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UNSTRUCTURED Clinical research is becoming more participant-centric by closely involving patients in study conceptualization and design, and shifting the setting of research to the home and community by employing decentralized methodologies for data collection. Many studies now include digital and non-digital outcome measures that capture symptoms, daily functioning and health-related quality of life measures in ways that are meaningful to and interpretable by patients. However, study patients are rarely privy to the benefits and insights that clinical research yields. In particular, there are two barriers to providing patients with the benefits of participating in research: studies that produce data that are inaccessible to participants (“unidirectional” data), and studies that create results that are incomprehensible to participants (“unilingual” data). To be both effective and engaging for the participant, clinical research can no longer be one-sided. Decentralized clinical studies leverage technology to ease the burden of data collection on participants, allowing them to contribute their data remotely without having to travel to specific study sites. Our experience through a direct-to-participant, decentralized study with myasthenia gravis patients illustrates that a more equalizing and empowering approach to conducting patient-centric research brings multiple benefits (Trial Registration: ClinicalTrials.gov NCT04590716). These include an improved overall trial experience; increased adherence levels to study tasks and assessments; and an opportunity for participants to gain a greater understanding of their symptoms, such as recognizing trigger factors for disease exacerbations.

Objectives To compare 3 mouthwashes: 0.20% chlorhexidine (CHX) with Anti-Discoloration System (ADS), 0.20% CHX and 0.12% CHX with 0.05% cetylpyridinium chloride (CPC), in terms of reduction of plaque and gingival bleeding and side effects. Methods Mild gingivitis patients were randomly divided into three Groups: they underwent professional oral hygiene and received instructions: oral rinse with 10 mL for 1', twice a day, 30' after tooth brushing, for 14 days. Primary outcomes were plaque and gingival bleeding, assessed with Plaque Control Record and Gingival Bleeding Index. Feedback questionnaire and spectrophotometer evaluated secondary outcomes: adverse events. Timing of the study was T0 (baseline), T1 (professional oral hygiene) and T2 (14th day after mouthwash use). Results Sixty-six patients were recruited, two patients dropped out, and 64 patients completed the study. PCR T1-T2 mean variation was 30.67 (SD = 15.22; 95% CI 23.55 to 37.80; P = 0.000), 19.93 (SD = 11.03; 95% CI 14.90 to 24.95; P = 0.000) and 16.24 (SD = 15.35; 95% CI 9.60 to 22.88; P = 0.000) respectively in Groups 0.2% CHX + ADS, 0.2% CHX and 0.12% CHX + CPC. GBI mean variation (T0-T2) was -9.82 (SD = 9.27; 95% CI -5.48 to 14.16; P = 0.000), -19.31 (SD = 11.33; 95% CI -14.15 to -24.47; P = 0.000) and -21.13 (SD = 12.56; 95% CI -15.70 to -26.56; P = 0.000) respectively in Groups 0.2% CHX + ADS, 0.2% CHX and 0.12% CHX + CPC. Statistical significance was found in lower efficacy of 0.2% CHX + ADS Group. Patients tolerated 0.12% CHX + CPC mouthwash better in bleeding perception (95.5%; P = 0.046), burning sensation (13.6%; P = 0.006), and mouthwash taste (100%; P = 0.000). Results on staining were no statistically significant (P = 0.106). Conclusions Addition of CPC allows reduction of CHX percentage in mouthwash formulation while keeping equal efficacy and less side effects. ADS addition decreases CHX efficacy in reducing plaque and bleeding, while resulting more tolerated than CHX.

Early and frequent patient mobilization substantially mitigates risk for post-intensive care syndrome and long-term functional impairment. We developed and tested computer vision algorithms to detect patient mobilization activities occurring in an adult ICU. Mobility activities were defined as moving the patient into and out of bed, and moving the patient into and out of a chair. A data set of privacy-safe-depth-video images was collected in the Intermountain LDS Hospital ICU, comprising 563 instances of mobility activities and 98,801 total frames of video data from seven wall-mounted depth sensors. In all, 67% of the mobility activity instances were used to train algorithms to detect mobility activity occurrence and duration, and the number of healthcare personnel involved in each activity. The remaining 33% of the mobility instances were used for algorithm evaluation. The algorithm for detecting mobility activities attained a mean specificity of 89.2% and sensitivity of 87.2% over the four activities; the algorithm for quantifying the number of personnel involved attained a mean accuracy of 68.8%.

Background Prevalence of peri-implantitis is directly proportional to the time of functional loading. The aim of this retrospective study was to assess the survival and success rates as well as the incidence of peri-implantitis among patients with a history of periodontitis and among implants with 1 to 10 years of functional loading. Methods We evaluated clinical records of periodontally compromised patients treated between January 1998 and July 2002, with implants enrolled in a supportive periodontal and peri-implant treatment follow-up program. The following assessment indexes during follow-up were recorded: suppuration on probing, modified bleeding on probing, probing depth, implant mobility, bone changes, and criteria of success of Albrektsson. Results Clinical data of 475 patients with 1,991 implants were analyzed for a period of 10 years of functional loading. The survival and success rates were 91.8% and 75.4%, respectively, and the cumulative incidence of peri-implantitis among patients was 24.4%. The survival rate was 96.1%, and the success rate was 83.7% among implants. The incidence of peri-implantitis exhibited a peak rate after the seventh year (2.1%). The prevalence of peri-implantitis increased from 3.2% to 9.7% between 5 and 10 years of follow-up, and the peri-implantitis rate among implants was 12.9% after 10 years of functional loading. Conclusion Peri-implantitis begins to appear more frequently after the fifth year of functional loading, especially between the seventh and eighth years of function.

Aim: early diagnosis and monitoring of caries lesions are the most important issues of primary and secondary prevention policies. The intraoral Vista Cam iX (Durr Dental, Bietigheim-Bissingen, Germany) uses the fluorescence phenomenon for a non-invasive, quantitative caries diagnosis. In order to make a precise evaluation the tooth surface must be completely cleaned and without biofilm. The current study aimed to evaluate the effects of biofilm removal, using air-polishing device (Combi, Mectron SpA) with glycine, on fluorescence VistaCam iX camera quantitative measurements of caries. Methods: Patients with complete permanent dentition without any kind of restorative treatments in the lateral and posterior section of upper and lower dental arches were enrolled. The occlusal surfaces of molars and premolars were photographed using the fluorescence terminal Proof of the intraoral camera VistaCam iX before and after air polishing glycine procedures, registering the highest value gained for each occlusal surface. Results: 133 cuspidate permanent teeth of patients aged between 13 and 25were analyzed. Descriptive analysis showed an average of 0.82 (SD= 0.65; Min= 0.00; Max= 1.80; Median= 1.20) and of 0.93 (SD= 0.60; Min= 0.00; Max= 1.70; Median=1.20) for values before and after treatment, respectively. The scores assigned by VistaCam iX Proof fluorescence based camera to the occlusal surfaces, after the air-polishing treatment, are averagely higher than those before treatment, especially in the diagnosis of initial tooth decay. Conclusions: Biofilm removal with glycine air-polishing improves the VistaCam camera accuracy in recognizing healthy tissue from the decayed one, due to the fact that air-polishing treatment increases the decayed tissue reaction to the fluorescence.

IntroductionDental practitioners are exposed to different occupational hazards during the course of their professional activity, such as physical, chemical, biological, ergonomic factors. The ergonomic hazards, caused by strained posture and prolonged repetitive movements, can induce musculoskeletal disorders. It occurs in 54–93% of dental professionals and involve the spine, shoulder and hand-wrist tract. Through a systematic review of international literature, we analyzed specific ergonomic risk factors and preventive measures of musculoskeletal disorders in professional dental activity.MethodsThis systematic review is coherent with the PRISMA statement. The scientific research on the major online databases was based on the following keywords: dentist, prevention, ergonomic, dentistry, musculoskeletal, neck pain, posture, ergonomics, work and occupational. The studies included in this review focus on disorders related to ergonomics and on the most effective preventive measures to be adopted. No restrictions were applied for language or publication type. We excluded reports not related to ergonomic prevention in dentistry, reports of minor academic significance, editorial articles, individual contributions, and studies published in scientific conferences.ResultsOnline research indicated 4188 references: PubMed (2919), Scopus (1257) e Cochrane Library (12). We excluded 3012 of these, because they were unrelated to ergonomics theme and 187 due to duplication. From the remaining 989 studies, 960 papers did not meet inclusion criteria and they were excluded. Therefore, we analyzed 29 articles, including 16 narrative reviews and 13 original article. The main risk factor for the development of musculoskeletal disorders found in our analysis is static posture adopted during work, highlighted in 87.5% of reviews and 84% of original articles. With regard to preventive measures, 75% of the reviews highlighted the importance of stretching after each working session and at the end of the working day, while 61.5% of the original articles emphasized the use of modern and ergonomic instruments.DiscussionThis review showed that static postures are strongly responsible in the etiology of musculoskeletal disorders. The awkward postures more frequently identified among dental professionals are: extreme forward-head and neck flexion; trunk inclination and rotation towards one side; lifting one or both shoulders; increased curvature of the thoracic vertebral column; incorrect positioning of the lower limbs with thigh-leg angle of less than 90°. It is really important to use of a modern workstation with appropriate ergonomic supports. Among the preventive ergonomic measures, literature has widely recognized the role of physical activity and of a neutral and balanced posture. The present review has some limits: a large part of the selected studies did not have a high methodological quality score and an inadequate statistical analysis.

Drosophila responds to Gram-negative bacterial infection by activating the immune deficiency (IMD) pathway, leading to production of antimicrobial peptides (AMPs). As a receptor for the IMD pathway, peptidoglycan-recognition protein (PGRP), PGRP-LC is known to recognize and bind monomeric peptidoglycan (DAP-type PGN) through its PGRP ectodomain and in turn activate the IMD pathway. The questions remain how PGRP-LC is activated in response to pathogen infection to initiate the IMD signal transduction in Drosophila. Here we present evidence to show that proteases such as elastase and Mmp2 can also activate the IMD pathway but not the TOLL pathway. The elastase-dependent IMD activation requires the receptor PGRP-LC. Importantly, we find that live Salmonella/E. coli infection modulates PGRP-LC expression/receptor integrity and activates the IMD pathway while dead Salmonella/E. coli or protease-deficient E. coli do neither. Our results suggest an interesting possibility that Gram-negative pathogen infection may be partially monitored through the structural integrity of the receptor PGRP-LC via an infection-induced enzyme-based cleavage-mediated activation mechanism.

Decreased levels of the prostate-specific homeobox protein NKX3.1 are correlated with hormone-refractory and metastatic prostate cancer. Thus, it is compelling to define the NKX3.1-regulated genes that may be important for the progression of the advanced stage of the disease. In this study, we showed that vascular endothelial growth factor-C (VEGF-C) is one such target gene of NKX3.1. NKX3.1 inhibited VEGF-C expression in prostate cancer, and the loss of NKX3.1 led to increased VEGF-C expression. Histone deacetylase 1 acted as a corepressor of VEGF-C expression along with NKX3.1. Activated RalA acted in synergy with the loss of NKX3.1 for VEGF-C transcription. Patients with deletions at chromosome 8p21.1-p21.2 as a sole deletion developed lymph node metastasis. Interestingly, the higher expression of VEGF-C in prostate cancer is also correlated with lymph node metastasis. Therefore, regulation of VEGF-C expression by NKX3.1 provides a possible mechanism by which the loss of NKX3.1 protein level leads to lymphangiogenesis in the late stages of advanced prostate cancer. [Cancer Res 2008;68(21):8770–8]

Developmental defects of enamel (DDE) are common oral manifestation of celiac disease whose onset can overlap to teeth calcification in permanent dentition. The defects of the enamel symmetrically and chronologically occur in all the four quadrants, particularly in maxillary and mandibular incisors and molars. Icon® infiltration technique is a minimally invasive procedure for DDE treatment. This paper reports two cases of treatment of celiac siblings with aesthetic purpose. The aesthetic evaluation was made by means of spectrophotometry as a standardized method. International Commision on Illumination (CIE) L*a*b*, ΔE variations, contrast ratio (CR), and opalescence, measured against black and white backgrounds before and after the treatment, provide all the quantitative information about the outcome of the Icon® infiltration technique. Icon® infiltration technique has been showed to be an effective procedure for DDE treatment.

Prostate cancer mortality is primarily due to failure to cure patients with metastatic disease. In its early stages, prostate cancer growth is enhanced by androgens. As such, the primary therapy for advanced (locally extensive or metastatic) prostate cancer consists of androgen deprivation therapy by pharmacotherapeutic or surgical means. Eventually, the tumor recurs owing to a transition from androgen-dependence to a highly metastatic and androgen refractory (androgen depletion-independent) phenotype. As the detailed molecular mechanism underlying this transition to a more aggressive phenotype is poorly understood, it has been difficult to develop effective treatments for this advanced stage of the disease. We have previously reported an increase in vascular endothelial growth factor-C (VEGF-C) expression in human prostate cancer cells after androgen withdrawal. We have also shown increased expression of the androgen receptor co-activator BAG-1L by VEGF-C, suggesting the involvement of this growth factor in transactivation of the androgen receptor, even at low concentrations of androgen. In our present study, we show that androgen deprivation of human prostate carcinoma cells activates the small GTPase, RalA, a molecule important for human oncogenesis. RalA activation leads to VEGF-C upregulation. We also show that elevated levels of intracellular reactive oxygen species in prostate cancer cells under androgen-ablated conditions is the major inducer of RalA activation and VEGF-C synthesis.

Androgen ablation therapy is eventually followed by a more metastatic and androgen-refractory stage of prostate cancer. The detailed molecular mechanism of this gradual transition is not clearly understood. Recent reports correlate the high abundance of vascular endothelial growth factor-C (VEGF-C) to the lymph node metastasis seen in human prostate cancer (Tsurusaki et al., 1999). In this study, we report that androgen ablation in LNCaP cells augment the transcriptional upregulation of VEGF-C and the downregulation of the IGF-IR pathway, due to androgen withdrawal, is a potential mechanism for this observed VEGF-C transcription. Forkhead transcription factor FOXO-1, activated by SIRT-1, was identified as the downstream molecule within this pathway. Furthermore, the VEGF-C-induced increase of Bag-IL expression in LNCaP cells suggests that VEGF-C plays a role in the androgen-independent reactivation of the androgen receptor, resulting in androgen-refractory prostate cancer growth.

RASSF1A may be the most frequently inactivated tumor suppressor identified in human cancer so far. It is a proapoptotic Ras effector and plays an important role in the apoptotic DNA damage response (DDR). We now show that in addition to DDR regulation, RASSF1A also plays a key role in the DNA repair process itself. We show that RASSF1A forms a DNA damage-regulated complex with the key DNA repair protein xeroderma pigmentosum A (XPA). XPA requires RASSF1A to exert full repair activity, and RASSF1A-deficient cells exhibit an impaired ability to repair DNA. Moreover, a cancer-associated RASSF1A single-nucleotide polymorphism (SNP) variant exhibits differential XPA binding and inhibits DNA repair. The interaction of XPA with other components of the repair complex, such as replication protein A (RPA), is controlled in part by a dynamic acetylation/deacetylation cycle. We found that RASSF1A and its SNP variant differentially regulate XPA protein acetylation, and the SNP variant hyperstabilizes the XPA-RPA70 complex. Thus, we identify two novel functions for RASSF1A in the control of DNA repair and protein acetylation. As RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage.

We previously reported the discovery of XB05, a synthetic small molecule with antiproliferative activity. XB05 was found to be a strong inhibitor of DNMT1 activity in cell-free and cell-based assays. However, screening in the NCI 60 tumor cell lines and analysis using COMPARE indicated a novel mechanism of action for XB05, different from standard demethylating agents such as 5-azacytidine (azaC) and decitabine. Here, we report on new research to further characterize XB05 activity. We have examined the effects of XB05 on clonogenicity, promoter methylation, gene expression, and DNMT1 protein. XB05 was found to inhibit colony formation of HCT116 colon carcinoma cells in a dose-dependent manner with a sub-micromolar IC50. Western blots of nuclear extracts from HCT116 cells treated for 72 h with 100 nM XB05 or 10 µM azaC (as positive control) showed greatly decreased levels of DNMT1, suggesting that binding to XB05 can induce degradation of DNMT1 (previous research indicates direct drug-enzyme binding). Analysis of CDKN2A promoter methylation by bisulfite modification and sequencing demonstrated heavy methylation in untreated HCT116 cells. This was reversed by treatment of with 100 nM XB05 or 10 µM azaC, resulting in re-expression of the gene (which encodes tumor suppressor, p16), as shown by qRT-PCR. Experiments to assess promoter methylation using multiplex arrays and to examine gene expression changes using DNA microarrays were recently completed and data analysis is ongoing. To evaluate in vivo activity, we treated mice bearing subcutaneous HCT116 xenografts by IP injection of XB05 with multiple doses of up to 10 mg/kg. There was no evidence of toxicity as judged by body weights and gross necropsies. The tumors of mice treated with XB05, although not significantly smaller than in control animals, were characterized by extensive necrosis in the center of the tumor, leading to a “hollow” tumor in the majority (12/20) of mice. No similar necrosis was observed in vehicle-treated or azaC-treated mice, suggesting that this effect is treatment related. Because induced necrosis is seen with vascular disrupting agents, we also examined the effect of XB05 on endothelial cells in an in vitro assay, and observed reproducible inhibition of endothelial tube formation at 400 nM or higher. In summary, our new data confirm that XB05 is a potent inhibitor of DNA methylation in cultured cancer cells, and provide the first evidence of in vivo activity, which may involve effects on the tumor vasculature, as well as the tumor itself. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5447.