Sex dependent differences of temporomandibular condylar bone mineral density distribution.

OBJECTIVE: The objective of this study was to examine whether bone mineral density (BMD) distribution in the mandibular condyle and facial morphology are associated with temporomandibular joint osteoarthritis (TMJ OA) using clinical cone beam computed tomography (CBCT) images. METHODS: CBCT images of 35 adults (16 male and 19 female) were examined to obtain TMJ OA counts, cephalometric analyses, and histograms of gray values that are proportional to BMD. Mean, standard deviation (SD), and low and high gray values at the 5th and 95th percentiles (Low5 and High5) of the histograms were measured. RESULTS: The female group had significantly higher values of TMJ OA counts, mean, and SD on the right mandibular condyle, High5 on both sides, and all gray value parameters for total (right + left) than the male group. CONCLUSION: Comprehensive analysis of BMD distribution in the mandibular condyle can provide useful information for prognosis of TMJ OA.

Practitioner Education and Feedback to Decrease Ciprofloxacin Prescriptions in Patients with Acute Uncomplicated Cystitis.

CONTEXT: Current guidelines recommend a nonfluoroquinolone agent as first-line treatment of acute uncomplicated cystitis (AUC) because of concerns of antimicrobial resistance and adverse effects. OBJECTIVE: To test whether a multifaceted intervention involving education and feedback reduced primary care practitioners' ciprofloxacin prescriptions for AUC therapy. DESIGN: Primary care practitioners at 3 medical offices participated: 65 in the intervention group and 51 in the control group. Intervention group participants received an educational lecture and emailed summary of antimicrobial guidelines, their AUC prescriptions were audited, and feedback was provided on inappropriate antibiotic choices. Prescriptions at AUC encounters were tracked during baseline, intervention, and postintervention periods. MAIN OUTCOME MEASURES: Proportion of AUC encounters at which ciprofloxacin was prescribed vs recommended first-line antibiotics. RESULTS: Intervention group participants had 5262 eligible AUC encounters, and control group participants had 5473. At baseline, ciprofloxacin was prescribed at 29.7% and 33.7% of eligible AUC encounters in the intervention and control groups, respectively (p = 0.003). After intervention, ciprofloxacin was prescribed at 10.8% of eligible AUC encounters in the intervention group and 34.3% in the control (p < 0.001). Adjusted odds ratios of ciprofloxacin prescription for AUC therapy were significantly lower in the intervention group during postintervention and intervention periods vs baseline (0.29, 95% confidence interval = 0.20-0.44, p < 0.001 and 0.80, 95% confidence interval = 0.66-0.97, p = 0.03). Adjusted odds ratios did not change over time in the controls. CONCLUSION: Educating primary care practitioners and conducting audit and feedback reduced their prescriptions of ciprofloxacin for AUC therapy.

Wearable Fetal Monitoring Solution for Improved Mobility During Labor & Delivery.

Electronic fetal monitoring (EFM) is used widely during labor & delivery, but existing solutions limit patient mobility, are uncomfortable, and do not consistently capture fetal heart rate (FHR) and uterine activity (UA) signals. A wireless EFM system was developed that features wearable US and tocodynamometer devices that conform to the body and do not require cables or belts. Benchtop testing demonstrated that the devices can accurately and consistently measure simulated FHRs and UAs over clinically meaningful ranges and body curvatures. The wearable EFM devices are expected to provide more reliable signal capture independent of maternal movement and repositioning, while also significantly improving patient comfort and mobility.

Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points.

Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit. CENP-A chromatin is shown to contain equimolar amounts of CENP-A and histones H2A, H2B, and H4, with no H3. Solid-state nanopore analyses show it to be nucleosomal in size. Thus, in contrast to models for hemisomes that briefly transition to octameric nucleosomes at specific cell cycle points or heterotypic nucleosomes containing both CENP-A and histone H3, human CENP-A chromatin complexes are octameric nucleosomes with two molecules of CENP-A at all cell cycle phases.

Wearable Ultrasound Array for Point-of-Care Imaging and Patient Monitoring.

A versatile, flexible piezoceramic array has been developed for a variety of ultrasound applications. The transducer can be configured as a linear or curvilinear transducer array, or mounted directly onto the body as a patch or wearable device. Results using a prototype 16-element array demonstrated equivalence to commercial linear array probes in accuracy of vessel diameter measurements in vascular phantoms. The ability to view needle insertion for peripherally inserted central catheter (PICC) procedures was also demonstrated. Opportunities for wearable ultrasound devices include point-of-care imaging, combat casualty care, ultrasound therapy, patient monitoring, and personal health.

Integrated Self-Management System for Improved Treatment of Asthma.

A mobile, affordable product that provides clinicians and patients with comprehensive asthma assessment is needed to improve asthma control. Our solution is an integrated system consisting of a portable, inexpensive, easy-to-use spirometer and a mobile application that communicates wirelessly with the spirometer. Results demonstrated that the wireless asthma management solution meets recommended American Thoracic Society (ATS) and European Respiratory Society (ERS) standards. The device is expected to empower patients to accurately self-assess their asthma for better self-management at home, work, or leisure.

A two-step mechanism for epigenetic specification of centromere identity and function.

The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.

The SUMO isopeptidase Ulp2p is required to prevent recombination-induced chromosome segregation lethality following DNA replication stress.

SUMO conjugation is a key regulator of the cellular response to DNA replication stress, acting in part to control recombination at stalled DNA replication forks. Here we examine recombination-related phenotypes in yeast mutants defective for the SUMO de-conjugating/chain-editing enzyme Ulp2p. We find that spontaneous recombination is elevated in ulp2 strains and that recombination DNA repair is essential for ulp2 survival. In contrast to other SUMO pathway mutants, however, the frequency of spontaneous chromosome rearrangements is markedly reduced in ulp2 strains, and some types of rearrangements arising through recombination can apparently not be tolerated. In investigating the basis for this, we find DNA repair foci do not disassemble in ulp2 cells during recovery from the replication fork-blocking drug methyl methanesulfonate (MMS), corresponding with an accumulation of X-shaped recombination intermediates. ulp2 cells satisfy the DNA damage checkpoint during MMS recovery and commit to chromosome segregation with similar kinetics to wild-type cells. However, sister chromatids fail to disjoin, resulting in abortive chromosome segregation and cell lethality. This chromosome segregation defect can be rescued by overproducing the anti-recombinase Srs2p, indicating that recombination plays an underlying causal role in blocking chromatid separation. Overall, our results are consistent with a role for Ulp2p in preventing the formation of DNA lesions that must be repaired through recombination. At the same time, Ulp2p is also required to either suppress or resolve recombination-induced attachments between sister chromatids. These opposing defects may synergize to greatly increase the toxicity of DNA replication stress.