Differences of Heart Rate Variability Between Happiness and Sadness Emotion States: A Pilot Study

This pilot study investigated the differences of heart rate variability (HRV) indices between two opposite emotion states: happiness and sadness, to reveal the differences of autonomic nervous system activity under different emotional states. Forty-eight healthy volunteers were enrolled for this study. Electrocardiography (ECG) signals were recorded under both emotion states with a random measurement order (first happiness emotion measurement then sadness or reverse). RR interval (RRI) time series were extracted from ECGs and multiple HRV indices, including time-domain (MEAN, SDNN, RMSSD and PNN50), frequency-domain (LFn, HFn and LF/HF) and nonlinear indices (SampEn and FuzzyMEn) were calculated. In addition, the effects of heart rate (HR) and mean artery pressure (MAP) on the aforementioned HRV indices were analyzed for both emotion states. The results showed that experimental order had no significant effect on all HRV indices from both happiness and sadness emotions (all P > 0.05). The key result was that among all nine HRV indices, six indices were identified having significant differences between happiness and sadness emotion states: MEAN (P = 0.028), SDNN (P = 0.002), three frequency-domain indices (all P < 0.0001) and FuzzyMEn (P = 0.047), whereas RMSSD, PNN50 and SampEn had no significant differences between the two emotion states. All indices, except for SampEn, had significant positive correlations (all P < 0.01) for the two emotion states. Four time-domain indices decreased with the increase of HR (all P < 0.01), while frequency-domain and nonlinear indices demonstrated no HR-related changes for each emotional state. In addition, all indices (time-domain, frequency-domain and nonlinear) showed no MAP-related changes. It concluded that HRV indices showed significant differences between happiness and sadness emotion states and the findings could help to better understand the inherent differences of cardiovascular time series between different emotion states in clinical practice

Period-2: a tumor suppressor gene in breast cancer

Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels

Chronic and Cumulative Adverse Life Events in Women with Primary Ovarian Insufficiency:An Exploratory Qualitative Study

BACKGROUND AND PURPOSE: Primary ovarian insufficiency (POI) has serious physical and psychological consequences due to estradiol deprivation, leading to increased morbidity and mortality. However, the causes of most POI cases remain unknown. Psychological stress, usually caused by stressful life events, is known to be negatively associated with ovarian function. It is important to explore high-frequency adverse life events among women with POI for future interventions. METHODS: Forty-three women (mean age=33·8 years) were recruited who were newly- diagnosed with idiopathic POI (FSH levels >40 IU/L) to participate in semi-structured interviews through convenience sampling. The main questions covered by the topic guide were designed to explore adverse life events prior to POI diagnosis. Interviews were audio recorded, transcribed and analyzed thematically. Data were analyzed from June 2019 to August 2020. RESULTS: Among the women with POI, mean age at diagnosis of POI was 33·8 years (range from 19 to 39 years), and the average time between the onset of irregular menstruation and POI diagnosis was 2.3 years. These women with POI had a relatively normal menstrual cycle before the diagnosis. A number of stressful life events prior to POI diagnosis were discussed by them as important factors influencing their health. Four core themes emerged: 1) persistent exposure to workplace stress, 2) persistent exposure to family-related adverse life events, 3) sleep problem/disturbance existed in women with POI before diagnosis, and 4) participants’ general cognition and concerns about POI. CONCLUSIONS: Persistent exposures to adverse life events related to work stress, family stress and sleep problem existed in women with POI. Our findings are consistent with the hypothesis that adverse life events play a role in the development of POI. Future research should investigate how social environmental factors influence POI disease risks, and whether provision of tailored interventions (i.e. preventing or mitigating impact of adverse life events) aimed at high-risk populations may help prevent new POI cases and improve conditions of women with POI. We gained an in-depth understanding of the experiences of these women via 1:1 qualitative method, and find adverse life events are frequent in women with POI prior to the diagnosis

Insulin and IGF1 enhance IL-17-induced chemokine expression through a GSK3B-dependent mechanism: a new target for melatonin\u27s anti-inflammatory action.

Obesity is a chronic inflammation with increased serum levels of insulin, insulin-like growth factor 1 (IGF1), and interleukin-17 (IL-17). The objective of this study was to test a hypothesis that insulin and IGF1 enhance IL-17-induced expression of inflammatory chemokines/cytokines through a glycogen synthase kinase 3β (GSK3B)-dependent mechanism, which can be inhibited by melatonin. We found that insulin/IGF1 and lithium chloride enhanced IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1) and C-C motif ligand 20 (Ccl20) in the Gsk3b(+/+) , but not in Gsk3b(-/-) mouse embryonic fibroblast (MEF) cells. IL-17 induced higher levels of Cxcl1 and Ccl20 in the Gsk3b(-/-) MEF cells, compared with the Gsk3b(+/+) MEF cells. Insulin and IGF1 activated Akt to phosphorylate GSK3B at serine 9, thus inhibiting GSK3B activity. Melatonin inhibited Akt activation, thus decreasing P-GSK3B at serine 9 (i.e., increasing GSK3B activity) and subsequently inhibiting expression of Cxcl1 and Ccl20 that was induced either by IL-17 alone or by a combination of insulin and IL-17. Melatonin\u27s inhibitory effects were only observed in the Gsk3b(+/+) , but in not Gsk3b(-/-) MEF cells. Melatonin also inhibited expression of Cxcl1, Ccl20, and Il-6 that was induced by a combination of insulin and IL-17 in the mouse prostatic tissues. Further, nighttime human blood, which contained high physiologic levels of melatonin, decreased expression of Cxcl1, Ccl20, and Il-6 in the PC3 human prostate cancer xenograft tumors. Our data support our hypothesis and suggest that melatonin may be used to dampen IL-17-mediated inflammation that is enhanced by the increased levels of insulin and IGF1 in obesity

Identification of gene mutations in six Chinese patients with maple syrup urine disease

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)—Sanger sequencing technology. Bioinformatics software analyzed the variants’ pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins.Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C&gt;T(p.A220V), c.818C&gt;T(p.T273I), c.1134C&gt;G(p.D378E), and c.1006G&gt;A(p.G336S); two non-sense mutations: c.1291C&gt;T(p.R431*) and c.331C&gt;T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing’s results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD’s differential diagnosis, early treatment, and prenatal diagnosis

Plasma lipidomic profiling of thiopurine-induced leukopenia after NUDT15 genotype-guided dosing in Chinese IBD patients

IntroductionThiopurines, azathiopurine (AZA) and mercaptopurine (6-MP) have been regularly used in the treatment of inflammatory bowel disease (IBD). Despite optimized dosage adjustment based on the NUDT15 genotypes, some patients still discontinue or change treatment regimens due to thiopurine-induced leukopenia.MethodsWe proposed a prospective observational study of lipidomics to reveal the lipids perturbations associated with thiopurine-induced leukopenia. One hundred and twenty-seven IBD participants treated with thiopurine were enrolled, twenty-seven of which have developed thiopurine-induced leucopenia. Plasma lipid profiles were measured using Ultra-High-Performance Liquid Chromatography-Tandem Q-Exactive. Lipidomic alterations were validated with an independent validation cohort (leukopenia n = 26, non-leukopenia n = 74).ResultsUsing univariate and multivariate analysis, there were 16 lipid species from four lipid classes, triglyceride (n = 11), sphingomyelin (n = 1), phosphatidylcholine (n = 1) and lactosylceramide (n = 3) identified. Based on machine learning feature reduction and variable screening strategies, the random forest algorithm established by six lipids showed an excellent performance to distinguish the leukopenia group from the normal group, with a model accuracy of 95.28% (discovery cohort), 79.00% (validation cohort) and an area under the receiver operating characteristic (ROC) curve (ROC-AUC) of 0.9989 (discovery cohort), 0.8098 (validation cohort).DiscussionOur novel findings suggested that lipidomic provided unique insights into formulating individualized medication strategies for thiopurines in IBD patients

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Rhetoric, cultural identity and intercultural communication in the film: China and Spain in the comparision between the Chinese director Zhang Yimou and the Spanish director Pedro Almodóvar = Retórica, identidad cultural y comunicación intercultural en el cine: China y España en la comparación entre el director chino Zhang Yimou y el español Pedro Almodóvar

403 p.El cine tiene el poder insuperable de entretener, educar e iluminar a las masas. El cine es un reflejo de la sociedad, que refleja nuestro pasado, presente y futuro. Y es una forma de comunicación, la forma de comunicación más poderosa, fuerte, efectiva y popular que ha sido adorada y admirada en todo el mundo. Se comunica mediante imágenes, especialmente imágenes humanas. Cada país tiene sus propias costumbres, estilos y valores. Son películas que reflejan esas costumbres o valores. El cine es universal, su atractivo es universal. Un tema universal siempre atrae a personas de todo el mundo independientemente de su raza, religión o idioma. El cine tiene reclamos legítimos para ser considerado como la forma de arte más duradera y sustentadora desde el siglo XX. Según la retórica, la identidad cultural y la comunicación trascultural, la tesis se divide, temática y cronológicamente, en tres partes, formas, tipos de contenido y comunicación. En la historia del cine de China, Zhang Yimou creó dos eras, lo que parece increíble incluso en la historia del cine mundial. Un período en el cual la película de arte chino va al mundo, con el hito de Sorgo rojo que ganó el Festival Internacional de Cine de Berlín, Golden Bear a la mejor película en 1988. Y la otra es la creación de un éxito de taquilla comercial en el mercado masivo doméstico de China, con el hito de Hero representado por las superestrellas del entretenimiento y la alta inversión en 2002. El objetivo de nuestra disertación es la investigación sobre el lenguaje fílmico como una forma de comunicar pensamientos relevantes, crítica social y filosófica a través de la imagen. Sin embargo, todavía es posible un análisis en profundidad de este tipo de productos, que puede leerse de acuerdo con varios niveles de interpretación. Sobre el significado obvio de estas películas, se puede encontrar la relación de la economía política entre el cine y la nación: Zhang Yimou y China, Pedro Almodóvar y España, a través de una lectura detallada de obras maestras

Managing liquidity along the supply chain: Supplier-base concentration and corporate cash policy

We find that customer firms with more concentrated supplier bases tend to hold higher levels of cash reserves. The positive relation between supplier-base concentration and cash holdings is more pronounced for firms with non-state ownership, higher market competition, worse inventory efficiency, more relationship-specific investment, central positions in the production networks, and headquarters located in regions with lower levels of financial development. Furthermore, we show that debt issuance enhances firms’ cash holdings when they have concentrated suppliers, and supplier-base concentration increases firms’ cash spending on R&D investment. Our study highlights the importance of supplier structure in shaping corporate cash polic