Impairments to the multisensory integration brain regions during migraine chronification: correlation with the vestibular dysfunction.

Objectives: Migraine is often combined with vestibular dysfunction, particularly in patients with chronic migraine (CM). However, the pathogenesis of migraine chronification leading to vestibular dysfunction is not fully understood. The current study investigated whether structural or functional impairments to the brain during migraine chronification could be associated with vestibular dysfunction development. Methods: The eligible participants underwent clinical assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) determined structural impairment by evaluating alterations in gray matter volume (GMV). Functional impairment was assessed by the mean amplitude of low-frequency fluctuation (mALFF). Furthermore, the resting-state functional connectivity (rsFC) of regions possessing impairment was examined with a seed-based approach. We also analyzed the correlations between altered neuroimaging features with clinical variables and performed multiple linear regression. Results: Eighteen CM patients, 18 episodic migraine (EM) patients, and 18 healthy controls (HCs) were included in this study. A one-way ANOVA indicated the group differences in mALFF. These were located within right supramarginal gyrus (SMG), left angular gyrus (AG), middle frontal gyrus (MFG), left middle occipital gyrus (MOG), right rolandic operculum (Rol) and left superior parietal gyrus (SPG). During rsFC analysis, the CM group had more enhanced rsFC of left SPG with left MOG than the EM and HC groups. The EM group revealed enhanced rsFC of left SPG with left AG than the CM and HC groups. In multiple linear regression, after controlling for age, body mass index (BMI) and disease duration, the rsFC of left SPG with left MOG (ß = 48.896, p = 0.021) was found to predict the total Dizziness Handicap Inventory (DHI) score with an explained variance of 25.1%. Moreover, the rsFC of left SPG with left MOG (ß = 1.253, p = 0.003) and right SMG (ß = -1.571, p = 0.049) were significant predictors of migraine frequency, accounting for a total explained variance of 73.8%. Conclusion: The functional impairments due to migraine chronification are primarily concentrated in the multisensory integration-related brain regions. Additionally, the rsFC of SPG with MOG can predict the frequency of migraine and the degree of vestibular dysfunction. Therefore, these neuroimaging features could be potential mechanisms and therapeutic targets for developing vestibular dysfunction in migraine.

Therapeutic efficacy and safety of Yinzhihuang granules with phototherapy in neonatal pathologic jaundice: An updated systematic review and meta-analysis.

BACKGROUND: Yinzhihuang granule, consisting of extracts of Artemisia capillaris Thunb., Gardenia jasminoides Ellis, Lonicera japonica Thunb., and Scutellaria baicalensis Georgi is a well-known traditional Chinese patent medicine for patients with liver injury in China. However, the effects and safety of its use for pathologic jaundice in newborns require further systematic evaluation. PURPOSE: To systematically evaluate the efficacy and safety of Yinzhihuang granules for the treatment of neonatal pathologic jaundice and to provide clinical evidence. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and VIP Database) and English databases (PubMed, EmBase, and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on Yinzhihuang granules for neonatal pathologic jaundice from the establishment of all databases to November 18, 2021. A meta-analysis was performed for selected data using STATA software. TSA software was used for trial sequential analyses of the total effective rate and adverse reactions. RESULTS: A total of 19 trials and 2,221 newborns with pathologic jaundice were included in this study. Outcome measures of clinical efficacy in the experimental group were higher than in controls, including total bilirubin (WMD = -30.34, 95% CI = -35.44 to -25.23, p < 0.001), direct bilirubin (WMD = -15.03, 95% CI = -23.54 to -6.52, p < 0.001), indirect bilirubin (WMD = -11.22, 95% CI = -17.50 to -4.95, p < 0.001), recovery time (WMD = -2.96, 95% CI = -3.92 to -2.00, p < 0.001), hospitalization time (WMD = -3.83, 95% CI = -4.89 to -2.76, p < 0.001), and liver function indices. There were statistically significant differences between the two groups. Likewise, the incidence of adverse reactions, including diarrhea, erythra, and fever decreased remarkably in the trial group (RR = 0.44, 95% CI =  0.33 to 0.59, p < 0.001). Publication bias did not exist. We verified the efficacy and safety of Yinzhihuang granules with phototherapy for pathologic jaundice in newborns according using TSA analysis. CONCLUSION: Yinzhihuang granules with phototherapy for neonatal pathologic jaundice are more effective than phototherapy alone. The incidence of ADRs does not increase with the application of Yinzhihuang granules. Due to the heterogeneity across the included studies, additional multicenter clinical trials with follow-ups are needed to confirm our findings.

Thermodynamics-Based Model Construction for the Accurate Prediction of Molecular Properties From Partition Coefficients.

Developing models for predicting molecular properties of organic compounds is imperative for drug development and environmental safety; however, development of such models that have high predictive power and are independent of the compounds used is challenging. To overcome the challenges, we used a thermodynamics-based theoretical derivation to construct models for accurately predicting molecular properties. The free energy change that determines a property equals the sum of the free energy changes (ΔGFs) caused by the factors affecting the property. By developing or selecting molecular descriptors that are directly proportional to ΔGFs, we built a general linear free energy relationship (LFER) for predicting the property with the molecular descriptors as predictive variables. The LFER can be used to construct models for predicting various specific properties from partition coefficients. Validations show that the models constructed according to the LFER have high predictive power and their performance is independent of the compounds used, including the models for the properties having little correlation with partition coefficients. The findings in this study are highly useful for applications in drug development and environmental safety.

The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer's Disease.

Cerebrospinal fluid (CSF) measurements of neurogranin (Ng) have emerged as a promising biomarker for cognitive decline in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The apolipoprotein E ε4 (APOE ε4) allele is by far the most consistent genetic risk factor for AD. However, it is not known whether the pathophysiological roles of Ng in MCI or AD are related to APOEε4. We stratified 250 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN) ε4 negative (CN ε4-), CN ε4 positive (CN ε4+), MCI ε4 negative (MCI ε4-), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4-), and AD ε4 positive (AD ε4+). CSF Ng levels were significantly increased in APOE ε4 carriers compared to APOE ε4 non-carriers with MCI. In addition, CSF Ng identified MCI ε4+ versus CN ε4-, but not MCI ε4- versus CN ε4-. Similarly, CSF Ng negatively correlated with Mini-Mental State Examination (MMSE) scores at baseline in the MCI ε4+ group. Our findings support the use of CSF Ng as a biomarker of synaptic pathology for AD. We propose that the roles of CSF Ng in the pathophysiology of MCI may be related to APOE ε4.

A general linear free energy relationship for predicting partition coefficients of neutral organic compounds.

Predicting the effects of organic compounds on environments and biological systems is an important objective for environmental chemistry and human health. The logarithm (to base 10) of the n-octanoll-water partition coefficient has been widely used to predict the mentioned properties. However, the suitability of this parameter for the purpose has been questioned, since the environments relating to the properties may be quite different from that of bulk n-octanol. In this study, we used a theoretical derivation approach to develop a model for predicting the partition coefficients of solutes between water and an organic solvent that may be similar to n-octanol or quite different from it. Our model relies on solute descriptors that can be calculated based on solute structures. It was used to predict the n-octanoll-water, hexadecanel-water and chloroforml-water partition coefficients of solutes. The calculated values of the examined parameters agreed well with their experimental counterparts. The model can find application in the accurate prediction of the effects of organic compounds on environments and the physicochemical properties of organic compounds by a full in-silico approach and can provide useful guidance for improving some properties of organic compounds.

Clinical features and outcomes of benign recurrent vertigo: A longitudinal study.

OBJECTIVE: To study the demographics, vertigo profiles, and outcomes of adult patients with benign recurrent vertigo (BRV). PATIENTS AND METHODS: This prospective study included patients with BRV who were admitted to a tertiary neurology clinic between June 2013 and June 2017. All patients underwent detailed clinical interviews and related examinations. A follow-up was then conducted through an outpatient or telephone interview. RESULTS: A total of 66 patients (48 females) were enrolled, and the mean age at the onset of vertigo was 35.2 years. Spontaneous vertigo was the most common type (77.8%), followed by positional vertigo (16.7%). The duration of vertigo attacks varied from minutes to 72 hours. A family history of migraine and/or recurrent vertigo was reported in 51.5% of patients. The overall response rate was 80.3%（53/66）after a median follow-up time of 32.5 months (range: 18-60 months). Forty (75.5%, of 53) patients still reported having vertigo attacks at the follow-up. The frequency of vertigo attacks was reduced in 32 (60.4%) patients and was unchanged in 8 (15.1%). Four (7.5%) cases developed into vestibular migraine, but none developed into Meniere's disease. CONCLUSION: The outcomes of patients with BRV were benign, and the frequency of vertigo is significantly reduced. Few cases developed into vestibular migraine.

Cognitive features of white matter lesions accompanied by different risk factors of cerebrovascular diseases.

BACKGROUND: The relationship between different risk factors and the cognitive impairment of white matter lesions (WML) remains poorly understood. OBJECTIVES: To investigate the features of cognitive impairment of patients diagnosed with WML accompanied by different risk factors of cerebrovascular diseases. MATERIAL AND METHODS: A total of 157 cases of WML patients were divided into no risk factor group (n = 26), hypertension group (n = 35), diabetes mellitus group (n = 27), dyslipidemia group (n = 30), and mixed factors group (n = 39). RESULTS: The severity of WML (Fazekas score) in the hypertension and mixed factors groups was higher than in the non-risk factors group. The Montreal Cognitive Assessment (MoCA) scores in the hypertension and mixed factors groups were lower than in the non-risk factors group. The scores of MoCA, immediate memory and delayed recall in the hypertension and mixed factors groups with Fazekas score ≥3 were lower than in the peer group with Fazekas score <3. The scores of MoCA and immediate memory in the hypertension and mixed factors groups with Fazekas score ≥3 were lower than in the non-risk factors group with Fazekas score ≥3. CONCLUSIONS: Hypertension aggravates the severity of WML and cognitive impairment. The severity of WML is positively correlated with the severity of cognitive impairment accompanied by these risk factors.

Diagnosis of Vertigo and Dizziness Syndromes in a Neurological Outpatient Clinic.

BACKGROUND: Dizziness and vertigo are frequent complaints of outpatients in the neurological department. Our objective was to explore the epidemiological category and clinical features of patients with dizziness or vertigo in the neurological outpatient department of a tertiary hospital. METHODS: We consecutively recruited all patients with dizziness and/or vertigo visiting the neurological outpatient clinic of the First Affiliated Hospital of Chongqing Medical University from January 2016 to June 2017. All patients were interviewed by 4 neurologists and they completed self-administered questionnaires. General physical and standardized neuro-otology bedside examinations were performed in all participants. Instrumental examinations and other related examinations were prescribed as needed. RESULTS: A total of 392 patients, 272 female and 120 male, were enrolled and the ratio of males to females was 1: 2.27. The mean age was 52.39 ± 13.87 years (range 11-90). Elderly patients (≥60 years) accounted for about one-third of the patients. Peripheral vestibular disorders accounted for 54.6% of patients, central vestibular disorders (including vestibular migraine [VM]) accounted for 22.4% of patients, psychogenic vertigo in 64 (16.3%), other reasons in 9 (2.3%) and unknown in 17 (4.3%). Benign paroxysmal positional vertigo (BPPV; 30.8%), psychiatric dizziness (20.5%), and VM (14.4%) were the 3 major vestibular diseases in patients under 60 years of age; however, BPPV (27.9%), central vertigo (21.7%), and Meniere's disease (11.7%) were more common in patients over 60 years of age. CONCLUSIONS: This study provided a classification and clinical features of vestibular disorders in a neurological outpatient department of a tertiary hospital in China. The spectrum of vertigo or dizziness is different between different age groups and clinicians should pay attention to this difference in clinical reasoning.

Patients with neutral lipid storage disease with myopathy (NLSDM) in Southwestern China.

OBJECTIVES: Neutral lipid storage disease with myopathy (NLSDM) is a rare metabolic myopathy occurring owing to mutations in the patatin like phospholipase domain containing 2 (PNPLA2) gene. Till date, less than 50 patients with PNPLA2 mutations have been reported. In this study, we describe the clinical, pathological, and genetic findings, and muscle magnetic resonance imaging (MRI) changes in four Chinese patients with NLSDM. PATIENTS AND METHODS: Peripheral blood smears were stained using Wright's stain. Muscle biopsies, muscle MRI, and sequence analysis of PNPLA2 gene were performed. RESULTS: All patients exhibited slowly progressive myopathy during adulthood. Cardiomyopathy, sensorineural hearing loss, hepatic adipose infiltration, and hypertriglyceridemia were observed in some patients. Jordan's anomaly was detected in the blood smears of all patients. Muscle biopsies revealed the presence of massive lipid droplets and rimmed vacuoles in two patients. MR images of the lower lumbar, pelvis, and lower extremities showed the involvement of posterior compartment muscles. The anterior compartment muscles were found to be less affected. Gene analysis for PNPLA2 revealed an identical homozygous mutation c.757 + 1G > T in all patients. CONCLUSION: Patients with NLSDM display clinical heterogeneities despite sharing the same mutation (c.757 + 1G > T) of the PNPLA2 gene, may suggest a founder effect in the region.

Water-induced formation of a chiral phenylalanine derivative supramolecule.

In biological systems, chiral self-assemblies are formed in water. To understand the role of water in the formation of supramolecular chirality, an amino acid derivative, N,N-diphenylalanine-3,4,9,10-perylenetetracarboxylicdiimide (PBI-Phe), was synthesized from perylene-3,4,9,10-tetracarboxylic dianhydride and phenylalanine. PBI-Phe self-assembled into a spherical structure in pure DMSO, but into a helical fiber structure in a solution of DMSO mixed with water. Furthermore, increasing the relative amount of water included in the solution led to an increase the supramolecular chirality.

Spectroscopic studies on the interaction of chromium (VI) and chromium (III) with keyhole limpet hemocyanin.

The interactions of keyhole limpet hemocyanin (KLH) with chromium nitrate, potassium dichromate, and chromate were investigated using fluorescence, UV-vis absorption and circular dichroism (CD) spectroscopy under simulated physiological conditions. The experimental results showed that the different forms of chromium could quench the intrinsic fluorescence of KLH following a static quenching mechanism rather than by dynamic collision, which indicated that a Cr-KLH complex was formed. The Stern-Volmer quenching constants for the interaction indicated that the binding reaction of KLH with Cr(VI) was stronger the binding of KLH with Cr(III). The thermodynamic values for binding of Cr(VI) to KLH are ΔH > 0 and ΔS > 0. By contrast, the values for the interaction of Cr(III) with KLH are ΔH < 0 and ΔS < 0. The results of synchronous fluorescence, UV-vis absorption and CD spectroscopy showed that the α-helical secondary structure and conformation of KLH were altered by different forms of chromium. Copyright © 2016 John Wiley & Sons, Ltd.

Formation and Controlled Drug Release Using a Three-Component Supramolecular Hydrogel for Anti-Schistosoma Japonicum Cercariae.

A novel three-component supramolecular hydrogel based on riboflavin, melamine and amino acid derivatives were constructed for controlled release of pesticides, Niclosamide derivatives. The formation of hydrogel may be attributed to self-assemble via hydrogen bonding and π-π interaction, which have been researched via scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) spectra. The rheological experiments showed that the hydrogel materials and drug-loaded hydrogel all demonstrated good mechanical strength and high stability. Further experimental results indicated that the drug-loaded hydrogels show large drug loadings, long-term release time and relatively higher efficiency to anti-cercariae in the water environment.

On-Surface Observation of the Formation of Organometallic Complex in a Supramolecular Network.

The on-surface formation of organometallic monomers or oligomers, especially in supramolecular network, attracts an extensive interest for chemists and material scientist. In this work, we have investigated metal coordination between zinc (II) phthalocyanine (ZnPc) and 1, 3-di (4-pyridyl) propane (dipy-pra) in the 2, 6, 11-tricarboxydecyloxy-3, 7, 10-triundecyloxy triphenylene (asym-TTT) supramolecular template by means of scanning tunneling microscopy (STM) on highly oriented pyrolytic graphite (HOPG) substrate under ambient conditions. The experimental results demonstrate that every two ZnPc molecules in one nano-reactor connect with each other through one dipy-pra molecule by metal-coordination interaction. In this coordinating process, the template of asym-TTT supramolecular networks plays a significant role.

Hierarchical self-assembly of amino acid derivatives into stimuli-responsive luminescent gels.

In this study, unique luminescent gels have been obtained from two components between amino acid functionalized perylene derivatives and 4,4'-bipyridyl units via hierarchical self-assembly. The luminescent gels have been investigated by means of ultraviolet spectra (UV), fluorescence spectra, Scanning Electron Microscopy (SEM) and Laser Scanning Confocal Microscopy (LSCM), which illustrate the strong fluorescence intensity of the gels. In order to further reveal the self-assembly driving forces, the two-dimensional (2D) self-assembly behaviours have been studied by scanning tunneling microscopy (STM) on a highly oriented pyrolytic graphite (HOPG) substrate at the solid-liquid interface, which indicates that the driving forces are attributed to the intermolecular hydrogen bonding and π-π stacking interactions. According to the interaction mode, these organogelators are found to rapidly transform from gels to solutions by adding triethylamine.

[Determination of multiple pesticide residues in honey using gas chromatography-mass spectrometry].

An analytical method was developed for the simultaneous determination of 23 pesticide residues in various commercial honeys. Meanwhile, the characteristic ions and fragmentation mechanism of three pesticides in the process of electron ionization mass spectrometry (EI/MS) were evaluated. After the optimization of different parameters such as the extraction solvent, pesticides were extracted from honey with ethyl acetate in an ultrasonic bath, cleaned up on a Florisil column by an elution of mixture of hexane and ethyl acetate (7:3, v/v), and analyzed by gas chromatography-electron ionization mass spectrometry (GC-EI/MS) in the selected ion monitoring mode (SIM) with PCB103 as internal standard. Recovery studies were performed at 50, 100 and 200 microg/kg fortification levels for each pesticide, and the recoveries ranged from 82% to 120% with relative st0ndard deviations between 1.8% and 11.0% for different pesticides. The limit of detection was less than 10.0 microg/kg for all the pesticides. The developed method was linear in the range of 10-500 microg/kg, with correlation coefficients larger than 0.995. Finally, the developed analytical method has been successfully applied to the determination of pesticide residues in several honey samples.

[Multiresidue determination of organophosphorus pesticide residues in vegetables and fruit by gas chromatography-negative ion chemical ionization-mass spectrometry].

An analytical method of gas chromatography coupled with negative ion chemical ionization-mass spectrometry for simultaneous determination of nine organophosphorus pesticide residues in vegetables and fruit has been developed, and the negative ions structure and partition mechanism of the nine organophosphorus pesticides were interpreted. Meanwhile, the matrix effect for sample analysis was discussed, and matrix-matched calibration for quantification was introduced to reduce the matrix effect in this method. Pesticides were extracted from sample with ethyl acetate in an ultrasonic bath, then determined by gas chromatography-mass spectrometry operated in negative chemical ionization mode and quantified in selective ion monitoring mode, and ethion was used as an internal standard. The detection limits of the method were 0.12-1.0 microg/kg for the nine organophosphorus pesticides, and the relative coefficients were higher than 0.9993. A blank sample (tomato) was spiked at 100, 400, 800 microg/kg for each pesticide, and the recoveries were determined to be from 78% to 126% with relative standard deviations from 0.58% to 14.7% for the pesticides.