Antimicrobial Efficacy of Different Irrigant Solutions Using a Novel Biofilm Model: An In Vitro Confocal Laser Scanning Microscopy Experiment.

AIM: To determine the ability of different irrigation solutions to biomechanically remove Enterococcus faecalis biofilm from a novel artificial root canal model during chemomechanical preparation. METHODS: High resolution micro-computer-tomography scans of a mandibular molar's mesial root were used to produce 50 identical 3D-printed resin root canal models. These were cultured with E.faecalis over seven days to generate biofilm and subjected to chemomechanical preparation using: saline; 17% ethylenediaminetetraacetic acid (EDTA) or 2% sodium hypochlorite (NaOCl) alongside positive/negative controls (n = 10). Canals were prepared to 40/.06 taper, with 1 mL irrigation between instruments, followed by 5 mL penultimate rinse, 30 s ultrasonic activation and 5 mL final rinse. Residual biofilm volume (pixels) was determined following immunofluorescent staining and confocal-laser-scanning-microscopy imaging. Statistical comparisons were made using Kruskal-Wallis with post-hoc Dunn's tests (α ⟨0.05). RESULTS: In all canal thirds, the greatest biofilm removal was observed with NaOCl, followed by EDTA and saline. The latter had significantly higher E.faecalis counts than NaOCl and EDTA (P ⟨0.01). However, no statistical differences were found between EDTA and NaOCl or saline and positive controls (P ⟩0.05). CONCLUSIONS: Within limitations of this model, 17% EDTA was found to be as effective as 2% NaOCl at eradicating E.faecalis biofilm following chemomechanical preparation. Further investigations with multi-species biofilms are encouraged.

What do 'omic technologies have to offer periodontal clinical practice in the future?

BACKGROUND AND OBJECTIVE: Periodontal diseases are the most common chronic inflammatory diseases of humans and a major cause of tooth loss. Inflammatory periodontitis is also a complex multifactorial disease involving many cell types, cell products and interactions. It is associated with a dysregulated inflammatory response, which fails to resolve, and which also fails to re-establish a beneficial periodontal microbiota. There is a rich history of biomarker research within the field of periodontology, but exemplary improvements in analytical platform technologies offer exciting opportunities for discovery. These include the 'omic technologies, such as genomics, transcriptomics, proteomics and metabolomics, which provide information on global scales that can match the complexity of the disease. This narrative review focuses on the recent advances made in in vivo human periodontal research by use of 'omic technologies. MATERIAL AND METHODS: The Medline database was searched to identify articles currently available on 'omic technologies with regard to periodontal research. RESULTS: One hundred and sixty-one articles focusing on biomarkers of and 'omic advances in periodontal research were analysed for their contributions to the understanding of periodontal diseases. CONCLUSION: The data generated by the use of 'omic technologies have huge potential to inform paradigm shifts in our understanding of periodontal diseases, but data management, analysis and interpretation require a thoughtful and systematic bioinformatics approach, to ensure meaningful conclusions can be made.

Biofilm formation on bone-anchored hearing aids.

OBJECTIVE: To investigate microbiological biofilm contamination of retrieved bone-anchored hearing aids. MATERIALS AND METHODS: Nine failed, retrieved bone-anchored hearing aids and 16 internal screws were examined by scanning electron microscopy. A fixture from a failing implant, which had been removed and disassembled under aseptic conditions, was cultured. Finally, an internal screw from a new, unimplanted fixture was examined by scanning electron microscopy. RESULTS: Debris was seen on the fixture and abutment of all bone-anchored hearing aids, and on the heads of the 16 internal screws. On eight screws, biofilm extended down the shaft to the threads, where it was several micrometres thick. Culture of a failing fixture yielded staphylococcus. The new, unimplanted fixture internal screw showed evidence of scratching and metallic debris on the threads, which may interfere with close fitting of the screw and subsequently facilitate microleakage. CONCLUSION: There may be a link between internal microbial contamination and failure of bone-anchored hearing aids.

The RASSF8 candidate tumor suppressor inhibits cell growth and regulates the Wnt and NF-kappaB signaling pathways.

The Ras-assocation domain family (RASSF) of tumor suppressor proteins until recently contained six proteins named RASSF1-6. Recently, four novel family members, RASSF7-10, have been identified by homology searches for RA-domain-containing proteins. These additional RASSF members are divergent and structurally distinct from RASSF1-6, containing an N-terminal RA domain and lacking the Sav/RASSF/Hpo (SARAH) domain. Here, we show that RASSF8 is ubiquitously expressed throughout the murine embryo and in normal human adult tissues. Functionally, RNAi-mediated knockdown of RASSF8 in non-small-cell lung cancer (NSCLC) cell lines, increased anchorage-independent growth in soft agar and enhanced tumor growth in severe combined immunodeficiency (SCID) mice. Furthermore, EdU staining of RASSF8-depleted cells showed growth suppression in a manner dependent on contact inhibition. We show that endogenous RASSF8 is not only found in the nucleus, but is also membrane associated at sites of cell-cell adhesion, co-localizing with the adherens junction (AJ) component beta-catenin and binding to E-cadherin. Following RASSF8 depletion in two different lung cancer cell lines using alternative small interfering RNA (siRNA) sequences, we show that AJs are destabilized and E-cadherin is lost from the cell membrane. The AJ components beta-catenin and p65 are also lost from sites of cell-cell contact and are relocalized to the nucleus with a concomitant increase in beta-catenin-dependent and nuclear factor-kappaB (NF-kappaB)-dependent signaling following RASSF8 depletion. RASSF8 may also be required to maintain actin -cytoskeletal organization since immunofluorescence analysis shows a striking disorganization of the actin- cytoskeleton following RASSF8 depletion. Accordingly, scratch wound healing studies show increased cellular migration in RASSF8-deficient cells. These results implicate RASSF8 as a tumor suppressor gene that is essential for maintaining AJs function in epithelial cells and have a role in epithelial cell migration.

Contributions to our understanding of T cell physiology through unveiling the T cell proteome.

Since the sequencing of the human genome was completed, attention has turned to examining the functionality of the molecular machinery, in particular of protein expression. Differential proteome analysis by two-dimensional electrophoresis has been adopted to study changes in T cell proteomes during T cell activation, and this work is increasing our understanding of the complexity of signals elicited across multiple pathways. The purpose of this review is to summarize the available evidence in the application of proteomic techniques and methodologies to understand T cell receptor activation from lipid raft and cytoskeletal rearrangements, through to signalling cascades, transcription factor modulation and changes in protein expression patterns. These include post-translational modifications, which are not encoded by the genome.

Urinary free cortisol levels among depressed men and women: differential relationships to age and symptom severity?

BACKGROUND: Preclinical and clinical models of depression suggest sex differences may be mediated at least in part, by differences in hormonal modulation of hypothalamic-pituitary-adrenal (HPA) axis activity. Unraveling the consequences of moderating influences from the effect of sexual dimorphism will be vital to elaborating models of pathophysiology. METHODS: The current study investigated urinary free cortisol (UFC) among younger adults with mild to moderate major depressive disorder to clarify the relationship with potential demographic and clinical moderators. RESULTS: Male patients had higher mean UFC levels than female patients. Moreover, significant interactions between age and severity were found among men, but not women. In contrast to prior findings, neither age nor severity effects on UFC levels were found among female patients. LIMITATIONS: Conclusions from the current study are limited by the absence of cortisol data from matched controls. Thus it was not possible to disentangle sex differences in baseline physiology from that of pathophysiological differences tied specifically to depression. CONCLUSIONS: Despite several methodological limitations, the interactions between sex and both age and severity in this large sample of depressed patients are suggestive of differential pathophysiology for regulation of UFC excretion, and could reflect a neuroprotective effect for estrogen among younger depressed women.

Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment.

BACKGROUND: Investigations of cognitive disturbances among patients with mood disorders have yielded inconsistent results. Although marked neuropsychologic deficits have been reported in elderly patients and in midlife patients with severe depression, the severity of cognitive impairments in medically healthy younger ambulatory adults with depression has not been well characterized. METHODS: A comprehensive battery of standard neuropsychologic tests and experimental computerized measures of cognitive functioning were administered to unmedicated ambulatory younger adults with mild to moderate nonbipolar depression and to a group of age- and gender-equated healthy subjects. RESULTS: Patients demonstrated a notable absence of widespread cognitive impairment. Deficits in executive functions were observed on the Wisconsin Card Sort Test but not on several other tests. Despite the absence of significant impairment on tests of attention, memory, and motor performance in the total sample, symptom severity and age of illness onset were correlated with poorer performance on some tests of cognitive functioning even after correction for age. CONCLUSIONS: These findings, derived from a large sample of unmedicated depressed outpatients, indicate that major depressive disorder in healthy younger ambulatory adults does not cause appreciable impairments in cognitive functioning in the absence of clinical and course-of-illness features.

Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity.

BACKGROUND: The locus coeruleus (LC) is the major noradrenergic cell body group in the brain. Although previous studies have examined changes in electrophysiologic activity of LC neurons produced by antidepressant drugs, only a small number have examined changes that occur with chronic drug administration, which is the therapeutically effective regimen, and only one group of investigators has assessed effects on activated (or "burst") firing of LC neurons under such treatment conditions. The present study assessed changes produced in rats by effective antidepressant treatments-several drugs given chronically (two tricyclic antidepressants, two selective serotonin reuptake inhibitors, and a monoamine oxidase inhibitor) as well as a series of electroconvulsive shocks (ECSs)-in single-unit electrophysiologic activity of LC neurons, measuring effects on spontaneous depolarization rate and also on sensory-evoked burst firing. METHODS: Drugs were administered via osmotic minipumps for either 14 or 30 days; ECSs were administered five times, with a 72-hour interval between each administration. Electrophysiologic recording of LC activity took place under halothane anesthesia on the last day of drug treatment or following a delay of 1 or 5 days after the final ECS. RESULTS: A common effect of all drugs tested and ECS treatment was to decrease LC spontaneous and sensory-evoked burst firing. CONCLUSIONS: The clinical efficacy of antidepressant medication and ECS may be mediated, in part, through reduction of LC neural activity. The findings reported here are consistent with recent indications that LC neurons are hyperactive in depressed individuals and with suggestions that some behavioral changes seen in depression can arise from consequences of rapidly depolarizing LC terminals, such as release of peptides.

Alternative pharmacotherapy. Patterns of patient use and family physician practice.

BACKGROUND: The use of alternative pharmacotherapies is rapidly increasing. Many persons who use purchased or prepared alternative medications are also cared for by family physicians. We describe patient usage of alternative pharmacotherapies and examine how family physicians handle this in medical practice. METHODS: We recorded data from structured interviews of 178 patients in an academic family medicine practice in a midsized southern city. We then examined the medical records of each participant who reported using some form of alternative pharmacotherapy to determine whether there was discussion of this use with the physician. RESULTS: Approximately one third of the patients reported using some form of alternative pharmacotherapy for 1 year or less, learning about alternative medications mostly from the media, and being generally satisfied with the results. Eighty-four percent of the patients reported not having been asked by their physician about their use of these drugs on the day of their office visit, and more than half reported never having been asked about their use of them. Medical record reviews indicated that for the most part physicians did not document having discussed or making recommendations about the use of alternative pharmacotherapies at any point in their relationship with the patient. CONCLUSIONS: Since many of their patients are using alternative pharmacotherapies, family physicians are encouraged to learn more about what their patients use, to institute easy system-wide changes to facilitate discussion about this use with their patients, to document alternative drugs used, and to give recommendations regarding them.

Depression and functioning in relation to health care use in sickle cell disease.

The purpose of the current study was to investigate depression and health care use in patients with sickle cell disease (SCD). Forty-four adults with SCD were interviewed and data from 43 participants, both with (n = 11) and without (n = 32) depression, were used for further analyses. Data from one potential subject were excluded on the basis of diagnosis. The full evaluation included the Structured Clinical Interview for DSM-III-R Disorders (SCID) and the Center for Epidemiologic Studies--Depression Scale (CES-D), as well as measures of psychosocial and behavioral functioning. Good between-instrument agreement was found between the self-report and interview-based measures of depression. However, the functioning data did not entirely support the use of a more stringent cutoff score on the CES-D. Findings suggest that the purpose of the evaluation should be factored into the decision-making process when determining which cutoff score should be utilized (i.e. what is the cost-benefit ratio for false-positives vs. false-negatives). A series of hierarchical regression analyses supported the finding that disease severity alone does not explain the level of functioning displayed by patients. More importantly, the patient's perceived functioning was the best indicator of health care use within a 1-year period. Furthermore, specific interventions that target negative thinking and distorted cognitions, as well as provide psychoeducation, such as cognitive-behavioral therapy, need to be further explored within this population.

Quality of life in breast cancer survivors: implications for developing support services.

PURPOSE/OBJECTIVES: Quality of life (QOL) is becoming more important in regard to breast cancer as treatment advances extend the period of survivorship. The purpose of this article is to share the results of a cancer center's attempt to evaluate the QOL needs of breast cancer survivors in order to provide improved supportive-care services. DESIGN: Descriptive mailed survey. SETTING: A medical center in southern California. SAMPLE: A random sample of breast cancer survivors (N = 298). METHODS: Breast cancer survivors completed a mailed survey that included major outcome variables of QOL and pain. Subjects were stratified by three age groups: younger than 40 years, 40-60 years, and older than 60 years. MAIN RESEARCH VARIABLES: QOL subscales (physical, psychological, social, and spiritual well-being) and overall QOL score and pain as assessed by the Brief Pain Inventory. FINDINGS: Results indicated continued physical demands of breast cancer, including fatigue and pain, as well as psychological burdens related to fear of breast cancer recurrence and anxiety. The social well-being domain indicated some unique aspects of QOL when applied to breast cancer survivorship such as the fear of breast cancer in female relatives. The spiritual well-being domain illustrated the unique QOL aspects of life-threatening illness such as living with uncertainty and maintaining hope. Breast cancer survivors also reported positive aspects and life changes after successfully facing breast cancer. CONCLUSIONS: Breast cancer survivors experience many demands of illness across the physical, psychological, social, and spiritual domains. IMPLICATIONS FOR NURSING PRACTICE: The study's findings can be useful in directing cancer centers' efforts to provide comprehensive care for breast cancer survivors. Nurses play a critical role in leading these efforts for supportive-care services intended to improve the QOL of breast cancer survivors.

Gender differences in outcomes among patients with cancer.

This study examined gender differences in 162 female and 65 male patients with cancer referred to home care. Data were collected before hospital discharge using the Multidimensional Functional Assessment Questionnaire, the Karnofsky Performance Status, and the Quality of Life-Cancer Scale. Controlling for age and stage of disease, the results showed that men reported significantly more cancer-related impairments, more limitations in activity of daily living, and poorer social resources than women. No gender differences were found in quality of life, perceived emotional health, perceived physical health, performance status, and comorbidity. Significant predictors of self-care activities were: for women perceived physical health, Karnofsky Performance Status, and stage of disease (58% variance explained); for men Karnofsky Performance Status and medication taken (67% variance explained). Gender differences should be considered in discharge planning to provide appropriate home care services for male and female patients with cancer.

Quality of life in breast cancer survivors as identified by focus groups.

Currently, over 1,700,000 women are living with breast cancer in the United States. These long-term survivors of breast cancer are challenged to redirect their energy from issues of cancer treatment and early side effects toward quality of life issues related to long-term survivorship, such as menopause, infertility, fear of recurrence, family distress, and uncertainty. In an attempt to obtain patient perspectives on quality of life and health care issues faced by breast cancer survivors, focus group methodology was utilized in the first year of a 2 year study. The sample was stratified to represent three age groups: < 40 years, 40-60 years, and > 60, and was intended to represent different developmental levels believed to have varying experiences with quality of life and potentially divergent needs following breast cancer diagnosis. Results of these focus groups revealed unique quality of life concerns of breast cancer survivors across four domains of physical, psychological, social, and spiritual well being. Each of these domains yields important implications for future research and clinical practice.

Physical and psychosocial outcomes in cancer patients: a comparison of different age groups.

In a cross-sectional study, we investigated the relationship between age, physical health, social and economic resources, functional status, activities of daily living (ADL) and disease-related variables of 227 patients with cancer. Using multidimensional outcome measures we examined age differences in three age groups (< 45, 46-65, > 65 years) and identified predictors of performing ADL. The results indicated that older patients have outcomes similar to those of younger patients. There were no significant differences in quality of life, performance status and physical health among the three age groups. The only areas where age-related differences were found were co-morbidity and cancer-related impairments. Patients aged 45-65 years and patients 65 years and older reported a higher level of co-morbidity and more cancer-related impairments than those aged 45 and younger. Although older patients had higher co-morbidity, they showed similar Karnofsky Performance Status (KPS) scores to those of their younger counterparts. The regression analysis revealed social resources, self-reported health, performance status and complexity of care as significant predictors of patients' ADL, but not age, co-morbidity or severity of treatment. The findings support the conclusion that differences in performing ADL between younger and older patients with cancer are minimal and tend to be due to co-morbidity. Thus, treatment should be decided by a patient's physical health rather than by age.

Self-care responses to illness of patients with various cancer diagnoses.

The purpose of this study was to examine the relationship between self-care responses and variables concerning health status, disease and treatment, socioeconomic resources, demographic characteristics, and health beliefs in a heterogeneous sample of 227 cancer patients referred to home care. Data were collected prior to discharge from the hospital using the OARS Functional Assessment Questionnaire, the Karnofsky Performance Status, the Multidimensional Health Locus of Control Scale, and the Preference for Participation in Care Tool. The results indicated that the variables related to health status, disease and treatment were highly correlated with self-care behavior (SCB), and to a lower extent to self-care preference (SCP). Karnofsky performance status, cancer-related impairments, perceived physical health, and stage of disease were identified as significant predictors of SCB explaining 57% of the variance. Age, gender, education, live-in resources, and perceived mental health were dominant predictors of SCP explaining only 17% of the variance. Further research endeavors should investigate other models that might prove to be better predictors of SCP.

Community-based educational programs for cancer nursing.

A United Way grant allowed the Department of Nursing Research and Education to make available its expertise in cancer nursing and establish itself as a resource for oncology. Community educational needs were assessed by a questionnaire sent to outside agencies prior to designing an oncology educational program. In a 9-month period, 57 classes at 21 different facilities representing 417 hours of instruction were provided. Nurses attending the classes totaled 1,175. Results showed an increase in scores from pre-test to post-test, indicating that participants demonstrated increased knowledge as a result of class participation. This funding provided the catalyst to prepare a large number of community hospital nurses in the complex care of oncology patients.

Anorexia, cachexia, and dysphagia: the symptom experience.

OBJECTIVES: To review the symptoms of anorexia, cachexia, and dysphagia and to provide information on nutritional assessment and interventions. DATA SOURCES: Published studies of anorexia, cachexia, and dysphagia, research abstracts, and review articles. CONCLUSIONS: Anorexia, cachexia, and dysphagia can cause severe alterations in nutrition in cancer patients that may lead to irreversible nutritional compromise and death. Nursing research must focus on symptom management of these three symptoms, the needs of the patient and family, and the impact of dysphagia on quality of life. IMPLICATIONS FOR NURSING PRACTICE: Assessment, objective evaluation, pharmacological interventions, and nutritional counseling are important interventions for patients with anorexia and cachexia. Swallowing therapy, food intake adjustments, oral hygiene, and supportive care are important measures needed by the patient with dysphagia.

Cytokines affect pseudomonas binding to tracheal cells via a neutrophil-mediated process.

Critical illness is often associated with gram-negative bacterial colonization of the airways, increasing the risk of nosocomial pneumonia. Cytokines, released in response to endotoxin, might contribute to this phenomenon by causing changes in epithelial cell binding of bacteria. To investigate this possibility, human monocytes and hamster pulmonary macrophages were cultured without or with Escherichia coli endotoxin (10 micrograms/ml) for 4 and 24 h. Hamster and human tracheal epithelial cells were treated with supernates from monocyte cultures for 24 h, and subsequent binding of 14C-labeled Pseudomonas aeruginosa to the epithelial cells was measured (percent adherence). In separate experiments, recombinant human (rh) tumor necrosis factor-alpha (TNF-alpha) (25 to 100 ng/ml) and interleukin-1 beta (IL-1 beta) (2,000 to 8,000 pg/ml) were added to hamster monolayers. Neither monocyte supernates nor purified cytokines were toxic to the epithelial cells for up to 48 h. There was no significant change in P. aeruginosa adherence to either hamster or human tracheal epithelial cells after 24 h of exposure to culture supernates from either endotoxin-stimulated human monocytes or hamster macrophages. Similarly, purified rhTNF and rhIL-1 exposure did not increase bacterial adherence. However, when polymorphonuclear leukocytes were coincubated with the monocyte supernates and epithelial cells, P. aeruginosa adherence was significantly increased. Moreover, this effect was enhanced by an epithelial cell-derived substance. Thus, while inflammatory cytokines may participate in enhancing bacterial colonization of the lung in vivo, they do not do so by a direct action on tracheal epithelial cells but can act via a neutrophil-dependent mechanism.