涂阳肺结核患者家庭密切接触儿童感染发病及预防的研究

目的观察涂阳肺结核患者家庭密切接触儿童感染发病情况,探讨儿童感染者预防性治疗方法。方法将涂阳肺结核患者家庭密切接触儿童与非涂阳肺结核患者密切接触儿童感染发病情况进行比较,对儿童感染者分组给予6H、12H、3HR、2HRZ等4种不同的方案进行预防性治疗,随访观察10年发病情况。结果涂阳肺结核患者家庭密切接触儿童感染率为63.6%,非涂阳肺结核患者家庭密切接触儿童感染率为10.4%,两组差异有统计学意义(P<0.05)。儿童结核感染者预防性治疗组完成治疗率达85%以上,经10年随访患病率为2.2%(4/182),4种方案平均药物不良反应发生率为8.6%。儿童结核感染者非预防性治疗组患病率达45.2%(47/104),两组差异有统计学意义(P<0.05)。结论涂阳肺结核患者家庭密切接触儿童属于结核病高危人群。早期发现涂阳肺结核患者并给予正规的抗结核治疗,积极动员其家庭成员尤其是儿童及时进行结核病筛查,是结核病管理的一个重要环节。儿童感染者预防性治疗可减少95.1%的结核病发病,是一种可靠预防结核感染的方法,在总体减轻结核病的影响可起到关键性作用。     

Spread of hepatitis C virus infection within families

In 1995, the intrafamilial spread of hepatitis C virus (HCV) was evaluated among 1379 household contacts of 585 HCV antibody-positive HCV RNA-positive subjects (index cases) in Italy. All index cases were patients with histologically proven chronic liver disease. The presence of antibodies to HCV (anti-HCV) was assessed by third-generation enzyme-linked immunosorbent assay (ELISA); the polymerase chain reaction (PCR) was used to test for HCV RNA. The overall anti-HCV prevalence among household contacts of index cases was 7.3% (101/1379); it was 15.6% in spouses and 3.2% in other relatives ( P <0.05; odds ratio (OR), 6.5; 95% confidence interval (CI), 3.5–8.6). Spouses married to index cases for longer than 20 years had a significantly higher anti-HCV prevalence than those married 20 years or less (19.8% vs 8.0%; P <0.05; OR, 2.8; 95% CI, 1.5–5.3). Parenteral risk factors were more likely to be reported in anti-HCV positive than in anti-HCV negative household contacts. After adjustment for confounders by multiple logistic regression analysis, age greater than 45 years (OR, 3.1; 95% CI, 1.6–5.3) and any parenteral exposure (OR, 3.7; 95% CI, 1.7–8.1), were the only independent predictors of the likelihood of anti-HCV positivity among household contacts. Spouses versus other relatives and length of marriage were both no longer associated. These findings suggest that sexual transmission does not seem to play a role in the intrafamilial spread of HCV infection.     

湖南省郴州市一起新型冠状病毒肺炎聚集性疫情流行病学调查

目的 通过分析郴州市一起新冠肺炎聚集性疫情相关病例发病确诊过程,探讨新冠病例早发现、早报告以及病例诊断和隔离观察解除的策略依据。 方法 对该起新冠肺炎聚集性疫情的病例和密切接触者进行现场流行病学调查,描述性分析流行病学史、临床和实验室资料。 结果 利用大数据比对监测,在转送监测对象至集中场所隔离医学观察时发现了新冠肺炎确诊病例何某华,由此发现一起新冠肺炎家庭聚集性疫情,何某的5名密切接触者中有3人发病确诊（包含1名重症病例）,其中重症病例黄某第7次新型冠状病毒核酸检测阳性进而确诊,密切接触者中胡某有流行病学史、血常规白细胞下降和肺炎影像学改变,但是5次咽拭子核酸检测阴性,未确诊。 结论 大数据比对监测对发现传染病有积极作用;早期对有流行病学史人员单独隔离医学观察对防止聚集性疫情发生有重要意义;将2次核酸检测阴性作为新冠肺炎病例的排除标准和将核酸检测阳性作为确诊新冠肺炎病例的必备条件,值得探讨,这都可能放走传染源,导致新冠肺炎传播。     

Accurate de novo structure prediction of large transmembrane protein domains using fragment-assembly and correlated mutation analysis

A new de novo protein structure prediction method for transmembrane proteins (FILM3) is described that is able to accurately predict the structures of large membrane proteins domains using an ensemble of two secondary structure prediction methods to guide fragment selection in combination with a scoring function based solely on correlated mutations detected in multiple sequence alignments. This approach has been validated by generating models for 28 membrane proteins with a diverse range of complex topologies and an average length of over 300 residues with results showing that TM-scores > 0.5 can be achieved in almost every case following refinement using MODELLER. In one of the most impressive results, a model of mitochondrial cytochrome c oxidase polypeptide I was obtained with a TM-score > 0.75 and an rmsd of only 5.7 Å over all 514 residues. These results suggest that FILM3 could be applicable to a wide range of transmembrane proteins of as-yet-unknown 3D structure given sufficient homologous sequences.     

Predictive energy landscapes for protein–protein association

We investigate protein–protein association using the associative-memory, water-mediated, structure, and energy model (AWSEM), a coarse-grained protein folding model that has been optimized using energy-landscape theory. The potential was originally parameterized by enforcing a funneled nature for a database of dimeric interfaces but was later further optimized to create funneled folding landscapes for individual monomeric proteins. The ability of the model to predict interfaces was not tested previously. The present results show that simulated annealing of the model indeed is able to predict successfully the native interfaces of eight homodimers and four heterodimers, thus amounting to a flexible docking algorithm. We go on to address the relative importance of monomer geometry, flexibility, and nonnative intermonomeric contacts in the association process for the homodimers. Monomer surface geometry is found to be important in determining the binding interface, but it is insufficient. Using a uniform binding potential rather than the water-mediated potential results in sampling of misbound structures that are geometrically preferred but are nonetheless energetically disfavored by AWSEM, as well as in nature. Depending on the stability of the unbound monomers, nonnative contacts play different roles in the association process. For unstable monomers, thermodynamic states stabilized by nonnative interactions correspond to productive, on-pathway intermediates and can, therefore, catalyze binding through a fly-casting mechanism. For stable monomers, in contrast, states stabilized by nonnative interactions generally correspond to traps that impede binding.     

Reintroducing OPV in Israel on the journey to global polio eradication – Estimation at a low rate of contraindicated population

IntroductionThe 2013 reemergence of wild poliovirus in Israel led to the reinstatement of a routine OPV vaccination. Fearing VAPP in immunocompromised, the MOH regulated contraindications for vaccination candidates and household contacts. In this study we estimate the size of the contraindicated population to OPV vaccination.MethodWe studied vaccination candidates aged 2–9 and 14–23 months and probable household contacts. Using the rate of contraindications extracted for each study group from a medical records database, a statistical model was built to estimate the probability of contraindications in candidates.Results3.9% of the 2–9-month-old study group and 4% of the 14–23-month-old group had contraindications by either self or household contacts.ConclusionA statistical model can provide an estimation of the contraindicated population and can be used in the future when devising vaccination campaigns. In contrast to concerns raised by the MOH, our findings show a smaller than anticipated contraindicated population.     

Comparison of increased overjet cases and controls: normative data for condylar positions

The aim was to compare normal overjet versus large overjet cases with clinically healthy temporomandibular joints (TMJ); to establish normative data regarding the difference between condylar positions in centric occlusion (CO) and maximum intercuspation (MI) and deflective CO contacts. Two study groups of normal overjet and large overjet cases consisted each of 33 subjects with no detectable clinical signs of temporomandibular disorder (TMD). CO-MI differences were recorded using the SAM Mandibular Position Indicator. Deflective contacts were examined on models mounted in CO. There was a significant difference between groups in the vertical (P = 0.030) and transverse (P = 0.008) range of movement from CO to MI, but not in the antero-posterior direction. There were no differences in the location of deflective contacts. Results of this study showed that patients with increased overjet show some differences compared with normal overjet patients, even in the non-patients. Further research on TMD patients is needed to find out about the role these features play in the aetiology and treatment of temporomandibular disorder (TMD). This study indicates that the clinician should be paying special attention to the TMJ status of patients with a large overjet.