Outcome of implants placed to retain craniofacial prostheses - A retrospective cohort study with a follow-up of up to 30 years

OBJECTIVES: To retrospectively assess the treatment outcomes of endosseous implants placed to retain craniofacial prostheses. MATERIAL AND METHODS: Patients with craniofacial defects resulting from congenital disease, trauma, or oncologic treatment had implant retained prostheses placed in the mastoid, orbital, or nasal region and then assessed over a period of up to 30 years. Implant survival rates were calculated with the Kaplan-Meier method. Clinical assessments consisted of scoring skin reactions under the prosthesis and the peri-implant skin reactions. Possible risk factors for implant loss were identified. Patient satisfaction was evaluated using a 10-point VAS-scale. RESULTS: A total of 525 implants placed in 201 patients were included. The median follow up was 71 months (IQR 28-174 months). Implants placed in the mastoid and nasal region showed the highest overall implant survival rates (10-year implant survival rates of 93.7% and 92.5%, respectively), while the orbital implants had the lowest overall survival rate (84.2%). Radiotherapy was a significant risk factor for implant loss (HR 3.14, p < 0.001). No differences in implant loss were found between pre- and post-operative radiotherapy (p = 0.89). Soft tissue problems were not frequently encountered, and the patients were highly satisfied with their implant-retained prosthesis. CONCLUSION: Implants used to retain craniofacial prostheses have high survival and patient satisfaction rates and can thus be considered as a predictable treatment option. Radiation is the most important risk factor for implant loss

The ParB-parS Chromosome Segregation System Modulates Competence Development in Streptococcus pneumoniae

ParB proteins bind centromere-like DNA sequences called parS sites and are involved in plasmid and chromosome segregation in bacteria. We previously showed that the opportunistic human pathogen Streptococcus pneumoniae contains four parS sequences located close to the origin of replication which are bound by ParB. Using chromatin immunoprecipitation (ChIP), we found here that ParB spreads out from one of these parS sites, parS(-1.6 degrees), for more than 5 kb and occupies the nearby comCDE operon, which drives competence development. Competence allows S. pneumoniae to take up DNA from its environment, thereby mediating horizontal gene transfer, and is also employed as a general stress response. Mutating parS(-1.6 degrees) or deleting parB resulted in transcriptional up-regulation of comCDE and ssbB (a gene belonging to the competence regulon), demonstrating that ParB acts as a repressor of competence. However, genome-wide transcription analysis showed that ParB is not a global transcriptional regulator. Different factors, such as the composition of the growth medium and antibiotic-induced stress, can trigger the sensitive switch driving competence. This work shows that the ParB-parS chromosome segregation machinery also influences this developmental process. IMPORTANCE Streptococcus pneumoniae (pneumococcus) is an important human pathogen responsible for more than a million deaths each year. Like all other organisms, S. pneumoniae must be able to segregate its chromosomes properly. Not only is understanding the molecular mechanisms underlying chromosome segregation in S. pneumoniae therefore of fundamental importance, but also, this knowledge might offer new leads for ways to target this pathogen. Here, we identified a link between the pneumococcal chromosome segregation system and the competence-developmental system. Competence allows S. pneumoniae to take up and integrate exogenous DNA in its chromosome. This process plays a crucial role in successful adaptation to-and escape from-host defenses, antibiotic treatments, and vaccination strategies. We show that the chromosome segregation protein ParB acts as a repressor of competence. To the best of our knowledge, this is the first example of a ParB protein controlling bacterial competence

A low Smc flux avoids collisions and facilitates chromosome organization in Bacillus subtilis

International audienceSMC complexes are widely conserved ATP-powered DNA-loop-extrusion motors indispensable for organizing and faithfully segregating chromosomes. How SMC complexes translocate along DNA for loop extrusion and what happens when two complexes meet on the same DNA molecule is largely unknown. Revealing the origins and the consequences of SMC encounters is crucial for understanding the folding process not only of bacterial, but also of eukaryotic chromosomes. Here, we uncover several factors that influence bacterial chromosome organization by modulating the probability of such clashes. These factors include the number, the strength, and the distribution of Smc loading sites, the residency time on the chromosome, the translocation rate, and the cellular abundance of Smc complexes. By studying various mutants, we show that these parameters are fine-tuned to reduce the frequency of encounters between Smc complexes, presumably as a risk mitigation strategy. Mild perturbations hamper chromosome organization by causing Smc collisions, implying that the cellular capacity to resolve them is limited. Altogether, we identify mechanisms that help to avoid Smc collisions and their resolution by Smc traversal or other potentially risky molecular transactions

Dexmedetomidine versus Midazolam in Procedural Sedation: A Systematic Review of Efficacy and Safety

Objectives To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. Materials and Methods We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (>= 18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications. Results We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar. Conclusions Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar

Control of Smc Coiled Coil Architecture by the ATPase Heads Facilitates Targeting to Chromosomal ParB/parS and Release onto Flanking DNA

Smc/ScpAB promotes chromosome segregation in prokaryotes, presumably by compacting and resolving nascent sister chromosomes. The underlying mechanisms, however, are poorly understood. Here, we investigate the role of the Smc ATPase activity in the recruitment of Smc/ScpAB to the Bacillus subtilis chromosome. We demonstrate that targeting of Smc/ScpAB to ParB/parS loading sites is strictly dependent on engagement of Smc head domains and relies on an open organization of the Smc coiled coils. We find that dimerization of the Smc hinge domain stabilizes closed Smc rods and hinders head engagement as well as chromosomal targeting. Conversely, the ScpAB sub-complex promotes head engagement and Smc rod opening and thereby facilitates recruitment of Smc to parS sites. Upon ATP hydrolysis, Smc/ScpAB is released from loading sites and relocates within the chromosome—presumably through translocation along DNA double helices. Our findings define an intermediate state in the process of chromosome organization by Smc

Outcome of implants placed to retain craniofacial prostheses – A retrospective cohort study with a follow-up of up to 30 years

Objectives: To retrospectively assess the treatment outcomes of endosseous implants placed to retain craniofacial prostheses. Material and Methods: Patients with craniofacial defects resulting from congenital disease, trauma, or oncologic treatment had implant retained prostheses placed in the mastoid, orbital, or nasal region and then assessed over a period of up to 30 years. Implant survival rates were calculated with the Kaplan–Meier method. Clinical assessments consisted of scoring skin reactions under the prosthesis and the peri-implant skin reactions. Possible risk factors for implant loss were identified. Patient satisfaction was evaluated using a 10-point VAS-scale. Results: A total of 525 implants placed in 201 patients were included. The median follow up was 71 months (IQR 28–174 months). Implants placed in the mastoid and nasal region showed the highest overall implant survival rates (10-year implant survival rates of 93.7% and 92.5%, respectively), while the orbital implants had the lowest overall survival rate (84.2%). Radiotherapy was a significant risk factor for implant loss (HR 3.14, p < 0.001). No differences in implant loss were found between pre- and post-operative radiotherapy (p = 0.89). Soft tissue problems were not frequently encountered, and the patients were highly satisfied with their implant-retained prosthesis. Conclusion: Implants used to retain craniofacial prostheses have high survival and patient satisfaction rates and can thus be considered as a predictable treatment option. Radiation is the most important risk factor for implant loss