Mortality outcomes based on ED qSOFA score and HIV status in a developing low income country

Objective

To evaluate the utility of the quick Sepsis-related Organ Failure Assessment (qSOFA) score to predict risks for emergency department (ED) and hospital mortality among patients in a sub-Saharan Africa (SSA) setting.

Neonatal lupus syndromes

Children born from mothers positive for autoantibodies against SSA/Ro and/or anti‐SSB/La ribonucleoproteins may develop heart conduction tissue damage resulting in atrioventricular block and/or transient skin rash, liver enzyme abnormalities and anaemia/thrombocytopenia. Additional transient electrocardiographic abnormalities (sinus bradycardia, QT interval prolongation) have been reported. Such clinical and laboratory manifestations are included in the so‐called neonatal lupus syndromes, independently whether the mother is suffering from a systemic autoimmune disease or is totally asymptomatic. The prevalence of the congenital heart block is around 2%, of neonatal rash around 20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 40% of cases. The risk of recurrence of complete heart block is almost 10 times higher in the following pregnancies. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Their long‐term outcome is generally more reassuring than previously assumed and arthralgias and xerophtalmia are the most common symptoms. A standard therapy for heart blocks detected in uterus is still a matter of investigation, although fluorinated corticosteroids have been reported to be effective on myocarditic signs when present. Serial echocardiograms and obstetric sonograms, performed at least every two weeks, starting from the 16 weeks gestation, are recommended in anti‐Ro/SSA positive pregnant women: the goal is to detect early fetal abnormalities, that might precede complete atrioventricular block and that might be a target of preventive therapy. Transplacental passage of maternal anti‐SSA/Ro ‐SSB/La IgG is thought to be pivotal in inducing tissue damage. However, the discordant appearance of the syndrome in twins does suggest a role also for fetal or environmental factors.     

Derailed B cell homeostasis in patients with mixed connective tissue disease

Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19 + CD27-IgD + CD38^high); (2) naive B cells (CD19 + CD27-IgD + CD38^low); (3) non-switched memory B cells (CD19 + CD27 + IgD+); (4) switched memory B cells (CD19 + CD27 + IgD-); (5) double negative (DN) memory B cells (CD19 + CD27-IgD-) and (6) plasma cells (CD19 + CD27^highIgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27^high B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.     

Immunization with 60 kD Ro peptide produces different stages of preclinical autoimmunity in a Sjögren's syndrome model among multiple strains of inbred mice

Sjögren's syndrome is a chronic illness manifested characteristically by immune injury to the salivary and lacrimal glands, resulting in dry mouth/eyes. Anti‐Ro [Sjögren's syndrome antigen A (SSA)] and anti‐La [Sjögren's syndrome antigen B (SSB)] autoantibodies are found frequently in Sjögren's subjects as well as in individuals who will go on to develop the disease. Immunization of BALB/c mice with Ro60 peptides results in epitope spreading with anti‐Ro and anti‐La along with lymphocyte infiltration of salivary glands similar to human Sjögren's. In addition, these animals have poor salivary function/low saliva volume. In this study, we examined whether Ro‐peptide immunization produces a Sjögren's‐like illness in other strains of mice. BALB/c, DBA‐2, PL/J, SJL/J and C57BL/6 mice were immunized with Ro60 peptide‐274. Sera from these mice were studied by immunoblot and enzyme‐linked immunosorbent assay for autoantibodies. Timed salivary flow was determined after pharmacological stimulation, and salivary glands were examined pathologically. We found that SJL/J mice had no immune response to the peptide from Ro60, while C57BL/6 mice produced antibodies that bound the peptide but had no epitope spreading. PL/J mice had epitope spreading to other structures of Ro60 as well as to La, but like C57BL/6 and SJL/J had no salivary gland lymphocytic infiltration and no decrement of salivary function. DBA‐2 and BALB/c mice had infiltration but only BALB/c had decreased salivary function. The immunological processes leading to a Sjögren's‐like illness after Ro‐peptide immunization were interrupted in a stepwise fashion in these differing mice strains. These data suggest that this is a model of preclinical disease with genetic control for epitope spreading, lymphocytic infiltration and glandular dysfunction.     

The auditory novelty system: An attempt to integrate human and animal research

In this account, we attempt to integrate two parallel, but thus far, separate lines of research on auditory novelty detection: (1) human studies of EEG recordings of the mismatch negativity (MMN), and (2) animal studies of single‐neuron recordings of stimulus‐specific adaptation (SSA). The studies demonstrating the existence of novelty neurons showing SSA at different levels along the auditory pathway's hierarchy, together with the recent results showing human auditory‐evoked potential correlates of deviance detection at very short latencies, that is, at 20–40 ms from change onset, support the view that novelty detection is a key principle that governs the functional organization of the auditory system. Furthermore, the generation of the MMN recorded from the human scalp seems to involve a cascade of neuronal processing that occurs at different successive levels of the auditory system's hierarchy.     

Urban legends series: Sjögren’s syndrome

Oral Diseases (2012) 19 , 46–58 Sjögren’s syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti‐SSA/Ro and anti‐SSB/La relevant for the diagnosis of SjS? (iv) Are the American‐European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti‐Ro/La autoantibodies, anti α‐fodrin IgA and anti‐MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS.     

Leaching of Titanium Dioxide Nanomaterials from Agricultural Soil Amended with Sewage Sludge Incineration Ash: Comparison of a Pilot Scale Simulation with Standard Laboratory Column Elution Experiments

Nanoscale titanium dioxide (nTiO₂ (Hombikat UV 100 WP)) was applied to sewage sludge that was incinerated in a large-scale waste treatment plant. The incineration ash produced was applied to soil as fertilizer at a realistic rate of 5% and investigated in pilot plant simulations regarding its leaching behavior for nTiO₂. In parallel, the applied soil material was subject to standard column leaching (DIN 19528) in order to test the suitability of the standard to predict the leaching of nanoscale contaminants from treated soil material. Relative to the reference material (similar composition but without nTiO₂ application before incineration) the test material had a total TiO₂ concentration, increased by a factor of two or 3.8 g/kg, respectively. In contrast, the TiO₂ concentration in the respective leachates of the simulation experiment differed by a factor of around 25 (maximum 91.24 mg), indicating that the added nTiO₂ might be significantly mobilisable. Nanoparticle specific analysis of the leachates (spICP-MS) confirmed this finding. In the standard column elution experiment the released amount of TiO₂ in the percolates between test and reference material differed by a factor of 4 to 6. This was also confirmed for the nTiO₂ concentrations in the percolates. Results demonstrate that the standard column leaching, developed and validated for leaching prediction of dissolved contaminants, might be also capable to indicate increased mobility of nTiO₂ in soil materials. However, experiments with further soils are needed to verify those findings.     

60 000 SSA抗原第230～241表位在系统性红斑狼疮中性粒细胞上的表达及意义

目的通过对伴中性粒细胞减少的系统性红斑狼疮(SLE)患者周围血中性粒细胞60000SSA抗原第230～241表位表达水平的检测,并与相关的临床指标分析比较,初步探讨这一表达的临床意义。方法用人工合成的60000SSA抗原第230～241表位(E230～241)寡肽,从课题组已成功构建的SSA噬菌体单链可变区(scFv)抗体库中筛选得相应的scFv单抗,用其标记18例伴粒细胞减少的SLE患者和10名正常人周围血中性粒细胞,流式细胞仪比较检测E230～241的表达程度,分析其与中性粒细胞计数、SLE病情活动指数(SLEDAI)、总病程、病情活动时间之间的关系,并比较重症和轻症SLE患者间这一表达程度的差别。结果SLE组患者E230～241的表达明显高于正常人(20±12vs7±5,P=0.001),且表达程度与粒细胞计数呈负相关(r=-0.686,P=0.002),与SLEDAI呈正相关(r=0.665,P=0.003),与病情活动时间呈正相关(r=0.571,P=0.013),与总病程无显著相关性(r=0.114,P=0.651);重症患者的表达程度明显高于病情相对较轻者(31±10vs12±8,P=0.001)。结论SLE患者周围血中性粒细胞增强表达E230～241,可能是其粒细胞减少的原因之一,并可能参与SLE其他系统的损害。     

椎弓根螺钉内固定术有关角度测量及其临床意义

目的 :为椎弓根螺钉内固定术提供椎弓根相关角度的解剖学资料。方法 :在 10 0例脊柱骨标本 (C2 ～L5)上 ,测量椎弓根长轴与椎体矢状面及上平面之间的夹角。结果 :绝对值 :E角C4 ～C5最大 ,L5次之 ,而T12 最小 ,总体出现两个高峰一个低谷值 ;F角胸段均较大 ,其中T4 最大 ,颈段及腰段较小 ,呈典型的“山峰”形趋势 ;C2～L5的E角和F角侧别间差异均无显著性 (P <0 0 5 ) ,而性别间差异E角均为男大于女 ,C2 ～T6有显著性差异(P <0 .0 5 ) ,而T7～L5无显著性差异 (P >0 .0 5 ) ;F角除C3 、C4 女大于男且差异有显著性 (P <0 0 5 )外 ,其余均为男大于女 ,C2 、C5～T12 差异有极显著性 (P <0 0 1) ,而L1～L5则无显著性差异 (P >0 0 5 )。结论 :E角和F角值均有明显的规律性 ,参照E角F角及椎弓根的骨质结构确定相应的TSA角及SSA角。