Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.     

La prematuridad: un antecedente de obligada consideración a la hora de valorar el complejo de células ganglionares de la retina

IntroductionPremature children birth and survival is becoming more frequent due to the improvement in obstetric and neonatal care. This makes it increasingly common to find patients with history of preterm birth in ophthalmology clinics, both in pediatric and adult ages. Premature birth can lead to ocular structural changes, being possible to affect the ganglion cell complex (GCC), among other structures, which can be studied using optical coherence tomography.Materials and methodsTo carry out a bibliographic review of the studies that analyze GCC in patients with a history of prematurity compared with patients born at term.ResultsSeveral studies that analyze GCC in patients with a history of prematurity are referenced and their results are studied.ConclusionsIn our clinical practice, knowing the history of prematurity is fundamental in the assessment of GCC measured by optical coherence tomography, since this layer is different in the patients with a history of prematurity compared to patients born at term.     

全身型幼年特发性关节炎患儿合并巨噬细胞活化综合征早期预警量表建立的研究

目的　总结全身型幼年特发性关节炎（sJIA）合并巨噬细胞活化综合征（MAS）的早期临床特征、实验室及辅助检查特点，筛选对诊断MAS有预警作用的检测指标，并量化形成量表，以达到快速对疾病“早识别，早治疗，降低病死率”的目的。方法　回顾性分析2006年1月至2016年1月，北京儿童医院风湿免疫科收治sJIA合并MAS患儿的病例资料，在临床及辅助检查观测指标中筛选出对早期诊断MAS有评估意义的候选指标；通过ROC曲线的方法选择最佳的诊断界限值（Cut-off值）；采用多因素Logistic回归分析MAS独立危险因素，效果以优势比（OR）表示，计算95％置信区间；经过同行评议对上述因素进行权重分值量化并最终形成积分表。结果　390例sJIA患儿，其中141例合并MAS。临床表现全部患儿均有高热、肝脾和（或）淋巴结进行性增大、血液系统受累，中枢神经系统受累患儿19例。单因素Logistic回归及ROC曲线分析结果显示，MAS组和重症sJIA组比较，10个变量存在显著差异（P<0.05）。Logistic回归分析结果显示，Fib ≤3.11g/L、WBC≤11.0×109/L、SF/ESR≥99.4及PLT≤260×109/L为MAS的独立危险因素。绘制模型ROC曲线，灵敏度和特异度分别为92.42%、81.20%。经过30位同行专家评议并投票，分别对上述患儿进行MAS诊断，并对各项临床表现及检验检查项目进行权重值评分，形成早期预警量表。结论　临床表现结合辅助检查结果，利用积分量表的形式，快速判断重症sJIA是否合并早期MAS，对诊断窗口提前，提高MAS诊断率，降低漏诊及前瞻性研究提供参考。     

Impact of HLA-G +3142C>G on the development of antibodies to blood group systems other than the Rh and Kell among sensitized patients with sickle cell disease

BackgroundPatients' inflammatory history is an important factor underlying red blood cell (RBC) alloimmunization, which is a frequent transfusion complication among individuals with sickle cell disease (SCD). HLA-G has been associated with different inflammatory and auto - immune diseases. Our goal was to verify whether the HLA-G + 3142 C>G and 14-bp Ins/Del variations are associated with RBC antibody development among SCD patients.MethodsThis was a single-center case-control study. SCD patients were randomly selected for the study and divided into two groups: ‘Alloimmunized’ and ‘Nonalloimmunized’ depending on the presence of irregular antibodies. The ‘Alloimmunized’group was further divided into two subgroups according to the presence of only antibodies against the Rh and Kell blood group systems or the existence of antibodies to antigens of the other blood group systems.ResultsA total of 213 patients were included in the study (110 alloimmunized and 103 non-alloimmunized). The ‘Alloimmunized’ and ‘Non-alloimmunized’ groups did not differ statistically regarding the HLA-G + 14 bp Ins/Del ( p = 0.494) and + 3142 C>G ( p = 0.334). Individuals who had only antibodies against the Rh and Kell antigens had a frequency of HLA-G + 3142GG genotype almost twice as high compared to the groupwith antibodies against less immunogenic antigens ( p = 0.043).ConclusionsThe genotype frequency of HLA-G + 3142 C>G differs among alloimmunized SCD patients, depending on the presence of antibodies against low immunogenic RBC antigens. This highlights a possible role played by the HLA-G molecule in the RBC alloimmunization process.     

Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma

ObjectivesMap regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Materials and methodsRetrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997–2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.ResultsRegional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2–3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9–9.3; T4 vs. T1: HR 2.3, 95% CI 1.2–4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2–16.1), upper alveolus (HR 3.2, 95% CI 1.0–4.7) or with LVI (HR 2.0, 95% CI 1.0–3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.ConclusionsFor lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3–4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.