Zoonotic coronavirus epidemics: Severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019

ObjectiveTo review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).Data SourcesPublished literature obtained through PubMed database searches and reports from national and international public health agencies.Study SelectionsStudies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency.ResultsAlthough SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy.ConclusionFurther data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.     

Improving the image quality of DWI in breast cancer: comparison of multi-shot DWI using multiplexed sensitivity encoding to conventional single-shot echo-planar imaging DWI

Objective:To compare diffusion-weighted images (DWI) acquired using single-shot echo-planar imaging (ss-EPI) and multiplexed sensitivity encoding (MUSE) in breast cancer.Methods20 females with pathologically confirmed breast cancer (age 51 ± 12 years) were imaged with ss-EPI-DWI and MUSE-DWI. ADC, normalised ADC (nADC), blur and distortion metrics and qualitative image quality scores were compared. The Crété-Roffet and Mattes mutual information metrics were used to evaluate blurring and distortion, respectively. In a breast phantom, six permutations of MUSE-DWI with varying parallel acceleration factor and number of shots were compared. Differences in ADC and nADC were compared using the coefficient of variation in the phantom and a paired t-test in patients. Differences in blur, distortion and qualitative metrics were analysed using a Wilcoxon signed-rank test.Results:There was a low coefficient of variation (<2%) in ADC between ss-EPI-DWI and all MUSE-DWI permutations acquired using the phantom. 22 malignant and three benign lesions were identified in 20 patients. ADC values measured using MUSE were significantly lower compared to ss-EPI for malignant but not benign lesions (p < 0.001, p = 0.21). nADC values were not significantly different (p = 0.62, p = 0.28). Blurring and distortion improved with number of shots and acceleration factor, and significantly improved with MUSE in patients (p < 0.001, p = 0.002). Qualitatively, image quality improved using MUSE.Conclusion:MUSE improves the image quality of breast DWI compared to ss-EPI.Advances in knowledge:MUSE-DWI has superior image quality and reduced blurring and distortion compared to ss-EPI-DWI in breast cancer.     

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.     

Adult attachment and gene polymorphisms of the dopamine D4 receptor and serotonin transporter (5-HTT)

Recently, the Dopamine D4 Receptor Gene (DRD4) and the Serotonin Transporter Gene (5-HTT) have been found to be candidate genes for infant attachment disorganization. The present study aimed to explore the relationship of these genes to adult attachment representations. The Adult Attachment Interview was used to assess attachment representations in 167 German adults. DNA from buccal cells was genotyped for the DRD4 VNTR Exon III and 5-HTT LPR polymorphisms with respect to the presence of the 7repeat allele and the short allele, respectively. DRD4 7repeat allele carriers were significantly more likely to be securely attached than those without 7repeat but only for subjects with unloving caregiver recollections. No association between the 5-HTT LPR polymorphism and adult attachment was found. These findings encourage further investigations to explore endophenotypical and mediating psychological processes between the DRD4 Gene and secure attachment patterns.     

中国儿童与老年健康证据转化平台的构建与应用

目的介绍并推广中国儿童与老年健康证据转化平台(Chinese Clearinghouse for Evidence Translation in Child & Aging Health,CCET)。方法分别成立儿童、老年健康顾问委员会,利用科学的评价量表评价筛选国内外相关的儿童、老年健康促进项目并由研究团队翻译转化。与兰州博阳软件工程有限公司合作,根据网站需呈现的内容与目标功能,共同规划设计网站框架与界面,初步建立站点。将转化的健康证据及其他信息资源（疾病基本情况、项目评价量表、研究报告标准等）上传使之在网站相应栏目中呈现,建立CCET网站,并通过微信和微博媒介定期传播儿童及老年健康最新进展、循证研究最新方法。结果CCET主要由儿童健康、老年健康、评价量表、报告标准、推广应用和老年抑郁症循证防治数据库6个版块组成。CCET儿童与老年健康促进项目由国内外专家采用科学的评价量表筛选和评价,转化的证据科学性强,目前已有相关研究机构和社区有意向参与CCET研究和应用转化项目。结论CCET致力于循证方法培训,建立国内健康干预项目的科学性和适用性评价系统,对国外证据转换后的后续干预项目培训,提升服务机构能力,以及综合干预课程研发。CCET信息全面、界面简单、用户友好,为促进我国儿童与老年健康提供证据支持。     

FGF23 Is Endogenously Phosphorylated in Bone Cells

Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi‐site O‐glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S‐X‐D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG‐SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14‐kDa carboxy‐terminal—but not the 17‐kDa N‐terminal—fragment. Sequential serine‐to‐alanine site‐directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy‐terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography‐coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23^R179Q, confirming labeling results. A phosphopeptide‐specific antibody was raised against phospho‐Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine‐phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone. © 2014 American Society for Bone and Mineral Research.     

Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

Spinal cord injury(SCI) is a devastating condition that produces significant changes in the lifestyle of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI: an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents(tamoxifen and a Src kinase family inhibitor known as PP2) that have been shown in our laboratory to produce neuroprotective(increase cell survival) and/or regenerative(axonal outgrowth) actions. The animal model used in our laboratory is adult female rat(~250 g) with a moderate contusion(12.5 mm) to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet(Innovative Research of America, Sarasota, FL, USA) or by intraperitoneal injections(1.5 mg/kg, every 3 days), respectively, to produce a long-term effect(28 days). Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regenerative activity in vertebrates with SCI.     

Obstructive sleep apnea and ischemic heart disease in southwestern US veterans: implications for clinical practice

This study describes associations between obstructive sleep apnea (OSA), intake of food rich in antioxidant nutrients, and ischemic heart disease (IHD) in military veterans. Subjects were male veterans (n=211), 54 to 85 years of age, and enrolled in primary care clinics at the Southern Arizona Veterans Affairs Health Care System (SAVAHCS), Tucson, AZ. Measures included the SAVAHCS Minority Vascular Center Questionnaire, the Sleep Heart Health Study Sleep Habits Questionnaire, the Arizona Food Frequency Questionnaire, height, weight, and blood pressure. Veterans with OSA were significantly more likely to be obese, to have elevated systolic blood pressure and physician-diagnosed IHD, more likely to undergo coronary angiography, and less likely to consume foods rich in cardioprotective antioxidants compared to veterans without OSA. After adjusting for confounding variables, the association between OSA and IHD remains significant [adjusted OR=2.99, confidence interval (CI)=1.07–8.42]. These data reinforce the importance of recognizing OSA within the veterans affairs health care system and suggest that early detection of OSA may improve veterans' health and well-being and reduce associated medical costs. This study was presented as a poster at the 17th Annual American Professional Sleep Society Meeting, Chicago, IL, USA June 3–8 2003