Genetic Risk Loci and Familial Associations in Migraine: A Genome-Wide Association Study in the Han Chinese Population of Taiwan.

BACKGROUND AND PURPOSE: Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. METHODS: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. RESULTS: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. CONCLUSIONS: This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

Longitudinal assessment of plasma biomarkers for early detection of cognitive changes in subjective cognitive decline.

Background: Individuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction. Objective: To identify plasma biomarkers for SCD. Methods: Fifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aß42, Aß40, t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline. Results: Higher baseline plasma Aß1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7-80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups (p > 0.05). Furthermore, lower baseline plasma Aß1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6-89.1%). At last, the changes in t-tau and Aß42 × t-tau could differentiate between the two SCD subgroups (p < 0.05). Conclusion: Baseline plasma Aß42 may help identify people with SCD and predict SCD progression. The role of plasma Aß42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer's disease require further investigation.

The Sound of Memory: Investigating Music Therapy's Cognitive Benefits in Patients with Dementia-A Network Meta-Analysis of Randomized Controlled Trials.

Numerous previous studies have shown the effectiveness of music therapy in enhancing cognitive functions in patients with dementia. Despite this, robust evidence in this field, especially concerning the comparison of different music therapy types, is lacking. Therefore, randomized controlled trials (RCTs) focusing on music therapy and cognitive functions in dementia patients, termed by "music" AND "dementia" OR "Alzheimer's disease" AND "cognitive", were identified from primary electronic databases to conduct this network meta-analysis (NMA). The primary outcome focused on the impact on cognitive functions, and the secondary outcome was the comparison of dropout rates between the intervention groups and the usual care control groups. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed for effect evaluation. This study protocol has been registered in IPLASY (INPLASY202430082). A total of 14 RCTs with 1056 participants were enrolled, examining interventions including Active Music Therapy (AMT), Active Music Therapy with Singing (AMT + Sing), Rhythmic Music Therapy (RMT), Listening to Music (LtM), and Singing (Sing). The results indicated that RMT, AMT + Sing, and AMT all significantly improve cognitive functions in dementia patients, of which the SMD were 0.76 (95% CI = 0.32-1.21), 0.79 (95% CI = 0.03-1.49), and 0.57 (0.18-0.96), respectively. Compared with the control group (usual care), no music therapy type was associated with an increased dropout risk. In conclusion, music therapy can improve cognitive functions in patients with dementia without increasing the risk of dropout, particularly RMT, AMT + Sing, and AMT.

Multifaceted Music Therapy for Depression in Dementia: A Network Meta-Analysis of Randomized Controlled Trials.

This study aimed to assess the efficacy of various music therapy interventions in ameliorating depressive symptoms in dementia patients, utilizing a network meta-analysis approach. We rigorously selected randomized controlled trials focused on music therapy for dementia with depressive symptoms from major electronic databases. The primary outcome measured was the impact on depressive symptoms, with the secondary outcome evaluating dropout rates across different intervention groups and standard care control groups. The research protocol has been duly registered with PROSPERO (Registration ID: CRD42023393059). Our network meta-analysis incorporated 14 randomized controlled trials involving a total of 1080 participants and examined a range of interventions, including active music therapy, listening to music, rhythmic music therapy, singing, and tailored music interventions. The analysis revealed that active music therapy combined with singing emerged as the most effective intervention, demonstrating a significant improvement in depressive symptoms in dementia patients (Standardized Mean Difference [SMD] = -0.89, 95% Confidence Interval [CI]: -1.48 to -0.30). In contrast, listening to music alone showed a smaller effect (SMD = -0.26, 95% CI: -0.71 to 0.20). This study was particularly noteworthy for not showing higher dropout rates compared to standard care, indicating its feasibility and acceptability in clinical settings. The findings of our study indicate that active music therapy combined with singing is an effective approach to reducing depressive symptoms in dementia patients, potentially due to enhanced social interaction. These results offer new perspectives for dementia care, suggesting a promising direction for further research and clinical application.

Anti-Hypertensive Effect of Solanum muricatum Aiton Leaf Extract In Vivo and In Vitro.

Hypertension is a global health problem and leads to cardiovascular disease and renal injury. Solanum muricatum Aiton leaf extract, rich in flavonoids, is known for its antioxidant capacity. However, the effects of Solanum muricatum Aiton leaf extract on hypertension combined with inflammatory complications were unknown. This study aimed to investigate the impact of Solanum muricatum Aiton leaf extract on hypertension in vivo and in vitro. In vivo, Solanum muricatum Aiton leaf extract led to decrease high blood pressure, improve heart, aorta, and kidney pathology, and enhance the antioxidative activity in spontaneously hypertensive rats (SHR). Our study demonstrated Solanum muricatum Aiton leaf extract inhibited angiotensin-converting enzyme (ACE), epithelial sodium channel (ENaC), sodium glucose co-transporters-1 (SGLT-1), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). In vitro, Solanum muricatum Aiton leaf extract improved the angiotensin II-induced reactive oxygen species (ROS) and mitochondrial membrane depolarization in NRK-52E cells. Besides, Solanum muricatum Aiton leaf extract could also decrease the expressions of ENaC, SGLT-1, and NF-κB in angiotensin II-treated NRK-52E cells. Solanum muricatum Aiton leaf can be suggested as a novel antihypertensive agent ameliorating hypertension via ACE inhibition, inflammation reduction, and ROS. PLE is a novel anti-hypertensive agent to ameliorate hypertension and its complications, including inflammation.

Unraveling the Structure-Property-Performance Relationships of Fused-Ring Nonfullerene Acceptors: Toward a C-Shaped ortho-Benzodipyrrole-Based Acceptor for Highly Efficient Organic Photovoltaics.

The high-performance Y6-based nonfullerene acceptors (NFAs) feature a C-shaped A-DA'D-A-type molecular architecture with a central electron-deficient thiadiazole (Tz) A' unit. In this work, we designed and synthesized a new A-D-A-type NFA, termed CB16, having a C-shaped ortho-benzodipyrrole-based skeleton of Y6 but with the Tz unit eliminated. When processed with nonhalogenated xylene without using any additives, the binary PM6:CB16 devices display a remarkable power conversion efficiency (PCE) of 18.32% with a high open-circuit voltage (Voc) of 0.92 V, surpassing the performance of the corresponding Y6-based devices. In contrast, similarly synthesized SB16, featuring an S-shaped para-benzodipyrrole-based skeleton, yields a low PCE of 0.15% due to the strong side-chain aggregation of SB16. The C-shaped A-DNBND-A skeleton in CB16 and the Y6-series NFAs constitutes the essential structural foundation for achieving exceptional device performance. The central Tz moiety or other A' units can be employed to finely adjust intermolecular interactions. The single-crystal X-ray structure reveals that ortho-benzodipyrrole-embedded A-DNBND-A plays an important role in the formation of a 3D elliptical network packing for efficient charge transport. Solution structures of the PM6:NFAs detected by small- and wide-angle X-ray scattering (SWAXS) indicate that removing the Tz unit in the C-shaped skeleton could reduce the self-packing of CB16, thereby enhancing the complexing and networking with PM6 in the spin-coating solution and the subsequent device film. Elucidating the structure-property-performance relationships of A-DA'D-A-type NFAs in this work paves the way for the future development of structurally simplified A-D-A-type NFAs.

Comparing Person-Fit and Traditional Indices Across Careless Response Patterns in Surveys.

Methods to identify carelessness in survey research can be valuable tools in reducing bias during survey development, validation, and use. Because carelessness may take multiple forms, researchers typically use multiple indices when identifying carelessness. In the current study, we extend the literature on careless response identification by examining the usefulness of three item-response theory-based person-fit indices for both random and overconsistent careless response identification: infit MSE outfit MSE, and the polytomous lz statistic. We compared these statistics with traditional careless response indices using both empirical data and simulated data. The empirical data included 2,049 high school student surveys of teaching effectiveness from the Network for Educator Effectiveness. In the simulated data, we manipulated type of carelessness (random response or overconsistency) and percent of carelessness present (0%, 5%, 10%, 20%). Results suggest that infit and outfit MSE and the lz statistic may provide complementary information to traditional indices such as LongString, Mahalanobis Distance, Validity Items, and Completion Time. Receiver operating characteristic curves suggested that the person-fit indices showed good sensitivity and specificity for classifying both over-consistent and under-consistent careless patterns, thus functioning in a bidirectional manner. Carelessness classifications based on low fit values correlated with carelessness classifications from LongString and completion time, and classifications based on high fit values correlated with classifications from Mahalanobis Distance. We consider implications for research and practice.

Sequence-controlled alternating block polychalcogenophenes: synthesis, structural characterization, molecular properties, and transistors for bromine detection.

Sequence-controlled polychalcogenophenes have attracted much interest in terms of synthesis, structure and function in polymer science. For the first time, we developed a new class of alternating block conjugated copolymers denoted as poly(alt-AB)x-b-(alt-AC)y where both blocks are constituted by an alternating copolymer. 3-Hexylthiophene (S), 3-hexylselenophene (Se) and 3-hexyltellurophene (Te) are used as A, B and C units to assemble three sequence-controlled polychalcogenophenes P(SSe)b(STe), P(SSe)b(SeTe) and P(STe)b(SeTe) which are prepared by adding two different Grignard monomers in sequence to carry out Ni(dppp)Cl2-catalyzed Kumada polymerization. The molecular weight, dispersity, and length of each block (x = y) and main-chain sequence can be synthetically controlled via the catalyst transfer polycondensation mechanism. The polymer structures, i.e. alternating block main chain with high side-chain regioregularity, are unambiguously confirmed by 1H-NMR and 13C-NMR. The optical and electrochemical properties of the polymers can be systematically fine-tuned by the composition and ratio of the chalcogenophenes. From GIWAXS measurements, all the polymers exhibited predominantly edge-on orientations, indicating that the packing behaviors of the alternating block polychalcogenophenes with high regioregularity are inherited from the highly crystalline P3HT. P(SSe)b(STe) exhibited a hole OFET mobility of 1.4 × 10-2 cm2 V-1 s-1, which represents one of the highest values among the tellurophene-containing polychalcogenophenes. The tellurophene units in the polymers can undergo Br2 addition to form the oxidized TeBr2 species which results in dramatically red-shifted absorption due to the alternating arrangement to induce strong charge transfer character. The OFET devices using the tellurophene-containing polychalcogenophenes can be applied for Br2 detection, showing high sensitivity, selectivity and reversibility.

A sandwich ELISA for the detection of mollusks and mollusk products.

Mollusks are a major allergenic food under the food allergen regulations of many countries and must be declared on food products to reduce the risk of allergic reactions. However, a reliable immunoassay for detecting edible mollusks (cephalopods, gastropods, and bivalves) has not been reported. In this study, the developed sandwich enzyme-linked immunosorbent assay (sELISA) detected 32 edible mollusk species in raw and heated without cross-reaction with non-mollusk species. The detection limits of the assay were 0.1 ppm for heated mollusks and 0.1-0.5 ppm for raw mollusks, depending on the mollusk species tested. The inter-assay and intra-assay coefficients of variation (CVs) were ≤14.83 and ≤8.11, respectively. The assay detected steamed, boiled, baked, fried, and autoclaved mollusk samples and all commercial mollusk products tested. In this study, we developed a mollusk-specific sELISA to protect people allergic to mollusks.

Shared alterations in hippocampal structural covariance in subjective cognitive decline and migraine.

Introduction: Subjective cognitive decline (SCD) and migraine are often comorbid. Hippocampal structural abnormalities have been observed in individuals with both SCD and migraine. Given the known structural and functional heterogeneity along the long axis (anterior to posterior) of the hippocampus, we aimed to identify altered patterns of structural covariance within hippocampal subdivisions associated with SCD and migraine comorbidities. Methods: A seed-based structural covariance network analysis was applied to examine large-scale anatomical network changes of the anterior and posterior hippocampus in individuals with SCD, migraine and healthy controls. Conjunction analyses were used to identify shared network-level alterations in the hippocampal subdivisions in individuals with both SCD and migraine. Results: Altered structural covariance integrity of the anterior and posterior hippocampus was observed in the temporal, frontal, occipital, cingulate, precentral, and postcentral areas in individuals with SCD and migraine compared with healthy controls. Conjunction analysis revealed that, in both SCD and migraine, altered structural covariance integrity was shared between the anterior hippocampus and inferior temporal gyri and between the posterior hippocampus and precentral gyrus. Additionally, the structural covariance integrity of the posterior hippocampus-cerebellum axis was associated with the duration of SCD. Conclusion: This study highlighted the specific role of hippocampal subdivisions and specific structural covariance alterations within these subdivisions in the pathophysiology of SCD and migraine. These network-level changes in structural covariance may serve as potential imaging signatures for individuals who have both SCD and migraine.

s-Indacene Revisited: Modular Synthesis and Modulation of Structures and Molecular Orbitals of Hexaaryl Derivatives.

Though s-indacene is an intriguing antiaromatic hydrocarbon of 12 π-electrons, it has been underrepresented due to the lack of efficient and versatile methods to prepare stable derivatives. Herein we report a concise and modular synthetic method for hexaaryl-s-indacene derivatives bearing electron-donating/-accepting groups at specific positions to furnish C2h-, D2h-, and C2v-symmetric substitution patterns. We also report the effects of substituents on their molecular structures, frontier molecular orbital (MO) levels, and magnetically induced ring current tropicities. Both theoretical calculations and X-ray structure analyses indicate that the derivatives of the C2h-substitution pattern adopt different C2h structures with significant bond length alternation depending on the electronic property of the substituents. Due to the nonuniform distribution of the frontier MOs, their energy levels are selectively modulated by the electron-donating substituents. This leads to the inversion of the HOMO and HOMO-1 sequences with respect to those of the intrinsic s-indacene as theoretically predicted and experimentally proven by the absorption spectra at visible and near-infrared regions. The NICS values and the 1H NMR chemical shifts of the s-indacene derivatives indicate their weak antiaromaticity. The different tropicities are explained by the modulation of the HOMO and HOMO-1 levels. In addition, for the hexaxylyl derivative, weak fluorescence from the S2 excited state was detected due to the large energy gap between the S1 and S2 states. Notably, an organic field-effect transistor (OFET) fabricated using the hexaxylyl derivative exhibited moderate hole carrier mobility, a result which opens the door for optoelectronic applications of s-indacene derivatives.

Effect of species, muscle location, food processing and refrigerated storage on the fish allergens, tropomyosin and parvalbumin.

Fish tropomyosin is a latest identified fish allergen without full understanding of its biochemical characteristics from the perspective of food allergen. Accordingly, the objective of this study was to investigate the effects of species, muscle location, food processing, and refrigerated storage on fish tropomyosin and compare with main fish allergen, parvalbumin. The result of mass spectrometry analysis revealed tropomyosin as the most abundant thermally stable protein in fish muscle. Fish tropomyosin was ubiquitous among all 28 edible fish species tested, abundant in fish skeletal muscle, resistant to common food processing, and resistant to refrigerated storage up to six days. By contrast, parvalbumin content varied between fish species and was not as thermally stable as tropomyosin under autoclaving. This study demonstrates the intrinsic and processing factors affecting fish allergens and provides valuable information for the presence of major fish allergens and practical consideration of fish allergen detection.

In Vitro and In Vivo Nephroprotective Effects of Nelumbo nucifera Seedpod Extract against Cisplatin-Induced Renal Injury.

Cisplatin has been considered a chemotherapeutic drug for treating human tumors, and one of the noteworthy side effects of cisplatin is nephrotoxicity. Amelioration of cisplatin-induced nephrotoxicity is necessary. Lotus seedpod extract (LSE) mainly composed of quercetin-3-glucuronide has been revealed for antioxidant and anti-tumor effects. However, the effects of LSE on cisplatin-induced nephrotoxicity are still unknown. This study aims to explore the in vitro and in vivo protective effect and possible mechanism of LSE on cisplatin-induced nephrotoxicity. Results showed that co-treatment of LSE with cisplatin raised the viability of rat renal tubular epithelial NRK-52E cells and decreased oxidative stress and cell apoptosis when compared to the cells treated with cisplatin alone. The molecular mechanisms analyzed found that LSE could reduce the expressions of apoptotic factors, including Bax, Bad, t-Bid, and caspases. In the in vivo study, LSE improved the cisplatin-induced levels of serum markers of kidney function, glomerular atrophy, and the degree of apoptosis in the kidneys. This is the first study to display that LSE prevents cisplatin-induced nephrotoxicity by reducing oxidative stress and apoptosis. Thus, LSE could be a novel and natural chemoprotective agent for cisplatin chemotherapy in the future.

Pathophysiology of Chronic Migraine: Insights from Recent Neuroimaging Research.

PURPOSE OF REVIEW: Chronic migraine (CM) is a highly disabling primary headache disorder with a substantial impact on patients' quality of life. Episodic migraine (EM) and CM are dynamic states; CM usually evolves from EM alongside increased headache frequency, comorbidities, and medication overuse, supporting the notion that migraine is a spectrum disorder. This narrative review aims to summarize neuroimaging studies to better understand the pathophysiology of CM. RECENT FINDINGS: Positron emission tomography studies have revealed abnormal energy metabolism and metabolic changes in the dorsal rostral pons in individuals with CM, suggesting that this structure has a key role in the pathophysiology of migraine generation and chronification. Magnetic resonance spectroscopy studies have suggested that thalamocortical pathway dysfunction may contribute to migraine chronification, while functional magnetic resonance imaging studies have highlighted that hypothalamic activity may be involved. Recent evidence highlights functional and structural alterations in cortical and subcortical pain-related brain regions in patients with CM. Whether these functional and structural abnormalities of the brain cause migraine chronification or are a consequence of repeated attacks is still debated. In the future, imaging patterns that predict the transformation from EM to CM should be identified.

Increased risk of sleep-related movement disorder in patients with Helicobacter pylori infection: A nationwide population-based study.

Background and purpose: Evidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population. Methods: The study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment. Results: Patients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26-3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90-5.30, p < 0.001), followed by patients aged 45-64 years (HR = 1.69, 95% CI = 1.26-2.90, p <0.01) and <45 years (HR = 1.49, 95% CI = 1.12-2.49, p < 0.01). Patients were most likely to develop SRMD 5 years or more after diagnosis of HPI (HR = 3.33, 95% CI = 1.97-5.89, p < 0.001). The increased risk of SRMD in male patients with HPI (HR = 2.73, 95% CI = 1.53-4.79, p < 0.001) was greater than in female patients (HR = 1.14, 95% CI = 1.04-1.65, p < 0.05). Conclusion: Patients with HPI were associated with an increased risk for SRMD, with a higher risk in men, aged ≥65 years, and diagnosed for more than 5 years.

Genetic Variants Associated With Subjective Cognitive Decline in Patients With Migraine.

The genetic association between subjective cognitive decline (SCD) and migraine comorbidity remains unclear. Furthermore, single nucleotide polymorphisms (SNP) associated with SCD have not been identified previously. Migraineurs were genotyped using an Affymetrix array. The correlation between different SNP variants in migraineurs with or without SCD and non-migraine controls was investigated. Migraineurs with or without SCD were further divided for the analysis of relevant SNP variants linked to migraine with aura (MA), migraine without aura (MoA), episodic migraine (EM), and chronic migraine (CM). Significant connectivity between SNPs and clinical indices in migraineurs and non-migraine controls with SCD were assessed using multivariate regression analysis. The rs144191744 SNP was found in migraineurs (p = 3.19E-08), EM (p = 1.34E-07), and MoA(p = 7.69E-07) with and without SCD. The T allele frequency for rs144191744 in TGFBR3 was 0.0054 and 0.0445 in migraineurs with and without SCD (odds ratio, 0.12), respectively. rs2352564, rs6089473 in CDH4, rs112400385 in ST18, rs4488224 and rs17111203 in ARHGAP29 SNPs were found, respectively, in non-migraineurs (p = 4.85E-06, p = 8.28E-06), MoA (p = 3.13E-07), and CM subgroups (p = 1.05E-07, 6.24E-07) with and without SCD. Rs144191744 closely relates to SCD with the all-migraine group and the EM and MoA subgroups. In conclusion, rs144191744 in TGFBR3 was significantly associated with SCD in migraineurs, especially in the EM, MoA, and female patient subgroups. Furthermore, three SNPs (rs112400385, rs4488224, and rs17111203) were associated with SCD in migraineurs but not in non-migraine controls.

A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

Alzheimer's disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis; however, the potential of trace metal biomarkers in predicting cognitive decline has not been evaluated. This study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. Participants (9 controls, 23 aMCI due to AD, and 8 AD dementia) underwent comprehensive cognitive tests, including the Mini-Mental State Examination (MMSE) and trace metal analysis. The correlations between the plasma trace element levels and annual MMSE changes during follow-up were analyzed. We found that an increase in disease severity was linked to lower plasma levels of boron (B), bismuth (Bi), thorium (Th), and uranium (U) (adjusted p < 0.05). Higher baseline calcium levels (r = 0.50, p = 0.026) were associated with less annual cognitive decline; those of B (r = −0.70, p = 0.001), zirconium (r = −0.58, p = 0.007), and Th (r = −0.52, p = 0.020) with rapid annual cognitive decline in the aMCI group; and those of manganese (r = −0.91, p = 0.035) with rapid annual cognitive decline in the AD group. Overall, our exploratory study suggests that plasma metal levels have great potential as in vivo biomarkers for aMCI and AD. Larger sample studies are necessary to confirm these results.

Identification of Novel Genetic Variants Associated with Insomnia and Migraine Comorbidity.

Purpose: Although insomnia and migraine are often comorbid, the genetic association between insomnia and migraine remains unclear. This study aimed to identify susceptibility loci associated with insomnia and migraine comorbidity. Patients and Methods: We performed a genome-wide association study (GWAS) involving 1063 clinical outpatients at a tertiary hospital in Taiwan. Migraineurs with and without insomnia were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0. We performed association analyses for the entire cohort and stratified patients into the following subgroups: episodic migraine (EM), chronic migraine (CM), migraine with aura (MA), and migraine without aura (MoA). Potential correlations between SNPs and clinical indices in migraine patients with insomnia were examined using multivariate regression analysis. Results: The SNP rs1178326 in the gene HDAC9 was significantly associated with insomnia. In the EM, CM, MA, and MoA subgroups, we identified 30 additional susceptibility loci. Multivariate regression analysis showed that SNP rs1178326 also correlated with higher migraine frequency and the Migraine Disability Assessment (MIDAS) questionnaire score. Finally, two SNPs that had been previously reported in a major insomnia GWAS were also significant in our migraineurs, showing a concordant effect. Conclusion: In this GWAS, we identified several novel loci associated with insomnia in migraineurs in a Han Chinese population in Taiwan. These results provide insights into the possible genetic basis of insomnia and migraine comorbidity.

Sex Differences in Chronic Migraine: Focusing on Clinical Features, Pathophysiology, and Treatments.

PURPOSE OF REVIEW: This review provides an update on sex differences in chronic migraine (CM), with a focus on clinical characteristics, pathophysiology, and treatments. RECENT FINDINGS: Approximately 6.8-7.8% of all migraineurs have CM, with an estimated prevalence of 1.4-2.2% in the general population. The economic burden caused by CM, including medical costs and lost working ability, is threefold higher than that caused by episodic migraine (EM). Notably, the prevalence of migraine is affected by age and sex. Female migraineurs with CM experience higher levels of headache-related disability, including longer headache duration, higher frequency of attacks, and more severely impacted efficiency at work. Sex hormones, including estrogen, testosterone, and progesterone, contribute to the sexually dimorphic characteristics and prevalence of migraine in men and women. Recent neuroimaging studies have indicated that migraine may have a greater impact and cause greater dysfunction in the organization of resting-state functional networks in women. Accumulating evidence suggests that topiramate, Onabotulinumtoxin A and calcitonin gene-related peptide (CGRP) monoclonal antibodies are effective as the preventative treatments for CM. Recent evidence highlights a divergence in the characteristics of CM between male and female populations. The data comparing the treatment response for CM regarding sex are lacking.

Music Intervention for Pain Control in the Pediatric Population: A Systematic Review and Meta-Analysis.

Music intervention (MI) has been applied as an effective adjunctive treatment for pain control in various clinical settings. However, no meta-analysis has yet been published on the analgesic effects of MI in infants and children. We performed a systematic review of PubMed, EMBASE, Web of Science, and Cochrane Library databases to identify randomized controlled trials (RCTs) with the keywords "pain" AND "music therapy" from inception to January 2022. Primary outcomes were pain intensity and vital signs. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed using a random effect model. Subgroup analyses with age groups, types of pain, and music styles were conducted. A total of 38 RCTs involving 5601 participants met the selection criteria. MI significantly decreased the pain levels (SMD = -0.57, p < 0.001), both in the newborn group (p = 0.007) and in the infant/children group (p < 0.001). MI significantly reduced heart rate (SMD = -0.50, p < 0.001) and respiratory rate (SMD = -0.60, p = 0.002) and increased peripheral capillary oxygen saturation (SMD = 0.44, p < 0.001). In subgroup analyses of types of pain, MI had significant effects on prick pain (p = 0.003), chronic and procedural pain (p < 0.001), and postoperative pain (p = 0.018). As for music styles, significant analgesic effects were observed for classical music (p < 0.001), kids' music (p < 0.001), and pop music (p = 0.001), but not for world music (p = 0.196), special composition (p = 0.092), and multiple music combinations (p = 0.420). In conclusion, our analysis provides supportive evidence about the efficacy of MI, especially classical, kids', and pop music, in controlling prick, procedural, and postoperative pain in the pediatric population.