The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by Zika virus.
- 作者列表："Pedrosa CDSG","Souza LRQ","Gomes TA","de Lima CVF","Ledur PF","Karmirian K","Barbeito-Andres J","Costa MDN","Higa LM","Rossi ÁD","Bellio M","Tanuri A","Prata-Barbosa A","Tovar-Moll F","Garcez PP","Lara FA","Molica RJR","Rehen SK
:The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.
: 巴西东北部 (NE) 地区通常经历干旱时期，有利于蓝藻大量繁殖，能够产生对人类和动物健康有影响的神经毒素。巴西历史上最严重的干燥期发生在 2012 年至 2016 年之间。巧合的是，与寨卡病毒 (ZIKV) 爆发相关的小头症发病率最高的发生在巴西的NE地区。在这项工作中，我们测试了一种假说，即沙霉素 (STX)，一种由淡水蓝藻 (raphidopsis raciborskii) 在南美洲产生的神经毒素，可能导致最严重的先天性寨卡综合征 (CZS) 全球描述的概况。质量监测显示，与巴西其他地区相比，NE的人类饮用水供应中蓝藻数量和STX发生率更高。实验上，我们描述了STX使人脑类器官祖细胞区域中ZIKV诱导的神经细胞死亡的数量增加了一倍，而妊娠前和妊娠期间长期摄入被STX污染的水导致ZIKV感染的免疫活性C57BL/6J小鼠后代的脑异常。我们的数据表明，产沙池毒素的蓝藻在NE的水库中分布广泛，可能是巴西ZIKV感染的共同危害。这些结果引起了公众对发生在干旱和/或淡水蓝藻水华频繁地区的虫媒病毒爆发后果的关注。
METHODS::Impairments in social cognition have been frequently described in 22q11.2 deletion syndrome (22q11.2DS) and are thought to be a hallmark of difficulties in social interactions. The present study addresses aspects that are critical for everyday social cognitive functioning but have received little attention so far. Sixteen children with 22q11.2DS and 22 controls completed 1 task of facial expression recognition, 1 task of attribution of facial expressions to faceless characters involved in visually presented social interactions, and 1 task of attribution of facial expressions to characters involved in aurally presented dialogues. All three tasks have in common to involve processing of emotions. All participants also completed two tasks of attention and two tasks of visual spatial perception, and their parents completed some scales regarding behavioural problems of their children. Patients performed worse than controls in all three tasks of emotion processing, and even worse in the second and third tasks. However, they performed above chance level in all three tasks, and the results were independent of IQ, age and gender. The analysis of error patterns suggests that patients tend to coarsely categorize situations as either attractive or repulsive and also that they have difficulties in differentiating emotions that are associated with threats. An isolated association between the tasks of emotion and behaviour was found, showing that the more frequently patients with 22q11.2DS perceive happiness where there is not, the less they exhibit aggressive behaviour.
METHODS:BACKGROUND:We describe the first radiographic clinic in the literature for DDH and how this novel clinic can significantly improve the efficiency and cost-effectiveness of service in a tertiary referral centre. AIMS:A radiographic clinic for the management of developmental dysplasia of the hip was introduced in 2017 in our institution. We performed a detailed cost analysis to assess the economic savings made with the introduction of this new clinic. We assessed the efficiency of the service by identifying how many unnecessary outpatient visits were prevented. We also assessed the difference in times from referral to review between the two clinics. METHODS:Analysis of the clinic activity in 2017 was possible as all data was collected prospectively by the DDH CNS and stored in our database. Cost analysis was performed, and the savings made per patient along with the financial benefit to our institution was recorded. RESULTS:The new radiographic clinic reduced the cost of reviewing one patient by €162.51 per patient. There was a 73% discharge rate from the clinic which prevented 251 unnecessary patient visits to the outpatient department over the course of the year. There was a significant 11-day reduction in waiting times between referral and review when comparing the radiographic to the conventional clinic (p < 0.05). CONCLUSIONS:A radiographic clinic for the management of developmental dysplasia of the hip has a significant effect on the efficiency and overall cost-effectiveness of service provision in a tertiary referral centre.
METHODS:INTRODUCTION:Triple pelvic osteotomy (TPO) involves periacetabular osteotomies of the ilium, ischium, and pubis to reorient the acetabulum. This operation is indicated in certain situations for the treatment of developmental dysplasia of the hip, dysplastic neuromuscular hips, and for containment of the femoral head in cases of Legg-Calvé-Perthes disease. METHODS:This retrospective cohort study compares radiographic outcomes of patients who underwent TPO using two different techniques and describes a novel single-incision direct lateral approach. TPO was performed on 22 patients by the senior author. The first 10 patients underwent TPO through a single-incision anterolateral approach. The last 12 patients underwent TPO using the direct lateral approach. Preoperative and postoperative pelvic radiographs were reviewed for each patient, and the migration index and center-edge angle were recorded. RESULTS:The migration index and center-edge angle were evaluated and were not found to be significantly different between the anterolateral and direct lateral groups. The direct lateral approach is described. CONCLUSION:The direct lateral approach for TPO is equivalent to the anterolateral approach on radiographic evaluation. Advantages of the direct lateral approach include direct visualization of the ischial osteotomy, effective mobilization of the acetabulum, and safety of the sciatic nerve.