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.     

不同剂量骨水泥PKP联合雌激素对绝经后女性骨质疏松性腰椎体压缩性骨折患者的影响

目的探讨不同剂量骨水泥PKP联合雌激素对绝经后女性骨质疏松性腰椎体压缩性骨折患者的影响。方法选取2015年1月至2018年6月我院收治的120例老年女性骨质疏松性腰椎体压缩性骨折患者为研究对象,按行PKP手术治疗时骨水泥注入的剂量不同分为三组(A组2-4 mL、B组4-5 mL、C组5-6 mL),所有患者均随访1年,比较术后三组患者VAS评分、ODI评分、伤椎椎体前缘高度、椎体中部高度及并发症的发生率。结果三组患者相比,治疗前VAS评分、ODI评分组间比较差异无显著性(P0.05);术后3天及1年后随访时,三组患者各项指标均较治疗前显著改善,组内比较差异具有显著性(P0.05),组间比较差异无显著性(P0.05);治疗前伤椎椎体前缘高度及椎体中部高度组间比较差异无显著性(P0.05);术后3天及1年后随访时,三组患者治疗后椎体前缘、中间高度均较术前明显增加(P0.05),组间比较椎体前缘高度:C组B组A组,椎体中间高度:C组B组A组,且组间比较有统计学差异(P0.05); A组患者并发症的发生率(12.5%)明显低于B组(30.0%)、C组(41.0%),有统计学差异(P0.05)。结论 PKP术中注入小剂量骨水泥(2-4 mL)对于治疗老年女性OVCFs具有良好的治疗效果及较高的安全性。     

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.     

An Evidence-Based Review of Total Body Irradiation

The purpose of this literature review is to investigate clinical treatment methods of total body irradiation within the context of a clinical department adopting a paediatric cohort with no existing technique. An extensive review of the literature was conducted using PubMed, Science Direct, Google Scholar, and Clinicians Knowledge Network. Articles were limited to nonhelical tomotherapy, nonparticle therapies, and those using hyperfractionated regimes. Total marrow irradiation was excluded because of national treatment and trial limitations. Of the numerous patient positioning methods present within the literature, the most comfortable and reproducible positioning methods for total body irradiation include both supine and the supine and/or prone combination. These positions increased stability and patient comfort during treatment, while also facilitating computed tomography data acquisition at the simulation stage. Ideally, dose calculations should be performed using a three-dimensional treatment planning system and quality assurance procedures that include in vivo dosimetry measurements. The available literature also suggests inhomogeneity correction factors and intensity modulation are superior to conventional open field techniques and should be implemented within developing protocols. Dynamic machine dose modulation is suggested to reduce department impact, removing the need for tissue compensators and accessory shielding devices, while providing significant improvements to treatment time and dose accuracy. Further long-term survival and intensity modulation studies are warranted, including direct comparisons of both dose modulation and treatment efficiency.     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

Optimization of immunohistochemical detection of collagen type II in osteochondral sections by comparing decalcification and antigen retrieval agent combinations

Bone containing tissues such as osteochondral joint are resistant to routine tissue processing, therefore require decalcification. This technique causes removal of mineral salts, but in the process may macerate the organic tissue, hence the need for tissue fixation. Such severe processing demands careful antigen retrieval to necessitate optimal staining. The aim of our study was to compare five different antigen retrieval protocols (heat retrieval and protein digestion) following decalcification of rabbit knee joints using two different techniques (20% formic acid and 10% ethylenediamine-tetra acetic acid: EDTA). Osteochondral sections were compared based on time required for decalcification, ease of sectioning, morphological integrity using HE staining and antigen preservation (Collagen type II) using immunohistochemistry. The two decalcification solutions did not impair the tissue morphology and ease of sectioning. Joints processed with formic acid decalcified four times faster than EDTA. Among the five antigen retrieval approaches, maximal collagen II uptake with minimal nonspecific staining was found with protein digestion (pronase and hyaluronidase) in both formic acid and EDTA sections. For osteo-chondral sections, we recommend using 10% EDTA for decalcification and pronase plus hyaluronidase for antigen retrieval if maintaining tissue morphology is crucial, whereas if time is of the essence, 20% FA with pronase plus hyaluronidase is the faster option while still preserving structural integrity. Clin. Anat. 33:343–349, 2020. © 2019 Wiley Periodicals, Inc.     

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.