The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo

Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development.     

上睑旋转皮瓣在内眦赘皮Y-V成形术中的应用

目的:探讨一种简单有效的内眦赘皮矫正方法。方法:对213例内眦赘皮"Y"形劈开插入"V"形三角瓣,同时利用重睑术中形成的上睑重睑皮瓣,旋转修复三角瓣上方继发性的缺损矫正内眦赘皮。结果:213例内眦赘皮明显的患者术后效果满意。随访6~12个月的所有病例术后重睑形态自然,内眦瘢痕不明显。13例早期内眦瘢痕增生,6个月后瘢痕软化变平效果满意。结论:利用上睑重睑旋转皮瓣辅助"Y-V"内眦赘皮形成术,有利于减少局部张力、矫正内眦赘皮而不留瘢痕,是一种行之有效的方法。     

Examining implicit bias of physicians who care for individuals with spinal cord injury: A pilot study and future directions

Context

Despite evidence that healthcare providers have implicit biases that can impact clinical interactions and decisions, implicit bias among physicians caring for individuals with spinal cord injury (SCI) has not been examined.

Objective

Conduct a pilot study to examine implicit racial bias of SCI physicians and its association with functioning and wellbeing for individuals with SCI.

Design

Combined data from cross-sectional surveys of individuals with SCI and their SCI physicians.

Setting

Four national SCI Model Systems sites.

Participants

Individuals with SCI (N = 162) and their SCI physicians (N = 14).

Outcome measures

SCI physicians completed online surveys measuring implicit racial (pro-white/anti-black) bias. Individuals with SCI completed questionnaires assessing mobility, physical independence, occupational functioning, social integration, self-reported health, depression, and life satisfaction. We used multilevel regression analyses to examine the associations of physician bias and outcomes of individuals with SCI.

Results

Physicians had a mean bias score of 0.62 (SD = 0.35), indicating a strong pro-white/anti-black bias. Greater physician bias was associated with disability among individuals with SCI in the domain of social integration (odds ratio = 4.80, 95% confidence interval (CI) = 1.44, 16.04), as well as higher depression (B = 3.24, 95% CI = 1.06, 5.41) and lower life satisfaction (B = −4.54, 95% CI= −8.79, −0.28).

Conclusion

This pilot study indicates that SCI providers are susceptible to implicit racial bias and provides preliminary evidence that greater implicit racial bias of physicians is associated with poorer psychosocial health outcomes for individuals with SCI. It demonstrates the feasibility of studying implicit bias among SCI providers and provides guidance for future research on physician bias and patient outcomes.     

Evaluations of guided bone regeneration in canine radius segmental defects using autologous periosteum combined with fascia lata under stable external fixation

BackgroundAlthough bone defect is one of the most common orthopaedic diseases, treatment remains a challenge and an issue of debate. Guided bone regeneration (GBR) is primarily accompanied by barrier membranes; however, optional membranes show some inherent flaws in clinical application. The purpose of this study was to observe the healing velocity and quality of repairing canine radius segmental defect using transferred autologous periosteum combined with fascia lata, which can provide better biological safety than other materials.ResultsBone union was seen in most individuals from the autologous periosteum combined with fascia lata group, within an average of 14.2 weeks. Histopathologic and SEM examinations both showed the different osteogenesis state between groups. Necropsy confirmed US findings with regard to distance of bone defects and location.ConclusionThese findings suggest that autologous periosteum combined with fascia lata is as effective as a GBR membrane, even in long tubular bone defects. With reliable biological safety, the autologous periosteum combined with fascia lata is expected to achieve increasing application in orthopaedic trauma patients.

Level of evidence

Not applicable, animal study.     

Anatomy Relationship around Internal Carotid Artery in the Endoscopic Surgery of Nasopharynx: A Study Based on Computed Tomography Angiography

Objective Anatomic knowledge is needed to avoid injury to internal carotid artery (ICA) during the endoscopic surgery around nasopharynx and its surrounding space. Design We prospectively studied the computed tomography angiography (CTA) data of 28 patients with image processing software. Special attention was given to ICA and various landmarks around nasopharynx. Results The anatomic relationship between ICA and different landmarks around nasopharynx was clearly presented in three-dimension. The fossa of Rosenmuller is the nearest point of the nasopharyngeal cavity to ICA. The opening of the Vidian canal in the middle cranial fossa could be either above, below, or at the level of the horizontal segment of petrous ICA. The pharyngeal trunk of the ascending pharyngeal artery can also be clearly identified in most reconstructed CTA images. Multiple anatomic relationships were also quantified. Conclusions Reconstructed CTA can provide key anatomic information for a safe and accurate endoscopic dissection around nasopharynx.     

Radiographic Anatomy of the Native Anterior Cruciate Ligament: a Systematic Review

BackgroundIn an attempt to improve the accuracy and reproducibility of tunnel positioning, radiographs are being analyzed in an attempt to recreate the native anatomy of the ACL. Understanding the native ACL radiographic anatomy is an essential prerequisite to understand the relevance of postoperative tunnel position.Questions/PurposesWe performed a systematic review of the literature to delineate the radiographic location of the native ACL femoral and tibial footprints.MethodsA search was performed in March 2014 in PubMed, the Cochrane Collaboration Library, and EMBASE to identify all studies that evaluated the native anterior cruciate ligament (ACL) anatomy on radiographs. Various measurement methods were used in each study, and averages were obtained of the data from studies with the same measurement methods.ResultsFifteen papers were identified (which included data on 177 femora and 207 tibiae in total). Evaluation of the femoral footprint using the quadrant method on lateral knee radiographs showed that the average percent distance location of the anteromedial (AM) bundle and posterolateral (PL) bundle was 22.8% (95% confidence interval (CI) 16.59–28.90) and 32.5% (95% CI 27.71–37.26) from the posterior condyle, respectively, and 23.2% (95% CI 19.52–26.94) and 50.0% (95% CI 46.16–53.76) from Blumensaat’s line, respectively. Using the Amis and Jacob method, the tibial footprint on the lateral knee radiograph average percent distances was 35.1% (95% CI 34.46–35.72) for the center of the AM bundle and 47.3% (95% CI 41.69–52.95) for the center of the PL bundle of the ACL. The femoral and tibial ACL footprints on the anteroposterior (AP) views of the knee were not well delineated by these studies.ConclusionThe information presented in this systematic review offers surgeons another important tool for accurate ACL footprint identification.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-014-9417-5) contains supplementary material, which is available to authorized users.