Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men

OBJECTIVE: Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma. METHODS: Forty-seven men (mean age 44 +/- 14 years; mean blood pressure [MBP] 101 +/- 12 mm Hg; mean body mass index [BMI] 26 +/- 3 kg/m(2)) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress. RESULTS: Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA "Stress Index" (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined "threat" and "challenge") correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). "Challenge" correlated more strongly with D-dimer stress change than "threat" (p = .020). Primary appraisal (DeltaR(2) = 0.098, beta = 0.37, p = .019), and particularly its subscale "challenge" (DeltaR(2) = 0.138, beta = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change. CONCLUSIONS: Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response.

Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair

Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. Statement of significance Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.

Complication and failure rates in patients treated for chronic periodontitis and restored with single crowns on teeth and/or implants

Objectives: To assess the biological and technical complication rates of single crowns on vital teeth (SC-V), endodontically treated teeth without post and core (SC-E), with a cast post and core (SC-PC) and on implants (SC-I). Material and methods: From 392 patients with chronic periodontitis treated and documented by graduate students during the period from 1978 to 2002, 199 were reexamined during 2005 for this retrospective cohort study, and 64 of these patients were treated with SCs. Statistical analysis included Kaplan–Meier survival functions and event rates per 100 years of object-time. Poisson regression was used to compare the four groups of crowns with respect to the incidence rate ratio of failures, and failures and complications combined over 10 years and the entire observation period. Results: Forty-one (64%) female and 23 (36%) male patients participated in the reexamination. At the time of seating the crowns, the mean patient age was 46.8 (range 24–66.3) years. One hundred and sixty-eight single unit crowns were incorporated. Their mean follow-up time was 11.8 (range 0.8–26.4) years. During the time of observation, 22 biological and 11 technical complications occurred; 19 SC were lost. The chance for SC-V (56) to remain free of any failure or complication was 89.3% (95% confidence interval [CI] 76.1–95.4) after 10 years, 85.8% (95% CI 66–94.5) for SC-E (34), 75.9% for SC-PC (39), (95% CI 58.8–86.7) and 66.2% (95% CI 45.1–80.7) for SC-I (39). Over 10 years, 95% of SC-I remained free of failure and demonstrated a cumulative incidence of failure or complication of 34%. Compared with SC-E, SC-I were 3.5 times more likely to yield failures or complications and SC-PC failed 1.7 times more frequently than did SC-E. SC-V had the lowest rate of failures or complications over the 10 years. Conclusions: While SCs on vital teeth have the best prognosis, those on endodontically treated teeth have a slightly poorer prognosis over 10 years. Crowns on teeth with post and cores and implant-supported SCs displayed the highest incidence of failures and complications.

Expression, localization, and functional model of cholesterol transporters in lactating and nonlactating mammary tissues of murine, bovine, and human origin

Members of the ATP-binding cassette (ABC) transporters play a pivotal role in cellular lipid efflux. To identify candidate cholesterol transporters implicated in lipid homeostasis and mammary gland (MG) physiology, we compared expression and localization of ABCA1, ABCG1, and ABCA7 and their regulatory genes in mammary tissues of different species during the pregnancy-lactation cycle. Murine and bovine mammary glands (MGs) were investigated during different functional stages. The abundance of mRNAs was determined by quantitative RT-PCR. Furthermore, transporter proteins were localized in murine, bovine, and human MGs by immunohistochemistry. In the murine MG, ABCA1 mRNA abundance was elevated during nonlactating compared with lactating stages, whereas ABCA7 and ABCA1 mRNA profiles were not altered. In the bovine MG, ABCA1, ABCG1, and ABCA7 mRNAs abundances were increased during nonlactating stages compared with lactation. Furthermore, associations between mRNA levels of transporters and their regulatory genes LXRalpha, PPARgamma, and SREBPs were found. ABCA1, ABCG1, and ABCA7 proteins were localized in glandular MG epithelial cells (MEC) during lactation, whereas during nonlactating stages, depending on species, the proteins showed distinct localization patterns in MEC and adipocytes. Our results demonstrate that ABCA1, ABCG1, and ABCA7 are differentially expressed between lactation and nonlactating stages and in association with regulatory genes. Combined expression and localization data suggest that the selected cholesterol transporters are universal MG transporters involved in transport and storage of cholesterol and in lipid homeostasis of MEC. Because of the species-specific expression patterns of transporters in mammary tissue, mechanisms of cholesterol homeostasis seem to be differentially regulated between species.

Advances in the prevention, management and treatment of community-acquired pneumonia

Despite the availability of powerful antibiotics, community-acquired pneumonia (CAP) remains one of the leading reasons for morbidity and mortality worldwide, and despite the availability of powerful antibiotics, there has been only little improvement in case fatality rates for many years. Consequently, it cannot be expected that novel antibiotics will substantially improve outcomes in CAP. Therefore, this review focuses on novel approaches that may reduce CAP-related mortality: the impact of immunomodulation by macrolides and fluoroquinolones and the prevention of CAP by pneumococcal vaccines.

The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model

Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression.

Complication and failure rates of fixed dental prostheses in patients treated for periodontal disease

Objectives: To evaluate the biological and technical complication rates of fixed dental prostheses (FDP) with end abutments or cantilever extensions on teeth (FDP-tt/cFDP-tt) on implants (FDP-ii/cFDP-ii) and tooth-implant-supported (FDP-ti/cFDP-ti) in patients treated for chronic periodontitis. Material and methods: From a cohort of 392 patients treated between 1978 and 2002 by graduate students, 199 were re-examined in 2005. Of these, 84 patients had received ceramo-metal FDPs (six groups). Results: At the re-evaluation, the mean age of the patients was 62 years (36.2–83.4). One hundred and seventy-five FDPs were seated (82 FDP-tt, 9 FDP-ii, 20 FDP-ti, 39 cFDP-tt, 15 cFDP-ii, 10 cFDP-ti). The mean observation time was 11.3 years; 21 FDPs were lost, and 46 technical and 50 biological complications occurred. Chances for the survival of the three groups of FDPs with end abutments were very high (risk for failure 2.8%, 0%, 5.6%). The probability to remain without complications and/or failure was 70.3%, 88.9% and 74.7% in FDPs with end abutments, but 49.8–25% only in FDPs with extensions at 10 years. Conclusions: In patients treated for chronic periodontitis and provided with ceramo-metal FDPs, high survival rates, especially for FDPs with end abutments, can be expected. The incidence rates of any negative events were increased drastically in the three groups with extension cFDPs (tt, ii, ti). Strategic decisions in the choice of a particular FDP design and the choice of teeth/implants as abutments appear to influence the risks for complications to be expected with fixed reconstruction. If possible, extensions on tooth abutments should be avoided or used only after a cautious clinical evaluation of all options.

Complication and failure rates of tooth-supported fixed dental prostheses after 7 to 19 years in function

The aims of this study were to reexamine patients who had received fixed dental prostheses (FDPs) more than 10 years prior, list the frequencies of observed technical and biologic failures and complications, and calculate the estimated failure and complication rates at 10 and 15 years.

Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines

Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients.