Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016

Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km² followed by three years (2014–2016) of evaluation at 300 baits/km². We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km² to 300/km² corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA.     

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Low bone mineral density in ambulatory persons with cerebral palsy? A systematic review

Purpose: Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I–III) was studied.

Materials and methods: Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score?≤??2.0. In addition, we focused on Z-score?≤??1.0 because this may indicate a tendency towards low bone mineral density.

Results: We included 16 studies, comprising 465 patients aged 1–65?years. Moderate and conflicting evidence for low bone mineral density (Z-score?≤??2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score?≤??1.0) for several body parts.

Conclusions: Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy.

• Implications for Rehabilitation

• Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP.

• Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view.

• If indicated, medication and fall prevention training should be prescribed.

     

使用棱镜重新定位双侧中心暗点患者视网膜物像的预试验

目的 本研究使用激光扫描检眼镜(SLO)评价双侧中央暗点患者使用棱镜后的眼球运动反应.方法 本预试验共招募6例有双侧中央暗点的年龄相关性黄斑变性(AMD)患者以及6例正常视力的志愿者.首先用Nidek MP-1微视野仪确认患者的中央暗点和优选视网膜注视点(PRL),然后用Rodenstock SLO,在将视标投射在优选视网膜注视点时拍下实时视网膜像,接着在受检者眼前加入6～8 PD的棱镜,要求受检者保持注视视标,这时通过视网膜标记来测量视网膜像的移位量,以及随后发生的优选视网膜注视点的再次注视.过程中平均移位量和再次注视时间通过图像软件(ImageJ software)来计算.结果 实验组再次注视时的移位量在3个像素点或11.66个弧分之内(x轴:2.90±3.92,y轴:2.53±4.18).对照组再次注视时的移位会准确些(x轴:0.33±1.15,y轴:0.89±2.50),但与实验组差异无统计学意义(tx=1.32,Px＞0.05;ty=0.80,Py＞0.05).对照组再次注视时间(0.98±0.19)s较实验组(2.83±1.63)s要短,差距有统计学意义(t=5.03,P＜0.01).其中有1例实验组受检者没有发生再次注视,其结果被排除并单独分析.结论 研究发现,双眼中央暗点患者对棱镜物像转移后的再注视反应与正常人接近,但实验组再注视明显较对照组慢,并有1例受检者没有发生再注视.该数据说明双侧中央暗点患者无论眼前有没有棱镜,都会利用相同的视网膜位置视物,因此,通过棱镜物像再定位的意义不大.     

去势比格犬腹部脂肪与相关血清学指标及骨密度的变化关系

目的通过建立去势比格犬模型,观察绝经早期腹部脂肪变化规律,并通过对脂肪与骨代谢相关血清学指标的测量与分析,探讨脂肪及骨代谢的关键影响因素。方法选取6只成年雌性比格犬进行去势术,分别在术前、术后4个月、6个月、10个月进行腰椎定量CT(quantatitive computed tomography,QCT)腹部脂肪面积、骨密度(bone mineral density,BMD)、MRI腰椎骨髓脂肪含量及血清学指标的检测,比较不同时间各指标的变化趋势及关系。结果比格犬腹内脂肪面积(visceral fat area,VFA)、皮下脂肪面积(subcutaneous fat area,SFA)、腹部总脂肪面积(total fat area,TFA)在术后6个月、10个月均增加(P0.05),术后10个月VFA增加百分比均值为84.39%,且为三者中最大;术后比格犬BMD并未明显降低。体重、BMD、瘦素(leptin,LP)、VFA、高密度脂蛋白(high-density lipoprotein,HDL)与SFA相关。SFA、体重、低密度脂蛋白(low-density lipoprotein,LDL)、内脏脂肪素(visfatin,VFN)与BMD相关。结论去势比格犬模型可用于研究绝经后雌激素缺乏所引起的脂肪代谢变化,但短期内BMD并未明显丢失,骨、脂肪代谢之间存在交互作用。     

基于机器学习的脑胶质瘤多模态影像分析

脑部胶质瘤是临床中常见的一种原发性脑肿瘤，具有复发率高、死亡率高以及治愈率低的特点。常规临床诊断主要依靠计算机断层扫描(CT)和磁共振成像(MRI)检查技术进行鉴别。随着成像技术和机器学习方法的不断发展，多模态影像智能分析技术已经逐步成为研究热点，在脑胶质瘤的病灶分割测量、肿瘤分级、预后生存周期预测和基因型辨别等方面具有重要的应用前景。本文重点介绍基于机器学习和多模态影像在脑胶质瘤临床辅助诊断和预后评估中的应用进展。     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

一氧化氮合酶在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达

目的：检测诱导型和内皮型一氧化氮合酶（iNOS 和eNOS）在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达。方法：采用免疫组织化学SABC法检测iNOS和eNOS在30例外阴慢性单纯性苔藓蜡块（LSC）、30例外阴硬化性苔藓蜡块（LS）和10例外阴正常皮肤中的表达，并以人原始造血细胞抗原（CD34）标记微血管内皮细胞，测量各组织的微血管密度（MVD）。结果：iNOS和eNOS在外阴正常皮肤中无表达；在LSC中iNOS和eNOS每视野平均阳性细胞数分别为14.83±3.79和17.86±4.82，高于LS的8.00±3.35和6.43±3.87，差异均有统计学意义（P＜0.05）；在LSC和正常皮肤中MVD分别为21.58±2.48和20.44±3.66，高于LS（10.34±2.83）。iNOS和eNOS的表达具有明显的正相关性（Kappa=0.811，P＜0.05）。结论：iNOS和eNOS可能与LSC炎症过程中的血管扩张有关；在LS皮损真皮中微血管减少，iNOS和eNOS可代偿性地改善LS的血液循环。