Investigation of Genetic Polymorphisms Related to the Outcome of Radiotherapy for Prostate Cancer Patients

The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy.     

Fetal Wound Healing Biomarkers

Fetal skin has the intrinsic capacity for wound healing, which is not correlated with the intrauterine environment. This intrinsic ability requires biochemical signals, which start at the cellular level and lead to secretion of transforming factors and expression of receptors, and specific markers that promote wound healing without scar formation. The mechanisms and molecular pathways of wound healing still need to be elucidated to achieve a complete understanding of this remodeling system. The aim of this paper is to discuss the main biomarkers involved in fetal skin wound healing as well as their respective mechanisms of action.     

Managing the Impact of Immunogenicity in an Era of Immunotherapy: From Bench to Bedside

Biotherapeutics have revolutionized our ability to treat life-threatening diseases. Despite clinical success, the use of biotherapeutics has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs). The multifactorial nature of immunogenicity has prevented a standardized approach for assessing this and each of the assessment methods developed so far does not exhibit high enough reliability to be used alone, due to limited predictiveness. This prompted the Roche Pharma Research and Early Development (pRED) Immunogenicity Working Group to establish an internal preclinical immunogenicity toolbox of in vitro/in vivo approaches and accompanying guidelines for a harmonized assessment and management of immunogenicity in early development. In this article, the complex factors influencing immunogenicity and their associated clinical ramifications are discussed to highlight the importance of an end-to-end approach conducted from lead optimization to clinical candidate selection. We then examine the impact of the resulting lead candidate categorization on the design and implementation of a multi-tiered ADA/immunogenicity assay strategy prior to phase I (entry into human) through early clinical development. Ultimately, the Immunogenicity Toolbox ensures that Roche pRED teams are equipped to address immunogenicity in a standardized manner, paving the way for lifesaving products with improved safety and efficacy.     

Intraoral scanners: An American Dental Association Clinical Evaluators Panel survey

BackgroundDentists may choose to integrate intraoral scanners (IOSs) into their practices, but there are many different IOS technologies and system generations to choose from, posing a challenge for dentists who want to invest in them.MethodsA survey of IOS use rates, advantages, satisfaction, and training was developed and deployed through Qualtrics to the 968 members of the American Dental Association Clinical Evaluators (ACE) Panel on February 19, 2021. Nonrespondents were sent reminders, and data were analyzed in SAS Version 9.4 (SAS).ResultsA total of 369 panelists responded to the survey. IOS use was split among the ACE Panel; 53% indicated they use one in their practice. The top reason respondents began using IOSs was to improve clinical efficiency (70%). Ninety percent of respondents use IOSs for single tooth-supported crowns, and 58% began using IOSs less than 4 years ago. Most users are at least mostly satisfied (91%) with the results. Among nonusers, the top reason for not using an IOS was the high level of financial investment (66%); 34% and 40% of nonusers are thinking of buying or training with IOSs in 2021, respectively.ConclusionsUptake of IOSs is split; most users are satisfied with their results, and nonusers cited financial barriers as the most common reason for not investing in one.Practical ImplicationsAs IOSs continue to penetrate the market and dentists are faced with a decision whether to invest in one, they will need guidance on how to choose the most appropriate device for their patients.     

Substance use education in US schools of pharmacy: A systematic review of the literature

Background: The authors sought to systematically review the quantity and quality of literature describing substance use disorders (SUDs) education in US schools of pharmacy and determine the effectiveness of the educational interventions employed. Methods: The authors conducted a systematic review of SUDs education studies in US pharmacy schools. All literature database searches were performed on April 30, 2016, in 5 databases: Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Embase.com, ERIC via FirstSearch, and CINAHL via EBSCOhost. The study authors conducted this systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-analyses guidelines and registered it with PROSPERO, which is an international prospective register of systematic reviews. The PROSPERO registration number is CRD42016037443. The study authors created a modified data extraction sheet based on the Best Evidence in Medical Education coding sheet. A Medical Education Research Study Quality Instrument (MERSQI) score was calculated for included articles. Results: From the 1626 retrieved records, 7 were included in the present review. The studies assessed students’ impressions and abilities regarding SUDs pre- and post-intervention. The mean ± SD MERSQI score of the 7 studies was 9.86 ± 1.21 (range: 8–11.5). The included articles assessed pharmacy students at various academic years, with the majority students in either their first or second year of pharmacy school, and described both required and elective courses. The educational interventions varied in design and outcomes measured. Education included nicotine, alcoholism, and SUDs in general. None of the included articles reported on education regarding opioid use disorders. Conclusions: The studies included in this systematic review demonstrate that teaching pharmacy students about SUDs produces a positive impact in their attitudes and knowledge on this subject.     

Acute administration of methionine and/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex

Metabolic Brain Disease - High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia...