Genetic mechanisms underlying local spontaneous brain activity in episodic migraine.

Advances in neuroimaging techniques during the past few decades have captured impaired functional brain activity in migraine disorders, yet the molecular mechanisms accounting for its alterations in migraine remain largely unknown. A total of 27 patients with episodic migraine (EM) and 30 matched healthy controls (HCs) underwent resting-state functional and structural magnetic resonance imaging (MRI) scans. Regional homogeneity (ReHo), low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) of fMRI were compared between the two groups. Based on the Allen Human Brain Atlas and risk genes in migraine, we identified gene expression profiles associated with ReHo alterations in EM. Compared with HCs, patients with EM showed increased ReHo in the left orbital part of the superior frontal gyrus (P < 0.05, cluster-level FWE-corrected). The expression profiles of 16 genes were significantly correlated with ReHo alterations in EM (P < 0.05/5,013, Bonferroni corrected). These genes were mainly enriched for transcription regulation, synaptic transmission, energy metabolism, and migraine disorders. Furthermore, the neural activation was positively correlated with Hamilton Rating Scale for Anxiety (HAMA) scores. To test the stability of our results, we repeated our procedure by using ALFF and fALFF and found these results had a high degree of consistency. Overall, these findings not only demonstrated that regional brain activity was increased in patients with EM, which was associated with emotional regulation but also provided new insights into the genetic mechanisms underlying these changes in migraine.

Alterations of amygdala volume and functional connectivity in migraine patients comorbid with and without depression.

OBJECTIVE: The comorbid relationship between migraine and depression has been well recognized, but its underlying pathophysiology is unclear. Here, we aimed to explore the structural changes of the amygdala and the abnormal functional connectivity of the centromedial amygdala (CMA) in migraineurs with depression. METHODS: High-resolution T1-weighted and functional magnetic resonance images were acquired from 22 episodic migraineurs with comorbid depression (EMwD), 21 episodic migraineurs without depression (EM), and 17 healthy controls (HC). Voxel-based morphometry and resting-state functional connectivity (rsFC) were applied to examine the intergroup differences in amygdala volume. RESULTS: The bilateral amygdala volume was increased in the EMwD and EM groups compared with the HC group, but there were no differences between the EMwD and EM groups. The right CMA exhibited decreased rsFC in the left dorsolateral prefrontal cortex (DLPFC) in the EMwD group compared with the EM group, while rsFC increased between the CMA and the contralateral DLPFC in the EM group compared with the HC group. In addition, the EM group showed decreased rsFC between the left CMA and the left pallidum compared with the HC group. CONCLUSIONS: Enlarged amygdala is an imaging feature of EM and EMwD. The inconsistency of rsFC between CMA and DLPFC between migraineurs with and without depression might indicate that decreased rsFC between CMA and DLPFC is a neuropathologic marker for the comorbidity of migraine and depression. The core regions might be a potential intervention target for the treatment of EMwD in the future.

Perceived stigma of COVID-19 patients in Shanghai, China, in the third year of the pandemic: a cross-sectional social impact survey.

INTRODUCTION: Social stigma associated with Covid-19 infection has been reported around the world. This paper investigates the level of self-reported perceived stigma among people infected with COVID-19 in Shanghai, China, in the third year of the pandemic to determine changes in perceived stigma and individual level variables associated with perceived stigma. METHODS: We conducted a self-reported two-part online survey (n = 144 responses) by employing a convenience sampling method of COVID-19 patients in Shanghai. The first part of the survey collects sociodemographic information of the respondents and the second part outlines 24 items of the Social Impact Scale (SIS), which measures individual level factors associated with stigma, namely social rejection, financial insecurity, internalized shame, and social isolation. We ran Wilcoxon signed-ranks test, Kruskal-Wallis test, and linear regression analysis to assess the levels of perceived stigma differences. RESULTS: The study finds that the overall level of self-reported stigma during the COVID-19 lockdowns in Shanghai in 2022 was at a lower level than that compared to the self-reported perceived stigma study in Wuhan in 2020. In Shanghai, the severity of the disease and hospitalization length had most impact on financial insecurity and feelings of social isolation. These experiences were not gendered. Recovery measures, including economic considerations, need to pay particular attention to those who experienced severe disease.

Antibiotic governance and use on commercial and smallholder farms in eastern China.

Introduction: China is one of the largest consumers of agricultural antibiotics in the world. While the Chinese government has been tightening its regulations to control antimicrobial resistance (AMR) from animal sources in recent years, the extent of antimicrobial oversight and the practices of antibiotic use in animal agriculture in China has not yet been explored. This study describes the practices of antimicrobial management in eastern China and current scenarios of antibiotic use in commercial farms and smallholder backyard farming. Methods: 33 semi-structured interviews were conducted with government agriculture officials, veterinary drug sellers, farmers and smallholders in two contrasting areas of rural Zhejiang and Jiangsu provinces, China. Interview transcripts were analyzed in NVivo12 using a thematic approach. Results: Findings revealed that although the governance of antibiotic use has made progress, especially in controlling irrational antibiotic use in commercial farms, smallholders are under-regulated due to a lack of resources and assumptions about their marginal role as food safety governance targets. We also found that smallholders resort to human antibiotics for the treatment of backyard animals because of economic constraints and lack of access to professional veterinary services. Discussion: More attention needs to be devoted to the local structural needs of farmers to reduce antibiotic misuse. Considering the extensive links of AMR exposure under the One Health framework, efforts to integrate smallholders in antibiotic governance are required to address the AMR burden systematically in China.

Functional connectivity and structural changes of thalamic subregions in episodic migraine.

BACKGROUND: The thalamus plays a crucial role in transmitting nociceptive information to various cortical regions involving migraine-related allodynia and photophobia. Abnormal structural and functional alterations related to the thalamus have been well established. However, it is unknown whether the brain structure and function of the thalamic subregions are differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing the structure and function of 16 thalamic subregions between patients with episodic migraine (EM) and healthy controls (HCs). METHODS: Twenty-seven patients with EM and 30 sex-, age- and education-matched HCs underwent resting-state functional and structural magnetic resonance imaging scans. Functional connectivity (rsFC), grey matter volume (GMV), and diffusion tensor imaging (DTI) parameters of each subregion of the thalamus were calculated and compared between the two groups. Furthermore, correlation analyses between neuroimaging changes and clinical features were performed in this study. RESULTS: First, compared with HCs, patients with EM exhibited decreased rsFC between the anterior-medial-posterior subregions of the thalamus and brain regions mainly involved in the medial system of the pain processing pathway and default mode network (DMN). Second, for the whole thalamus and each of its subregions, there were no significant differences in GMV between patients with EM and HCs (P > 0.05, Bonferroni corrected). Third, there was no significant difference in DTI parameters between the two groups (P > 0.05). Finally, decreased rsFC was closely related to scores on the Hamilton Rating Scale for Anxiety (HAMA) and Big Five Inventory (BFI) scales. CONCLUSION: Selective functional hypoconnectivity in the thalamic subregions provides neuroimaging evidence supporting the important role of thalamocortical pathway dysfunction in episodic migraine, specifically, that it may modulate emotion and different personality traits in migraine patients.

Understanding the Implementation of Antimicrobial Policies: Lessons from the Hong Kong Strategy and Action Plan.

In 2017, the Hong Kong Strategy and Action Plan on Antimicrobial Resistance 2017-2022 (HKSAP) was announced with the aim of tackling the growing threat of antimicrobial resistance (AMR) in Hong Kong. However, little is known about how the planned activities have been implemented. In this study, we examine the status of implementation of the HKSAP using the Smith Policy Implementation Process Model. Semi-structured interviews with 17 informants found that important achievements have been made, including launching educational and training activities targeting the public, farmers, and healthcare professionals; upgrading the AMR surveillance system; and strengthening AMR stewardship and infection control. Nevertheless, participants also identified barriers to greater implementation, such as tensions across sectors, ongoing inappropriate drug use and prescription habits, insufficient human and technical resources, as well as a weak accountability framework. Environmental factors such as the COVID-19 pandemic also affected the implementation of HKSAP. Our study indicated that expanding engagement with the public and professionals, creating a collaborative environment for policy implementation, and building a well-functioning monitoring and evaluation system should be areas to focus on in future AMR policies.

Overexpression of BDNF in the ventrolateral periaqueductal gray regulates the behavior of epilepsy-migraine comorbid rats.

OBJECTIVE: To investigate the effects of brain-derived neurotrophic factor (BDNF) overexpression in the ventrolateral periaqueductal gray (vlPAG) on behavioral changes in epilepsy-migraine comorbid rats. METHOD: We used an adeno-associated virus (AAV)-mediated vector to supplement BDNF in the vlPAG area prior to the establishment of a pilocarpine-nitroglycerin (Pilo-NTG) combination-induced comorbid model of epilepsy and migraine. Seizure- and migraine-related behaviors were analyzed. Cell loss and apoptosis in vlPAG were detected through hematoxylin-eosin (HE) and TUNEL staining. Immunofluorescence staining analyses were employed to detect expressions of BDNF and its receptor, tyrosine kinase B (TrkB), in vlPAG. Immunohistochemical staining was conducted to detect expressions of c-Fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG). RESULTS: Comparing to control group, AAV-BDNF injected comorbid group showed lower pain sensitivity, scratching head, and spontaneous seizures accompanied by the downregulation of c-Fos labeling neurons and CGRP immunoreactivity in the TNC and TG. However, these changes were still significantly higher in the comorbid group than those in both epilepsy and migraine groups under the same intervention. CONCLUSION: These data demonstrated that supplying BDNF to vlPAG may protect structural and functional abnormalities in vlPAG and provide an antiepileptic and analgesic therapy.

Amplitude of Low-Frequency Fluctuation With Different Clinical Outcomes in Patients With Generalized Tonic-Clonic Seizures.

Background: Generalized tonic-clonic seizures (GTCS) are associated with significant disability and sudden unexpected death when they cannot be controlled. We aimed to explore the underlying neural substrate of the different responses to antiseizure drugs between the seizure-free (SF) and non-seizure-free (NSF) patients with GTCS through the amplitude of low-frequency fluctuation (ALFF) method. Methods: We calculated ALFF among the SF group, NSF group, and healthy controls (HCs) by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data. One-way ANOVA was used to compare the ALFF of the three groups, and post-hoc analysis was done at the same time. Pearson's correlation analysis between ALFF in the discrepant brain areas and the clinical characteristics (disease course and age of onset of GTCS) was calculated after then. Results: A significant group effect was found in the right fusiform gyrus (R.FG), left fusiform gyrus (L.FG), left middle occipital gyrus (L.MOG), right inferior frontal gyrus (R.IFG), right precentral gyrus (R.PreG), right postcentral gyrus (R.PostG), and left calcarine sulcus (L.CS). The SF and NSF groups both showed increased ALFF in all discrepant brain areas compared to HCs except the R.IFG in the NSF group. Significantly higher ALFF in the bilateral FG and lower ALFF in the R.IFG were found in the NSF group compared to the SF group. Conclusions: Higher ALFF in the bilateral FG were found in the NSF group compared to the SF and HC groups. Our findings indicate that abnormal brain activity in the FG may be one potential neural substrate to interpret the failure of seizure control in patients with GTCS.

Decreased Resting-State Functional Connectivity of Periaqueductal Gray in Temporal Lobe Epilepsy Comorbid With Migraine.

Objective: Patients with temporal lobe epilepsy (TLE) are at high risk for having a comorbid condition of migraine, and these two common diseases are proposed to have some shared pathophysiological mechanisms. Our recent study indicated the dysfunction of periaqueductal gray (PAG), a key pain-modulating structure, contributes to the development of pain hypersensitivity and epileptogenesis in epilepsy. This study is to investigate the functional connectivity of PAG network in epilepsy comorbid with migraine. Methods: Thirty-two patients with TLE, including 16 epilepsy patients without migraine (EwoM) and 16 epilepsy patients with comorbid migraine (EwM), and 14 matched healthy controls (HCs) were recruited and underwent resting functional magnetic resonance imaging (fMRI) scans to measure the resting-state functional connectivity (RsFC) of PAG network. The frequency and severity of migraine attacks were assessed using the Migraine Disability Assessment Questionnaire (MIDAS) and Visual Analog Scale/Score (VAS). In animal experiments, FluoroGold (FG), a retrograde tracing agent, was injected into PPN and its fluorescence detected in vlPAG to trace the neuronal projection from vlPAG to PPN. FG traced neuron number was used to evaluate the neural transmission activity of vlPAG-PPN pathway. The data were processed and analyzed using DPARSF and SPSS17.0 software. Based on the RsFC finding, the excitatory transmission of PAG and the associated brain structure was studied via retrograde tracing in combination with immunohistochemical labeling of excitatory neurons. Results: Compared to HCs group, the RsFC between PAG and the left pedunculopontine nucleus (PPN), between PAG and the corpus callosum (CC), was decreased both in EwoM and EwM group, while the RsFC between PAG and the right PPN was increased only in EwoM group but not in EwM group. Compared to EwoM group, the RsFC between PAG and the right PPN was decreased in EwM group. Furthermore, the RsFC between PAG and PPN was negatively correlated with the frequency and severity of migraine attacks. In animal study, a seizure stimulation induced excitatory transmission from PAG to PPN was decreased in rats with chronic epilepsy as compared to that in normal control rats. Conclusion: The comorbidity of epilepsy and migraine is associated with the decreased RsFC between PAG and PPN.

Case Report: Migraine-Like Headache With Visual Aura Initiated by Endovascular Coiling Treatment for a Posterior Cerebral Artery Aneurysm.

Cervical, anterior, and middle cerebral artery aneurysm is a causative factor for migraine, and endovascular treatment usually improves migraine headache. Posterior cerebral artery (PCA) aneurysm is a rare condition, and its association with migraine is very rarely reported. In addition, endovascular coiling treatment causing migraine-like headache has never been reported. Here, we describe a newly developed migraine-like headache with visual aura after endovascular coiling treatment for PCA aneurysm in a 31-year-old female patient. One month after the endovascular therapy, the patient stopped using the antiplatelet agents clopidogrel and aspirin and presented with an episodic headache attack twice a month with typical migraine features, including visual aura, right-sided temporal throbbing pain accompanied with nausea, vomiting, and photophobia. The recurrence of migraine-like headache with visual aura was terminated by clopidogrel administration. The generation of the migraine-like headache with visual aura is probably associated with microemboli due to endovascular coiling. This case supports the hypothesis that migraine with aura can be associated with microemboli of variant origins.

Sonographic hypoechogenicity of brainstem raphe nucleus is correlated with electroencephalographic spike frequency in patients with epilepsy.

BACKGROUND: Brainstem raphe nucleus (BRN) hypoechogenicity in transcranial sonography (TCS) has been demonstrated in patients with major depression, possibly representing a sonographic manifestation of serotonergic dysfunction in depression. Most patients with epilepsy with comorbid depression exhibit hypoechogenic BRN in TCS. However, the role of BRN in the pathogenesis of epilepsy is unclear. This study aimed to evaluate the correlation of BRN echogenicity with epilepsy itself, and the echogenicity of other midbrain structures and the size of lateral ventricle (LV) will also be evaluated in patients with epilepsy. METHODS: Thirty-six patients with epilepsy without depression and 37 healthy controls were recruited. Sonographic echogenicity of BRN, caudate nucleus (CN), lentiform nucleus (LN), substantia nigra (SN), and the width of frontal horns of the lateral ventricles (LV) and the third ventricle (TV) were evaluated with TCS. The frequency of interictal epileptiform discharges (IEDs) was assessed with ambulatory electroencephalogram (AEEG). RESULTS: Hypoechogenicity of BRN was depicted in 36.1% of patients with epilepsy and 18.9% of controls, showing no significant difference. Patients with epilepsy with BRN hypoechogenicity had higher epileptic discharge index (EDI) than those with normal BRN echogenecity. Especially, higher EDI in patients with BRN hypoechogenicity was observed during the sleep period but not during awake period. The width of TV was significantly larger in patients with epilepsy than that in controls. We did not find any difference between patients with epilepsy and controls in the echogenicity of CN, LN, and SN, as well as in the width of frontal horn of LV. CONCLUSIONS: Hypoechogenic BRN is correlated with a high frequency of epileptic discharges in electroencephalogram (EEG), especially during sleep period but not during awake period, indicating that BRN alterations may play a potential role in the pathogenesis of epilepsy in association with sleep cycle.

The epidemiology of primary headaches in patients with multiple sclerosis.

OBJECTIVE: Recent studies have shown a pathophysiologic link between headache and multiple sclerosis (MS), but the prevalence of primary headaches among patients with MS differs substantially across studies. This meta-analysis aimed to comprehensively gather available evidence to estimate the prevalence of primary headaches among patients with MS. METHOD: We systematically searched the electronic databases including PubMed, Embase, and Scopus for cohort, case-control, cross-sectional studies that measured the prevalence of headache among patients with MS. Two reviewers independently screened titles and abstracts to identify the eligible studies and the full texts of the included studies were reviewed. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the included literatures. We then conducted a meta-analysis using Stata Software 15.0 to calculate the pooled prevalence of headaches among patients with MS and assess the source of heterogeneity. RESULTS: We identified 16 eligible studies covering a total of 3,560 patients with MS. The pooled estimated prevalence of primary headaches among patients with MS was 56%. The statistical heterogeneity was moderate with I2 of 82.1% (p < .001). Both a visual inspection of the funnel plot and Egger' regression tests revealed no significant publication bias (p = .44). The pooled estimated prevalence of migraine (55%) was higher in comparison with that of tension-type headache (20%). The prevalence of migraine subtype was 16% and 10% for migraine without aura and migraine with aura, respectively. The pooled prevalence of primary headache in case-control group (57%) was approximately in line with the cross-sectional group (56%). CONCLUSION: The overall prevalence of primary headaches among patients with MS was considerably high. Clinical screening of headache among patients with MS will be helpful to formulate an individualized treatment plans and alleviate the physical and mental impact of the disease.

Enhancing the insecticidal activity of new Bacillus thuringiensis X023 by copper ions.

BACKGROUND: A new Bacillus thuringiensis X023 (BtX023) with high insecticidal activity was isolated in Hunan Province, China. The addition of metals (Cu, Fe, Mg and Mn) to the medium could influence the formation of spores and/or insecticidal crystal proteins (ICPs). In previous studies, Cu ions considerably increased the synthesis of ICPs by enhancing the synthesis of poly-ß-hydroxy butyrate. However, the present study could provide new insights into the function of Cu ions in ICPs. RESULTS: Bioassay results showed that wild strain BtX023 exhibited high insecticidal activity against Plutella xylostella. The addition of 1 × 10-5 M Cu2+ could considerably increase the expression of cry1Ac and vip3Aa, and the insecticidal activity was enhanced. Quantitative real-time polymerase chain reaction (qRT-PCR) and proteomic analyses revealed that the upregulated proteins included amino acid synthesis, the glyoxylate pathway, oxidative phosphorylation, and poly-ß-hydroxy butyrate synthesis. The Cu ions enhanced energy metabolism and primary amino acid synthesis, will providing abundant raw material accumulation for ICP synthesis. CONCLUSION: The new strain BtX023 exerted a strong insecticidal effect on P. xylostella by producing ICPs. The addition of 1 × 10-5 M Cu2+ in the medium could considerably enhance the expression of the cry1Ac and vip3Aa genes, thereby further increasing the toxicity of BtX023 to Helicoverpa armigera and P. xylostella by enhancing energy synthesis, the glyoxylate cycle, and branched-chain amino acids synthesis, but not poly-ß-hydroxy butyrate synthesis.

The Comorbid Relationship Between Migraine and Asthma: A Systematic Review and Meta-Analysis of Population-Based Studies.

Objective: Recent studies have indicated a pathophysiologic link between migraine and asthma. This meta-analysis aimed to comprehensively estimate the risk ratio for migraine in asthma as well as that of asthma in migraine based on available evidence. Method: We systematically searched the electronic databases including PubMed, Web of Science, and SCOPUS for population-based studies that measured either the odds or the risk of asthma in subjects with migraine as well as that of migraine in subjects with asthma. The titles and abstracts were screened by two independent reviewers to identify eligible studies, and this was followed by full-text review of the included studies. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of included literature. A meta-analysis was conducted with Review Manager 5.3 Software to calculate the odds ratio (OR) for case-control and cross-sectional studies and either relative ratio (RR) or hazard ratio (HR) for cohort studies, and the source of heterogeneity was assessed. Subgroup and sensitivity analyses were conducted, and the I2 test were used to assess the source of heterogeneity. The funnel plot, Galbraith plot, and Egger's test were used to evaluate publication bias. Results: Fifteen published studies covering a total of 1,188,780 individuals were identified. Pooled analysis indicated that migraine was associated with increased odds (OR = 1.54; 95% CI: 1.34~1.77) and risk for asthma (HR = 1.42; 95% CI: 1.26~1.60), and asthma associated with increased odds (OR = 1.45; 95% CI: 1.22~1.72) and risk for migraine (HR = 1.47; 95% CI: 1.41~1.52). Conclusion: Migraine is a potential risk indicator for asthma, and vice versa, asthma is a potential risk indicator for migraine. However, future prospective cohort studies are warranted to provide more evidence concerning the detailed association between migraine and asthma.