Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash.sup.TM methylated quantification colorimetric assay. These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population

Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

Negative functional magnetic resonance imaging (fMRI) response in the striatum has been observed in several studies during peripheral sensory stimulation, but its relationship between local field potential (LFP) remains to be elucidated. We performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit high LFP–CBV correlation was found in the ipsilateral and contralateral sensory cortices (r=0.89 and 0.95, respectively), the striatal CBV responses were neither positively, nor negatively correlated with LFP (r=0.04), demonstrating that the negative striatal CBV response is not originated from net regional inhibition. To further identify whether this negative CBV response can serve as a marker for striatal functional recovery, two groups of rats (n=5 each) underwent 20- and 45-minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was found in the ipsilateral striatum in both groups immediately after stroke. Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group compared with the 45-minute MCAO group (P<0.05). This study shows that fMRI signals could differ significantly from LFP and that the observed negative CBV response has potential to serve as a marker for striatal functional integrity in rats

Trends of polypharmacy among older people in Asia, Australia and the United Kingdom: a multinational population-based study

BACKGROUND: Polypharmacy among older people represents a global challenge due to its association with adverse drug events. The reported prevalence of polypharmacy varies widely across countries, and is particularly high in Asian countries. However, there is no multinational study using standardised measurements exploring variations in prescribing trends. OBJECTIVE: To compare polypharmacy trends in older people in Asia, Australia and the United Kingdom. DESIGN: Multinational, retrospective, time-trend, observational study using a common study protocol. SETTING: Outpatient and community settings. SUBJECTS: All individuals aged ≥ 65 years between 2013 and 2016. METHODS: We defined polypharmacy as the concomitant use of ≥5 medications for ≥45 days per year. We estimated the annual prevalence of polypharmacy and calculated average annual percentage change (AAPC) to assess the time trends. RESULTS: A total of 1.62 million individuals were included in this study. The highest prevalence of polypharmacy was observed in Hong Kong (46.4%), followed by Taiwan (38.8%), South Korea (32.0%), the United Kingdom (23.5%) and Australia (20.1%) in 2016. For the time trend, the Asian region showed a steady increase, particularly in Hong Kong and South Korea (AAPC: Hong Kong, 2.7%; South Korea, 1.8%; Taiwan, 1.0%). However, Australia and the United Kingdom showed a decreasing trend (Australia, −4.9%; the United Kingdom, −1.1%). CONCLUSIONS: Polypharmacy prevalence in older people was higher in Hong Kong, Taiwan and South Korea, with an increasing trend over time, compared with Australia and the United Kingdom. Our findings underline the necessity to monitor polypharmacy among older people in Asia by conducting government-level interventions and introducing medicine-optimisation strategies