Single-dose combination nanovaccine induces both rapid and durable humoral immunity and toxin neutralizing antibody responses against Bacillus anthracis

Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where improvement would lead to a more practical and effective vaccine for use in the case of an exposure event. Identification of more effective adjuvants and novel delivery platforms is necessary to improve not only the effectiveness of the anthrax vaccine, but also enhance its shelf stability and ease-of-use. Polyanhydride particles have proven to be an effective platform at adjuvanting the vaccine-associated adaptive immune response as well as enhancing stability of encapsulated antigens. Another class of adjuvants, the STING pathway-targeting cyclic dinucleotides, have proven to be uniquely effective at inducing a beneficial inflammatory response that leads to the rapid induction of high titer antibodies post-vaccination capable of providing protection against bacterial pathogens. In this work, we evaluate the individual contributions of cyclic di-GMP (CDG), polyanhydride nanoparticles, and a combination thereof towards inducing neutralizing antibody (nAb) against the secreted protective antigen (PA) from B. anthracis. Our results show that the combination nanovaccine elicited rapid, high titer, and neutralizing IgG anti-PA antibody following single dose immunization that persisted for at least 108 DPI.     

皮桥袢式回肠造口在腹腔镜低位直肠前切除术中应用价值研究

目的 探讨皮桥袢式回肠造口方法在腹腔镜低位直肠前切除术中的应用价值。方法 回顾性分析2015年1月至2019年6月在长江大学附属荆州医院结直肠肛门外科因低位直肠癌行腹腔镜低位直肠前切除术联合回肠造口80例病人资料。根据回肠造口方式不同分为皮桥袢式回肠造口组（40例）和传统袢式回肠造口组（40例）。比较两组病人术后造口相关并发症及满意度的差异。结果 皮桥袢式回肠造口组和传统袢式回肠造口组病人比较，基本资料差异均无统计学意义（P>0.05），手术操作时间、造口旁疝及造口处伤口感染发生率差异无统计学意义［（21.1±3.3）min vs.（21.2±3.8）min，15.0%（6/40）vs.17.5%（7/40），0（0/40）vs .2.5%（1/40），P均>0.05］；皮桥袢式回肠造口组在术后VAS评分、DET评分及皮肤黏膜分离发生率均较传统袢式回肠造口组下降［（0.8±0.7）vs.（2.5±1.4），（1.8±1.5）vs.（6.4±3.6），2.5%（1/40）vs.62.5%（25/40），P均<0.05］；两组病人术后均未出现造口脱垂、造口回缩、造口狭窄；护士及病人对造口满意度评分调查比较，皮桥袢式回肠造口组均高于传统袢式回肠造口组［（2.9±0.3）vs.（2.6±0.5），（2.4±0.7）vs.（2.0±0.7），P均<0.05］。结论 皮桥袢式回肠造口在腹腔镜低位直肠前切除术中较传统袢式回肠造口更具优势，可显著减少术后造口相关并发症及增加护士、病人满意度。     

Influence of coronary stenosis location on diagnostic performance of machine learning-based fractional flow reserve from CT angiography

BackgroundCompared with invasive fractional flow reserve (FFR), coronary CT angiography (cCTA) is limited in detecting hemodynamically relevant lesions. cCTA-based FFR (CT-FFR) is an approach to overcome this insufficiency by use of computational fluid dynamics. Applying recent innovations in computer science, a machine learning (ML) method for CT-FFR derivation was introduced and showed improved diagnostic performance compared to cCTA alone. We sought to investigate the influence of stenosis location in the coronary artery system on the performance of ML-CT-FFR in a large, multicenter cohort.MethodsThree hundred and thirty patients (75.2% male, median age 63 years) with 502 coronary artery stenoses were included in this substudy of the MACHINE (Machine Learning Based CT Angiography Derived FFR: A Multi-Center Registry) registry. Correlation of ML-CT-FFR with the invasive reference standard FFR was assessed and pooled diagnostic performance of ML-CT-FFR and cCTA was determined separately for the following stenosis locations: RCA, LAD, LCX, proximal, middle, and distal vessel segments.ResultsML-CT-FFR correlated well with invasive FFR across the different stenosis locations. Per-lesion analysis revealed improved diagnostic accuracy of ML-CT-FFR compared with conventional cCTA for stenoses in the RCA (71.8% [95% confidence interval, 63.0%–79.5%] vs. 54.8% [45.7%–63.8%]), LAD (79.3 [73.9–84.0] vs. 59.6 [53.5–65.6]), LCX (84.1 [76.0–90.3] vs. 63.7 [54.1–72.6]), proximal (81.5 [74.6–87.1] vs. 63.8 [55.9–71.2]), middle (81.2 [75.7–85.9] vs. 59.4 [53.0–65.6]) and distal stenosis location (67.4 [57.0–76.6] vs. 51.6 [41.1–62.0]).ConclusionIn a multicenter cohort with high disease prevalence, ML-CT-FFR offered improved diagnostic performance over cCTA for detecting hemodynamically relevant stenoses regardless of their location.     

基于数据挖掘的吕英教授治疗自闭症语言障碍的用药规律分析＊

目的 基于中医传承辅助平台软件（TCMISS，V2.5）对吕英教授治疗自闭症语言障碍的处方进行数据挖掘，探索其病因病机及组方规律。方法 收集吕英教授治疗自闭症语言障碍的医案，将其方药信息录入TCMISS，借助该平台集成的关联规则、改进互信息法、复杂系统熵聚类法、无监督熵层次聚类法等分析方法探索吕英教授治疗自闭症语言障碍的药物组方规律。结果 共筛选出120个医案，包含处方共120首，涉及中药89味，其中使用频次前6味中药为桂枝、鸡蛋花、白术、泽泻、石膏、桔梗，药性以寒、温为主，药味以甘、苦居多，归经多属肺、脾、肝经。通过关联规则分析所得的用药模式中，使用频次最高的为桂枝与鸡蛋花、桂枝与泽泻、白术与桂枝，进一步分析得到的核心药物为泽泻、桂枝、白术，为五苓散的药物组成，并基于复杂熵聚类方法演化出6首新处方。结论 吕英教授治疗自闭症语言障碍以阳明“气血津”不足和三焦气化功能失常为主要病机线路，清解阳明伏火、加强阳明本体液津血的生化化生及恢复三焦气化功能正常为主要治法，其核心代表方剂为木防己汤和五苓散。     

Splenic Artery Embolization after Delayed Splenic Rupture Following Blunt Trauma: Is Nonoperative Management Still an Option in This Cohort?

Patients treated with splenic artery embolization (SAE) >48 hours after a blunt injury for a delayed splenic rupture (DSR) were assessed for the need for a subsequent splenectomy. Thirty-four patients underwent SAE for DSR over 10 years at our level 1 trauma center, performed at a median of 4.5 days after the injury (interquartile range = 5.5), and the patients were followed up for a median of 11 months (interquartile range = 31). There were 3 occurrences of rebleeds, and 2 patients required splenectomy (5.9%). This study showed that treatment with SAE after DSR results in splenic salvage in 94.1% of patients.     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Validation of the Insomnia Severity Index (ISI) for identifying insomnia in young adult cancer survivors: comparison with a structured clinical diagnostic interview of the DSM-5 (SCID-5)

ObjectivesInsomnia is a common problem affecting young adult cancer survivors (YACS) even years after treatment, yet it often goes unidentified and untreated. The Insomnia Severity Index is a widely-used insomnia measure, but has not been studied as an insomnia screener for YACS. The goal of this study was to validate the ISI in YACS by determining its utility in identifying YACS with insomnia disorder diagnosed with the Structured Clinical Interview for the DSM-5 (SCID-5).Methods250 YACS completed the ISI and SCID-5 Insomnia Module. Area under the curve (AUC) was calculated to reflect the ISI's discrimination between YACS with and without SCID-5 insomnia disorder. An ISI cut-off score with sensitivity ≥0.85 and specificity ≥0.75 was deemed acceptable.ResultsOf 250 participants, 52 met criteria for SCID-5 insomnia disorder diagnosis. The ISI had excellent discrimination, with an AUC = 0.91. A cut-off score ≥8 met study clinical screening criteria with sensitivity of 0.85 and specificity of 0.77. A cut-off score ≥7 with a higher sensitivity (0.96) but lower specificity (0.70) was noted as a potential alternative. Cut-off scores ≥12 and ≥ 14 were recommended for applications prioritizing overall accuracy.ConclusionsResults support validity of the ISI for identifying YACS with insomnia disorder. For clinical screening, data support the use of an ISI cut-off score ≥8 in YACS, and additional cut-off scores were found for research purposes or higher sensitivity. Results of this study and prior studies of the ISI offer important reminders that cut-off scores derived from different populations are not generalizable.