Specific alterations of regional myocardial work in strength-trained athletes using anabolic androgenic steroids compared to athletes with genetic hypertrophic cardiomyopathy

Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.

Large,multifocal or portal vein-invading hepatocellular carcinoma(HCC)downstaged by Y90 using personalized dosimetry:safety,pathological results and outcomes after surgery

Background:Transarterial radioembolization(TARE)has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas(HCCs)with high rates of complete pathological necrosis(CPN)on liver explants.In patients with portal vein tumoral thrombus(PVTT),multifocal or large tumors,TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population.Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.Methods:In this retrospective study,we evaluated safety,radiological and pathological response and outcomes in HCC patients with PVTT,multifocal or large tumors,who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry.Results:Between December 2015 and October 2021,18 unresectable patients(14/18 with PVTT)had surgery(16 resections,2 liver transplantations)6.2 months(range,2-14.6 months)after a single Y90 treatment.No 90-day mortality was reported.Objective modified response criteria in solid tumors(mRECIST)response were noted in all but one patient.Complete and extensive(50-99%)necrosis was observed in 36%and 45%of tumors,respectively.The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis(P=0.045).Median overall survival and progression-free survival(PFS)were respectively of 61.8 months[95%CI:31.4 months-not reached(NR)]and 49.3 months(95%CI:14 months-NR).PFS was longer in patients with complete imaging response[median NR(none recurred or died)vs.21.5 months(95%CI:10.1 months-NR),P<0.001]and in those with complete pathological response[median NR vs.22.5 months(95%CI:10.1 months-NR),P<0.001].Conclusions:Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT,large or multifocal HCC.Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure.

SNAP23-Kif5 complex controls mGlu1 receptor trafficking

Metabotropic glutamate 受体在哺乳动物的大脑在有刺激性的触处和控制 synaptic 传播被表示。这些受体涉及众多的 patho 生理的功能。然而，很少对为他们指向的细胞内部的运输和膜负责的分子的决定因素被知道。这里，我们调查了分子的马达和为 trafficking 和这个组的膜本地化负责的适配器蛋白质的性质我在有教养的海马趾的神经原的 metabotropic glutamate mGlu1 postsynaptic 受体。在 proteomic 研究，我们识别了联系 synaptosome 的蛋白质 23 (SNAP23 ) 并且是的分子的马达 Kif5 kinesin 蛋白质与 mGlu1 交往受体。我们显示出那 SNAP23，然而并非 Kif5，直接与 mGlu1 受体 carboxyl 终点交往。使用一条再结合途径损害或提高在 SNAP23 和 Kif5 之间的相互作用，我们发现 SNAP23-Kif5 建筑群沿着微导管控制 mGlu1 受体的 trafficking。在劈开实验以后的另外的荧光恢复允许我们在指向的受体房间表面识别建筑群的一个角色。在结论，我们的学习显示那树枝状的进程 Kif5-SNAP23 建筑群贡献合适的 mGlu1 受体 trafficking 和房间表面表示。