Vitamin D and genetic ancestry are associated with apoptosis rates in benign and malignant prostatic epithelium.

PURPOSE: Vitamin D metabolites may be protective against prostate cancer (PCa). We conducted a cross-sectional analysis to evaluate associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. EXPERIMENTAL DESIGN: Benign and tumor epithelial punch biopsies of participants with clinically localized PCa underwent indirect TUNEL staining. Serum levels of 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D were assessed immediately before radical prostatectomy; levels of prostatic 25(OH)D were obtained from the specimen once the prostate was extracted. Ancestry informative markers were used to estimate the percentage of genetic West African, Native American, and European ancestry. RESULTS: One hundred twenty-one newly diagnosed men, age 40-79, were enrolled between 2013 and 2018. Serum 25(OH)D correlated positively with both tumor (ρ = 0.17, p = 0.03), and benign (ρ = 0.16, p = 0.04) prostatic epithelial TUNEL staining. Similarly, prostatic 25(OH)D correlated positively with both tumor (ρ = 0.31, p < 0.001) and benign (ρ = 0.20, p = 0.03) epithelial TUNEL staining. Only Native American ancestry was positively correlated with tumor (ρ = 0.22, p = 0.05) and benign (ρ = 0.27, p = 0.02) TUNEL staining. In multivariate regression models, increasing quartiles of prostatic 25(OH)D (ß = 0.25, p = 0.04) and Native American ancestry (ß = 0.327, p = 0.004) were independently associated with tumor TUNEL staining. CONCLUSIONS: Physiologic serum and prostatic 25(OH)D levels and Native American ancestry are positively associated with the degree of apoptosis in tumor and benign prostatic epithelium in clinically localized PCa. Vitamin D may have secondary chemoprevention benefits in preventing PCa progression in localized disease.

Efficacy and safety of darolutamide in Black/African-American patients from the phase III ARAMIS study.

Aim: Darolutamide significantly improved metastasis-free survival (MFS) and overall survival (OS) versus placebo in the phase III ARAMIS study. We evaluated outcomes in Black/African-American patients in ARAMIS. Materials & methods: Patients with nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554) plus androgen-deprivation therapy. The primary end point was MFS. Secondary end points included OS and safety. Results: In 52 (3.4%) Black/African-American patients, darolutamide improved MFS (median: not reached vs 12.4 months) and OS (3-year survival rates: 100 vs 71%) versus placebo. The safety profile of darolutamide in Black/African-American patients was consistent with that of all ARAMIS patients. Conclusion: In Black/African-American patients, darolutamide improved MFS and OS and was well tolerated, consistent with the overall ARAMIS population.

In patients with prostate cancer that has stopped responding to androgen-deprivation therapy, or 'ADT,' and has not spread to other parts of the body (known as nonmetastatic castration-resistant prostate cancer, or 'nmCRPC'), darolutamide is an oral treatment option. Darolutamide added to ADT was tested in patients with nmCRPC in a large international study called ARAMIS and was found to prolong the time that patients were free from their cancer spreading compared with patients who received ADT alone. This report provides information on the effect of darolutamide in the 52 Black/African­American patients who took part in ARAMIS. In these patients, darolutamide showed similar effects on lowering the risk of their cancer spreading and was well tolerated.

Association of LTF, ENAM, and AMELX polymorphisms with dental caries susceptibility: a meta-analysis.

BACKGROUND: This meta-analysis evaluated the association of LTF, ENAM, and AMELX polymorphisms with dental caries susceptibility. METHODS: We searched the Scopus, PubMed/Medline, Web of Science, and Cochrane Library databases to retrieve articles published by October 2019. Review Manager 5.3 software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The results of publication bias tests were retrieved by Comprehensive Meta-Analysis 2.0 software. RESULTS: A total of 150 relevant records were identified; out of which, 16 were entered into the analysis (4 studies assessed LTF, 11 ENAM, and 11 AMELX polymorphisms). Of all polymorphisms, there was a significant association only between ENAM rs3796704 polymorphism and dental caries susceptibility. Both ENAM rs3796704 and AMELX rs17878486 polymorphisms had a significant association with dental caries risk in the Caucasian ethnicity and the studies including caries-free control group. CONCLUSIONS: The results of this meta-analysis showed that the G allele and the GG genotype of ENAM rs3796704 were associated with an increased risk of caries in the case group compared with the control group. But there was no association between LTF rs1126478, ENAM (rs1264848 and rs3796703), and AMELX (rs946252, rs17878486, and rs2106416) polymorphisms and dental caries susceptibility.

Dendrimer-Based Platform for Effective Capture of Tumor Cells after TGFß1-Induced Epithelial-Mesenchymal Transition.

Detection of circulating tumor cells (CTCs) relying on their expression of epithelial cell markers, such as epithelial cell adhesion molecule (EpCAM), has been commonly used. However, this approach unlikely captures CTCs that have undergone the process of epithelial-mesenchymal transition (EMT). In this study, we have induced EMT of in vitro prostate (PCa) and breast cancer (BCa) cell lines by treatment of transforming growth factor ß 1 (TGFß1), a pleiotropic cytokine with transition-regulating activities. We found that the TGFß1-treated, post-EMT cells exhibited up to a 45% reduction in binding affinity to antibodies against EpCAM (aEpCAM). To overcome this limitation, we designed our capture platform that integrates a unique combination of biomimetic cell rolling, dendrimer-mediated multivalent binding, and antibody cocktails of aEpCAM/aEGFR/aHER-2. Our capture surfaces resulted in up to 98% capture efficiency of post-EMT cells from mixtures of TGFß1-treated and untreated cancer cells spiked in culture media and human blood. In a clinical pilot study, our CTC device was also able to capture rare CTCs from PCa patients with significantly enhanced capture sensitivity and purity compared to the control surface with aEpCAM only, demonstrating its potential to provide a reliable detection solution for CTCs regardless of their EMT status.

Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients.

PURPOSE: To investigate the correlation between serum 25 hydroxyvitamin D, prostatic 25 hydroxyvitamin D, and serum 1,25 dihydroxyvitamin D, and their respective associations with prostatic tumor proliferation at the time of radical prostatectomy. METHODS: In this cross-sectional analysis of 119 men undergoing radical prostatectomy, serum from whole blood and expressed prostatic fluid was collected on the day of surgery. Tumor proliferation was measured in the dominant tumor on formalin-fixed prostatectomy tissues by immunohistochemical staining for Ki67 and quantified by Aperio imaging analysis. RESULTS: The sample included 88 African Americans (74%) and 31 (26%) European Americans. Serum and prostatic levels of 25 hydroxyvitamin D were correlated with each other (Spearman's rho (ρ) = 0.27, p = 0.004), and there was also a correlation between serum 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D (ρ = 0.34, p < 0.001). Serum and prostatic 25 hydroxyvitamin D levels were not correlated with Ki67 staining in tumor cells. Serum 1,25 dihydroxyvitamin D was inversely correlated with Ki67 staining in tumor cells (ρ = - 0.30, p = 0.002). On linear regression, serum 1,25 dihydroxyvitamin D was negatively associated with Ki67 staining in tumor cells (ß - 0.46, 95% CI - 0.75, - 0.04, p = 0.04). CONCLUSION: The correlation between physiologic serum levels of 25 hydroxyvitamin D with both prostatic 25 hydroxyvitamin D and serum 1,25 dihydroxyvitamin D suggests that serum levels are reasonable biomarkers of vitamin D status. Furthermore, serum 1,25 dihydroxyvitamin D has an inverse association with Ki67 staining in tumor cells at physiologic levels and may protect against tumor progression.

A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort.

BACKGROUND: Predictive models that take race into account like the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) and the new Prostate Biopsy Collaborative Group (PBCG) RC have been developed to equitably mitigate the overdiagnosis of prostate specific antigen (PSA) screening. Few studies have compared the performance of both calculators across racial groups. METHODS: From 1485 prospectively recruited participants, 954 men were identified undergoing initial prostate biopsy for abnormal PSA or digital rectal examination in five Chicago hospitals between 2009 and 2014. Discrimination, calibration, and frequency of avoided biopsies were calculated to assess the performance of both risk calculators. RESULTS: Of 954 participants, 463 (48.5%) were Black, 355 (37.2%) were White, and 136 (14.2%) identified as Other. Biopsy results were as follows: 310 (32.5%) exhibited no cancer, 323 (33.9%) indolent prostate cancer, and 321 (33.6%) clinically significant prostate cancer (csPCa). Differences in area under the curve (AUC)s for the detection of csPCa between PCPT and PBCG were not statistically different across all racial groups. PBCG did not improve calibration plots in Blacks and Others, as it showed higher levels of overprediction at most risk thresholds. PCPT led to an increased number of avoidable biopsies in minorities compared to PBCG at the 30% threshold (68% vs. 28% of all patients) with roughly similar rates of missed csPCa (23% vs. 20%). CONCLUSION: Significant improvements were noticed in PBCG's calibrations and net benefits in Whites compared to PCPT. Since PBCG's improvements in Blacks are disputable and potentially biases a greater number of low risk Black and Other men towards unnecessary biopsies, PCPT may lead to better biopsy decisions in racial minority groups. Further comparisons of commonly used risk calculators across racial groups is warranted to minimize excessive biopsies and overdiagnosis in ethnic minorities.

Salivary Profile in Adult Type 2 Diabetes Mellitus Patients: A Case-control Study.

OBJECTIVE: To evaluate salivary factors in type 2 diabetes melliuts patients. METHODS: The case-control study was conducted from June to November 2016 at Kermanshah University of Medical Sciences, Kermanshah, Iran, and comprised patients with type 2 diabetes mellitus and healthy controls matched in terms of age and gender. Unstimulated saliva samples were collected in the morning after an overnight fast of 8-12 hours. The samples were centrifuged at 1500 rpm for 5 minutes, and every isolated transparent liquid was immediately frozen at a temperature of -45ºC in a tube. The test sample was later aspirated, and readings were taken. The data was analyzed using SPSS 16.. RESULTS: Of the 200 subjects, 100(50%) were diabetic patients and 100(50%) were healthy controls. The two groups were matched with regard to age, gender, diabetes duration, serum glucose, and glycated haemoglobin (p>0.05 each). In terms of laboratory variables, there were significant differences between the groups related to urea, phosphorus, pH, and glucose (p<0.05 each). Urea and glucose levels were higher in the patient group than the controls (p<0.05 each). Also, calcium and total protein levels were higher in male patients compared to female patients (p < 0.0 5 each) . CONCLUSIONS: Salivary pH, urea, calcium, phosphorus, glucose, and total protein levels could be bio chemical parameters for screening, diagnosis and monitoring of diabetes .

Salivary and Serum Interferon-Gamma/Interleukin-4 Ratio in Oral Lichen Planus Patients: A Systematic Review and Meta-Analysis.

Background and Objectives: Interferon-gamma (IFN-γ)/interleukin-4 (IL-4) ratio may indicate a change in the immune response with a potential pathological effect presented in oral lichen planus (OLP) patients. Herein, this meta-analysis evaluated the role of serum and salivary interferon-gamma/interleukin-4 ratio in the severity and development of OLP. Materials and Methods: The Scopus, Cochrane Library, PubMed, and Web of Science databases were systematically searched to retrieve the relevant studies published up from the database inception to March 2019. The crude mean difference (MD) and 95% confidence interval (CI) were calculated by RevMan 5.3 software using a random-effects model. A sensitivity analysis was performed on the results using the CMA 2.0 software. A total of 98 studies were retrieved from the databases, of which at last seven studies were included in this meta-analysis. Results: The findings showed that the pooled MDs of serum and salivary IFN-γ/IL-4 ratio were -0.22 (95% CI: -1.16, 0.72; p = 0.64) and 0.17 (95% CI: -1.50, 1.84; p = 0.84) in OLP patients compared to controls, respectively. In addition, the pooled MDs of serum and salivary IFN-γ/IL-4 ratio were -0.15 (95% CI: -0.53, 0.23; p = 0.43) and -0.39 (95% CI: -0.63, -0.15; p = 0.001) in patients with erythematous/ulcerative subtype compared to patients with reticular subtype, respectively. Conclusions: In conclusion, the results of meta-analysis demonstrated that serum and salivary IFN-γ/IL-4 ratio cannot play a major role in OLP development and severity.

Serum and Salivary IgA, IgG, and IgM Levels in Oral Lichen Planus: A Systematic Review and Meta-Analysis of Case-Control Studies.

Immunoglobulins (IgA, IgG, and IgM) are significant anti-inflammatory factors. The meta-analysis aimed to assess the serum and salivary levels of Igs as more important immunoglobulins in patients affected by oral lichen planus (OLP) compared to the healthy controls. Four databases, including PubMed/Medline, Scopus, Web of Science, and Cochrane Library as well as Iranian databases were checked up to January 2018 without language restriction. The quality of each involved study was done using the Newcastle⁻Ottawa Quality Assessment Scale (NOS) questionnaire. A random-effects model analysis was done by RevMan 5.3 software applying the mean difference (MD) plus 95% confidence intervals (CIs). The CMA 2.0 software was applied to calculate the publication bias among the studies. Out of 70 studies found in the databases, 8 studies were involved and analyzed in the meta-analysis. The meta-analysis included 282 OLP patients and 221 healthy controls. The pooled MDs of serum levels of IgA, IgG, and IgM were -0.13 g/L [95% CI: -0.24, -0.02; P = 0.02], 1.01 g/L [95% CI: -0.91, 2.93; P = 0.30], and -0.06 g/L [95% CI: -0.25, 0.14; P = 0.56], respectively; whereas, the salivary IgA and IgG levels were 71.54 mg/L [95% CI: 12.01, 131.07; P = 0.02] and 0.59 mg/L [95% CI: -0.20, 1.38; P = 0.14], respectively. Considering the few studies performed on saliva, the results suggested that the salivary levels, especially IgA level had higher values than the serum levels. Therefore, the salivary immunoglobulins can play a significant function in the OLP pathogenesis.

Interleukin-6 levels in the serum and saliva of patients with oral lichen planus compared with healthy controls: a meta-analysis study.

Interleukin-6 (IL-6) is a cytokine that contributes to the pathogenesis of oral lichen planus (OLP). The aim of this meta-analysis study is the evaluation of IL-6 levels in the serum and saliva of patients with OLP compared with healthy controls. We searched the studies in 5 databases: PubMed/Medline, Scopus, ScienceDirect, Web of Science, and Cochrane Library, from 1983 to Oct 31, 2016. Eleven studies were analysed for the meta-analysis study. The reviewers independently evaluated the quality of each included study using the Newcastle-Ottawa Quality Assessment Scale (NOS). A random-effects meta-analysis, using Comprehensive Meta-Analysis software version 2.0, was used to reflect the variation in studies. Heterogeneity between estimates was evaluated by the Q and I2 statistics and for the Q statistic; heterogeneity was considered for p < 0.1. Eleven studies included 529 OLP patients and 333 healthy controls. The review identified two different biomaterials used for IL-6 assays: saliva and serum. The mean quality score of eleven studies was 7 (high quality). Estimates pooled from 6 studies showed significant high saliva IL-6 levels in OLP patients compared with healthy controls (the standardised difference in means (SDM) = 4.534, 95% CI = 1.915-7.153, p = 0.001). Also, estimates pooled from 7 studies showed significantly high serum IL-6 levels in OLP patients compared with healthy controls (SDM = 1.482, 95% CI = 0.524-2.439, p = 0.002). The higher levels of IL-6 in saliva compared with serum suggest that measurement of this marker in saliva may be more useful than serum for diagnostic and therapeutic aims.

A systematic review and meta-analysis study of salivary and serum interleukin-8 levels in oral lichen planus.

INTRODUCTION: Interleukin-8 (IL-8) is an important mediator of the host response to injury and inflammation that the clinical severity of oral lichen planus (OLP) is associated with elevated serum IL-8 levels. AIM: To evaluate serum and salivary IL-8 levels of the OLP patients compared with the healthy controls and measurement of IL-8 level in which sample is more valuable. MATERIAL AND METHODS: Five databases including PubMed/Medline, Web of Science, Science Direct, Cochrane Library and Scopus were searched for the evaluation of serum and salivary IL-8 levels of the OLP patients compared with the healthy controls in the English abstract. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for checking the quality of the studies. A random-effect model was used for calculating the mean difference (MD) and 95% confidence intervals (CIs). RESULTS: Nine studies were included in the meta-analysis. The pooled estimate showed a significant difference between two groups that the salivary IL-8 level in the OLP patients was higher than the healthy controls (MD = 766.32 pg/ml, 95% CI: 394.90-1137.75; p < 0.0001) and also the serum IL-8 level in the OLP patients was higher than the healthy controls (MD = 8.38 pg/ml, 95% CI: 3.32-13.44; p = 0.001). CONCLUSIONS: The higher levels of IL-8 in saliva compared with serum suggest that measurement of this marker in saliva may be more useful than serum measurements for determining therapeutic and diagnostic aims.

Efficacy of palifermin on oral mucositis and acute GVHD after hematopoietic stem cell transplantation (HSCT) in hematology malignancy patients: a meta-analysis of trials.

AIM OF THE STUDY: Herein, this meta-analysis study evaluated the efficacy of palifermin after HSCT on the incidence and severity of OM or aGVHD in hematologic malignancy patients in randomized clinical trials (RCTs). MATERIALS AND METHODS: To compare the efficacy of palifermin on adverse events, OM and aGVHD compared with placebo, we searched databases of PubMed/Medline, Web of Science and Cochrane Library for RCTs based on a number of criteria. RESULTS: There was no difference observed in the incidence of OM and aGVHD between two groups. The subgroup analysis didn't show significant differences in two groups for aGVHD grade 2-4 (odds ratio [OR] = 1.54, 95% confidence interval (CI): 0.70-3.39, p = 0.28), aGVHD grade 3-4 (OR = 0.97, 95% CI: 0.48-1.94, p = 0.92), OM grade 2-4 (OR = 0.76, 95% CI: 0.42-1.38, p = 0.37) and OM grade 3-4 (OR = 0.54, 95% CI: 0.25-1.15, p = 0.11], but erythema as an adverse effect in palifermin group was higher than placebo group (OR = 1.86, 95% CI: 1.10-3.15, p = 0.02]. CONCLUSIONS: This meta-analysis of six clinical trials found no statistically significant difference in OM and aGVHD grades in patients receiving 60 µg/kg/day dose of palifermin compared with those receiving a placebo. However, oral mucosal erythema was more prevalent among patients receiving palifermin than patients receiving a placebo.

Radical prostatectomy versus observation for localized prostate cancer.

BACKGROUND: The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS: During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Association between alcohol dehydrogenase polymorphisms (rs1229984, rs1573496, rs1154460, and rs284787) and susceptibility to head and neck cancers: A systematic review and meta-analysis.

OBJECTIVE: Head and neck cancer (HNC) is a prevalent and complex group of malignancies with increasing incidence globally. Alcohol dehydrogenases (ADHs) play a crucial role in alcohol metabolism, and their polymorphisms have been linked to HNC risk. This systematic review and meta-analysis aims to evaluate the association between ADH polymorphisms and susceptibility to HNCs, incorporating additional analyses and adding more studies to increase power and accuracy of the results. DESIGN: Subgroup analysis, meta-regression analysis, and sensitivity analyses were conducted to explore potential differences within the data and assess the stability of pooled odds ratios (ORs). To mitigate the risk of false conclusions from meta-analyses, a trial sequential analysis was performed. RESULTS: For ADH1B rs1229984, the pooled OR (95 % confidence interval (CI)) was 0.73 (0.65, 0.82), 0.42 (0.35, 0.50), 0.57 (0.44, 0.73), 0.56 (0.50, 0.62), and 0.80 (0.73, 0.88), as well as for ADH7 rs1573496, the pooled OR was 0.72 (0.62, 0.85), 0.36 (0.17, 0.74), 0.76 (0.64, 0.91), 0.80 (0.71, 0.91), and 0.38 (0.18, 0.78) with a p < 0.05 in all allelic, homozygous, heterozygous, recessive, and dominant models, respectively. However, no significant association was found between the ADH7 rs1154460 and rs284787 polymorphisms and the risk of HNC with pooled ORs of 1.11 (p = 0.19) and 1.09 (p = 0.24) for the recessive model, respectively. The ethnicities, tumor subsites, control sources, sample sizes, quality scores, and Hardy-Weinberg equilibrium statuses were confounding factors. CONCLUSION: The ADH1B rs1229984 and ADH7 rs1573496 polymorphisms are significantly associated with a reduced risk of HNC.

Surface Topography Steer Soft Tissue Response and Antibacterial Function at the Transmucosal Region of Titanium Implant.

Metallic dental implants have been extensively used in clinical practice due to their superior mechanical properties, biocompatibility, and aesthetic outcomes. However, their integration with the surrounding soft tissue at the mucosal region remains challenging and can cause implant failure due to the peri-implant immune microenvironment. The soft tissue integration of dental implants can be ameliorated through different surface modifications. This review discussed and summarized the current knowledge of topography-mediated immune response and topography-mediated antibacterial activity in Ti dental implants which enhance soft tissue integration and their clinical performance. For example, nanopillar-like topographies such as spinules, and spikes showed effective antibacterial activity in human salivary biofilm which was due to the lethal stretching of bacterial membrane between the nanopillars. The key findings of this review were (I) cross-talk between surface nanotopography and soft tissue integration in which the surface nanotopography can guide the perpendicular orientation of collagen fibers into connective tissue which leads to the stability of soft tissue, (II) nanotubular array could shift the macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2) and manipulate the balance of osteogenesis/osteoclasia, and (III) surface nanotopography can provide specific sites for the loading of antibacterial agents and metallic nanoparticles of clinical interest functionalizing the implant surface. Silver-containing nanotubular topography significantly decreased the formation of fibrous encapsulation in per-implant soft tissue and showed synergistic antifungal and antibacterial properties. Although the Ti implants with surface nanotopography have shown promising in targeting soft tissue healing in vitro and in vivo through their immunomodulatory and antibacterial properties, however, long-term in vivo studies need to be conducted particularly in osteoporotic, and diabetic patients to ensure their desired performance with immunomodulatory and antibacterial properties. The optimization of product development is another challenging issue for its clinical translation, as the dental implant with surface nanotopography must endure implantation and operation inside the dental microenvironment. Finally, the sustainable release of metallic nanoparticles could be challenging to reduce cytotoxicity while augmenting the therapeutic effects.

Diet adherence dynamics and physiological responses to a tomato product whole-food intervention in African-American men.

Tomatoes may have beneficial effects on prostate health. Efficacy trials would require long-term adherence to high levels of tomato product (TP) consumption. Therefore, factors that affect adherence in men most at risk and whether increased consumption of TP negatively affects diet and health are important concerns. Cancer-free African­American (AA) men (n 36) with mean serum prostate-specific antigen of 7.4 SD 5.6) ng/ml were randomised to consume one serving of TP/d or a control diet for 3 months. Mean intervention group lycopene intake rose to 464%, with negligible control group increase. Plasma lycopene levels rose by 53 and 40% in the intervention group in months 1 and 3, respectively (P < 0.0001), with no control group change. The intervention group's barriers to adherence score was inversely associated with both dietary (r -0.49, P = 0.02) and plasma lycopene concentration (r -0.37, P = 0.02). Their TP disadvantage score negatively correlated with the 3-month plasma lycopene concentrations (r -0.37, P = 0.008) and their weekly incentives and impediments were remarkably stable, 'concern for prostate health' being the most consistent over time. 'Liking tomatoes' and 'study participation' decreased in citation frequency at weeks 6 and 9, respectively. No major shifts occurred in dietary cholesterol or saturated fat, with no adverse effects on gastrointestinal complaints, serum total cholesterol, body weight or blood pressure. Lower socio-economic status AA men at higher prostate cancer risk can successfully achieve a whole food intervention goal with a corresponding rise in plasma lycopene concentrations, with no adverse effects on self-selected diet quality or health parameters.

Evaluation of Beta-Defensin 1 and Mannose-Binding Lectin 2 Polymorphisms in Children with Dental Caries Compared to Caries-Free Controls: A Systematic Review and Meta-Analysis.

Background and objective: Some variants in defensin beta 1 (DEFB1) and mannose-binding lectin 2 (MBL2) genes can be associated with oral diseases. Herein, we designed a systematic review and meta-analysis to evaluate the association of DEFB1 (rs11362, rs1799946, and rs1800972) and MBL2 (rs7096206 and rs1800450) polymorphisms with the susceptibility to dental caries (DC) in children. Materials and methods: A systematic literature search was conducted in the PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases until 3 December 2022, without any restrictions. The odds ratio (OR), along with a 95% confidence interval (CI) of the effect sizes, are reported. Analyses including a subgroup analysis, a sensitivity analysis, and funnel plot analyses were conducted. Results: A total of 416 records were identified among the databases, and nine articles were entered into the meta-analysis. A significant relationship was found between the T allele of DEFB1 rs11362 polymorphism and DC susceptibility, and the T allele was related to an elevated risk of DC in children (OR = 1.225; 95%CI: 1.022, 1.469; p = 0.028; I2 = 0%). No other polymorphisms were associated with DC. All articles were of moderate quality. Egger's test in homozygous and dominant models demonstrated a significant publication bias for the association of DEFB1 rs1799946 polymorphism with DC risk. Conclusions: The results demonstrated that the T allele of DEFB1 rs11362 polymorphism had an elevated risk for DC in children. However, there were only few studies that evaluated this association.

Impact of genomic testing on urologists' treatment preference in favorable risk prostate cancer: A randomized trial.

INTRODUCTION: The Oncotype Dx Genomic Prostate Score (GPS) is a 17-gene relative expression assay that predicts adverse pathology at prostatectomy. We conducted a novel randomized controlled trial to assess the impact of GPS on urologist's treatment preference for favorable risk prostate cancer (PCa): active surveillance versus active treatment (i.e., prostatectomy/radiation). This is a secondary endpoint from the ENACT trial which recruited from three Chicago hospitals from 2016 to 2019. METHODS: Ten urologists along with men with very low to favorable-intermediate risk PCa were included in the study. Participants were randomly assigned to standardized counseling with or without GPS assay. The main outcome was urologists' preference for active treatment at Visit 2 by study arm (GPS versus Control). Multivariable best-fit binary logistic regressions were constructed to identify factors independently associated with urologists' treatment preference. RESULTS: Two hundred men (70% Black) were randomly assigned to either the Control (96) or GPS arm (104). At Visit 2, urologists' preference for prostatectomy/radiation almost doubled in the GPS arm to 29.3% (29) compared to 14.1% (13) in the Control arm (p = 0.01). Randomization to the GPS arm, intermediate NCCN risk level, and lower patient health literacy were predictors for urologists' preference for active treatment. DISCUSSION: Limitations included sample size and number of urologists. In this study, we found that GPS testing reduced urologists' likelihood to prefer active surveillance. CONCLUSIONS: These findings demonstrate how obtaining prognostic biomarkers that predict negative outcomes before treatment decision-making might influence urologists' preference for recommending aggressive therapy in men eligible for active surveillance.

The Most Common Vitamin D Receptor Polymorphisms (ApaI,FokI, TaqI, BsmI, and BglI) in Children with Dental Caries: A Systematic Review and Meta-Analysis.

Vitamin D participates in the calcification of enamel and dentin and the appropriate immune responses to oral microbial infections. We aimed to assess the association between the most common vitamin D receptor (VDR) polymorphisms (ApaI,FokI, TaqI, BsmI, and BglI) and the risk of dental caries in children. METHODS: PubMed/MEDLINE, Cochrane Library, Web of Science, and Scopus databases were comprehensively searched until 19 January 2021. Meta-analysis with odds ratios as the effect estimate along with 95% confidence intervals and subgroup analysis were conducted using Review Manager 5.3 software. Publication bias and sensitivity analyses were conducted by Comprehensive Meta-Analysis, version 2.0 software. RESULTS: Seventy-eight studies were retrieved from the databases, with nine studies included in the final analysis. Based on five genetic models, there was no association between ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410), FokI (rs2228570), and BglI (rs739837) polymorphisms and susceptibility to dental caries, except for the FokI (rs10735810) polymorphism. CONCLUSION: Among the VDR polymorphisms considered, an association was found between the FokI (rs10735810) polymorphism and the risk of dental caries, with a protective role of the f allele and ff genotype.

Evaluation of Serum and Salivary Iron and Ferritin Levels in Children with Dental Caries: A Meta-Analysis and Trial Sequential Analysis.

BACKGROUND AND OBJECTIVE: Dental caries appears to be related to iron deficiency anemia and to low ferritin levels. In the present meta-analysis, we report salivary and serum iron and ferritin levels in children with dental caries, compared to healthy controls. MATERIALS AND METHODS: We searched in Web of Science, Cochrane Library, Scopus, and PubMed/Medline databases to extract studies published until 25 July 2021. We calculated mean differences (MD) and 95% confidence intervals (CI) of salivary and serum iron and ferritin levels in children with dental caries, always compared to healthy controls. In addition, we applied a trial sequential analysis (TSA). RESULTS: A total of twelve articles covering thirteen studies were included in the meta-analysis. The pooled MD for salivary iron level was -5.76 µg/dL (p = 0.57), and -27.70 µg/dL (p < 0.00001) for serum iron level: compared to healthy controls, children with dental caries did not show different salivary iron levels, while children with caries had significantly lower serum iron levels. The pooled MD of salivary ferritin level was 34.84 µg/dL (p = 0.28), and the pooled MD of serum ferritin level was -8.95 µg/L (p = 0.04): compared to healthy controls, children with dental caries did not have different salivary iron levels, but significantly lower serum ferritin levels. CONCLUSIONS: The findings of the present meta-analysis showed that salivary levels of iron and ferritin did not differ between children with and without caries, though compared to healthy controls, children with caries had significantly lower salivary and serum iron and ferritin levels. The results are of practical and clinical importance: Possibly, iron and ferritin supplementation might prevent or attenuate dental caries in children at risk. Further, children with caries might suffer from further iron- and ferritin-related health issues. Lastly, serum blood samples, but not saliva samples inform accurately about the current iron and ferritin concentrations in children with or without caries.