Loss of function of male-specific lethal 3 (Msl3) does not affect spermatogenesis in rodents.

BACKGROUND: Male-specific lethal 3 (Msl3) is a member of the chromatin-associated male-specific lethal MSL complex, which is responsible for the transcriptional upregulation of genes on the X chromosome in males of Drosophila. Although the dosage complex operates differently in mammals, the Msl3 gene is conserved from flies to humans. Msl3 is required for meiotic entry during Drosophila oogenesis. Recent reports indicate that also in primates, Msl3 is expressed in undifferentiated germline cells before meiotic entry. However, if Msl3 plays a role in the meiotic entry of mammals has yet to be explored. RESULTS: To understand, if Msl3a plays a role in the meiotic entry of mammals, we used mouse spermatogenesis as a study model. Analyses of single-cell RNA-seq data revealed that, in mice, Msl3 is mostly expressed in meiotic cells. To test the role of Msl3 in meiosis, we used a male germline-specific Stra8-iCre driver and a newly generated Msl3flox conditional knock-out mouse line. Msl3 conditional loss-of-function in spermatogonia did not cause spermatogenesis defects or changes in the expression of genes related to meiosis. CONCLUSIONS: Our data suggest that, in mice, Msl3 exhibits delayed expression compared to Drosophila and primates, and loss-of-function mutations disrupting the chromodomain of Msl3 alone do not impede meiotic entry in rodents.

Optimization of a Series of 2,3-Dihydrobenzofurans as Highly Potent, Second Bromodomain (BD2)-Selective, Bromo and Extra-Terminal Domain (BET) Inhibitors.

Herein, a series of 2,3-dihydrobenzofurans have been developed as highly potent bromo and extra-terminal domain (BET) inhibitors with 1000-fold selectivity for the second bromodomain (BD2) over the first bromodomain (BD1). Investment in the development of two orthogonal synthetic routes delivered inhibitors that were potent and selective but had raised in vitro clearance and suboptimal solubility. Insertion of a quaternary center into the 2,3-dihydrobenzofuran core blocked a key site of metabolism and improved the solubility. This led to the development of inhibitor 71 (GSK852): a potent, 1000-fold-selective, highly soluble compound with good in vivo rat and dog pharmacokinetics.

Change in modifiable dementia risk factors during COVID-19 lockdown: The experience of over 50s in Tasmania, Australia.

INTRODUCTION: Containment measures implemented to minimize the spread of coronavirus disease 2019 (COVID-19) are reported to be negatively affecting mental health, diet, and alcohol consumption. These factors, as well as poor cardiometabolic health and insufficient physical and cognitive activity, are known to increase the risk of developing dementia. COVID-19 "lockdown" measures may have exacerbated these dementia risk factors among people in mid-to-later life. METHODS: We compared longitudinal data from before (October 2019) and during (April-June 2020) the first COVID-19 lockdown period in Tasmania, Australia. Participants (n = 1671) were 50+ years of age and engaged in a public health program targeting dementia risk reduction, with one-third participating in the Preventing Dementia Massive Open Online Course (PD-MOOC). Regression models were used to assess changes in smoking, alcohol use, body mass index (BMI), diet, physical exercise, cognitive and social activity, anxiety and depression, and management of cholesterol, diabetes, and blood pressure. Where significant changes were noted, the moderating influence of being in current employment, living with others, and completing the PD-MOOC was tested. RESULTS: Although friend networks contracted marginally during lockdown, no detrimental effects on modifiable dementia risk factors were noted. Anxiety levels and alcohol consumption decreased, there was no change in depression scores, and small but significant improvements were observed in cognitive and physical activity, smoking, diet, and BMI. Stronger improvements in cognitive activity were observed among people who were cohabiting (not living alone) and both cognitive activity and adherence to the MIND diet (Mediterranean-DASH diet Intervention for Neurological Delay) improved more for people who participated in the PD-MOOC. DISCUSSION: Longitudinal data did not show widespread negative effects of COVID-19 lockdown on modifiable dementia risk factors in this sample. The results counter the dominant narratives of universal pandemic-related distress and suggest that engaging at-risk populations in proactive health promotion and education campaigns during lockdown events could be a protective public health strategy.

Widespread divergent transcription from bacterial and archaeal promoters is a consequence of DNA-sequence symmetry.

Transcription initiates at promoters, DNA regions recognized by a DNA-dependent RNA polymerase. We previously identified horizontally acquired Escherichia coli promoters from which the direction of transcription was unclear. In the present study, we show that more than half of these promoters are bidirectional and drive divergent transcription. Using genome-scale approaches, we demonstrate that 19% of all transcription start sites detected in E. coli are associated with a bidirectional promoter. Bidirectional promoters are similarly common in diverse bacteria and archaea, and have inherent symmetry: specific bases required for transcription initiation are reciprocally co-located on opposite DNA strands. Bidirectional promoters enable co-regulation of divergent genes and are enriched in both intergenic and horizontally acquired regions. Divergent transcription is conserved among bacteria, archaea and eukaryotes, but the underlying mechanisms for bidirectionality are different.

Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.

Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a "blank slate" culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.

Can a renal nurse assess fluid status using ultrasound on the inferior vena cava? A cross-sectional interrater study.

INTRODUCTION: Ultrasound of the inferior vena cava (IVC-US) has been used to estimate intravascular volume status and fluid removal during a hemodialysis session. Usually, renal nurses rely on other, imprecise methods to determine ultrafiltration. To date, no study has examined whether renal nurses can reliably perform ultrasound for volume assessment and for potential prevention of intradialytic hypotension. This pilot study aimed to determine if a renal nurse could master the skill of performing and correctly interpreting Point of Care Ultrasound on patients receiving hemodialysis. METHODS: After receiving theoretical training and performing 100 training scans, a renal nurse performed 60 ultrasound scans on 10 patients. These were categorized by the nurse into hypovolemic, euvolemic, or hypervolemic through measurement of the maximal diameter and degree of collapse of the IVC. Scans were subsequently assessed for adequacy and quality by two sonologists, who were blinded to each other's and the nurse's results. FINDINGS: The interrater reliability of 60 scans was good, with intraclass correlation 0.79 (95% confidence interval (CI) =0.63-0.87) and with a good interrater agreement for the following estimation of intravascular volume (Cohen's weighted Kappa κw = 0.62), when comparing the nurse to an expert sonographer. DISCUSSION: A renal nurse can reliably perform ultrasound of the IVC in hemodialysis patients, obtaining high quality scans for volume assessment of hemodialysis patients. This novel approach could be more routinely applied by other renal nurses to obtain objective measures of patient volume status in the dialysis setting.

A systematic review of implant-supported overdentures in the edentulous maxilla, compared to the mandible: how many implants?

BACKGROUND AND AIM: There is now overwhelming evidence from systematic reviews that a two implant overdenture is the first choice of treatment for the edentulous mandible. Conversely, consensus is lacking for implant-supported maxillary overdentures. Therefore, we systematically reviewed the treatment outcome of concepts used for implant-supported maxillary overdentures, focusing on the survival of implants, survival of maxillary overdentures and condition of the implant surrounding hard and soft tissues after a mean observation period of at least 1 year. MATERIAL AND METHODS: MEDLINE (1950 to December 2013), EMBASE (1966 to December 2013) and CENTRAL (1800 to December 2013) were searched to identify eligible studies. Two reviewers independently assessed the articles using specific study design-related quality assessment forms. RESULTS: Out of 195 primarily selected articles, 24 studies fulfilled the inclusion criteria. A metaanalysis showed an implant survival rate of 98.1% and overdenture survival of 99.5% per year in the case of ≥ 6 implants and a splinted (bar) anchorage. In the case of ≤ 4 implants and a splinted (bar) anchorage, implant survival rate and overdenture survival were 97.0% and 96.9% per year, respectively. In the case of ≤ 4 implants and a non-splinted anchorage (ball, locator, telescopic crown), implant survival rate and overdenture survival were 88.9% and 98.8% per year, respectively. The condition of the peri-implant tissues was not reported in most studies. CONCLUSIONS: An implant-supported maxillary overdenture (all studies ≥ 4 implants) provided with a splinted anchorage is accompanied with a high implant and overdenture survival rate (both >95% per year), while there is an increased risk of implant loss when ≤ 4 implants with a non-splinted anchorage are used.

Overdentures on primary mandibular implants in patients with oral cancer: a follow-up study over 14 years.

We aimed to assess oral functioning, patients' satisfaction, condition of peri-implant tissues, and survival of implants up to 14 years after their insertion in patients with oral cancer who had had mandibular overdentures placed over primary implants. Endosseous dental implants were inserted prospectively in the interforaminal region of the mandible during resection of the tumour in 164/180 patients with oral cancer. All 58 patients were evaluated by questionnaires and clinical assessments during a final assessment in 2012. Implant-retained mandibular overdentures were inserted, and prosthetic rehabilitation and oral functioning were not associated with primary site or stage of the tumour, number or type of implants inserted, or the type of reconstruction. Over time the peri-implant mucosa was usually free of inflammation. More implants were lost in patients treated by radiotherapy (27/318, 8.5%) than in those not so treated (1/206, 0.5%). Patients who had been treated by irradiation reported more problems in oral functioning and less satisfaction than those who had not. Patients with an implant-retained mandibular overdenture reported fewer problems in oral functioning than patients without an overdenture. Primary insertion of an implant should be routinely incorporated in the surgical planning for patients with oral cancer, as oral functioning in those wearing mandibular overdentures improved considerably and peri-implant health was at least reasonable.

Inflammation is more distinct in temporomandibular joint osteoarthritis compared to the knee joint.

PURPOSE: Most of the current understanding of articular cartilage maintenance and degradation is derived from large load-bearing synovial joints, in particular the knee joint. The aim of this study was to identify valuable degradation markers for cartilage degradation in the temporomandibular joint (TMJ) by comparing the relative concentrations of carboxyterminal telopeptides of collagen types I and II (CTX-I and CTX-II), cartilage oligomeric matrix protein (COMP), and prostaglandin E2 (PGE2) in synovial fluid (SF) of TMJ and knee joints with cartilage degradation. MATERIALS AND METHODS: In this cross-sectional comparative study, participants were recruited from the University Medical Center Groningen, The Netherlands. Patients with TMJ osteoarthritis were compared with patients with knee osteoarthritis. The outcome variables were the relative SF concentrations of CTX-I, CTX-II, COMP, and PGE2. An independent samples Mann-Whitney U test was used to compare the relative concentrations. RESULTS: Thirty consecutive patients (9 male, 21 female; mean age, 40.1 yr; standard deviation, 15.3 yr) with TMJ osteoarthritis and 31 consecutive patients (20 male, 11 female; mean age, 37.4 yr; standard deviation, 13.7 yr) who were scheduled for arthroscopy of the knee joint participated in this study. Significant differences were found between relative concentrations of COMP (P = .000) and PGE2 (P = .005), and no significant differences were found between relative concentrations of CTX-I (P = .720) and CTX-II (P = .242). CONCLUSIONS: Relative SF concentrations of COMP and PGE2 showed significant differences between the TMJ and the knee joint, suggesting that there are differences in pathophysiology and that the inflammatory component may be more distinct in the TMJ.

Minimally invasive harvesting of adipofascial scapular flaps.

INTRODUCTION: Scapular flaps are a reliable system for reconstruction. Disadvantages of reconstruction with these flaps include unsightly scars at the donor site due to wound healing under excessive tension and the use of skin grafts. Minimally invasive harvesting techniques may reduce potential donor-site morbidity. There has been no report on endoscopically assisted harvesting of the scapular adipofascial flap. METHODS: Two patients with large defects are reviewed. Endoscopically assisted minimally invasive techniques for harvest of scapular adipofascial flaps were used in reconstruction of these soft-tissue defects. RESULTS: Both defects were successfully reconstructed in the primary setting without any donor-site wound complications. CONCLUSIONS: This is the first time that a scapular flap has been harvested successfully with a minimally invasive technique for reconstruction. This technique allows the use of a scapular flap as a pedicled flap or as a free flap. Minimally invasive harvest of the adipofascial scapular flap has the advantages of short incision and better cosmesis of the donor site, for scarring is minimized and the incision can be closed primarily without skin grafting therefore reducing donor-site morbidity compared with the traditional open technique.

Accuracy and reproducibility of dental replica models reconstructed by different rapid prototyping techniques.

INTRODUCTION: Rapid prototyping is a fast-developing technique that might play a significant role in the eventual replacement of plaster dental models. The aim of this study was to investigate the accuracy and reproducibility of physical dental models reconstructed from digital data by several rapid prototyping techniques. METHODS: Twelve mandibular and maxillary conventional plaster models from randomly chosen subjects were selected and served as the gold standard. The plaster models were scanned to form high-resolution 3-dimensional surface models in .stl files. These files were converted into physical models using 3 rapid prototyping techniques: digital light processing, jetted photopolymer, and 3-dimensional printing. Linear measurements on the plaster models were compared with linear measurements on the rapid prototyping models. One observer measured the height and width of the clinical crowns of all teeth (first molar to first molar) on all models (plaster and replicas) using a digital caliper. All models were measured 5 times with a 2-week interval between measurements. RESULTS: The intraobserver agreement was high (intraclass correlation coefficient >0.94). The mean systematic differences for the measurements of the height of the clinical crowns were -0.02 mm for the jetted photopolymer models, 0.04 mm for the digital light processing models, and 0.25 mm for the 3-dimensional printing models. For the width of the teeth, the mean systematic differences were -0.08 mm for the jetted photopolymer models, -0.05 mm for the digital light processing models, and -0.05 mm for the 3-dimensional printing models. CONCLUSIONS: Dental models reconstructed by the tested rapid prototyping techniques are considered clinically acceptable in terms of accuracy and reproducibility and might be appropriate for selected applications in orthodontics.

Oral appliance versus continuous positive airway pressure in obstructive sleep apnea syndrome: a 2-year follow-up.

STUDY OBJECTIVES: Oral appliance therapy has emerged as an important alternative to continuous positive airway pressure (CPAP) in treating patients with obstructive sleep apnea syndrome (OSAS). In this study we report about the subjective and objective treatment outcome of oral appliance therapy and CPAP in patients with OSAS. DESIGN: Cohort study of a previously conducted randomized clinical trial. SETTING: University Medical Center, Groningen, The Netherlands. PATIENTS OR PARTICIPANTS: One hundred three patients with OSAS. INTERVENTIONS: CPAP and oral appliance therapy (Thornton Adjustable Positioner type-1, Airway Management, Inc., Dallas, TX, USA). MEASUREMENTS AND RESULTS: Objective (polysomnography) and subjective (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Medical Outcomes Study 36-item Short Form Health Survey [SF-36]) parameters were assessed after 1 and 2 years of treatment. Treatment was considered successful when the apnea-hypopnea index (AHI) was < 5 or showed substantial reduction, defined as reduction in the index of at least 50% from the baseline value to a value of < 20 in a patient without OSAS symptoms while undergoing therapy. Regarding the proportions of successful treatments, no significant difference was found between oral appliance therapy and CPAP in treating mild to severe OSAS in a 2-year follow-up. More patients (not significant) dropped out under oral appliance therapy (47%) compared with CPAP (33%). Both therapies showed substantial improvements in polysomnographic and neurobehavioral outcomes. However, CPAP was more effective in lowering the AHI and showed higher oxyhemoglobin saturation levels compared to oral appliance therapy (P < 0.05). CONCLUSIONS: Oral appliance therapy should be considered as a viable treatment alternative to continuous positive airway pressure (CPAP) in patients with mild to moderate obstructive sleep apnea syndrome (OSAS). In patients with severe OSAS, CPAP remains the treatment of first choice. CLINICAL TRIAL INFORMATION: The original randomized clinical trial, of which this study is a 2-year follow-up, is registered at ISRCTN.org; identifier: ISRCTN18174167; trial name: Management of the obstructive sleep apnea-hypopnea syndrome: oral appliance versus continuous positive airway pressure therapy; URL: http://www.controlled-trials.com/ISRCTN18174167.

Alteration of cartilage degeneration and inflammation markers in temporomandibular joint osteoarthritis occurs proportionally.

PURPOSE: There is a growing interest in markers for cartilage degradation in synovial joints because of their potential diagnostic and prognostic value. Therefore, the aim of this study was to identify valuable degradation markers for temporomandibular joint (TMJ) osteoarthritis (OA) by comparing the relative concentrations of carboxyterminal telopeptides type I and II (CTX-I and II), cartilage oligomeric matrix protein (COMP), and prostaglandin E2 (PGE2) in the synovial fluid (SF) of TMJs with OA with those of healthy symptom-free TMJs. MATERIALS AND METHODS: In this cross-sectional case-control study, participants were recruited from the University Medical Center Groningen (Groningen, the Netherlands). Cases were defined as patients with TMJ OA, and control patients had symptom-free TMJs. The outcome variables were the relative concentrations of CTX-I, CTX-II, COMP, and PGE2 in osteoarthritic TMJ SF compared with symptom-free joints. An independent-samples Mann-Whitney U test was used to compare the relative concentrations. RESULTS: Thirty cases (9 male, 21 female; mean age, 40.1 yr; standard deviation, 15.3 yr) and 10 controls (5 male, 5 female; mean age, 30.3 yr; standard deviation, 10.8 yr) were studied. No significant differences in relative concentrations of CTX-I (P = .548), CTX-II (P = .842), COMP (P = .140), and PGE2 (P = .450) were found between the groups. Unexpected low relative concentrations of CTX-I and high relative concentrations of CTX-II were observed. CONCLUSIONS: Assumed changes in the SF concentration of CTX-I, CTX-II, COMP, and PGE2 in TMJ OA seem to occur proportionally. Furthermore, the unexpected large contribution of CTX-II suggests that this marker may be useful to quantify cartilage degradation in TMJ OA.

Lavage therapy versus nonsurgical therapy for the treatment of arthralgia of the temporomandibular joint: a systematic review of randomized controlled trials.

AIMS: To carry out a systematic review of randomized controlled trials (RCTs) to investigate in patients with arthralgia of the temporomandibular joint (TMJ) the effectiveness of TMJ lavage compared to nonsurgical treatment with regard to pain intensity and mandibular range of motion. METHODS: The electronic databases Cochrane Controlled Trials Register (1960-2012), PubMed÷Medline (1966-2012), and Embase (1966-2012) were systematically searched for relevant RCTs. References of relevant articles were searched for additional studies, as well as citing reports. Two authors independently performed data extraction by using predefined quality indicators. Relevant outcome data included reduction in pain, as assessed by a visual analog scale (VAS) or a pain score, and maximal mouth opening (MMO) before and 6 months after treatment. Included trials were combined using fixed and random effects meta-analysis. RESULTS: Three RCTs (222 patients) were included for meta-analysis. The statistically significant overall standardized mean difference (SMD) (P < .001) with regard to pain intensity was -1.07 (95% CI = -1.38, - 0.76) in favor of TMJ lavage. The MMO did not change significantly (P > .05, SMD = .05 [95% CI = -0.33, 0.23]). CONCLUSIONS: The results suggest that lavage of the TMJ may be slightly more effective than nonsurgical treatment for pain reduction. However, this difference is not likely to be clinically relevant.

Implant decontamination during surgical peri-implantitis treatment: a randomized, double-blind, placebo-controlled trial.

AIM: The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. MATERIAL & METHODS: Thirty patients (79 implants) with peri-implantitis were treated with resective surgical treatment consisting of apically re-positioned flap, bone re-contouring and surface debridement and decontamination. Patients were randomly allocated to decontamination with 0.12% CHX + 0.05% CPC (test-group) or a placebo-solution (without CHX/CPC, placebo-group). Microbiological parameters were recorded during surgery; clinical and radiographical parameters were recorded before (pre-) treatment (baseline), and at 3, 6 and 12 months after treatment. RESULTS: Nine implants in two patients in the placebo-group were lost due to severe persisting peri-implantitis. Both decontamination procedures resulted in significant reductions of bacterial load on the implant surface, but the test-group showed a significantly greater reduction than the placebo-group (log 4.21 ± 1.89 versus log 2.77 ± 2.12, p = 0.006). Multilevel analysis showed no differences between both groups in the effect of the intervention on bleeding, suppuration, probing pocket depth and radiographical bone loss over time. CONCLUSION: Implant surface decontamination with 0.12% CHX + 0.05% CPC in resective surgical treatment of peri-implantitis leads to a greater immediate suppression of anaerobic bacteria on the implant surface than a placebo-solution, but does not lead to superior clinical results. The long-term microbiological effect remains unknown.

Comparison between conventional and piezoelectric surgical tools for maxillary sinus floor elevation. A randomized controlled clinical trial.

AIM: The aim of this study was to assess the performance of conventional rotative instruments and a piezoelectric device for maxillary sinus floor elevation surgery, and to assess whether application of a resorbable membrane reduces resorption of an augmented site in a randomized clinical trial. MATERIALS AND METHODS: Thirty-six consecutive patients (59.2 ± 10.7 years, range 38-76 years) needing bilateral sinus floor elevation surgery agreed to participate in this study. In a parallel split mouth design randomized clinical trial, in which the allocation of the surgical technique to be used on the determined sites was randomly assigned, one site was always treated with conventional rotative instruments (control group) and the other site with piezosurgery (test group). In addition, in a random order, the grafted sites were covered with a collagen membrane or no membrane. After a healing period of 3-4 months implants were placed. RESULTS: Comparison of clinical features of the test and control sites revealed no differences with regard to wound healing and complications (perforations of the sinus membrane) during or postsurgery (p = .458, p = 1.0, respectively). A clinically insignificant, but statistically shorter operation time was observed when using conventional rotative instruments (11.1 ± 2.4 minutes) than using piezosurgery (15.1 ± 2.9 minutes; p < .001). In both groups, application of a resorbable membrane did not result in less horizontal bone resorption (membrane: 1.43 mm, no membrane: 1.06 mm; p = .062); All 193 implants could be placed with primary stability. One year after functional loading, survival rate was 100%. CONCLUSION: It can be concluded that, for maxillary sinus floor elevation surgery, a piezoelectric device shows no advantages over rotative instruments as well as that placement of a barrier membrane did not reduce resorption of the augmented site.

Does hypoxia-reperfusion injury occur in osteoarthritis of the temporomandibular joint?

AIMS: To determine the available evidence in the literature for whether hypoxia-reperfusion injury plays a role in the pathogenesis of joint diseases in general and of osteoarthritis (OA) of the temporomandibular joint (TMJ) in particular. METHODS: The electronic databases CENTRAL, PubMed, and EMBASE were systematically searched. The search strategy combined thesaurus terms "reperfusion injury" and "joints" and excluded "tourniquet," which possibly induces iatrogenic reperfusion injury. Inclusion and exclusion criteria were applied, data were extracted, and quality was assessed. RESULTS: Four studies could be included, investigating four different aspects of the hypoxia-reperfusion mechanism in joints. All studies investigated several arthritides in the knee or shoulder joint and were observational studies, except for one section of one of the studies, which was a randomized controlled trial. These studies do not provide any evidence to support or reject the hypothesis that hypoxia reperfusion occurs in TMJ OA. Positive but weak evidence is provided to support the hypothesis that hypoxia-reperfusion injury occurs in OA of the knee joint. Furthermore, some results of the included studies suggest differences between OA and other types of arthritis in relation to the hypoxia-reperfusion mechanism. CONCLUSION: There is no evidence to support or reject the hypothesis that hypoxia reperfusion occurs in TMJ OA, and limited evidence is provided to support that hypoxia-reperfusion injury occurs in OA of the knee joint. Since the studies suggest differences between OA and other types of arthritis in relation to hypoxia-reperfusion mechanisms, further research in this field needs to distinguish OA from other types of arthritis.

Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on temporomandibular side effects.

The objective of this study was to assess variations in the occurrence of temporomandibular disorders (TMDs) and the risk of developing pain and function impairment of the temporomandibular complex in obstructive sleep apnea syndrome (OSAS) patients treated with either an oral appliance (mandibular advancement device) or continuous positive airway pressure (CPAP) in a 2-year follow-up study. In addition, we assessed the relationship between the mean mandibular protrusion and the frequency of wearing the appliance during follow-up with the occurrence of pain and function impairment of the temporomandibular complex. Fifty-one patients were randomized to oral appliance therapy and 52 patients to CPAP therapy. TMDs (diagnosed according to the Axis I Research Diagnostic Criteria for TMD), pain intensity and disability and mandibular function impairment were recorded at baseline, after 2 months, 1 year and 2 years of therapy. Only in the initial period of treatment the occurrence of pain-related TMDs was considerably higher (24%) in the oral appliance group compared to CPAP (6%). Oral appliance therapy furthermore resulted in more temporomandibular pain compared to CPAP (odds ratio 2.33, 95% confidence interval (1.22-4.43)). However, there were no limitations in mandibular function in both groups during the (entire) follow-up period. Although generally not serious and of transient nature, oral appliance therapy results in more pain-related TMDs in the initial period of use compared with CPAP therapy. Oral appliance therapy is associated with increased pain in the temporomandibular complex in the initial period of use. Because of the transient nature, this pain is not a reason to contra-indicate an oral appliance in OSAS patients. Moreover, TMDs and the risk of developing pain and function impairment of the temporomandibular complex appear limited with long-term oral appliance use.

Reliability and the smallest detectable difference of measurements on 3-dimensional cone-beam computed tomography images.

INTRODUCTION: The aim of this study was to determine the reliability and the measurement error (by means of the smallest detectable error) of 17 commonly used cephalometric measurements made on 3-dimensional (3D) cone-beam computed tomography images. METHODS: Twenty-five cone-beam computed tomography scans were randomly selected, and 3D images were rendered, segmented, and traced with the SimPlant Ortho Pro software (version 2.1, Materialise Dental, Leuven, Belgium). This was repeated twice by 2 observers during 2 sessions at least 1 week apart. Measurement error was determined by means of the smallest detectable difference. Differences were analyzed with Wilcoxon signed rank tests. Intraobserver and interobserver reliability values were calculated by means of intraclass correlation coefficients (ICC) based on absolute agreement. RESULTS: There were great variations of measurement errors between the angular (range, 0.88°-6.29°) and linear (range, 1.33-3.56 mm) variables. The greatest measuring error was associated with the dental measurements U1-FHPL, L1-MdPL. and L1-FHPL (range, 3.80°-6.29°). ANB angle was the only variable with a measuring error of 1° or less for both observers. The intraobserver agreement of all measurements was very good (ICC, 0.86-0.99). Except for SN-FHPL (ICC, 0.76), interobserver agreement was very good (ICC, >0.88). CONCLUSIONS: The measurement errors of 3D cephalometric measurements (except for the ANB angle) can be considered clinically relevant. This questions the use of linear and angular 3D measurements to detect true treatment effects when a high level of accuracy is required.