A comparative study of heterogeneous antibiotic resistance of microbial populations in conventional periprosthetic tissue cultures and sonication fluid cultures of orthopaedics explanted prostheses

European Journal of Orthopaedic Surgery & Traumatology - “Heterogeneity” describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of...     

New applications of squalene synthase inhibitors: Membrane cholesterol as a therapeutic target

Squalene synthase (SQS) inhibitors, mostly known as antihyperlipidemic agents for controlling blood cholesterol levels, have been increasingly used to study alterations of the cholesterol content in cell membranes. As such, SQS inhibitors have been demonstrated to control cellular activities related to cancer cell proliferation and migration, neuron degeneration, and parasite growth. While the mechanisms behind the effects of cellular cholesterol are still being revealed in detail, the evidence for SQS as a therapeutic target for several seemingly unrelated diseases is increasing. SQS inhibitors may be the next promising candidates targeting the three remaining primary therapeutic areas, beyond cardiovascular disease, which still need to be addressed; their application as anticancer, antimicrobial, and antineurodegenerative agents appears promising for new drug discovery projects underway.     

Introduction to Neurogenetics

Genetic variation can directly cause or increase susceptibility to neurologic diseases. An explosion of new genetic technologies has enabled the characterization of specific genes responsible for many neurologic diseases and has provided fundamentally new insight into their pathophysiology. These advancements, along with recent breakthroughs in gene therapy, are beginning to result in the translation of an individual's genetic sequence into targeted treatment strategies. This review aims to introduce key genetic concepts and to illustrate how these principles apply in cases of rare, single-gene neurologic diseases as well as more common, polygenic diseases that are encountered frequently in clinical practice.     

The influence of mild posterior capsular opacification on spectral domain optical coherence tomography retinal nerve fiber layer thickness

International Ophthalmology - Τo investigate whether Yag laser capsulotomy, in addition to restoring ocular media transparency, may also significantly alter retinal nerve fiber layer (RNFL)...     

Identification of a Conserved Chromosomal Region Encoding Klebsiella pneumoniae Type 1 and Type 3 Fimbriae and Assessment of the Role of Fimbriae in Pathogenicity

Type 3 fimbriae are expressed by most clinical Klebsiella pneumoniae isolates and mediate adhesion to host structures in vitro. However, the role of type 3 fimbriae in K. pneumoniae virulence has not been evaluated by use of in vivo infection models. In this study, the type 3 fimbrial gene cluster (mrk) of the clinical isolate C3091 is described in detail. The mrk gene cluster was revealed to be localized in close proximity to the type 1 fimbrial gene cluster. Thus, a 20.4-kb fimbria-encoding region was identified and found to be highly conserved among different K. pneumoniae isolates. Interestingly, a homologue to PecS, known as a global regulator of virulence in Erwinia chrysanthemi, was identified in the fimbria-encoding region. Comparison to the previously characterized plasmid encoded mrk gene cluster revealed significant differences, and it is established here that the putative regulatory gene mrkE is not a part of the chromosomally encoded type 3 fimbrial gene cluster. To evaluate the role of type 3 fimbriae in virulence, a type 3 fimbria mutant and a type 1 and type 3 fimbria double mutant was constructed. Type 3 fimbria expression was found to strongly promote biofilm formation. However, the fimbria mutants were as effective at colonizing the intestine as the wild type, and their virulence was not attenuated in a lung infection model. Also, in a urinary tract infection model, type 3 fimbriae did not influence the virulence, whereas type 1 fimbriae were verified as an essential virulence factor. Thus, type 3 fimbriae were established not to be a virulence factor in uncomplicated K. pneumoniae infections. However, since type 3 fimbriae promote biofilm formation, their role in development of infections in catheterized patients needs to be elucidated.Klebsiella pneumoniae is recognized as an important opportunistic pathogen and is a common cause of urinary tract infections, respiratory tract infections, and septicemia, especially in immunocompromised individuals (37). K. pneumoniae is ubiquitous in the environment, and epidemiological studies have revealed that infections are frequently preceded by colonization of the patient''s gastrointestinal tract (33). In recent years an emerging syndrome of community-acquired pyogenic liver abscess caused by highly virulent K. pneumoniae strains has occurred (22, 24, 29, 54). These infections often occur in otherwise healthy individuals and are frequently complicated by devastating dissemination of the infection to the eyes and central nervous system. The rising incidence of serious K. pneumoniae infections stresses the need to elucidate the pathogenic mechanism of this important pathogen.The ability of bacteria to adhere to tissue surfaces in the host is an important step in the development of infection. Most clinical K. pneumoniae isolates express two types of fimbrial adhesins, type 1 and type 3 fimbriae (37). Type 1 fimbriae are well characterized and found in the majority of enterobacterial species (23). They mediate adhesion to mannose-containing structures present on host cells or in the extracellular matrix. A number of studies have shown that type 1 fimbriae play a significant role in the ability of Escherichia coli to infect the urinary tract (5, 26, 34, 47). In agreement with this, we have recently established that type 1 fimbriae are an important virulence factor in K. pneumoniae urinary tract infection (50).Compared to type 1 fimbriae, type 3 fimbriae are thin (4 to 5 nm in diameter) nonchanneled fimbriae (11, 25). They are characterized by their ability to agglutinate tannic acid treated, but not native, erythrocytes in a mannose-resistant manner; also referred to as mannose-resistant Klebsiella-like hemagglutination. In addition to Klebsiella species, type 3 fimbriae are common in Enterobacter, Serratia, Proteus, and Providencia isolates (4). Type 3 fimbriae belong to the chaperone-usher class fimbriae and are encoded by the mrk gene cluster, which includes the mrkA gene encoding the major fimbrial subunit and mrkD encoding the fimbrial adhesin responsible for mannose-resistant Klebsiella-like hemagglutination (1). The MrkD adhesin has been shown to mediate adhesion to collagen structures (51); however, the exact identity of the MrkD receptor remains elusive. In vitro studies have revealed that type 3 fimbriae mediate adhesion to different structures in human kidney and lung tissue and epithelial cells from human urine sediments, as well as in endothelial and bladder epithelial cell lines (16, 51, 52, 53). Furthermore, type 3 fimbriae have been established to play a significant role in K. pneumoniae biofilm formation (9, 20, 27). Historically, type 3 fimbriae have not been associated with E. coli; however, most recently two independent studies have reported type 3 fimbria expression in E. coli strains (3, 36). Intriguingly, in both studies type 3 fimbriae were encoded by conjugative plasmids and found to profoundly enhance the ability of E. coli to form biofilm. Type 3 fimbria-mediated biofilm formation and in vitro binding to different host structures indicate that type 3 fimbriae may play a significant role in virulence. However, thus far the influence of type 3 fimbriae on the pathogenicity of K. pneumoniae has not been investigated by use of in vivo models. In the present study, we constructed isogenic fimbria mutants to evaluate the influence of fimbriae in virulence using relevant in vivo infection models. Furthermore, a fimbria-encoding chromosomal region in K. pneumoniae including both the type 1 and the type 3 fimbrial gene clusters was identified.     

PKP治疗骨质疏松性多节段椎体压缩性骨折的临床应用研究

目的 探讨经皮椎体后凸成形术(PKP)治疗骨质疏松性多节段椎体压缩性骨折的疗效和安全性.方法 采用Skv膨胀式椎体成形器或球囊扩张对骨质疏松性椎体压缩性骨折65例238椎(其中Sky组20例,球囊组45例)行经皮椎体后凸成形术治疗.在X线片上测量术前、术后的椎体前缘、中线、后缘的高度及术后后凸畸形纠正范围.术前的临床所见及随访结果 均采用Oswestry功能障碍指数和疼痛视觉模糊评分进行评定.结果 65例术后24 h内疼痛症状明显缓解或消失.后凸畸形纠正范围11～26°,平均17°.随访9～46个月,平均24.8个月,患者诉明显疼痛,X线片示椎体高度未见明显丢失,未出现严重并发症.术后3个月及最后随访时Oswestry功能障碍指数和VAS评分均较术前有明显改善(P<0.05).Sky组与球囊组疗效比较无显著性差异(P<0.05).结论 Sky膨胀式椎体成形器及球囊扩张PKP治疗多发性骨质疏松性椎体压缩性骨折,均能迅速缓解疼痛,恢复椎体高度,但球囊对于一次治疗多椎体病变更为经济、适用.     

Foot and ankle injuries during the Athens 2004 Olympic Games

Background

The purpose of this study was to assess the level of air contamination with bacteria after surgical hydrodebridement and to determine the effectiveness of hydro surgery on bacterial reduction of a simulated infected wound.

Methods

Four porcine samples were scored then infected with a broth culture containing a variety of organisms and incubated at 37°C for 24 hours. The infected samples were then debrided with the hydro surgery tool (Versajet, Smith and Nephew, Largo, Florida, USA). Samples were taken for microbiology, histology and scanning electron microscopy pre-infection, post infection and post debridement. Air bacterial contamination was evaluated before, during and after debridement by using active and passive methods; for active sampling the SAS-Super 90 air sampler was used, for passive sampling settle plates were located at set distances around the clinic room.

Results

There was no statistically significant reduction in bacterial contamination of the porcine samples post hydrodebridement. Analysis of the passive sampling showed a significant (p < 0.001) increase in microbial counts post hydrodebridement. Levels ranging from 950 colony forming units per meter cubed (CFUs/m³) to 16780 CFUs/m³ were observed with active sampling of the air whilst using hydro surgery equipment compared with a basal count of 582 CFUs/m³. During removal of the wound dressing, a significant increase was observed relative to basal counts (p < 0.05). Microbial load of the air samples was still significantly raised 1 hour post-therapy.

Conclusion

The results suggest a significant increase in bacterial air contamination both by active sampling and passive sampling. We believe that action might be taken to mitigate fallout in the settings in which this technique is used.