Search

Background and Objectives: Older adults report unmet oral health care needs and barriers in access to care, due in part to provider attitudes and discomfort towards treating older patients. Our study asked: What is known from the literature about the use of undergraduate dentistry programmes to influence dental students' attitudes, perceptions and comfort towards treating geriatric patients? And how can interdisciplinary care facilitate the ability of dentists to work with geriatric patients?, Materials and Methods: A scoping review and stakeholder consultation followed established methodological guidelines. Four databases and two grey literature sources were searched. Two researchers independently selected articles using predefined inclusion criteria. Pertinent information was inputted into an iteratively developed extraction table. NVivo 12 was used to organise the extracted data into themes. Key findings were confirmed through stakeholder consultation., Results: Sixty-eight articles were included in the scoping review. Five key themes emerged: (1) Curricular targets; (2) Intervention components; (3) Dentist and patient factors; (4) The role of interdisciplinary care; and (5) Post-graduation insights on knowledge-seeking patterns. Stakeholder consultations involved 19 participants from Southwestern Ontario and generally confirmed our findings., Conclusions: Inconsistent reporting of multiple intervention dimensions constrains our ability to strengthen this knowledge. Future interventions and their reporting could be improved by adopting "willingness to treat" as an overarching, multi-faceted concept which encompasses knowledge on ageing, attitudes towards older patients, perceived competence and empathy. Stakeholder interviews complemented these findings., (© 2024 The Author(s). Gerodontology published by Gerodontology Association and John Wiley & Sons Ltd.)

Purpose/objectives: Older adults frequently report unmet oral healthcare needs. Current research suggests a lack of provider willingness to perform geriatric dental care plays a role in limiting older adults' access to dental services. To better understand the acceptance of geriatric dentistry programming in Ontario, and to explore considerations for successful implementation, we completed consultations with dental students and dental education stakeholders. Findings from a scoping review we conducted previously (Alicia C. Brandt and Cecilia S. Dong) were used to guide this research., Methods: Consultations involved a questionnaire and semi-structured individual interviews. Descriptive and parametric statistics such as Pearson's bivariate correlation and One-way analysis of variance were completed on questionnaire data using SPSS V.28. Interview data were transcribed verbatim, and the content was analyzed using emergent coding and thematic analysis in NVivo. Student and faculty data were analyzed separately and then consolidated., Results: Ten students and 12 dental faculty members completed the questionnaire of which ten students and nine faculty members also participated in interviews. Themes were organized into barriers and facilitators, with a subsection on interprofessional collaboration. Barriers included: 1. Student anxiety and skill level; 2. Constraints of the learning environment; 3. Patient factors; and 4. Knowledge gaps. Facilitators included: 1. Learning environment and culture; 2. Volume of exposure; 3. Soft skills; and 4. Desired interventions., Conclusions: Both students and faculty stakeholders demonstrated acceptance of geriatric dentistry programming at the undergraduate dentistry level that supports improved access to care for this population. Pilot programs integrating different intervention elements which were viewed as most promising would be beneficial., (© 2024 The Authors. Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Purpose: The dietary practices (DPs) of university students are influenced by many external factors. Therefore, we investigate how the DPs of students in Germany changed during the SARS-CoV-2 pandemic, what the main motivations were for those changes, and what effect the closure of university catering had on the DPs of students., Methods: A total of 560 students from two universities in Lübeck (Germany) were surveyed online during a pilot phase. The final online questionnaire was subsequently administered at 10 other German universities (399 respondents). The questionnaire surveyed sociodemographic factors, dietary habits, food consumption frequencies, and the relevance of university catering before and during the SARS-CoV-2 pandemic., Results: Regarding changes in DPs, similarities to previous studies were found, especially positive eating behaviors and an increasing interest in health- and nutrition-related sustainability. Students prepared meals freshly more often during the pandemic; consumed legumes, plant-based meats and dairy alternatives more often; and reduced their consumption of meat and milk compared to before the pandemic. The consumption frequency of sweets also decreased. It was observed that students consider eating communal in the university canteen to be highly relevant for their social interactions, which was only possible to a limited extent during the pandemic., Conclusion: In Germany, the DPs of university students as well as criteria regarding health and sustainability changed during the first 2 years of the SARS-CoV-2 pandemic. The social aspect of DPs became evident due to closed university catering. Still, changes in dietary patterns and eating habits were positively related to health and revealed some differences in the cross section of the population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dreyer, Brandt, Lichtenstein, Sina and Smollich.)

The aim of this study was twofold: first, to develop an experimental technique as a tool to investigate learning outcomes of spontaneous, naturalistic second language (L2) learning under controlled laboratory conditions; and second, to explore how this technique can be used to understand the basic conditions and limits of this learning. Two variants of a dialogue game were tested in which corrective L2 input was provided to the learners, but the learning aspect was camouflaged. Participants were German learners of Dutch who are known to display persistent grammatical gender errors in Dutch owing to incorrect first language (L1)-L2 transfer. In Experiment 1, the participant and a 'virtual partner' (audio-recordings) took turns in describing cards using gender-marked article-noun phrases. However, the majority of the participants became aware of learning articles as goal of the experiment, either because of the way we asked participants about the goal of the experiment or because of the task used. Therefore, we changed both aspects and used a dialogue-memory game in Experiment 2, which indeed led only a minority (28%) to suspect the real goal of the study. In both experiments, participants showed substantial learning of word gender (on average 13.8 percentage points increase in accuracy) after only one instance of correct input. A manipulation of the number of trials (lag) between correct input and production did not affect results. Furthermore, the 72% of 'naïve' participants in Experiment 2 showed as much learning as the full sample. Thus, the new paradigm offers important insights into the determinants of naturalistic learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Newly synthesized small GTPases in the Ras and Rho families are prenylated by cytosolic prenyltransferases and then escorted by chaperones to membranes, the nucleus, and other sites where the GTPases participate in a variety of signaling cascades. Understanding how prenylation and trafficking are regulated will help define new therapeutic strategies for cancer and other disorders involving abnormal signaling by these small GTPases. A growing body of evidence indicates that splice variants of SmgGDS (gene name RAP1GDS1) are major regulators of the prenylation, post-prenylation processing, and trafficking of Ras and Rho family members. SmgGDS-607 binds pre-prenylated small GTPases, while SmgGDS-558 binds prenylated small GTPases. This review discusses the history of SmgGDS research and explains our current understanding of how SmgGDS splice variants regulate the prenylation and trafficking of small GTPases. We discuss recent evidence that mutant forms of RabL3 and Rab22a control the release of small GTPases from SmgGDS, and review the inhibitory actions of DiRas1, which competitively blocks the binding of other small GTPases to SmgGDS. We conclude with a discussion of current strategies for therapeutic targeting of SmgGDS in cancer involving splice-switching oligonucleotides and peptide inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brandt, Koehn and Williams.)

The chaperone protein SmgGDS promotes cell-cycle progression and tumorigenesis in human breast and nonsmall cell lung cancer. Splice variants of SmgGDS, named SmgGDS-607 and SmgGDS-558, facilitate the activation of oncogenic members of the Ras and Rho families of small GTPases through membrane trafficking via regulation of the prenylation pathway. SmgGDS-607 interacts with newly synthesized preprenylated small GTPases, while SmgGDS-558 interacts with prenylated small GTPases. We determined that cancer cells have a high ratio of SmgGDS-607:SmgGDS-558 (607:558 ratio), and this elevated ratio is associated with reduced survival of breast cancer patients. These discoveries suggest that targeting SmgGDS splicing to lower the 607:558 ratio may be an effective strategy to inhibit the malignant phenotype generated by small GTPases. Here we report the development of a splice-switching oligonucleotide, named SSO Ex5, that lowers the 607:558 ratio by altering exon 5 inclusion in SmgGDS pre-mRNA (messenger RNA). Our results indicate that SSO Ex5 suppresses the prenylation of multiple small GTPases in the Ras, Rho, and Rab families and inhibits ERK activity, resulting in endoplasmic reticulum (ER) stress, the unfolded protein response, and ultimately apoptotic cell death in breast and lung cancer cell lines. Furthermore, intraperitoneal (i.p.) delivery of SSO Ex5 in MMTV-PyMT mice redirects SmgGDS splicing in the mammary gland and slows tumorigenesis in this aggressive model of breast cancer. Taken together, our results suggest that the high 607:558 ratio is required for optimal small GTPase prenylation, and validate this innovative approach of targeting SmgGDS splicing to diminish malignancy in breast and lung cancer., Competing Interests: Competing interest statement: F.R. is an employee of Ionis Pharmaceuticals. F.R., M.T.M., and C.L.W. have patents pending with the US Patent and Trademark Office for the SSOs and the targeting approach.

Purpose: Germline CDH1 pathogenic variants (PV) are associated with hereditary diffuse gastric cancer and lobular breast cancer. Although prevalence of CDH1 PV is low in the general population, detection of these variants is increasing with the growing use of multigene panel testing. Little is known about the experiences of individuals tested for CDH1 variants in the multigene panel testing era., Methods: Participants recruited from the Prospective Registry of Multiplex Testing completed a cross-sectional self-report survey regarding CDH1 genetic testing experiences, medical management, and psychosocial adaptation., Results: Discordance existed in interpretations of CDH1 results; 13.3% of cases had disagreements in variant classifications among commercial laboratories, and 21.4% had disagreements between participant self-report and ClinVar classification. Survey data were available from 57 individuals reporting either PV (n = 16) or variants of uncertain significance (VUS; n = 41). Those with PV were more likely than those with VUS to report receiving a recommendation for prophylactic gastrectomy, although only 40.0% of those with PV received this recommendation. Participants with VUS were less satisfied with their health care providers' knowledge and reported less CDH1 knowledge, distress, and worry about discrimination. Participants with PV perceived greater breast cancer risks, but similar gastric cancer risks, as those with VUS., Conclusion: Few individuals with CDH1 PV report receiving recommendations for prophylactic gastrectomy, and no differences in perceived gastric cancer risk were observed based on participants' CDH1 results, suggesting serious unmet informational needs., Competing Interests: AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST AND DATA AVAILABILITY STATEMENT Disclosures provided by the authors and data availability statement (if applicable) are available with this article at DOI https://doi.org/10.1200/PO.18.00300. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Jessica M. Long Employment: DePuy Synthes Companies (I) Stock and Other Ownership Interests: DePuy Synthes Companies (I) Travel, Accommodations, Expenses: DePuy Synthes Companies (I) Fergus J. Couch Consulting or Advisory Role: AstraZeneca Research Funding: GRAIL Travel, Accommodations, Expenses: GRAIL, Qiagen, Ambry Genetics Judy E. Garber Consulting or Advisory Role: Novartis (I), Pfizer (I), SV Life Sciences (I), GTx (I), Helix BioPharma, ORIC Pharmaceuticals (I) Research Funding: Novartis (I), Ambry Genetics, Susan G. Komen for the Cure (I), AACR, Diana Helis Henry Medical Foundation (I), James P. Wilmot Foundation (I), Adrienne Helis Malvin Medical Research Foundation (I), Global Biological Standards Institute (I), Breast Cancer Research Foundation Mark E. Robson Honoraria: AstraZeneca, Pfizer Consulting or Advisory Role: McKesson, AstraZeneca Research Funding: AstraZeneca (Inst), Myriad Genetics (Inst), InVitae (Inst), Pfizer (Inst), Abbvie (Inst), Tesaro (Inst), Medivation (Inst) Travel, Accommodations, Expenses: AstraZeneca Susan M. Domchek Honoraria: AstraZeneca, Clovis Oncology, Bristol-Myers Squibb Research Funding: AstraZeneca (Inst), Clovis Oncology (Inst), Pharmamar (Inst), No other potential conflicts of interest were reported.

The original article [1] was initially published with the following list of authors: Allison Werner-Lin, Shana L. Merrill, and Amanda C. Brandt. This author list is now corrected as follows: Allison Werner-Lin, Shana L. Merrill, Amanda C. Brandt, Rachel E. Barnett, & Ellen T. Matloff.

Families often express difficulty to their providers and request guidance regarding the task of communicating with children about potential adult-onset inherited cancer risks. This disclosure is often complicated by the parent's ongoing adjustment to their mutation status, guilt at potential transmission of the mutation to the child, concern over inciting distress in children, and the varied capacities of children in the home to understand genetic information. Providers often do not have adequate resources to support or facilitate disclosure of genetic test results to children. Optimally, communication about inherited cancer risk is an open, ongoing process within the family. We recommend that parents tailor conversations to the child's developmental, cognitive, emotional, and behavioral abilities to support comprehension. Based on well-established theories of child development, empirical research on family communication of hereditary cancer risk, and clinical counseling experience, we offer recommendations for parental disclosure of genetic risk to children, case examples with critical discussion of relevant topics, common child questions with sample scripted responses, and additional printed and online resources.

The chaperone protein and guanine nucleotide exchange factor SmgGDS (RAP1GDS1) is a key promoter of cancer cell proliferation and tumorigenesis. SmgGDS undergoes nucleocytoplasmic shuttling, suggesting that it has both cytoplasmic and nuclear functions that promote cancer. Previous studies indicate that SmgGDS binds cytoplasmic small GTPases and promotes their trafficking to the plasma membrane. In contrast, little is known about the functions of SmgGDS in the nucleus, or how these nuclear functions might benefit cancer cells. Here we show unique nuclear localization and regulation of gene transcription pathways by SmgGDS. Strikingly, SmgGDS depletion significantly reduces expression of over 600 gene products that are targets of the DREAM complex, which is a transcription factor complex that regulates expression of proteins controlling the cell cycle. The cell cycle regulators E2F1, MYC, MYBL2 (B-Myb) and FOXM1 are among the DREAM targets that are diminished by SmgGDS depletion. E2F1 is well known to promote G1 cell cycle progression, and the loss of E2F1 in SmgGDS-depleted cells provides an explanation for previous reports that SmgGDS depletion characteristically causes a G1 cell cycle arrest. We show that SmgGDS localizes in nucleoli, and that RNAi-mediated depletion of SmgGDS in cancer cells disrupts nucleolar morphology, signifying nucleolar stress. We show that nucleolar SmgGDS interacts with the RNA polymerase I transcription factor upstream binding factor (UBF). The RNAi-mediated depletion of UBF diminishes nucleolar localization of SmgGDS and promotes proteasome-mediated degradation of SmgGDS, indicating that nucleolar sequestration of SmgGDS by UBF stabilizes SmgGDS protein. The ability of SmgGDS to interact with UBF and localize in the nucleolus is diminished by expressing DiRas1 or DiRas2, which are small GTPases that bind SmgGDS and act as tumor suppressors. Taken together, our results support a novel nuclear role for SmgGDS in protecting malignant cells from nucleolar stress, thus promoting cell cycle progression and tumorigenesis.

Purpose: Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer., Methods: BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy., Results: One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02)., Conclusion: Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history.

Objective: To compare models of the postoperative hospital treatment phase after myocardial revascularization., Design: A pilot randomized controlled trial., Setting: Hospital patients in a hospital setting., Subjects: Thirty-two patients with indications for myocardial revascularization were included between January 2008 and December 2009, with a left ventricular ejection fraction (LVEF) ≥50%, 1-second forced expiratory volume (FEV(1)) ≥60 and forced vital capacity (FVC) ≥60% of predicted value., Interventions: Patients were randomly placed into two groups: one performed prescribed exercises according to the model proposed by the American College of Sports Medicine (ACSM) and the other according to a periodized model., Main Measures: Partial pressure of O(2) (P o (2)) and arterial O(2) saturation (Sao (2)), percentage of predicted FVC and total distance on the six-minute walking test (6MWT)., Results: Twenty-seven patients were re-evaluated upon release from the hospital (ACSM = 14 and PP = 13). Five patients extubated for more than 6 hours in the postoperative period were excluded from the sample. In the preoperative period the variables P o (2), Sao (2), % FVC and 6MWT were similar. In the postoperative period, a reduction was observed for all parameters in both groups. Upon comparison of the groups, a difference was observed in P o (2) (ACSM = 68.0 ± 4.3 vs. PP = 75.9 ± 4.8 mmHg; P < 0.001), Sao (2) (ACSM = 93.5 ± 1.4 vs. PP = 94.8 ± 1.2%; P = 0.018) and 6MWT (ACSM = 339.3 ± 41.7 vs. PP = 393.8 ± 25.7 m; P < 0.001). There was no difference in % FVC., Conclusion: Patients after myocardial revascularization following a periodized model of exercise presented a better intra-hospital evolution when compared to those using the ACSM model.

10-15% of invasive epithelial ovarian cancer is attributable to hereditary breast and ovarian cancer. The identification of BRCA1/BRCA2 mutations in women with ovarian cancer allows for accurate predictive genetic testing of their at-risk relatives, who can then avail themselves of early detection and risk reduction strategies. In the case of women with recurrent progressive ovarian cancer, the window of opportunity for genetic testing can be particularly limited. Here we describe our perspective on providing genetic counseling during these patients' end of life care, incorporating two illustrative examples from our clinical practice. While these situations pose unique challenges, they also present a significant opportunity to benefit the patient and her family. Further attention and research should be directed towards provision of genetic counseling and testing during end of life care.

Approximately 5-10% of cancers are caused by an inherited predisposition. Individuals affected by hereditary cancer are often concerned about transmitting a predisposition to cancer to their children. Preimplantation genetic diagnosis (PGD) is a technology that allows embryos without a deleterious mutation associated with a hereditary cancer syndrome to be identified and implanted. The aim of this study is to assess the knowledge, attitudes, and clinical experience of physicians regarding PGD for hereditary cancer predisposition syndromes. Hereditary Breast and Ovarian Cancer (HBOC) and Familial Adenomatous Polyposis (FAP) are two hereditary cancer syndromes highlighted in this present study. A survey assessing physicians' attitudes, knowledge, and clinical practice was completed by a total of 373 gynecologic oncologists (GYN ONCs) and obstetrics and gynecologists (OB/GYNs). Physicians had a limited knowledge of PGD for hereditary cancer; however, physicians reported PGD was an appropriate option for patients with either HBOC or FAP. Although GYN ONCs were more likely to care for patients with hereditary cancer (P < 0.001), they were less likely than OB/GYNs to refer their patients to a PGD specialist (P = 0.004). While 80% of GYN ONCs and 91% of OB/GYNs would refer patients to a PGD specialist, clinical experience indicates that only 29% actually referred their patients. Since 68% of physicians had incorrect or limited knowledge of PGD for hereditary cancer, there is a need for additional education.

Self-presentation via favorable self-descriptions may not lead to the desired impression, whereas positive descriptions by others may be more effective because they seem less susceptible to motivated bias. In four experiments, we investigated whether person descriptions have more impact on impressions when provided by third parties than by targets themselves. Results showed that target impressions were consistently more in line with the target description when positive sociability-related or positive competency-related information was given by a third party than by the target. This source effect always occurred for ratings of claimed traits. In addition, ratings of the target's sociability were also affected when the claim was about competency. Source effects were not obtained for negative self-descriptions. The results are discussed in terms of the presumed underlying process on the basis of mediation data.

Three studies investigated the effects of self-construal activation on behavior conducive to interpersonal proximity. Study 1 revealed that compared with control participants, participants who were primed with the independent (or personal) self sat further away from where they anticipated another person would sit in a waiting room. Results of Study 2 indicated that participants primed with the interdependent (or social) self sat closer to the anticipated other person than did those primed with the independent self. Finally, Study 3 used the chronic self-construal of participants to predict the seating distance in dyadic settings. Results showed that greater independence of participants' self-construals was associated with greater spatial distance during the interaction. Together, the studies provide clear evidence that self-construal activation automatically influences interpersonal behavior as reflected in the actual distance between the self and others. Results are discussed in terms of the functions and motives connected to self-construals.

The degradation of N,N',N"-triethylenethiophosphoramide (thiotepa) in aqueous solutions has been investigated over the pH range 1-14. Samples were analyzed using a high-performance liquid chromatographic system with UV detection. The degradation kinetics were studied as a function of pH, sodium chloride concentration and temperature. The degradation of thiotepa follows pseudo first order kinetics. The pH-log kobs profile shows that thiotepa is most stable in the pH range 7-11. At pH?11 chloride has no influence on the degradation rate. The degradation products were isolated and the structures identified by mass spectrometry. Chloro adducts of thiotepa are generated in the presence of sodium chloride and in acidic medium. In the pH range 7-11 only the mono-chloro adduct of thiotepa could be found. No detectable degradation products were formed at pH?11., (Copyright.)