Direct temporal characterization of sub-3-fs deep UV pulses generated by resonant dispersive wave emission.

We report on the complete temporal characterization of ultrashort pulses, generated by resonant dispersive wave emission in gas-filled hollow-capillary fibers, with energy in the microjoule range and continuously tunable from the deep-ultraviolet to the ultraviolet. Temporal characterization of such ultrabroad pulses, particularly challenging in this spectral region, was performed using an all-in-vacuum setup for self-diffraction frequency resolved optical gating (SD-FROG). Sub-3-fs pulses were measured, tunable from 250 nm to 350 nm, with a minimum pulse duration of 2.4 ± 0.1 fs.

Interictal Cognitive Deficits in Migraine Sufferers: A Meta-Analysis.

While a significant proportion of the population suffer from migraine, the existing research literature does not provide a clear indication as to whether migraineurs experience objective cognitive deficits outside of acute migraine attacks. This meta-analysis was conducted to investigate which cognitive domains if any were affected by migraine, by synthesising the existing research quantitatively. The meta-analysis was prospectively registered with the PROSPERO International prospective register of systematic reviews (registration no.: CRD42019134138). A search of the electronic databases PubMed, Ovid MEDLINE, and PsycINFO was conducted for journal articles published between January 1980 and January 2020. Seventeen studies met the inclusion criteria, allowing for the calculation of pooled effect sizes between migraineurs (with and without aura) and healthy controls in the several cognitive domains. During the interictal period, migraineurs demonstrated a moderate, negative effect on complex attention immediate and delayed memory, spatial cognition, and executive functioning. This effect was not attributable to migraine history, attack frequency, or participant age. However, the lack of performance validity testing, and limited data on mood symptomatology and migraine medication use in the included studies may be confounds potentially overestimating the magnitude of effect. Comparison with a clinical control group, which may have accounted for some these extraneous variables, was unable to be conducted. Recommendations for comprehensive future neuropsychological research are provided.

[Detection rate and clinical significance of regions of homozygosity in prenatal genetic diagnosis].

Objective: To detect the incidence and analyze the clinical significance of regions of homozygosity (ROH) through the single nucleotide polymorphism array (SNP array). Methods: The SNP array detection results of 5 116 pregnant women in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2020 were retrospectively analyzed. The pregnant women with ROH (5 Mb as the threshold) were followed up to analyze the relationship between ROH and abnormal fetal phenotype. Whole exon sequencing was performed in 4 cases of consanguineous marriage to detect potential recessive causative genes in the ROH region. Results: (1) A total of 39 cases of ROH were detected, with a positive rate of 0.76% (39/5 116). Among them, 25 cases (64%, 25/39) were detected only on single chromosome, and chromosome 11 had the highest detection rate, suggesting the risk of uniparental disomy; fourteen cases (36%,14/39) were detected on multiple chromosomes, most commonly on chromosomes 11, 1, 3, 4 and 8. (2) The number of cases and detection rate of ROH detected by different prenatal diagnosis indicators were as follows: 12 cases (1.78%, 12/676) in pregnant women with abnormal non-invasive prenatal testing result, 12 cases (0.37%, 12/3 284) in pregnant women with ultrasound abnormality, 4 cases (4/4) in pregnant women with consanguineous marriage, 3 cases (0.92%, 3/326) in pregnant women with previous adverse pregnancy, 2 cases (1.15%, 2/174) in pregnant women with high risk of serology in screening, 2 cases (4.00%, 2/50) in pregnant women with abnormal fetal chromosomal karyotype, 2 cases (0.79%, 2/253) in pregnant women with advanced maternal age, 1 case (0.56%, 1/178) in pregnant women with related parental genetic factors and 1 case (0.58%, 1/171) in pregnant women with the other factors. (3) The follow-up results of 39 cases of prenatal ROH showed that there were 16 cases of term birth, 15 cases of termination of pregnancy, 2 cases of preterm births, 1 case of fetal death and 5 cases lost to follow-up. Conclusions: Chromosomal ROH phenomenon is not rare. By analyzing the detection rate of ROH in prenatal diagnosis, combined with the results of fetal phenotype and postpartum follow-up, the clinical characteristics of ROH are discussed, so as to better understand the relationship between ROH and its phenotype.

The combination therapy of HIF1α inhibitor LW6 and cisplatin plays an effective role on anti-tumor function in A549 cells.

Hypoxia-inducible factor 1α (HIF1α) has been demonstrated to be involved in the resistance of various human cancer cells to chemotherapies. However, the correlation between HIF1α and the sensitivity of human non-small cell lung cancer (NSCLC) cells to cisplatin has not been illuminated. The aim of the present study was to investigate the effects of HIF1α on drug resistance in NSCLC cells. A549 cells were incubated in 21% or 0.5% O2 followed by the assessment of the level of HIF1α with qRT-PCR and western blot and ROS level by DCFH-DA assays. Effects of hypoxia or HIF1α inhibitor LW6 on the proliferation and apoptosis of A549 cells were evaluated via CCK-8 and flow cytometry assays. IC50 of A549 cells to cisplatin was determined by MTT assay. The mitochondrial membrane potential (MMP) was measured via JC-1 staining. Moreover, the expression of apoptosis related protein (Bcl-2, Bax) and drug resistance related proteins (MDR1, MRP1) were measured by western blotting. Exposure of A549 cells to 1% O2 significantly up-regulated HIF1α expression, maintained cell viability to cisplatin but decreased the ROS level, which promoted chemoresistance to cisplatin. LW6-treated A549 cells showed an increase in ROS level that blocked the hypoxia induced resistance to cisplatin and in addition, decreased expression of MDR1 and MRP1 in cisplatin-treated cells. This study revealed that hypoxia-improved cisplatin chemoresistance of NSCLC cells by regulated MDR1 and MRP1 expression via HIF1α/ROS pathway is reversed by LW6, suggesting that LW6 may act as effective sensitizer in chemotherapy for NSCLC.

Micronutrient status of populations and preventive nutrition interventions in South East Asia.

Objectives Since the 1990s, programs for the control of micronutrient deficiencies became a public health priority for many governments, including the countries partnering the project "Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia" (SMILING): Cambodia, Indonesia, Laos-PDR, Thailand and Vietnam. The aim of this study was to map which micronutrient deficiencies have been addressed and which interventions were in place in the SMILING countries. Methods The mapping covered the period up to 2012. Updated information from relevant surveys after 2012 is included in this paper after the completion of the SMILING project. The mapping of micronutrient status was limited to either national or at least large-scale surveys. Information on nutrition interventions obtained through a systematic mapping of national programs combined with a snowball collection from various sources. Results Among the five SMILING countries, Thailand differed historically by an early implementation of a nationwide community-based nutrition program, contributing to reductions in undernutrition and micronutrient deficiencies. For Cambodia, Indonesia, Laos PDR, and Vietnam, some national programs addressing micronutrients have been implemented following adjusted international recommendations. National surveys on micronutrient status were scattered and inconsistent across the countries in design and frequency. Conclusion for practice In conclusion, some micronutrient deficiencies were addressed in national interventions but the evidence of effects was generally lacking because of limited nationally representative data collected. Improvement of intervention programs to efficiently reduce or eliminate micronutrient deficiencies requires more systematic monitoring and evaluation of effects of interventions in order to identify best practices.

Functional Specialization of Cellulose Synthase Isoforms in a Moss Shows Parallels with Seed Plants.

The secondary cell walls of tracheary elements and fibers are rich in cellulose microfibrils that are helically oriented and laterally aggregated. Support cells within the leaf midribs of mosses deposit cellulose-rich secondary cell walls, but their biosynthesis and microfibril organization have not been examined. Although the Cellulose Synthase (CESA) gene families of mosses and seed plants diversified independently, CESA knockout analysis in the moss Physcomitrella patens revealed parallels with Arabidopsis (Arabidopsis thaliana) in CESA functional specialization, with roles for both subfunctionalization and neofunctionalization. The similarities include regulatory uncoupling of the CESAs that synthesize primary and secondary cell walls, a requirement for two or more functionally distinct CESA isoforms for secondary cell wall synthesis, interchangeability of some primary and secondary CESAs, and some CESA redundancy. The cellulose-deficient midribs of ppcesa3/8 knockouts provided negative controls for the structural characterization of stereid secondary cell walls in wild type P. patens Sum frequency generation spectra collected from midribs were consistent with cellulose microfibril aggregation, and polarization microscopy revealed helical microfibril orientation only in wild type leaves. Thus, stereid secondary walls are structurally distinct from primary cell walls, and they share structural characteristics with the secondary walls of tracheary elements and fibers. We propose a mechanism for the convergent evolution of secondary walls in which the deposition of aggregated and helically oriented microfibrils is coupled to rapid and highly localized cellulose synthesis enabled by regulatory uncoupling from primary wall synthesis.

[Influence of short-term intensive insulin therapy on plasma concentration of lipoprotein-associated phospholipase A(2) and secretory phospholipase A(2) in newly diagnosed type 2 diabetic patients].

The aim of the study was to explore the effect and its clinical relevance of short-term intensive insulin treatment on plasma concentrations of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and secretory phospholipase A(2) (sPLA(2)) in newly diagnosed type 2 diabetes mellitus (T2DM). Ninety newly diagnosed T2DM patients were recruited and received continuous subcutaneous insulin infusion (CSII) for about 2 weeks. After CSII, sPLA(2) levels [173.78 (80.95, 278.09) µg/L] were significantly decreased compared with the levels before [219.33 (130.03, 337.30) µg/L], P<0.01, while no statistic significant changes could be viewed in Lp-PLA(2) levels. Correlation analysis showed that the changes of Lp-PLA(2) and sPLA(2) were both positively correlated with the changes of homeostasis model assessment of insulin resistance(HOMA-IR)after CSII (r=0.537, 0.493 respectively, all P<0.05). The Lp-PLA(2) and sPLA(2) level reduction after CSII might help to protect the patients from diabetic macroangiopathy. Trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-10001618.

[Predictive value of cardiac magnetic resonance-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis].

Objective: To evaluate the predictive value of cardiac magnetic resonance (CMR)-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis. Methods: Forty patients, who referred for acute viral myocarditis in our hospital from September 2011 to September 2015, were prospectively enrolled in this study.All patients were examined by CMR during hospitalization for acute viral myocarditis (baseline) and after 12 months.The CMR sequences include: two dimension steady state free precession, 2D SSFP; triple inversion recovery, triple IR; early gadolinium enhancement; phase sensitive inversion recovery turbo field echo, PSIR TFE. Results: Thirty out of 40 patients with susceptive acute viral myocarditis met the CMR criteria of acute viral myocarditis (Lake Louise Criteria) (LL+ ) and the other 10 patients did not meet the diagnostic criteria (LL-). Left ventricular ejection fraction (LVEF) values were significantly lower in LL+ group than in LL- group at baseline and at 12 months after discharge (P<0.01 or 0.05, respectively). The baseline left ventricular end-systolic volume index (LVESVI) was significantly higher in LL+ group than in LL- group (P<0.05) and was similar between the groups at 12 months follow up.Left ventricular end-diastolic volume index (LVEDVI )was similar between the two groups at baseline and at 12 months follow up.LVEF was significantly higher during 12 months follow up compared to baseline in LL+ group and remained unchanged in LL- group during the two time points.LVESVI and LVEDVI remained unchanged at baseline and during 12 months follow up both in LL+ and LL- groups (P>0.05). Results showed that LL+ , edema ratio (ER) positive and global relative enhancement (gRE) positive were associated with significant increase of LVEF at 12 months follow up.However, LL-, ER negative, gRE negative, late gadolinium enhancement(LGE) negative and LGE positive linked with unchanged LVEF at 12 months follow up (P>0.05). Patients were further divided into LVEF increase (ΔLVEF≥5%) group and non LVEF increase group (ΔLVEF<5%), the results of Chi-square test showed that LL+ and ER positive were related to the improvement of LVEF (P<0.05), while gRE and LGE were not associated with improvement of cardiac function (P>0.05). Multiple linear regression analysis, using ER, gRE and LGE as independent variables and LVEF as dependent variables, showed that the presence of myocardial edema was the strongest independent predictor of an increase in LVEF at follow up (full model: non-standardized coefficient 0.445, P=0.043; reduced model: non-standardized coefficient 0.442, P=0.12). Conclusion: Cardiac magnetic resonance imaging monitoring is valuable to observe the cardiac function and morphology changes in patients with acute viral myocarditis, and myocardial edema imaging is the most powerful parameter to predict the improvement of LVEF in this patient cohort.

Retrospective seroepidemiological study of chikungunya infection in South Asia, Southeast Asia and the Pacific region.

Chikungunya virus (CHIKV) and Ross River virus (RRV) of the genus Alphavirus, family Togaviridae are mainly transmitted by Aedes mosquitoes and the symptoms they cause in patients are similar to dengue. A chikungunya (CHIK) outbreak re-emerged in several Asian countries during 2005-2006. This study aimed to clarify the prevalence of CHIKV infection in suspected dengue patients in six countries in South Asia and Southeast Asia. Seven hundred forty-eight serum samples were from dengue-suspected patients in South Asia and Southeast Asia, and 52 were from patients in Fiji. The samples were analysed by CHIKV IgM capture ELISA, CHIKV IgG indirect ELISA and focus reduction neutralization test against CHIKV or RRV. CHIK-confirmed cases in South Asia, particularly Myanmar and Sri Lanka, were 4·6%, and 6·1%, respectively; and in Southeast Asia, particularly Indonesia, the Philippines and Vietnam, were 27·4%, 26·8% and 25·0%, respectively. It suggests that CHIK was widely spread in these five countries in Asia. In Fiji, no CHIK cases were confirmed; however, RRV-confirmed cases represented 53·6% of suspected dengue cases. It suggests that RRV is being maintained or occasionally entering from neighbouring countries and should be considered when determining a causative agent for dengue-like illness in Fiji.

[Comparison on metabolic disorders and uric acid levels between patients with primary aldosteronism and essential hypertension].

Objective: To compare the incidence of metabolic disorders and uric acid (UA) levels between patients with primary aldosteronism (PA) and essential hypertension (EH), and to explore factors associated with UA levels in these patients. Methods: A total of 117 PA and 117 EH patients individually matched by sex, age, blood pressure and duration of hypertension were recruited from in-hospital patients who were hospitalized in our department because of suspicion of secondary hypertension from January 2008 to December 2014. Clinical data including metabolic disorders and UA levels were analyzed. Results: (1) Body mass index (BMI), waist circumference, plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA) were significantly higher in EH than in PA group (all P<0.05). Prevalence of diabetes mellitus or impaired glucose tolerance (DM+ IGT) was significantly higher in EH than in PA group (41.9% (49/117) vs. 17.1% (20/117), P<0.01). The prevalence of metabolic syndrome (MS) was also significantly higher in EH than in PA group (51.3% (60/117) vs. 24.8% (29/117), P<0.01). (2) EH patients had higher homeostasis model assessment for insulin resistance (HOMA-IR) and lower insulin sensitivity index composite (ISI comp) than PA patients, but basic insulin secretion index (HOMA-ß) and modified ß cell function index (MBCI) were significantly lower in PA than in EH group (P<0.05). (3) With regard to target organs damages, PA patients revealed higher 24-hour urinary protein, urinary albumin excretion rate (UAER), urinary IgG, urinary α-1 microglobulin, left ventricular mass index and lower urine specific gravity than EH patients (all P<0.05). There was no significant difference in estimated glomerular filtration rate (eGFR) between two groups (P=0.103). (4) UA level was significantly lower in PA group than in EH group ((314.00±89.52) µmol/L vs. (379.16±101.25) µmol/L, P<0.01). Higher plasma aldosterone concentration and lower plasma renin activity were associated with lower UA level in PA group. Conclusions: Compared with sex, age and hypertension duration matched EH patients, PA patients revealed lower UA level and less severe abnormalities of glucose and lipid metabolism, but are associated with severer renal and cardiac damages. The reduced UA level in PA patients is possibly due to the high plasma aldosterone concentration and low plasma renin activity.

Clinical use of iterative 4D-cone beam computed tomography reconstructions to investigate respiratory tumor motion in lung cancer patients.

BACKGROUND: Cone beam computed tomography (CBCT) provides means for respiratory resolved volumetric imaging of the thorax. However, merely sorting the acquired projections into respiratory phases and performing a series of conventional three-dimensional (3D) reconstructions lead to clinically prohibitive reconstruction artifacts. This problem can be mitigated by iterative 4D reconstruction. We present a clinical evaluation of two iterative 4D-CBCT reconstruction algorithms during stereotactic body radiation therapy. MATERIAL AND METHODS: Two types of iterative 4D-CBCT reconstructions were performed utilizing: 1) total variation (TV) minimization; and 2) optical flow (OF) based deformable registration between phases. The reconstructions were initially evaluated on a lung phantom with a moveable target insert. Subsequently, 4D-CBCT reconstructions were performed for 19 patients on 2-3 CBCT projection datasets previously acquired for conventional 3D-CBCT reconstruction (∼650 half-fan projections per scan in a full one-minute gantry rotation). The 4D reconstructions were imported into a treatment planning system, where the gross tumor volume (GTV) was delineated and used to extract the tumor motion amplitude. RESULTS: For both phantom and patient scans, the iterative 4D-CBCT reconstructions had sufficient quality for GTV delineation when the breathing period was faster than 3.5 seconds (15 of 19 patients), but not for slower breathing periods (4 patients). The 3D tumor motion amplitude for the patients was significantly lower (p = 10(-6), Wilcoxon signed rank test) in the OF reconstructions (mean 4.0 mm) than in the TV reconstructions (mean 5.3 mm). CONCLUSION: TV and OF iterative 4D-CBCT reconstruction of the thorax in a lung phantom and for 19 patients was demonstrated from standard CBCT scans and used to estimate the daily lung tumor motion.

A survey of rodent-borne pathogens carried by wild Rattus spp. in Northern Vietnam.

To examine the prevalence of human pathogens carried by rats in urban areas in Hanoi and Hai Phong, Vietnam, we live-trapped 100 rats in January 2011 and screened them for a panel of bacteria and viruses. Antibodies against Leptospira interrogans (22·0%), Seoul virus (14·0%) and rat hepatitis E virus (23·0%) were detected in rats, but antibodies against Yersinia pestis were not detected. Antibodies against L. interrogans and Seoul virus were found only in adult rats. In contrast, antibodies to rat hepatitis E virus were also found in juvenile and sub-adult rats, indicating that the transmission mode of rat hepatitis E virus is different from that of L. interrogans and Seoul virus. Moreover, phylogenetic analyses of the S and M segments of Seoul viruses found in Rattus norvegicus showed that Seoul viruses from Hai Phong and Hanoi formed different clades. Human exposure to these pathogens has become a significant public health concern.

The tubercular disease in immigrants without documents: new diagnostic settings adopted in Milan, Italy.

The tubercular disease (TB) is "the disease of poverty and people in need", spread in the poorest countries and among the less wealthy people of the western world (immigrants). In Italy the health authority has recently defined precise diagnostic and therapeutic patterns for TB. The social and health Association Naga in Milan with the Regional Reference Centre for TB, designed a screening system. In Naga's surgery all the undocumented immigrants, coming to Italy from countries with high TB incidence (> 100/100000) and high immigration rates, are screened by a questionnaire created by the Swiss Lung League; the suspect cases are sent to a designed centre for a second level of investigation. The use of this form allows to set a first selection based on the patients' anamnestic history, thus avoiding the intradermal reaction that, due to its low selectivity, could cause a 4 times higher crowding of the designed secondary centers.

Evaluation of freshwater heavy metals accumulation effect on oxidative stress, Metallothionein biosynthesis and histopathology of Procambarus clarkii (Girard,1985) collected from three locations in the Delta region, Egypt.

BACKGROUND: In this study, the effect of heavy metals accumulation influence was evaluated on adult crayfish Procambarus clarkii (Decapoda, Astacidea) collected from three different Governmental locations (Kafr El-Shaikh, El-Menofya, and El-Gharbiya) of the Egyptian Delta. The activity of super oxidase dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) of gills, hepatopancreas, and muscle tissue were measured. SDS Polyacrylamide gel electrophoresis (SDS-PAGE) and West blotting technique were performed to detect MT Protein expression. RESULTS: The results revealed that Kafr El-Shaikh reflected the highest Superoxide dismutase (SOD), Catalase, and Glutathione S-transferase (GST) activity levels (97.2 u/100 mg, 28.5 u/100 mg, and 8.3 nmol mg (-1) protein min (-1) respectively. Superior protein polymorphism % (30%) remarked collected Freshwater crayfish P. clarkii from Kafr El-Shaikh location. Varied protein polymorphism % was shown between collected crayfish from El-Menofya, and El-Gharbiya locations (5.5 and 6.2 respectively) Increasing Metallothioneins intensity (15.4%) for collected Freshwater crayfish Procambarus clarkii from Kafr El-Shaikh Location. CONCLUSION: Heavy metal stress influences antioxidant status and also induces increasing Metallothioneins intensity, especially samples that were collected from the Kafr El-Shaikh area.

Posterior tibial artery flap versus radial forearm flap in oral cavity reconstruction and donor site morbidity.

The repair of soft tissue defects after oral cavity cancer resection is challenging. The aim of this study was to compare the outcomes and donor site morbidity of the radial forearm free flap (RFF) and posterior tibial artery perforator flap (PTAF) for oral cavity reconstruction after cancer ablation. All patients who underwent oral cavity reconstruction with a RFF or PTAF between January 2017 and December 2019 were included retrospectively in this study. All flaps were harvested with a long adipofascial extension. The donor site defects were closed with a triangular full-thickness skin graft harvested adjacent to the flap. Flap outcomes and donor site complications were recorded and compared. The study included 145 patients; 30 underwent reconstruction with a RFF and 115 with a PTAF. No significant difference between the PTAF and RFF was observed concerning the flap survival rate (98.3% vs 96.7%), flap harvest time (53.39 vs 49.28 min), hospital stay (12.3 vs 15.2 days), or subjective functional and cosmetic outcomes. The PTAF showed a larger vascular calibre (P < 0.05), greater flap thickness (P = 0.002), and lower frequency of surgical site infection (P = 0.055) when compared to the RFF. No significant difference was observed between the pre- and postoperative ranges of ankle and wrist movements. The PTAF is an excellent alternative to the RFF for the repair of oral cavity defects, with the additional advantages of a well-hidden scar on the lower extremity, larger vascular calibre, and lower frequencies of postoperative donor site morbidities.

Prevalence and characteristics of gastroesophageal reflux disease in pregnant women.

INTRODUCTION AND AIMS: The prevalence of gastroesophageal reflux disease (GERD) has been reported to be increasing in recent years. However, there have been few reports on the prevalence of GERD during pregnancy in the Asian population. The aim of our study was to evaluate the prevalence and characteristics of GERD in Vietnamese pregnant women. MATERIALS AND METHODS: This cross-sectional study was conducted at the antenatal clinic of the Nhan Dan Gia Dinh Hospital, Ho Chi Minh, Vietnam. Four hundred females, at various stages of pregnancy, were enrolled. GERD was diagnosed if there was troublesome heartburn and/or acid regurgitation, at least once a week, during the current pregnancy. RESULTS: The overall prevalence of GERD in pregnancy was 38.5% (154/400). The prevalence of GERD in the third trimester was significantly higher than that in the second trimester (46.8% vs. 30.7%, P=0.008) and tended to be higher than its prevalence in the first trimester (46.8% vs. 35.4%, P=0.051). In the pregnant women with GERD, the frequency of regurgitation was significantly higher than that of heartburn (92.9% vs. 30.5%, P<0.001). Those typical symptoms were more prevalent in the daytime, compared with nighttime. CONCLUSION: Our study showed that GERD was prevalent during pregnancy in Vietnam. In the pregnant women with GERD, regurgitation was much more common than heartburn, and those typical reflux symptoms occurred more frequently in the daytime, compared with nighttime.

Heart failure is independently associated with white matter lesions: insights from the population-based LIFE-Adult Study.

AIMS: White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML. METHODS AND RESULTS: The LIFE-Adult Study is a population-based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0-1, and 334 (13.4%) had Fazekas score of 2-3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54-62). Age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2-3) with HF was 2.8 (95% CI 1.2-6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend). CONCLUSIONS: In addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML.

Comparison of approaches for efficient gene silencing induced by microRNA-based short hairpin RNA and indicator gene expression.

MicroRNA-based short hairpin RNAs (shRNAs) are natural inducers of RNA interference and have been increasingly used in shRNA expression strategies. In the present study, we compared the efficiencies of exogenous green fluorescence protein (GFP) and endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) knockdown and red fluorescent protein (RFP) indicator expression mediated by three differently designed plasmids. RFP was introduced either at the 5' end, at the 3' end of the human mir155-based target gene (TG) (e.g., GFP or GAPDH) shRNA expression cassette (EC), or at the 3' end of the chimeric intron-containing TG shRNA EC. Comparisons with the control vector showed an obvious reduction of GFP or GAPDH expression with the various shRNA expression plasmids (P < 0.05). When RFP was located at the 5' end or at the 3' end of the TG shRNA EC, RFP expression was low; whereas when RFP was connected with the chimeric intron-containing TG shRNA EC, RFP expression was high. Taken together, this study demonstrated an efficient plasmid design for both TG silencing induced by microRNA-based shRNA and indicator gene expression in vitro.