizens aged 0–64, and the cumulative number of vaccinations. Notably, because there are many COVID‐19 variants with different characteristics, reaching a consensus AR among experts is difficult. Thus, different ARs were compared, and the most representative AR was identified for subsequent analysis. The main findings show that only Kaohsiung City was efficient, and Taipei City was the third worst due to inefficient operations. In addition, the administrative divisions were classified into four groups using cluster analysis based on the decomposition of aggregate efficiency to the contributions of the three outputs. The findings presented in this paper serve as a reference for both local government administrators and citizens, offering insights into relative efficiency and improvement directions. Moreover, they also provide guidance for resource allocation, future strategy adjustment, and development for central government administrators and citizens worldwide.
Animal Models of Chronic Migraine Chou, Tse-Ming; Chen, Shih-Pin
Current pain and headache reports,
06/2018, Letnik:
22, Številka:
6
Journal Article
Recenzirano
Purpose of Review
Chronic migraine (CM) is a recalcitrant subtype of migraine which causes high degrees of disability, poor treatment responses, and frequent recurrences in sufferers. However, the ...pathophysiological mechanisms underlying the development and chronification of migraine attacks remain incompletely understood. A validated animal model could help to decipher the pathogenic mechanism of the disease, facilitating the development of possible therapeutic strategies for CM. In this review, we aimed to summarize current animal models of CM and discuss the validity of these models.
Recent Findings
Several methods have been available to induce recurrent headache-like behaviors or biochemical changes in rodents, including repeated dural application of inflammatory soup, chronic systemic infusion of nitroglycerin, repeated administration of acute migraine abortive treatment to simulate medication overuse headache, or genetic modification. These models exhibit some features that are believed to be associated with migraine; however, none of the model can recapitulate all the clinical phenotypes found in humans and each has its own weakness.
Summary
The complex features of CM increase the difficulty of constructing a proper animal model. Nonetheless, currently available models are valid to certain degrees. Future directions might consider simulating the spontaneity and chronicity of migraine by combining known genetic substrates and allostatic loads into the same model.
Background
Many single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or ...subtypes are scarce. We aimed to investigate the associations of pre-identified migraine susceptibility loci in Taiwanese with migraine endophenotypes or subtypes, including chronic migraine and allodynia.
Methods
The associations of six SNPs identified from our previous study, including
TRPM8
rs10166942,
LRP1
rs1172113,
DLG2
rs655484,
GFRA1
rs3781545,
UPP2
rs7565931, and
GPR39
rs10803531, and migraine endophenotypes, including chronic migraine and allodynia were tested. Significant associations in the discovery cohort were validated in the replication cohort. The adjusted odds ratios (aOR) were calculated after controlling for confounders.
Results
In total, 1904 patients (mean age 37.5 ± 12.2 years old, female ratio: 77.7%) including 1077 in the discovery cohort and 827 in the replication cohort were recruited. Of them, 584 (30.7%) had chronic migraine. Of the 6 investigated SNPs,
TRPM8
rs10166942 T allele-carrying patients were more likely to have chronic migraine than non-T allele carriers in both discovery and replication cohorts and combined samples (33.7% vs. 25.8%,
p
= 0.004, aOR = 1.62). In addition, T allele carriers reported more allodynic symptoms than non-T allele carriers (3.5 ± 3.7 vs. 2.6 ± 2.8,
p
< 0.001). However, allodynia severity did not differ between episodic and chronic migraine patients. No further correlations between genetic variants and endophenotypes were noted for the other SNPs.
Conclusions
TRPM8
may contribute to the pathogenesis of chronic migraine. However, our study did not support allodynia as a link between them. The underlying mechanisms deserve further investigations.
Background
Noninvasive vagus nerve stimulation (nVNS) has recently emerged as a promising therapy for migraine. We previously demonstrated that vagus nerve stimulation inhibits cortical spreading ...depression (CSD), the electrophysiological event underlying migraine aura and triggering headache; however, the optimal nVNS paradigm has not been defined.
Methods
Various intensities and doses of nVNS were tested to improve efficacy on KCl-evoked CSD frequency and electrical threshold of CSD in a validated rat model. Chronic efficacy was evaluated by daily nVNS delivery for four weeks. We also examined the effects of nVNS on neuroinflammation and trigeminovascular activation by western blot and immunohistochemistry.
Results
nVNS suppressed susceptibility to CSD in an intensity-dependent manner. Two 2-minute nVNS 5 min apart afforded the highest efficacy on electrical CSD threshold and frequency of KCl-evoked CSD. Daily nVNS for four weeks did not further enhance efficacy over a single nVNS 20 min prior to CSD. The optimal nVNS also attenuated CSD-induced upregulation of cortical cyclooxygenase-2, calcitonin gene-related peptide in trigeminal ganglia, and c-Fos expression in trigeminal nucleus caudalis.
Conclusions
Our study provides insight on optimal nVNS parameters to suppress CSD and suggests its benefit on CSD-induced neuroinflammation and trigeminovascular activation in migraine treatment.
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