原发性干燥综合征生物标志物的研究进展

目前原发性干燥综合征(pSS)诊断仍然依赖于侵入性小涎腺活检手术,常导致其早期诊断异常艰难,因此筛选特定生物标志物可能对pSS诊断和个体化治疗极为有益。本文回顾传统标志物及与B细胞活化和表观遗传相关的新标志物,并综述组学标志物研究进展。尽管生物标志物前景较好,但其可靠性仍需扩大样本量进行验证。     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.     

Identifying current uses of return to work screening tests and their effectiveness of reducing the risk of reinjury in athletic occupations – A systematic review

ObjectiveTo identify the current return-to-work (RTW) screening tests conducted for athletic occupations following injury and their effectiveness of reducing reinjury risk.MethodsA search was made of multiple databases (BioMed Central, CINAHL through ebscohost, EMBASE, Google Scholar, PUBMED, Scopus, SPORTDiscus and Web of Science) from their inception to March 2022, using relevant terms to identify articles meeting predefined inclusion/exclusion criteria. The search, data extraction, risk of bias, and evaluation of the certainty of the findings were completed independently by two authors. To understand the effectiveness of screening tests and their impact in reducing in reinjury rates, results were split into the following three time points: “Short-term” (≤1 year), “Medium-term” (≥2 years) and “Long-term” (≥3 years).ResultsFive studies (n = 507) met the inclusion criteria. There was a very low level of certainty for the effectiveness of screening tools reducing reinjury risk at short-term, medium-term and long-term follow ups. Only one study recorded a large effect in the reducing reinjury risk.ConclusionThe results demonstrated very low level of certainty for the effectiveness of screening tests reducing the risk of reinjury. A gap in our understanding currently exists for the effectiveness of RTW screening tests in tactical athletic occupations following injury and further research investigating is required.     

Performance of the new FilmArray Blood Culture Identification 2 panel and its potential impact on clinical use in patients with Gram-negative bacteremia

IntroductionRapid diagnostic tests have been developed recently for rapid species or resistance genes identification, offering the potential to improve the selection of appropriate antibiotics. The newly developed FilmArray Blood Culture Identification 2 (BCID2) panel, which can identify more species and resistance genes, such as extended-spectrum beta-lactamase, is expected to make an impact on antimicrobial practice.MethodsThe consecutive 50 inpatients with Gram-negative bacilli bacteremia were enrolled to this retrospective single-center study. In addition to the existing FilmArray Blood Culture Identification (BCID) panel, we have implemented BCID2 panel for positive blood culture. The sensitivity and specificity of BCID and BCID2 panel were respectively calculated, and a simulation study of time to effective, optimal and de-escalation therapy was performed based on BCID or BCID2 result.ResultsA total of 52 Gram-negative organisms in 50 patients were identified from blood cultures. Of these, 45 (87%) organisms were detected by BCID2 panel, which was more than BCID panel (41 organisms, 79%). BCID2 panel detected 5 CTX-M genes, which were concordant with conventional method. The time to effective therapy did not differ between BCID arm and BCID2 arm; however, the median time to optimal therapy (34 h in BCID arm and 26 h in BCID2 arm, P = 0.0007) and the median time to de-escalation therapy (42 h in BCID arm and 22 h in BCID2 arm, P = 0.0005) were significantly shortened.ConclusionsThis simulation study of BCID2 panel showed high sensitivity and specificity, and the potential impact on shortening the time to optimal and de-escalation therapy.     

Usefulness of discography,discoblock and a new mechanical method for identifying a painful segment/disc

BackgroundWe previously described a procedure for eliciting deep spatial discrimination of individual segments in the healthy lumbar spine of normal subjects: the percutaneous mechanical provocation (PMP) test. Our goal was to devise a method for accurate identification of the spinal level of pathology in chronic low back pain (CLBP). In the present study, we validated the PMP test, using a subgroup of CLBP patients with isthmic spondylolisthesis (IS). Because there is clinical consensus that IS back pain originates in the slipped segment/disc, the level of pathology can be directly compared to the result of the PMP test. The test is agnostic with respect to the underlying pathological mechanism, and therefore might be useful in identifying the involved segment(s) irrespective of the painful structure.MethodsIn 37 patients with confirmed IS (slippage 3–15 mm), we compared sensitivity between the PMP test, the widely used provocative discography test and the discoblock test.ResultsThe PMP test reliably identified the slip level in patients with IS, with sensitivity of 92%. Accepting the slipped disc as the origin of pain in IS, the sensitivity of the provocative discography and discoblock tests were 49% and 35%, respectively: i.e., too low to be contributive in clinical practice.ConclusionsThe PMP test reliably identified the origin of localized pain in IS as the slip level, but should be used with care in CLBP patients in selecting discogenic pain patients for fusion surgery, since the specificity of the test is not known and it may be positive for any origin of localized pain.