Chromosome remodeling and differentiation of tetraploid embryos during preimplantation development

Although it is known that the tetraploid embryo contributes only to the placenta, the question of why tetraploid embryos differentiate into placenta remains unclear. To study the effect of electrofusion on the development of mouse tetraploid oocytes, mouse two‐cell embryos were fused and cultured in vitro in Chatot‐Ziomek‐Bavister medium. After electrofusion, two chromosome sets from the tetraploid blastomere were individually duplicated before nuclear fusion. At 8–10 hr after electrofusion, each chromosome set was condensing and the nuclear membrane was breaking down. Around 12–14 hr after electrofusion, the two chromosome sets had combined together and had reached the second mitotic metaphase, at this point with 8n sets of chromosomes. Interestingly, we discovered that expression of OCT4, an inner cell mass cells biomarker, is lost by the tetraploid expanded blastocysts, but that CDX2, a trophectoderm cells biomarker, is strongly expressed at this stage. This observation provides evidence clarifying why tetraploid embryos contribute only to trophectoderm. Developmental Dynamics 240:1660–1669, 2011. © 2011 Wiley‐Liss, Inc.     

肠道病毒71型山东临沂分离株全基因组序列分析

目的 自1例死亡患儿的标本中分离EV71,并分析其全基因组序列特点,研究其基因序列的改变是否与其神经毒力有关.方法 咽拭子标本采自山东临沂市人民医院1例死亡患儿,在人横纹肌瘤细胞(RD)上分离EV71,分段扩增获得EV71的全序列,用BLAST、Bioedit和MEGA 4进行序列分析.结果 获得1株EV71分离株SDLY107,基因组全长7405 bp,全基因组核苷酸序列与2008年的阜阳株Fuyang.Anhui.P.R.C/17.08/2同源性最高,为98.6%,与原型株BrCr/70的同源性为80.0%,与神经毒型株MS/87的同源性为86.5%.系统进化分析表明,SDLY107与中国大陆的北京株、河南株、广西株、深圳株、兰州株、阜阳株、重庆株、浙江株的亲缘关系较近,按照传统的VP1基因分型方法,可归为C4亚型,是近年来我国大陆流行的主要基因亚型.氨基酸序列分析发现,SDLY107与其他毒株相比,有2个特有的突变(E947D,K1873R).结论 SDLY107分离株属于C4亚型,氨基酸突变E947D和K1873R可能与EV71的致病性有关.

Abstract：

Objective To isolate enterovirus 71 from a death children,and analyze whether the neurovirulence was related to the variation of nucleotide and amino acid. Methods Enterovirus 71 was isolated from throat swabs which were colleted from Shandong Linyi People's Hospital. The full length genome was sequenced by amplification with RT-PCR and sequencing of 9 overlapped gene fragments covering full length of the genomes. The nucleotide and amino acid sequenced was aligned by BLAST, Bioedit and MEGA 4. Results A strain of enterovirus 71 was isolated and named as SDLY107. The full length was 7405 bp. The results of homology analysis of overall nucleotide sequence showed that strain Fuyang. Anhui. P. R. C/17.08/2 had highest homology (98.6%)with strain SDLY107, and the homology was 80.0% between strain SDLY107 with prototype strain BrCr/70,and 86. 5% between strain SDLY107 with nerve strain MS/87. Phylogenetic analysis showed that the phylogeny was close between SDLY107 with some isolated strains from Chinese Mainland, such as Beijing, Henan, Guangxi, Sbenzhen, Lanzhou, Fuyang, Chongqing and Zhejiang strains, which was clustered for C4 subtype. The results of amino acid sequence analysis showed that there were 2 mutations, E947D and K1873R, for strain SDLY107. Conclusion SDLY107 belonged to C4 subtype, amino acid mutations E947D and K1873R of which may be relevant to the pathogenicity of EV71.     

DNA methylation profile during multistage progression of pulmonary adenocarcinomas

Multiple genetic and epigenetic alterations are known to be involved in the carcinogenesis of peripheral pulmonary adenocarcinoma (ADC). However, epigenetic abnormalities have not been extensively investigated in the following multistage progression sequence: atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to invasive ADC. To determine the potential role of promoter methylation during ADC development of the lung, we examined methylation status in 20 normal, 20 AAH, 30 AIS, and 60 ADC lung tissues and compared methylation status among the lesions. The MethyLight assay was used to determine the methylation status of 18 CpG island loci, which were hypermethylated in ADC compared to noncancerous lung tissues. The mean number of methylated CpG island loci was significantly higher in ADC than in AAH and AIS, (p < 0.003 between ADC and AAH, p < 0.005 between ADC and AIS). Aberrant methylation of HOXA1, TMEFF2, and RARB was frequently observed in preinvasive lesions, including AAH and AIS. Furthermore, methylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was significantly more frequent in invasive ADC than AAH or AIS. Our results indicate that epigenetic alterations are involved in the multistep progression of pulmonary ADC development, and aberrant CpG island methylation accumulates during multistep carcinogenesis. In addition, aberrant methylation of HOXA1, TMEFF2, and RARB occurred in preinvasive lesions, which indicates that epigenetic alterations of these genes are involved in the early stages of pulmonary ADC development. In contrast, hypermethylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was more frequent in invasive ADC than in preinvasive lesions, which indicates that methylation of these genes occurs later during tumor invasion in the AAH–AIS–ADC sequence.     

Regional and Chronological Variation of Chemosensory Dysfunction in COVID-19: a Meta-Analysis

BackgroundOlfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease 2019 (COVID-19). However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear. Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction.MethodsOut of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a meta-analysis. Calculating the data extracted from each study, the weighted summary prevalence of olfactory and gustatory dysfunction was estimated using a Freeman-Tukey transformation with models based on random-effects assumptions. A meta-analysis of variance compared the prevalence of olfactory and gustatory dysfunction according to regional, chronological, demographic, and methodologic factors, respectively.ResultsThe overall pooled prevalence rates of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalence rates of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalence rates of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment.ConclusionThe regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.     

Right Ventricular Longitudinal Conduction Delay in Patients with Brugada Syndrome

BackgroundThe mechanism of Brugada syndrome (BrS) is still unclear, with different researchers favoring either the repolarization or depolarization hypothesis. Prolonged longitudinal activation time has been verified in only a small number of human right ventricles (RVs). The purpose of the present study was to demonstrate RV conduction delays in BrS.MethodsThe RV outflow tract (RVOT)-to-RV apex (RVA) and RVA-to-RVOT conduction times were measured by endocardial stimulation and mapping in 7 patients with BrS and 14 controls.ResultsPatients with BrS had a longer PR interval (180 ± 12.6 vs. 142 ± 6.7 ms, P = 0.016). The RVA-to-RVOT conduction time was longer in the patients with BrS than in controls (stimulation at 600 ms, 107 ± 9.9 vs. 73 ± 3.4 ms, P = 0.001; stimulation at 500 ms, 104 ± 12.3 vs. 74 ± 4.2 ms, P = 0.037; stimulation at 400 ms, 107 ±12.2 vs. 73 ± 5.1 ms, P = 0.014). The RVOT-to-RVA conduction time was longer in the patients with BrS than in controls (stimulation at 500 ms, 95 ± 10.3 vs. 62 ± 4.1 ms, P = 0.007; stimulation at 400 ms, 94 ±11.2 vs. 64 ± 4.6 ms, P = 0.027). The difference in longitudinal conduction time was not significant when isoproterenol was administered.ConclusionThe patients with BrS showed an RV longitudinal conduction delay obviously. These findings suggest that RV conduction delay might contribute to generate the BrS phenotype.     

Changes in electroencephalographic power and bicoherence spectra according to depth of dexmedetomidine sedation in patients undergoing spinal anesthesia

Background: Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting.Patients and Methods: Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode.Results: The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high β and γ power decreased significantly (P <0.001). α and spindle power increased significantly under light and moderate sedation (P <0.001 in light vs baseline and deep sedation; P = 0.002 and P <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; P = 0.008 and P <0.001 in light sedation vs moderate and deep sedation, respectively; P = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; P=0.053).Conclusions: The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.     

From nonalcoholic fatty liver disease to metabolic-associated fatty liver disease: Big wave or ripple?

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.     

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878     

Developing a Framework for Pandemic COVID-19 Vaccine Allocation: a Modified Delphi Consensus Study in Korea

BackgroundThis study presents a framework for determining the allocation and distribution of the limited amount of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsAfter analyzing the pandemic strategies of the major organizations and countries and with a literature review conducted by a core panel, a modified Delphi survey was administered to 13 experts in the fields of vaccination, infectious disease, and public health in the Republic of Korea. The following topics were discussed: 1) identifying the objectives of the vaccination strategy, 2) identifying allocation criteria, and 3) establishing a step-by-step vaccination framework and prioritization strategy based on the allocation criteria. Two rounds of surveys were conducted for each topic, with a structured questionnaire provided via e-mail in the first round. After analyzing the responses, a meeting with the experts was held to obtain consensus on how to prioritize the population groups.ResultsThe first objective of the vaccination strategy was maintenance of the integrity of the healthcare system and critical infrastructure, followed by reduction of morbidity and mortality and reduction of community transmission. In the initial phase, older adult residents in care homes, high-risk health and social care workers, and personal support workers who work in direct contact with coronavirus disease 2019 (COVID-19) patients would be prioritized. Expansion of vaccine supply would allow immunization of older adults not included in phase 1, followed by healthcare workers not previously included and individuals with comorbidities. Further widespread vaccine supply would ensure availability to the extended adult age groups (50–64 years old), critical workers outside the health sector, residents who cannot socially distance, and, eventually, the remaining populations.ConclusionThis survey provides the much needed insight into the decision-making process for vaccine allocation at the national level. However, flexibility in adapting to strategies will be essential, as new information is constantly emerging.