Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

3-D Ultrasound Imaging Reliability of Measuring Dysplasia Metrics in Infants

Developmental dysplasia of the hip is a hip abnormality that ranges from mild acetabular dysplasia to irreducible femoral head dislocations. While 2-D B-mode ultrasound (US)-based dysplasia metrics or disease metrics are currently used clinically to diagnose developmental dysplasia of the hip, such estimates suffer from high inter-exam variability. In this work, we propose and evaluate 3-D US-derived dysplasia metrics that are automatically computed and demonstrate that these automatically derived dysplasia metrics are considerably more reproducible. The key features of our automatic method are (i) a random forest-based learning technique to remove regions across the coronal axis that do not contain bone structures necessary for dysplasia-metric extraction, thereby reducing outliers; (ii) a bone segmentation method that uses rotation-invariant and intensity-invariant filters, thus remaining robust to signal dropout and varying bone morphology; (iii) a novel slice-based learning and 3-D reconstruction strategy to estimate a probability map of the hypoechoic femoral head in the US volume; and (iv) formulae for calculating the 3-D US-derived dysplasia metrics. We validate our proposed method on real clinical data acquired from 40 infant hip examinations. Results show a considerable (around 70%) reduction in variability in two key 3-D US-derived dysplasia metrics compared with their 2-D counterparts.     

经颅直流电刺激对精神分裂症伴迟发性运动障碍患者空间 工作记忆的影响

目的 探讨经颅直流电刺激（tDCS）对精神分裂症伴迟发性运动障碍（TD）患者空间工作记 忆的影响。方法 选取2017 年6 月至2018 年1 月来源于苏州市广济医院、苏州市社会福利总院、太仓市 精神卫生中心、南充市第六人民医院四家精神专科医院的38 例住院精神分裂症伴TD 患者，随机分为试 验组（21 例）和对照组（17 例）。研究期间，两组患者均接受常规药物治疗，试验组予以tDCS 治疗，采用的 电流为2 mA，刺激部位为左侧背外侧前额叶皮质及对侧眶上缘；对照组相应地予以伪tDCS 治疗。在基 线期、治疗15 次结束后及2 周后进行随访，采用剑桥神经心理自动化成套测试（CANTAB）中的空间工作 记忆（SWM）模块分别对两组患者进行认知测评。结果 在完成15 次治疗后，试验组SWM 指标分析中 的总错误数［31.00（28.50，49.00）］、平均第一次响应时间（4 盒子）［3 289.500（1 871.750，5 018.000）ms］、 平均第一次响应时间（6 盒子）［2 862.500（2 128.500，4 672.250）ms］、平均第一次响应时间（8 盒子） ［3 328.500（2 611.250，5 120.750）ms］与对照组比较，差异无统计学意义（P＞ 0.05）；试验组SWM 指标分 析中的策略分［19.00（17.00，20.00）］低于对照组［21.00（19.50，23.00）］，差异有统计学意义（P ＜ 0.05）。 在2 周后的随访中，两组的SWM 各指标比较，差异均无统计学意义（P＞ 0.05）。结论 tDCS 可能对精神 分裂症患者使用策略的能力有即刻改善效应。     

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Background The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions.Methods This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting.Findings Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey.Conclusions The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.Subject terms: Breast cancer, Surgical oncology, Health care economics, Quality of life, Health policy     

Papel del personal técnico superior en imagen para el diagnóstico durante la pandemia COVID-19: importancia de la organización y planificación en la primera línea

The COVID-19 pandemic and the consequent declaration of a state of alarm have required changes throughout the entire health system and diagnostic imaging departments are no exception.In our department, these circumstances led to an immediate restructuring of the working dynamics of our group of imaging technologists that had an important role in the front lines of the battle. To ensure that these new needs were met, the staff had to be trained and distributed into different areas and working groups; moreover, new protective measures and protocols had to be adopted in the working environment. We also defined different care circuits for patients with COVID-19 and those without COVID-19, incorporating new technologies, adapting existing resources to the new scenario, and creating a circuit for the rapid diagnosis of COVID-19. This paper also provides detailed recommendations for organizing radiology departments in the case of new outbreaks of COVID-19.