Identification of genetic susceptibility for Chinese migraine with depression using machine learning.

Background: Migraine is a common primary headache that has a significant impact on patients' quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background. Objective: The aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort. Methods: In this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom's MALDI-TOF iPLEX platform. Results: In univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS). Conclusion: The study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.

Acrylamide Exposure Impairs Ovarian Tricarboxylic Acid Cycle and Reduces Oocyte Quality in Mouse.

Acrylamide (AAM), a compound extensively utilized in various industrial applications, has been reported to induce toxic effects across multiple tissues in living organisms. Despite its widespread use, the impact of AAM on ovarian function and the mechanisms underlying these effects remain poorly understood. Here, we established an AAM-exposed mouse toxicological model using 21 days of intragastric AAM administration. AAM exposure decreased ovarian coefficient and impaired follicle development. Further investigations revealed AAM would trigger apoptosis and disturb tricarboxylic acid cycle in ovarian tissue, thus affecting mitochondrial electron transport function. Moreover, AAM exposure decreased oocyte and embryo development potential, mechanically associated with pericentrin and phosphorylated Aurora A cluster failure, leading to meiotic spindle assembly defects. Collectively, these results suggest that AAM exposure may lead to apoptosis, glucose metabolic disorders, and mitochondrial dysfunction in ovary tissue, ultimately compromising oocyte quality.

Aristolochic acid I exposure triggers ovarian dysfunction by activating NLRP3 inflammasome and affecting mitochondrial homeostasis.

Aristolochic acids are widely distributed in the plants of Aristolochiaceae family and Asarum species. Aristolochic acid I (AAI) is the most frequent compound of aristolochic acids, which can accumulate in the soil, and then contaminates crops and water and enters the human body. Research has shown that AAI affects the reproductive system. However, the mechanism of AAI's effects on the ovaries at the tissue level still needs to be clarified. In this research, we found AAI exposure reduced the body and ovarian growth in mice, decreased the ovarian coefficient, prevented follicular development, and increased atretic follicles. Further experiments showed that AAI upregulated nuclear factor-κB and tumor necrosis factor-α expression, activated the NOD-like receptor protein 3 inflammasome, and led to ovarian inflammation and fibrosis. AAI also affected mitochondrial complex function and the balance between mitochondrial fusion and division. Metabolomic results also showed ovarian inflammation and mitochondrial dysfunction due to AAI exposure. These disruptions reduced the oocyte developmental potential by forming abnormal microtubule organizing centers and expressing abnormal BubR1 to destroy spindle assembly. In summary, AAI exposure triggers ovarian inflammation and fibrosis, affecting the oocyte developmental potential.

Chloroacetonitrile exposure induces endoplasmic reticulum stress and affects spindle assembly in mouse oocytes.

Chloroacetonitrile (CAN) is a halogenated acetonitrile often produced while disinfecting drinking water. Previous studies have shown that maternal exposure to CAN interferes with fetal development; however, the adverse effects on maternal oocytes remain unknown. In this study, in vitro exposure of mouse oocytes to CAN reduced maturation significantly. Transcriptomics analysis showed that CAN altered the expression of multiple oocyte genes, especially those associated with the protein folding process. CAN exposure induced reactive oxygen species production, accompanied by endoplasmic reticulum (ER) stress and increased glucose regulated protein 78, C/EBP homologous protein and activating transcription factor 6 expression. Moreover, our results indicated that spindle morphology was impaired after CAN exposure. CAN disrupted polo-like kinase 1, pericentrin and p-Aurora A distribution, which may be an origin inducer that disrupts spindle assemble. Furthermore, exposure to CAN in vivo impaired follicular development. Taken together, our findings indicate that CAN exposure induces ER stress and affects spindle assembly in mouse oocytes.

Cobalt chloride exposure disturbs spindle assembly and decreases mouse oocyte development potential.

Cobalt is a kind of heavy metal which is widely used in petrochemical and biomedical industries. Animal studies have reported that cobalt would exert systemic toxicity, but its effects on the ovarian function in mammals, especially for oocyte quality remains unknown. In the present study, we report that cobalt chloride treatment affects ovary coefficient and follicular growth. Oocytes in cobalt chloride exposed mice exhibited a decreased development potential, with the evidence of decreased occurrence rate of germ vesicle breakdown and polar body extrusion. Besides, cobalt chloride disorganized meiotic spindle formation and movement, mechanically associated with affecting TACC3 and Ac-a-tubulin levels, and disturbing actin reorganization. In addition, cobalt chloride exposure result in mitochondrial cristae structures disappear, cluster distribution and potential depolarization. Altogether, these findings suggest that cobalt chloride impairs the ovarian follicle growth and affects oocyte development by disrupted spindle assembly and mitochondrial function.

3-MCPD exposure enhances ovarian fibrosis and reduces oocyte quality in mice.

3-monochloro-1,2-propanediol (3-MCPD) is a food contaminant believed to be harmful to human health. Previous studies showed that 3-MCPD exerts toxic effects in multiple tissues, but whether 3-MCPD affects female reproductive function remained unknown. Here, using mouse gastric lavage models, we report that 3-MCPD exposure for four weeks affected body growth, decreased the ovary/body weight ratio, and increased atretic follicle numbers. Expression levels of follicular development-related factors decreased. Further studies found that ovaries from 3-MCPD exposed mice had activated the Transforming Growth Factor-ß (TGF-ß) signaling pathway and promoted ovarian fibrosis. Increased TNF-α, IL-1 and NF-κB expression also indicated the occurrence of ovarian inflammation. Exposure to 3-MCPD stimulated the caspase pathway and enhanced granulosa cell apoptosis. Consistent with disrupted ovarian homeostasis, 3-MCPD exposure interfered with mitochondrial function, generated more reactive oxygen species, increased ferrous ion and lipid peroxidation levels, and resulted in decreased oocyte development potential. Collectively, these findings indicated that 3-MCPD exposure induced ovarian inflammation and fibrosis, and caused disorders of mitochondrial function and ferrous ion homeostasis in oocytes, which consequently disturbed follicle maturation and reduced oocyte quality.

Triptolide exposure induces oxidative stress and decreases oocyte quality in mouse.

Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 µg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.

Ninj2 regulates Schwann cells development by interfering laminin-integrin signaling.

Rationale: Myelin sheath is an important structure to maintain normal functions of the nerves. Nerve Injury-Induced Protein 2 (Ninj2) was found upregulated in Schwann cells (SC) upon injury. However, whether and how Ninj2 plays a role in myelination remain unknown. Methods: In this study, we use transmission electron microscope imaging, immunofluorescent imaging, and behavioral tests to show the effects of Ninj2 on myelination and remyelination in peripheral nervous system (PNS) of SC-specific Ninj2 knockout mice (Dhhcre/+;Ninj2fl/fl ). For mechanism studies, we use RNA-Seq analysis to show the Ninj2-related pathways, and co-immunoprecipitation/mass-spectrometry to identify the Ninj2-interacting proteins in SCs. Furthermore, we evaluate the effect of integrin inhibitor GRGDSP during remyelination. Results: Ninj2 negatively regulates SC development. Ninj2-deficient mice exhibit precocious myelination phenotype, as well as the accelerated remyelination process after sciatic nerve injury. Loss of Ninj2 promotes myelination by promoting SC proliferation to augment its population. Mechanistically, Ninj2 interacted with ITGB1 on SC membrane, which inhibits laminin-integrin signaling. Removal of Ninj2 induces the activity of laminin-integrin signaling, resulting in the improved myelination in the Dhhcre/+;Ninj2fl/fl mice. Inhibition of laminin-integrin signaling by integrin inhibitor GRGDSP sufficiently delays the remyelination process in the Dhhcre/+;Ninj2fl/fl mice with sciatic nerve injury. Conclusion: Our study found Ninj2 as a negative regulator in the network controlling myelination in the PNS.

[Application and evaluation of comfort nursing in caries treatment using light-cured resin].

PURPOSE: This study was carried out to evaluate the value of comfort nursing in light curing resin-treated dental caries by means of patient satisfaction survey. METHODS: One hundred and twenty-eight cariogenic patients, who were treated from January 2017 to December 2017 in Shanghai Ninth People's Hospital, were enrolled and randomly assigned as experimental group and control group, respectively(n=64). Cariogenic lesions were treated with light-cured resin, patients in the control group received conventional four-handed operation nursing, while patients in the experimental group received modified comfortable nursing throughout the entire treatment course. The self-designed satisfaction questionnaires were issued, and the patients were required to fill them out after the treatment and nursing were definitely completed. The designed questionnaire was divided into two major parts, including nursing care and nursing operation, which was further subdivided into 10 detailed scoring items. The satisfaction survey of nursing was analyzed between two groups statistically to evaluate the effort of comfort nursing using SPSS 19.0 software package. RESULTS: No significant differences in the treatment environment was observed between the two groups(P＞0.05), while upgraded satisfaction were observed in patients from the experimental group compared to those from the control group on the aspects of nursing care, namely, appearance, service attitude, explanation and health knowledge promotion(P＜0.05). Among the five scoring standards of nursing operation, which was consist of timely initiative nursing, position nursing, eye nursing, effective nursing and nursing procedures, the satisfaction scores from the experimental group were significantly higher than those from the control group(P＜0.05). The total collected data demonstrated that the overall satisfaction of the experimental group was significantly improved compared to that of the control group (94% vs 75%, P＜0.01). CONCLUSIONS: Comfort nursing not only strengthens the professionalism of oral operation, but also improves the patient's experience, facilitating to promote the harmony between doctors and patients.

Acrylonitrile exposure triggers ovarian inflammation and decreases oocyte quality probably via mitochondrial dysfunction induced apoptosis in mice.

Acrylonitrile is an organic chemical synthetic monomer that is widely used in food packaging and manufacturing. Animal studies have reported that acrylonitrile is carcinogenic and toxic, but the effects on the female reproductive function in mammals are unknown. In the present study, we report that acrylonitrile treatment affects ovarian homeostasis in mice, resulting in impaired follicular development. Follicles in acrylonitrile-exposed mice exhibited high levels of inflammation and apoptosis, and acrylonitrile treatment interfered with oocyte development. Transcriptomics analysis showed that acrylonitrile altered the expression of oocyte genes related to apoptosis, oxidative stress, endoplasmic reticulum stress, and autophagy. Further molecular tests revealed that acrylonitrile induced early apoptosis, DNA damage, elevated levels of reactive oxygen species, endoplasmic reticulum abnormalities, and lysosomal aggregation. We also observed disruption of mitochondrial structure and distribution and depolarization of membrane potential. Finally, acrylonitrile treatment in female mice decreased the number and weight of offspring. Altogether, these findings suggest that acrylonitrile impairs the stability of the ovarian internal environment, which in turn affects oocyte development and reduces the number of offspring.

Navigating change in the era of COVID-19: The role of top leaders' charismatic rhetoric and employees' organizational identification.

The Novel Coronavirus (COVID-19) pandemic has had tremendous and swift effects on organizational change. This study examined how organizations can leverage leadership and employee resources to facilitate positive change outcomes. Drawing from the self-concept based motivational theory of charismatic leadership and substitutes for leadership theory, the current study proposed a theoretical model connecting top leaders' charismatic rhetoric, employees' affective commitment to change, and employees' turnover intention. Furthermore, the study investigated contingencies that may modify the relationship between leadership communication and followers' outcomes. Results from an online panel of 417 U.S. employees showed that top leaders' use of charismatic rhetoric during change led to followers' affective commitment to change, which decreased their turnover intention. Furthermore, employees' organizational identification moderated this relationship. When employees have low identification with their organizations, top leaders' charismatic rhetoric to address the immediate change is more needed.

Efficacy of Monitoring Platelet Function by an Automated PL-12 Analyzer During the Treatment of Acute Cerebral Infarction With Antiplatelet Medicine.

METHODS: All participants were administered with oral aspirin (100 mg/d) for 7 days. Blood samples were then collected and platelet function evaluated by an automated PL-12 analyzer, TEG, and the platelet count drop method. We found that platelet counts determined by the traditional platelet drop method were significantly lower in the PL-12 sensitive group and significantly higher in the PL-12 insensitive group (P < 0.05). Furthermore, MAR measured by PL-12 was positively correlated with the MA values determined by TEG and the platelet drop method (r = 0.322, r = 0.036, respectively, P < 0.05), More importantly, the PL-12 analyzer showed the largest AUC (0.748) with a sensitivity of 87.4% and a specificity of 57.4%, indicating PL-12 analyzer using in platelet aggregation evaluation of ACI patients more credibly and accuracy. Additionally, genetic analysis showed that the polymorphic of A-allele in the PEAR1 (rs12041331) gene was significantly increased in the PL-12 sensitive group rather than in the PL-12 insensitive group (P < 0.05), suggesting the predictive value of PL-12 analyzer for the prognosis of ACI patients was superior to the other methods tested herein. Our analyses demonstrate that PL-12 analysis offer a new superior technology for monitoring antiplatelet drug efficacy and for clinical prognosis of ACI patients, which has the advantages of simplicity, speed, and automation in platelet aggregation measurement.

CELSR1 Is a Positive Regulator of Endothelial Cell Migration and Angiogenesis.

Cadherin is an epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a key component of the noncanonical Wnt/planar cell polarity (PCP) pathway that critically regulates endothelial cell proliferation and angiogenesis. In this study, we examined the biological significance of CELSR1 in endothelial cell migration and angiogenesis. For this, we applied both gain-of-function and loss-of-function approaches. To increase the endogenous expression of CELSR1, we used the transcription activator-like effector (TALE) technology and constructed an artificial TALE-VP64 activator. To knock down the expression of CELSR1, we generated lentivirus containing short hairpin RNA sequences targeting different regions of CELSR1 mRNA. Following up- or down-regulation of CELSR1 in human aortic endothelial cells (HAEC), we assessed in vitro cell proliferation by MTT assay, migration by scratch and transwell migration assays, and angiogenesis by tube formation analysis. We found that CELSR1 was endogenously expressed in human umbilical vein endothelial cells (HUVEC) and HAEC. When focusing on HAEC, we found that upregulating CELSR1 expression significantly promoted cell growth, while knocking down CELSR1 inhibited the growth (p < 0.05). Using both scratch and transwell migration assays, we observed a positive correlation between CELSR1 expression and cell migratory capability. In addition, CELSR1 upregulation led to higher levels of tube formation in HAEC, while downregulating CELSR1 expression decreased tube formation (p < 0.05). Mechanistically, CELSR1-regulated migration and tube formation was mediated through disheveled segment polarity protein 3 (Dvl3). In conclusion, CELSR1 plays an important role in regulating multiple phenotypes of endothelial cells, including proliferation, migration, and formation of capillary-like structures.

[Identification of the scope of practice for dental nurses with Delphi method].

PURPOSE: To identify the practice scope of dental nurses under the new situations. METHODS: The draft of scope of practice for dental nurses was based on theoretical analysis, literature review and consultation of advisory panel, and the final scope of practice for dental nurses was established by using the Delphi method. Statistical analysis was implemented using coefficient of variation, Kendall W with SPSS 17.0 software package. RESULTS: Thirty experts were consulted twice by using the Delphi method. The effective rates of two rounds of questionnaire were 100% and 73.3%, respectively. The authority coefficient was 0.837, and the P value of expert coordination coefficients W was less than 0.05. There were totally 116 suggestions from the experts, and 96 were accepted. The scope of practice for dental nurses was finally established, including 4 primary indexes and 25 secondary indexes. CONCLUSIONS: The scope of practice for dental nurses under the new situations is established in China through scientific methods. It is favorable for position management of dental nurses and may promote the development of nurse specialists in dental clinic.

The correlation of hippocampal T2-mapping with neuropsychology test in patients with Alzheimer's disease.

OBJECTIVES: 1) To deduce T2, the inverse of the transverse relaxation rate (R2), in the hippocampus of healthy adults; 2) to investigate the brain iron deposition in Alzheimer's disease (AD) patients and age-matched healthy controls using T2-values. METHODS: T2-weighted data from the bilateral-hippocampi of ten AD patients and sixty healthy controls were collected at six echo time points using multi-slice multi-echo turbo spin echo (MSME-TSE) imaging on a 3.0 T MR-scanner, followed by the neuropsychological testing. The correlations between T2-values and Mini-Mental State Examination (MMSE) scores were investigated on group-wise basis (covariates in the group-wise analyses: gender, age, side and healthy/AD). RESULTS: There were no significant differences in hippocampal T2-values on intra-gender and inter-gender basis (P > 0.05). Hippocampal T2-values of both sides were similar (right: 85.2±2.4 milliseconds; left: 85.3±2.5 milliseconds). The bilateral hippocampal T2 values correlated moderately with age (right: r = -0.59; left: -0.58; P < 0.001). The AD-group had significantly lower T2-values in the hippocampus when compared to normal controls (P < 0.001) and such low T2-values had a strong positive correlation with the MMSE score (R (2) = 0.97; P < 0.05). CONCLUSION: Patients with AD showed significantly lower T2 values, which can be attributed to the increased iron depositions in the hippocampus. A positive correlation between T2-values and cognition scores suggests that quantitative T2 can be used in the early diagnosis of AD and in the monitoring of the treatment response.

Limited hippocampal neurogenesis in SAMP8 mouse model of Alzheimer's disease.

Increasing adult neurogenesis in the hippocampal formation (HF) has been proposed as a potential foundation for neuronal repair in Alzheimer's disease (AD), but the evidence remains controversial. We used P8 strain of senescence-accelerated mice (SAMP8) as a model of AD to investigate changes in adult neurogenesis. We examined new proliferating cells and their survival in the dentate gyrus (DG) of the HF using 5-bromodeoxyuridine (BrdU) labeling and investigated newborn cell development and differentiation with a combination of phenotype markers. In 5-month-old SAMP8, the number of BrdU(+) cells in the DG was significantly increased relative to controls, in accordance with the rising numbers of doublecortin-positive (DCX(+)) immature neurons. Some of these BrdU(+) cells migrated to cornu ammonis 1 (CA1), possibly related to the compensation of neuronal loss. However, the capacity of neurogenesis to compensate neuronal loss during neurodegeneration was limited. First, only half of the BrdU(+) cells survived 4weeks after mitosis, and even fewer developed into neuron-specific nuclear protein positive (NeuN(+)) mature neurons. Second, the number of BrdU(+) cells and DCX(+) cells was decreased in 10-month-old SAMP8, which exhibited progressive neurodegeneration. In addition, the results provided insight into astrocytes as a crucial component of the neurogenic niche. The number of newborn astrocytes and expression of glial fibrillary acidic protein (GFAP) were diminished in the DG of SAMP8 animals, possibly explaining the insufficient neurogenesis. Thus, stimulating limited neurogenesis in AD by improving the neurogenic niche may have therapeutic potential.