Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase(PI3 K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3 K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting(GV24) and Baihui(GV20) acupoints, with a dilatational wave(1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3 K/Akt signaling pathwayrelated factors Beclin-1, mammalian target of rapamycin(mTOR), and PI3 K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3 K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting(GV24) and Baihui(GV20) acupoints activated the PI3 K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China(approval No. 8150150901) on March 10, 2016.     

Forecasting respiratory infectious outbreaks using ED-based syndromic surveillance for febrile ED visits in a Metropolitan City

Background

Monitoring and detecting sudden outbreaks of respiratory infectious disease is important. Emergency Department (ED)-based syndromic surveillance systems have been introduced for early detection of infectious outbreaks. The aim of this study was to develop and validate a forecasting model of respiratory infectious disease outbreaks based on a nationwide ED syndromic surveillance using daily number of emergency department visits with fever.

Physical health-related quality of life among older adults with personality disorders

Objectives: Personality Disorders (PDs) are associated with a multitude of negative consequences. The negative PD effects on health can be even more burdensome for older adults given the physical and social functioning changes that occur with age; however, the majority of research examining the influence of PDs focuses on younger adults. The present study seeks to investigate the relationship between PDs and physical health-related quality of life (PHRQoL) in adults over the age of 50.

Methods: Data for 16,884 adults ages 50 and older from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC) were analyzed. Multiple linear regression models were analyzed to investigate the relationships of seven PDs and participants’ PHRQoL.

Results: All PDs except histrionic and avoidant PD had statistically significant negative associations with PHRQoL scores, indicating that respondents diagnosed with PDs were expected to have lower PHRQoL than those without PDs, after controlling for sociodemographic characteristics. When psychosocial covariates were added to the model, only dependent, obsessive-compulsive and paranoid PDs were significantly related to PHRQoL score.

Conclusions: For adults ages 50 and older, a diagnosis of PD was weakly associated with lower PHRQoL scores for three PDs, however this is unlikely to be a causal association. The strength of the relationship between PDs and PHRQoL varies by type of PD. Given the higher rates of functional and social changes that occur with age, future research should focus on potential causes of worse physical health among older adults with PDs.     

Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells

There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies     

Rosai-Dorfman Disease: Importance of 18F FDG PET/CT to Determine Extension and Extranodal Involvement

Rosai-Dorfman disease or sinus histiocytosis with lymphadenopathy is a rare benign histiocytic proliferative disorder of unknown etiology first described in 1969. It typically affects older females and most common presentation is with massive lymphadenopathy and nonspecific systemic symptoms; therefore, it is often confused with lymphoproliferative disorders [1, 2]. We present the case of a 69-year-old woman with nasal obstruction as only complaint. Laboratory tests showed normal leukocyte count with elevated ANC (absolute neutrophil count), normal RBC count with normal MCV (mean corpuscular volume) and MCH (mean corpuscular hemoglobin), elevated ESR (erythrocyte sedimentation rate), and normal IgG, IgA, and IgM values. Evaluation revealed a nasopharyngeal mass, which was biopsied and reported emperipolesis with positive CD68 and S-100; typical and differential findings of this disease [1, 2]. ¹⁸F FDG PET/CT was performed to determine the extent and involvement of the disease. Considering the presence of few symptoms and no significant laboratory abnormality, treating physicians decided to start a regimen of corticosteroids (prednisolone) for a period of 4 months, after which a follow-up with ¹⁸F FDG PET/CT will be performed.     

Short or Long Sleep Duration and CKD: A Mendelian Randomization Study

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Concomitants of menopause-specific quality of life in premenopausal and post-menopausal women living in South Korea

ABSTRACT

The present study investigated the concomitants of menopause-specific quality of life among premenopausal and postmenopausal women. Based on the Wilson and Cleary model of quality of life, this cross-sectional study recruited 329 women of age 40–65 years following operational convenience. The study was conducted in the office of the Korea Population, Health and Welfare Association (KPHWA) in Incheon, South Korea. Data collected on sociodemographic characteristics, social support, biological/physiological characteristics, the Pittsburgh Sleep Quality Index (PSQI-K), and self-rated health. Menopause-specific quality of life questionnaire (MENQOL) was used in this study. Hierarchical multiple linear regression analysis was performed. The study found that social support and self-rated health were negatively correlated with MENQOL in premenopausal women, while the income level and self-rated health were negatively associated with MENQOL in postmenopausal women. Sleep quality was positively correlated with MENQOL in both premenopausal and postmenopausal women. The study results indicate the need for tailored approaches based on menopausal status. Especially, social support may help improve the MENQOL of premenopausal women, while in postmenopausal women, improved sleep quality may enhance their menopause-specific quality of life.     

Is interleukin-2 an optimal marker for diagnosing tuberculosis infection? A systematic review and meta-analysis

Abstract

Background

Latent tuberculosis infection (LTBI) is a huge reservoir for the deadlier TB disease. Accurate identification of LTBI is a key strategy to eliminate TB. Therefore, a systematic review and meta-analysis approach was used to assess diagnostic potential of IL-2 for LTBI.