Determining the interviewer effect on CQ Index outcomes: a multilevel approach

Background  

The CQ Index for the elderly, a quality-of-care questionnaire administered by conducting interviews, is used to assess clients' experiences in Dutch nursing homes and homes for the elderly. This article describes whether inter-interviewer differences influence the perceived quality of healthcare services reported by residents, the size of this interviewer effect and the influence of the interviewer characteristics on CQ Index dimensions for public reporting.     

The course of the superficial peroneal nerve in relation to the ankle position: anatomical study with ankle arthroscopic implications

Despite the fact that the superficial peroneal nerve is the only nerve in the human body that can be made visible; iatrogenic damage to this nerve is the most frequently reported complication in anterior ankle arthroscopy. One of the methods to visualize the nerve is combined ankle plantar flexion and inversion. In the majority of cases, the superficial peroneal nerve can be made visible. The portals for anterior ankle arthroscopy are however created with the ankle in the neutral or slightly dorsiflexed position and not in combined plantar flexion and inversion. The purpose of this study was to undertake an anatomical study to the course of the superficial peroneal nerve in different positions of the foot and ankle. We hypothesize that the anatomical localization of the superficial peroneal nerve changes with different foot and ankle positions. In ten fresh frozen ankle specimens, a window, only affecting the skin, was made at the level of the anterolateral portal for anterior ankle arthroscopy in order to directly visualize the superficial peroneal nerve, or if divided, its terminal branches. Nerve movement was assessed from combined 10° plantar flexion and inversion to 5° dorsiflexion, standardized by the Telos stress device. Also for the 4th toe flexion, flexion of all the toes and for skin tensioning possible nerve movement was determined. The mean superficial peroneal nerve movement was 2.4 mm to the lateral side when the ankle was moved from 10° plantar flexion and inversion to the neutral ankle position and 3.6 mm to the lateral side from 10° plantar flexion and inversion to 5° dorsiflexion. Both displacements were significant (P < 0.01). The nerve consistently moves lateral when the ankle is manoeuvred from combined plantar flexion and inversion to the neutral or dorsiflexed position. If visible, it is therefore advised to create the anterolateral portal medial from the preoperative marking, in order to prevent iatrogenic damage to the superficial peroneal nerve.     

Syndesmosis and deltoid ligament injuries in the athlete

Purpose

Injury to the syndesmosis and deltoid ligament is less common than lateral ligament trauma but can lead to significant time away from sport and prolonged rehabilitation. This literature review will discuss both syndesmotic and deltoid ligament injuries without fracture in the professional athlete.

Methods

A narrative review was performed using PUBMED, OVID, MEDLINE and EMBASE using the key words syndesmosis, injury, deltoid, ankle ligaments, and athlete. Articles related to the topic were included and reviewed.

Results

The incidence of syndesmotic injury ranges from 1 to 18 % of ankle sprains. This may be underreported and is an often missed injury as clinical examination is generally not specific. Both MRI and ultrasonography have high sensitivities and specificities in diagnosing injury. Arthroscopy may confirm the diagnosis, and associated intra-articular pathology can be treated at the same time as surgical stabilization. Significant deltoid ligament injury in isolation is rare, there is usually associated trauma. Major disruption of both deep and superficial parts can lead to ankle dysfunction. Repair of the ligament following ankle fracture is not necessary, but there is little literature to guide the management of deltoid ruptures in isolation or in association with syndesmotic and lateral ligament injuries in the professional athlete.

Conclusion

Management of syndesmotic injury is determined by the grade and associated injury around the ankle. Grade I injuries are treated non-surgically in a boot with a period of non-weight bearing. Treatment of Grade II and III injuries is controversial with little literature to guide management. Athletes may return to training and play sooner if the syndesmosis is surgically stabilized. For deltoid ligament injury, grade I and II sprains should be treated non-operatively. Unstable grade III injuries with associated injury to the lateral ligaments or the syndesmosis may benefit from operative repair.

Level of evidence

IV.     

A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis

Introduction

Aberrant turnover of the actin cytoskeleton is intimately associated with cancer cell migration and invasion. Frequently however, evidence is circumstantial, and a reliable assessment of the therapeutic significance of a gene product is offset by lack of inhibitors that target biologic properties of a protein, as most conventional drugs do, instead of the corresponding gene. Proteomic studies have demonstrated overexpression of CapG, a constituent of the actin cytoskeleton, in breast cancer. Indirect evidence suggests that CapG is involved in tumor cell dissemination and metastasis. In this study, we used llama-derived CapG single-domain antibodies or nanobodies in a breast cancer metastasis model to address whether inhibition of CapG activity holds therapeutic merit.

Methods

We raised single-domain antibodies (nanobodies) against human CapG and used these as intrabodies (immunomodulation) after lentiviral transduction of breast cancer cells. Functional characterization of nanobodies was performed to identify which biochemical properties of CapG are perturbed. Orthotopic and tail vein in vivo models of metastasis in nude mice were used to assess cancer cell spreading.

Results

With G-actin and F-actin binding assays, we identified a CapG nanobody that binds with nanomolar affinity to the first CapG domain. Consequently, CapG interaction with actin monomers or actin filaments is blocked. Intracellular delocalization experiments demonstrated that the nanobody interacts with CapG in the cytoplasmic environment. Expression of the nanobody in breast cancer cells restrained cell migration and Matrigel invasion. Notably, the nanobody prevented formation of lung metastatic lesions in orthotopic xenograft and tail-vein models of metastasis in immunodeficient mice. We showed that CapG nanobodies can be delivered into cancer cells by using bacteria harboring a type III protein secretion system (T3SS).

Conclusions

CapG inhibition strongly reduces breast cancer metastasis. A nanobody-based approach offers a fast track for gauging the therapeutic merit of drug targets. Mapping of the nanobody-CapG interface may provide a platform for rational design of pharmacologic compounds.     

The effectiveness of bonded composite restorations in the treatment of painful,cracked teeth: six-month clinical evaluation

This study investigated the clinical efficacy of a bonded resin composite restoration with and without cuspal coverage for the treatment of painful, cracked teeth. Patients in a private dental practice who presented with complaints were selected. Inclusion criteria were sensitivity to cold, biting and a clinically-visible crack after removal of the existing restoration. All 40 teeth were restored with a three-step total etch system (Phosphoric acid/Clearfil SA primer/PhotoBond), 20 with cuspal coverage and 20 without. Patients were interviewed at one week, five weeks and six months regarding the presence of pain. In addition, the teeth were clinically examined after six months to reveal any sensitivity. At one week, patients reported that 12 teeth (30%) were free of pain and 28 teeth (70%) still had symptoms. At five weeks, patients reported that 25 teeth (62.5%) were free of pain and 13 teeth (32.5%) still had symptoms. Two teeth (5%) needed endodontic treatment after two and five weeks. At six months, patients reported that 30 teeth (75%) were functioning without any complaints. Upon clinical examination, only 20 teeth (50%) were free of symptoms. No statistically significant difference between the results of the teeth treated with and without cuspal coverage could be shown (Fischer's exact test at p<0.05).     

Correction of Murine Rag2 Severe Combined Immunodeficiency by Lentiviral Gene Therapy Using a Codon-optimized RAG2 Therapeutic Transgene

Recombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We report the development of lentiviral vectors with the spleen focus forming virus (SF) promoter driving codon-optimized human RAG2 (RAG2co), which improved phenotype amelioration compared to native RAG2 in Rag2^−/− mice. With the RAG2co therapeutic transgene, T-cell receptor (TCR) and immunoglobulin repertoire, T-cell mitogen responses, plasma immunoglobulin levels and T-cell dependent and independent specific antibody responses were restored. However, the thymus double positive T-cell population remained subnormal, possibly due to the SF virus derived element being sensitive to methylation/silencing in the thymus, which was prevented by replacing the SF promoter by the previously reported silencing resistant element (ubiquitous chromatin opening element (UCOE)), and also improved B-cell reconstitution to eventually near normal levels. Weak cellular promoters were effective in T-cell reconstitution, but deficient in B-cell reconstitution. We conclude that immune functions are corrected in Rag2^−/− mice by genetic modification of stem cells using the UCOE driven codon-optimized RAG2, providing a valid optional vector for clinical implementation.     

Determination of consistent patterns of range of motion in the ankle joint with a computed tomography stress-test

Background

Measuring the range of motion of the ankle joint can assist in accurate diagnosis of ankle laxity. A computed tomography-based stress-test (3D CT stress-test) was used that determines the three-dimensional position and orientation of tibial, calcaneal and talar bones. The goal was to establish a quantitative database of the normal ranges of motion of the talocrural and subtalar joints. A clinical case on suspected subtalar instability demonstrated the relevance the proposed method.

Methods

The range of motion was measured for the ankle joints in vivo for 20 subjects using the 3D CT stress-test. Motion of the tibia and calcaneus relative to the talus for eight extreme foot positions were described by helical parameters.

Findings

High consistency for finite helical axis orientation (n) and rotation (θ) was shown for: talocrural extreme dorsiflexion to extreme plantarflexion (root mean square direction deviation (η) 5.3° and θ: SD 11.0°), talorucral and subtalar extreme combined eversion–dorsiflexion to combined inversion–plantarflexion (η: 6.7°, θ: SD 9.0° and η:6.3°, θ: SD 5.1°), and subtalar extreme inversion to extreme eversion (η: 6.4°, θ: SD 5.9°). Nearly all dorsi – and plantarflexion occurs in the talocrural joint (θ: mean 63.3° (SD 11°)). The inversion and internal rotation components for extreme eversion to inversion were approximately three times larger for the subtalar joint (θ: mean 22.9° and 29.1°) than for the talocrural joint (θ: mean 8.8° and 10.7°). Comparison of the ranges of motion of the pathologic ankle joint with the healthy subjects showed an increased inversion and axial rotation in the talocrural joint instead of in the suspected subtalar joint.

Interpretation

The proposed diagnostic technique and the acquired database of helical parameters of ankle joint ranges of motion are suitable to apply in clinical cases.