Effects of accelerated intermittent theta-burst stimulation in modulating brain of Alzheimer's disease.

Intermittent theta-burst stimulation (iTBS) is emerging as a noninvasive therapeutic strategy for Alzheimer's disease (AD). Recent advances highlighted a new accelerated iTBS (aiTBS) protocol, consisting of multiple sessions per day and higher overall pulse doses, in brain modulation. To examine the possibility of applying the aiTBS in treating AD patients, we enrolled 45 patients in AD at early clinical stages, and they were randomly assigned to either receive real or sham aiTBS. Neuropsychological scores were evaluated before and after treatment. Moreover, we detected cortical excitability and oscillatory activity changes in AD, by the single-pulse TMS in combination with EEG (TMS-EEG). Real stimulation showed markedly better performances in the group average of Auditory Verbal Learning Test scores compared to baseline. TMS-EEG revealed that aiTBS has reinforced this memory-related cortical mechanism by increasing cortical excitability and beta oscillatory activity underlying TMS target. We also found an enhancement of local natural frequency after aiTBS treatment. The novel findings implicated that high-dose aiTBS targeting left DLPFC is rapid-acting, safe, and tolerable in AD patients. Furthermore, TMS-related increase of specific neural oscillation elucidates the mechanisms of the AD cognitive impairment ameliorated by aiTBS.

Efficacy of transcranial photobiomodulation in the treatment for major depressive disorder: A TMS-EEG and pilot study.

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.

Targeted de novo phasing and long-range assembly by template mutagenesis.

Short-read sequencers provide highly accurate reads at very low cost. Unfortunately, short reads are often inadequate for important applications such as assembly in complex regions or phasing across distant heterozygous sites. In this study, we describe novel bench protocols and algorithms to obtain haplotype-phased sequence assemblies with ultra-low error for regions 10 kb and longer using short reads only. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ∼50% of cytosines to uracils. Sequencing libraries are made from both mutated and unmutated templates. Using de Bruijn graphs and paired-end read information, we assemble each mutated template and use the unmutated library to correct the mutated bases. Templates are partitioned into two or more haplotypes, and the final haplotypes are assembled and corrected for residual template mutations and PCR errors. With sufficient template coverage, the final assemblies have per-base error rates below 10-9. We demonstrate this method on a four-member nuclear family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.

Copolymerization of single-cell nucleic acids into balls of acrylamide gel.

We show the use of 5'-Acrydite oligonucleotides to copolymerize single-cell DNA or RNA into balls of acrylamide gel (BAGs). Combining this step with split-and-pool techniques for creating barcodes yields a method with advantages in cost and scalability, depth of coverage, ease of operation, minimal cross-contamination, and efficient use of samples. We perform DNA copy number profiling on mixtures of cell lines, nuclei from frozen prostate tumors, and biopsy washes. As applied to RNA, the method has high capture efficiency of transcripts and sufficient consistency to clearly distinguish the expression patterns of cell lines and individual nuclei from neurons dissected from the mouse brain. By using varietal tags (UMIs) to achieve sequence error correction, we show extremely low levels of cross-contamination by tracking source-specific SNVs. The method is readily modifiable, and we will discuss its adaptability and diverse applications.

Magnetic Field-Enhanced Electrocatalytic Oxygen Evolution on a Mixed-Valent Cobalt-Modulated LaCoO3 Catalyst.

Extensive efforts to enhance the oxygen evolution reaction (OER) catalytic performance of transition metal oxides mainly concentrate on the extrinsic morphology tailoring, lattice doping, and electrode interface optimizing. Nevertheless, little room is left for performance improvement using these methods and an obvious gap still exists compared to the precious metal catalysts. In this work, a novel "mixed-valent cobalt modulation" strategy is presented to enhance the electrocatalytic OER of perovskite LaCoO3 (LCO) oxide. The valence transition of cobalt is realized by ethylenediamine post reduction procedure at room temperature, which further induces the variation of magnetic properties for LCO catalyst. The optimized LCO catalyst with Co2+ /Co3+ of 1.98 % exhibits the best OER activity, and the overpotential at 10 mA cm-2 current density is decreased by 170 mV compared pristine LCO. Impressively, the ferromagnetic LCO catalyst can perform magnetic OER enhancement. By application of an external magnetic field, the overpotential of LCO at 10 mA cm-2 can be further decreased by 20 mV compared to that of under zero magnetic field, which arises from the enhanced energy states of electrons and accelerated electron transfer process driven by magnetic field. Our findings may provide a promising strategy to break the bottleneck for further enhancement of OER performance.

High sensitivity closed-loop Rb optically pumped magnetometer for measuring nuclear magnetization.

Rb optically pumped magnetometer (OPM) based on electron paramagnetic resonance (EPR) show advantages to measure the nuclear magnetization and have succeeded in fundamental physics and rotation sensing, etc. The magnetometry sensitivity is a key performance of these Rb OPMs which should be improved. In this study, a high sensitivity Rb OPM is demonstrated theoretically and experimentally. To improve the sensitivity, acousto-optic modulation based on balanced detection is applied to suppress the probe noises. Compared with the conventional optical rotation detection for this OPM configuration, the probe noise shows a significant suppression especially in low frequencies. Eventually, a simultaneous dual-axis transverse measurement with 30 fT/Hz1/2 sensitivity is achieved in a 200 Hz bandwidth and a 250nT linear working range. In addition, we utilize a closed-loop feedback to improve the stability and enlarge the transverse measurement range to 10µT order of magnitude while maintain the open-loop performances. A quasi-static magnetic field measurement can also be achieved in the longitudinal direction in the closed-loop mode. This OPM can serve for the nuclear magnetization measurement with a high sensitivity especially in environments with a large magnitude of the external magnetic field.

[Association of vitamin D gene polymorphisms and serum 25-hydroxyvitamin D in Chinese women of childbearing age].

OBJECTIVE: To analyze the relationship between vitamin D(VitD)-related single nucleotide polymorphism(SNP) and 25-hydroxyvitamin D(25(OH) D) levels and VitD nutritional status. METHODS: A total of 1507 women of childbearing age aged 18-45 were selected from the sample bank of "2015 Chinese adult chronic disease and nutrition monitoring". Basic information(including region, season, age, height, weight, etc. ) of the subjects was collected. The SNPs related to VitD metabolism were screened, and the improved multiple ligase detection reaction was used for SNP testing. Liquid chromatography tandem mass spectrometry was used to determine the serum 25(OH)D concentration. The effects of genotypes on 25(OH)D level and VitD deficiency were analyzed by generalized linear model and binary logistic regression model, respectively. RESULTS: After adjusting for latitude, region, region type, season and age, CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 were associated with serum 25(OH)D levels in women of childbearing age. The risk of VitD deficiency in individuals carrying GG genotype at rs2282679 was significantly higher than that in individuals carrying TT genotype(OR=2.466, 95%CI 1.690-3.598, P<0.001), and the risk of VitD deficiency in individuals carrying A allele at rs2228570 was lower than that in individuals carrying G allele(OR_(AA)=0.625, 95%CI 0.446-0.876, P_(AA)=0.006;OR_(GA)=0.661, 95%CI 0.502-0.869, P_(GA)=0.003). CONCLUSION: The genotype distribution of CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 may be related to serum 25(OH)D level or VitD nutritional status of Chinese women of childbearing age.

[Exploring study on the cutoff of vitamin D deficiency in Chinese adults].

OBJECTIVE: To study the relationship between 25-hydroxyvitamin D [25(OH)D] concentration and intact parathyroid hormone(iPTH) concentration in the Chinese non-clinical population aged 18-44 y, and to explore the threshold value of determining the appropriate nutritional status of vitamin D. METHODS: A total of 650 plasma samples of adults aged 18-44 years old were selected from the established biological samples' bank of Chinese Chronic Diseases and Nutrition Survey(CCDNS, 2015-2018). Basic information(including age, gender, region type, season, etc. ) was collected by questionnaires, and the waist circumference, height and weight of the subjects were determined unified. North and South area was divided by Qinling Mountains and Huaihe River. The serum 25(OH)D concentration was determined by high performance liquid chromatography tandem mass spectrometer, and the iPTH was determined by electronic chemiluminescence method. The relationship of 25(OH)D and iPTH were analyzed by partial correlation analysis, and the threshold of 25(OH)D was analyzed by locally weighted scatter plot smoothing method after adjusting the iPTH by age, season of blood draw, BMI, waist, sex and latitude. RESULTS: A total of 623 serum samples(293 male, 330 female) of 25(OH)D concentration and iPTH concentration were analyzed after excluding samples with poor blood sample quality. Significant higher 25(OH)D concentration was found in male than female(P<0. 0001). And the samples from the southern China had higher 25(OH)D concentration than those from the northern China(P<0. 0001). Samples from autumn had higher 25(OH)D concentration than those from spring and winter(P<0. 0001). The 25(OH)D concentration of samples from cities was lower than that of rural areas(P=0. 018). The inversely relationship between 25(OH)D concentration and iPTH concentration was observed when the 25(OH)D was below 17. 6 ng/mL for both sexes. The threshold of 25(OH)D for male was 16. 2 ng/mL and it was 25. 6 ng/mL for female. CONCLUSION: The threshold and the relationship between 25(OH)D and iPTH differs by sex among Chinese adults aged 18-44 y. Further study is needed to evaluate the sex-specific ranges of optimal vitamin D.

[Consistency evaluation of human serum 25-hydroxyvitamin D using liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay].

OBJECTIVE: Comparison of liquid chromatography-tandem mass spectrometry(LC-MS/MS) and enzyme-linked immunosorbent assay(ELISA) for the detection of 25(OH)D concentration in human serum and the diagnosis of vitamin D deficiency. METHODS: In the serum pool of "National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention", 500 serum samples of women aged 18 to 45 years old were randomly selected, and 25(OH)D levels were measured by ELISA and LC-MS/MS for the same serum sample, respectively. The LC-MS/MS column was Waters XBridge BEH C_(18)(2. 1 mm×50 mm, 2. 5 µm). The correlation between the two method was tested by correlation analysis, regression analysis and consistency test. The Endocrine Society and Institute of Medicine recommendations were used to determine the deficiency of vitamin D, and the McNemar test, Kappa coefficient and diagnostic test were used to diagnose the consistency of vitamin D deficiency. RESULTS: The regression equation for the 25(OH)D concentration measured by the two method was y_(LC-MS/MS)=-0. 035+1. 007×x_(ELISA)(r=0. 877), and the average deviation between the two was 4. 48% and the intraclass correlation coefficient was 0. 87. The 25(OH)D concentration was less than 12 and 20 ng/mL as a criterion for vitamin D deficiency, and the Kappa coefficients were greater than 0. 60(0. 64 and 0. 74). CONCLUSION: When serum 25(OH)D level was detected by LC-MS/MS and ELISA, the correspondence of the two method was fine. Taking the "gold standard" LC-MS/MS method as a reference, the ELISA method was used to determine human vitamin D deficiency with good sensitivity and specificity, which can be used for the accurate and rapid detection of large-scale population samples.

[Blood copper, zinc, calcium, magnesium and iron distribution in rural China aged 6-12 in 2002 and 2012].

OBJECTIVE: To investigate the distribution and changes of blood copper, zinc, calcium, magnesium and iron in Chinese rural children aged 6 to 12 years in 2002 and 2012. METHODS: A total of 3420 blood samples were randomly selected from the China Nutrition and Health Survey 2002 and 2012. Metal concentrations in whole blood were determined by inductively coupled mass spectrometry(ICP-MS) after the dilution of 0. 5%(V/V) HNO_3 and 0. 05%(V/V) Triton-X-100. The changes between 2002 and 2012 of blood five elements concentration in children of 6-12 years in rural China were compared. RESULTS: The median of blood levels of copper, zinc, calcium, magnesium and iron in 2002 were 1. 02(95% CI 0. 79-1. 32), 4. 88(95% CI 3. 17-6. 77), 58. 59(95% CI 44. 97-74. 24), 41. 56(95% CI 33. 01-52. 28) and 423. 21(95% CI 338. 83-540. 69) mg/L, respectively. And in 2012, the median values were 1. 00(95% CI 0. 75-1. 31), 5. 12(95% CI 3. 17-7. 37), 63. 36(95% CI 41. 14-79. 16), 41. 78(95% CI 30. 89-52. 53) and 422. 06(95% CI 297. 83-522. 56) mg/L, respectively. There were significant differences in blood copper, zinc, calcium and iron levels in general, gender and age. There were also significant area differences in the distribution of copper, zinc, calcium, magnesium and iron, but the changes were opposite. CONCLUSION: In 2002 and 2012, there were differences in the blood distribution of Cu, Zn, Ca, Mg and Fe of children aged 6-12 in rural China in terms of general, gender, age and area.

Impact of Detergents on Membrane Protein Complex Isolation.

Detergents play an essential role during the isolation of membrane protein complexes. Inappropriate use of detergents may affect the native fold of the membrane proteins, their binding to antibodies, or their interaction with partner proteins. Here we used cadherin-11 (Cad11) as an example to examine the impact of detergents on membrane protein complex isolation. We found that mAb 1A5 could immunoprecipitate Cad11 when membranes were solubilized by dodecyl maltoside (DDM) but not by octylglucoside, suggesting that octylglucoside interferes with Cad11-mAb 1A5 interaction. Furthermore, we compared the effects of Brij-35, Triton X-100, cholate, CHAPSO, Zwittergent 3-12, Deoxy BIG CHAP, and digitonin on Cad11 solubilization and immunoprecipitation. We found that all detergents except Brij-35 could solubilize Cad11 from the membrane. Upon immunoprecipitation, we found that ß-catenin, a known cadherin-interacting protein, was present in Cad11 immune complex among the detergents tested except Brij-35. However, the association of p120 catenin with Cad11 varied depending on the detergents used. Using isobaric tag for relative and absolute quantitation (iTRAQ) to determine the relative levels of proteins in Cad11 immune complexes, we found that DDM and Triton X-100 were more efficient than cholate in solubilization and immunoprecipitation of Cad11 and resulted in the identification of both canonical and new candidate Cad11-interacting proteins.

Nonlinear relationship between gonadotropin total dose applied and live birth rates in non-PCOS patients: a retrospective cohort study.

The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction < 0.05).

Magnetically functionalized hydrogels for high-throughput genomic applications.

Single-cell genomics has revolutionized tissue analysis by revealing the genetic program of individual cells. The key aspect of the technology is the use of barcoded beads to unambiguously tag sequences originating from a single cell. The generation of unique barcodes on beads is mainly achieved by split-pooling methods, which are labor-intensive due to repeated washing steps. Towards the automation of the split-pooling method, we developed a simple method to magnetize hydrogel beads. We show that these hydrogel beads provide increased yields and washing efficiencies for purification procedures. They are also fully compatible with single-cell sequencing using the BAG-Seq workflow. Our work opens the automation of the split-pooling technique, which will improve single-cell genomic workflows.

Free and bioavailable 25-hydroxyvitamin D thresholds for bone metabolism and their associations with metabolic syndrome in Chinese women of childbearing age.

Objective: The free hormone hypothesis suggests that free and bioavailable 25-hydroxyvitamin D [25(OH)D] may better reflect vitamin D bioactivity. This study aimed to determine the free and bioavailable 25(OH)D characteristics, estimate their thresholds based on parathyroid hormone (PTH) and bone turnover markers (BTMs), assess their associations with the risk of metabolic syndrome (MetS), and evaluate their potential advantages. Methods: A cross-sectional study was conducted using a nationally representative database (n = 1,505, female, 18-45 years). Serum total 25(OH)D, vitamin D-binding protein, albumin, PTH, and BTMs [osteocalcin, ß-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (ß-CTX), and procollagen type 1 N-terminal propeptide (P1NP)] were measured. Free 25(OH)D and bioavailable 25(OH)D were calculated. The threshold associations of 25(OH)D with PTH and BTMs were analyzed. The relationship between 25(OH)D and MetS risk was examined. An intervention study was then performed in 39 women (18-47 years) to assess the associations of increasing 25(OH)D with PTH and BTMs after vitamin D supplementation. Results: In the cross-sectional study, the three forms of 25(OH)D were found to have similar distribution characteristics. Free and bioavailable 25(OH)D correlated well with total 25(OH)D. Significant total 25(OH)D cutoffs were observed for PTH (14.19 ng/mL and 18.03 ng/mL), osteocalcin (15.14 ng/mL), ß-CTX (14.79 ng/mL), and P1NP (15.08 ng/mL). Free and bioavailable 25(OH)D cutoffs were only found for P1NP (3.47 pg/mL and 1.66 ng/mL, respectively). A total 25(OH)D of <15.14 ng/mL was marginally associated with a higher risk of reduced high-density lipoprotein cholesterol (HDL-C) [odd ratios (OR) = 1.371 (0.991-1.899)]. The ORs of higher versus lower free and bioavailable 25(OH)D levels for reduced HDL-C were 0.770 (0.621-0.956) and 0.772 (0.622-0.958), respectively. The results of the intervention study indicated that PTH and BTMs responded more sensitively to total 25(OH)D than to free or bioavailable 25(OH)D. Conclusion: Free and bioavailable 25(OH)D only had a threshold effect on P1NP. The active 25(OH)D thresholds could be used for risk assessment of reduced HDL-C. However, no superiority of free or bioavailable 25(OH)D was found based on the response of PTH and BTMs to changes in 25(OH)D in Chinese women of childbearing age following vitamin D supplementation. Clinical trial registration: http://www.chictr.org.cn, ChiCTR2200058290.

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex.

AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.

Association of Serum 25(OH)D with Metabolic Syndrome in Chinese Women of Childbearing Age.

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China. Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders. Results: Body mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS's components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980−2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (<14.22 ng/mL) was significantly related to the risk of elevated waist circumference (WC) (OR = 1.612 (1.014−2.561)) and TG (OR = 2.210 (1.318−3.706)), and reduced HDL-C (OR = 1.639 (1.206−2.229)) after adjusting for the confounders among these women. Moreover, these relationships were not affected by vitamin D metabolism-related gene polymorphisms. Conclusion: After comprehensively considering various influencing factors, significant associations between insufficient serum 25(OH)D and MetS's components, including elevated WC, TG, and reduced HDL-C, were observed. However, MetS, hypertension, and hyperglycemia were not found independently associated with 25(OH)D levels.

Combined functional and structural imaging of brain white matter reveals stage-dependent impairment in multiple system atrophy of cerebellar type.

Advances in fMRI of brain white matter (WM) have established the feasibility of understanding how functional signals of WM evolve with brain diseases. By combining functional signals with structural features of WM, the current study characterizes functional and structural impairments of WM in cerebelar type multiple system atrophy, with the goal to derive new mechanistic insights into the pathological progression of this disease. Our analysis of 30 well-diagnosed patients revealed pronounced decreases in functional connectivity in WM bundles of the cerebellum and brainstem, and concomitant local structural alterations that depended on the disease stage. The novel findings implicate a critical time point in the pathological evolution of the disease, which could guide optimal therapeutic interventions. Furthermore, fMRI signals of impaired WM bundles exhibited superior sensitivity in differentiating initial disease development, which demonstrates great potential of using these signals to inform disease management.

Effects of hyperventilation with face mask on brain network in patients with epilepsy.

OBJECTIVES: During the ongoing pandemic of COVID-19, wearing face masks was recommended, including patients with epilepsy doing the hyperventilation (HV) test during electroencephalogram (EEG) examination somewhere. However, evidence was still limited about the effect of HV with face mask on cortical excitability of patients with epilepsy. The motivation of this work is to make use of the graph theory of EEG to characterize the cortical excitability of patients with epilepsy when they did HV under the condition wearing a surgical face mask. METHODS: We recruited 19 patients with epilepsy and 17 normal controls. All of participants completed two HV experiments, including HV with face mask (HV+) and HV without a mask (HV). The interval was 30 min and the sequence was random. Each experiment consisted of three segments: resting EEG, EEG of HV, and EEG of post-HV. EEG were recorded successively during each experiment. Participants were asked to evaluate the discomfort degree using a questionnaire when every HV is completed. RESULTS: All of the participants felt more uncomfortable after HV + . Moreover, not only HV decreased small-worldness index in patients with epilepsy, but also HV + significantly increased the clustering coefficient in patients with epilepsy. Importantly, the three-way of Mask*HV*Epilepsy showed interaction in the clustering coefficient in the delta band, as well as in the path length and the small-worldness index in the theta band. CONCLUSIONS: The results of this study indicated that patients with epilepsy showed the increased excitability of brain network during HV + . We should pay more attention to the adverse effect on brain network excitability caused by HV + in patients with epilepsy. In the clinical practice under the COVID-19 pandemic, it is important that the wearing face mask remain cautious for the individuals with epilepsy when they carried out HV behavior such as exercise (e.g., running, etc.).

Association of whole blood copper, magnesium and zinc levels with metabolic syndrome components in 6-12-year-old rural Chinese children: 2010-2012 China National Nutrition and Health Survey.

BACKGROUND: Metabolic syndrome (MetS) is significantly associated with the risk of cardiovascular disease and its prevalence is showing a trend of getting younger. Previous studies on the relationship between elements and MetS were mostly reported in adults with single element analysis, while reports in children with combined effects of multiple elements were very limited. The aim of this study is to investigate the association between whole blood Cu, Mg and Zn in both single and combined effects and MetS components in rural Chinese children aged 6-12 years based on the data from 2010-2012 China National Nutrition and Health Survey. METHODS: A total of 911 children (51.2% male, 48.7% female) aged 6-12 years were included. Basic characteristics and MetS component parameters were collected and determined by trained stuffs. Elements were detected by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Multivariate logistic regression analysis was performed to examine the independent relationship between elements and MetS components. RESULTS: In single metal analysis, copper was positively associated with elevated waist (OR = 2.00, 1.18-3.28) and all of the metals were associated with elevated TG. And the comprehensive analysis of multiple elements were mostly consistent with the results of single element analysis (low Cu + high Zn with elevated TG (OR = 2.21, 1.18-4.13), high Cu + low Mg with elevated TG (OR = 0.40, 0.16-0.95), high Cu + high Mg with elevated waist (OR = 2.03, 1.26-3.27)), except the combination of Zn and Mg (high Zn + low Mg with reduced HDL-C (OR = 0.47, 0.28-0.77)). CONCLUSIONS: Our study suggested Cu, Zn and Mg in children are indeed associated with metabolic syndrome components, whether in single element or multi-element combined analysis. The results will be confirmed through additional cohort research.

Threshold for Relationship between Vitamin D and Parathyroid Hormone in Chinese Women of Childbearing Age.

Background: The aim of this study was to assess the relationship between serum 25-hydroxyvitamin D [25(OH)D] and serum intact parathyroid hormone (PTH) in Chinese childbearing women, and to estimate the optimum threshold of 25(OH)D that maximally inhibits the PTH, which is considered to be the optimal status for vitamin D sufficiency. Methods: Serum samples were selected from the biological samples' bank of the Chinese Chronic Diseases and Nutrition Survey (CCDNS) 2015. The serum 25(OH)D concentration was determined by liquid chromatography tandem mass spectrometry and the serum PTH was determined by electronic chemiluminescence. Simple linear and partial correlation analysis, locally weighted regression smooth scatterplot (LOESS), nonlinear least squares estimation (NLS), and segmented regression (SR) were utilized to estimate the relationship of 25(OH)D and PTH, and to determine the threshold of 25(OH)D. Results: A total of 1568 serum samples of 25(OH)D concentration and PTH concentration were analyzed. A significant inverse relationship between 25(OH)D and PTH concentration was observed below 15.25 (14.22-16.28) ng/mL, and PTH decreased slowly with the increase of 25(OH)D above 16.75 (15.43-18.06) ng/mL after adjusting by age, latitude, city type, season, corrected calcium, and phosphorus. A very short plateau of PTH was found at 15.25 ng/mL and 16.75 ng/mL in terms of 25(OH)D according to LOESS, NLS, and SR. Conclusions: The serum 25(OH)D was negatively correlated with the serum PTH. The threshold of VitD sufficiency was found in the range of 14.22-18.06 ng/mL in terms of serum 25(OH)D concentration for Chinese childbearing women aged 18-44 years old.