In-vitro-Studie zur antibakteriellen Wirkung von Kiefernkernholz-Extrakt auf orale Mundspezies

In dieser In-vitro-Studie wurde ein Kiefernkernholzextrakt – KKH- (Wilms®) untersucht. Das aus dem Kernholz der Kiefer extrahierte Substrat wurde in Bezug auf seine antibakteriellen Eigenschaften gegenüber 28 kariogenen und parodontalpathogenen Mikroorganismen getestet. Es wurden zeit- und konzentrationsabhängige Untersuchungen durchgeführt, in denen das Verhalten von Einzelkeimen gegenüber KKH-Extrakten geprüft wurde. Jede mikrobielle Spezies wurde dazu für 10, 30 und 60 Minuten vier unterschiedlichen KKH-Extrakt Konzentrationen (0,05-, 0,1-, 0,5-, 1-fach) ausgesetzt. Weiterhin wurde die minimale Hemmstoffkonzentration bestimmt. Ebenfalls sollte der Frage nachgegangen werden, inwiefern sich Etablierung bzw. Reifung von Biofilmen beeinflussen lassen. Auf handelsüblichen Objektgläsern wurden dafür Biofilme aus aeroben und anaeroben Spezies entwickelt. Vor und nach der Formation der Biofilme wurden die Glasträger fünf Minuten dem KKH-Extrakt ausgesetzt. Die Ergebnisse dieser Studie zeigten; dass KKH-Extrakte antibakteriell wirken. Das Ausmaß der Keimreduktion ist abhängig von der Zeit und der Spezies. Eine Wirksamkeit von bereits geringen Konzentrationen besteht gegenüber anaeroben parodontopathogenen Spezies (Porphyromonas gingivalis). Hingegen erweisen sich sogenannte „Superinfektionserregern“ (Candida albicans u. Enterococcus faecalis) als resistent gegenüber KKH-Extrakten. Eine keimmindernde Wirkung auf bereits vorhandene Biofilme ist nicht vorhanden, jedoch erscheint die Biofilmbildung auf mit KKH-Extrakt benetzten Oberflächen vermindert. Schlussfolgernd können KKH-Extrakte in Mundspüllösungen, Zahnpasten etc. insbesondere die antiinfektiöse Parodontitistherapie unterstützen. Die Anwendung von KKH-Extrakten sollte Gegenstand klinischer Studien sein

Attitudes toward Precision Treatment of Smoking in the Southern Community Cohort Study

Background: Precision interventions using biological data may enhance smoking treatment, yet are understudied among smokers who are disproportionately burdened by smoking-related disease. Methods: We surveyed smokers in the NCI-sponsored Southern Community Cohort Study, consisting primarily of African-American, low-income adults. Seven items assessed attitudes toward aspects of precision smoking treatment, from undergoing tests to acting on results. Items were dichotomized as favorable (5 = strongly agree/4 = agree) versus less favorable (1 = strongly disagree/2 = disagree/3 = neutral); a summary score reflecting generalized attitudes was also computed. Multivariable logistic regression tested independent associations of motivation (precontemplation, contemplation, and preparation) and confidence in quitting (low, medium, and high) with generalized attitudes, controlling for sociodemographic factors and nicotine dependence. Results: More than 70% of respondents endorsed favorable generalized attitudes toward precision medicine, with individual item favorability ranging from 64% to 83%. Smokers holding favorable generalized attitudes reported higher income and education (P \u3c 0.05). Predicted probabilities of favorable generalized attitudes ranged from 63% to 75% across motivation levels [contemplation vs. precontemplation: adjusted odds ratio (AOR) = 2.10, 95% confidence interval (CI), 1.36–3.25, P = 0.001; preparation vs. precontemplation: AOR = 1.83, 95% CI, 1.20–2.78, P = 0.005; contemplation vs. preparation: AOR = 1.15, 95% CI, 0.75–1.77, P = 0.52] and from 59% to 78% across confidence (medium vs. low: AOR = 1.91, 95% CI, 1.19–3.07, P = 0.007; high vs. low: AOR = 2.62, 95% CI, 1.68–4.10, P \u3c 0.001; medium vs. high: AOR = 0.73, 95% CI, 0.48–1.11, P = 0.14). Conclusions: Among disproportionately burdened community smokers, most hold favorable attitudes toward precision smoking treatment. Individuals with lower motivation and confidence to quit may benefit from additional intervention to engage with precision smoking treatment. Impact: Predominantly favorable attitudes toward precision smoking treatment suggest promise for future research testing their effectiveness and implementation

A salvage pathway maintains highly functional respiratory complex I

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Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials

Abstract Background Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients’ decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial. Methods/design Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients’ understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes. Discussion PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers. Trial registration Clinical Trials.gov registration number: NCT02906241 (September 8, 2016)

A salvage pathway maintains highly functional respiratory complex I

Regulation of the turnover of complex I (CI), the largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and the assembly. Here, we report that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions. This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI. Our results also identify ClpXP activity as an unforeseen target for therapeutic interventions in the large group of mitochondrial diseases characterized by the CI instability. Maintenance and quality control of the mitochondrial respiratory chain complexes responsible for bulk energy production are unclear. Here, the authors show that the mitochondrial protease ClpXP is required for the rapid turnover of the core N-module of respiratory complex I, which happens independently of other modules in the complex

Feasibility of precision smoking treatment in a low-income community setting: results of a pilot randomized controlled trial in The Southern Community Cohort Study

Abstract Background The feasibility of precision smoking treatment in socioeconomically disadvantaged communities has not been studied. Methods Participants in the Southern Community Cohort Study who smoked daily were invited to join a pilot randomized controlled trial of three smoking cessation interventions: guideline-based care (GBC), GBC plus nicotine metabolism-informed care (MIC), and GBC plus counseling guided by a polygenic risk score (PRS) for lung cancer. Feasibility was assessed by rates of study enrollment, engagement, and retention, targeting > 70% for each. Using logistic regression, we also assessed whether feasibility varied by age, sex, race, income, education, and attitudes toward precision smoking treatment. Results Of 92 eligible individuals (79.3% Black; 68.2% with household income < $15,000), 67 (72.8%; 95% CI 63.0–80.9%) enrolled and were randomized. Of these, 58 (86.6%; 95% CI 76.4–92.8%) engaged with the intervention, and of these engaged participants, 43 (74.1%; 95% CI 61.6–83.7%) were retained at 6-month follow-up. Conditional on enrollment, older age was associated with lower engagement (OR 0.83, 95% CI 0.73–0.95, p = 0.008). Conditional on engagement, retention was significantly lower in the PRS arm than in the GBC arm (OR 0.18, 95% CI 0.03–1.00, p = 0.050). No other selection effects were observed. Conclusions Genetically informed precision smoking cessation interventions are feasible in socioeconomically disadvantaged communities, exhibiting high enrollment, engagement, and retention irrespective of race, sex, income, education, or attitudes toward precision smoking treatment. Future smoking cessation interventions in this population should take steps to engage older people and to sustain participation in interventions that include genetic risk counseling. Trial registration: ClinicalTrials.gov No. NCT03521141, Registered 27 April 2018, https://www.clinicaltrials.gov/study/NCT0352114