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BACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.

ObjectiveFew studies have evaluated the effects of visual remediation strategies in schizophrenia despite abundant evidence of visual-processing alterations in this condition. We report preliminary, case-study-based evidence regarding the effects of visual remediation in this population.MethodWe describe implementation of a visual-perceptual training program called ULTIMEYES (UE) and initial results through 3 brief case studies of individuals with schizophrenia. UE targets broad-based visual function, including low-level processes (e.g., acuity, contrast sensitivity) as well as higher level visual functions. Three inpatients, recruited from a research unit, participated in at least 38 sessions 3 to 4 times per week for approximately 25 min per session. Contrast sensitivity (a trained task), as well as acuity and perceptual organization (untrained tasks), were assessed before and after the intervention. Levels of progression through the task are also reported.ResultsUE was well tolerated by the participants and led to improvements in contrast sensitivity, as well as more generalized gains in visual acuity in all 3 participants and perceptual organization in 2 participants. Symptom profiles were somewhat different for each participant, but all were symptomatic during the intervention. Despite this, they were able to focus on and benefit from training. The adaptive nature of the training was well suited to the slower progression of 2 participants.Conclusions and implications for practiceThese case studies set the stage for further research, such as larger, randomized controlled trials of the intervention that include additional assessments of perceptual function and measures of cognition, social cognition, and functional outcomes. (PsycINFO Database Record

Objective: Examine the association between sex, race, ethnicity, and family income, and the intersectionality between these identities, and sustained or cultivated paths in surgery in medical school. Methods: This retrospective cohort study examines US medical students who matriculated in academic years 2014-2015 and 2015-2016. Data were provided by the Association of American Medical Colleges, including self-reported sex, race, ethnicity, family income, interest in surgery at matriculation, and successful placement into a surgical residency at graduation. This study examined 2 outcomes: (1) sustained path in surgery between matriculation and graduation for students who entered medical school with an interest in surgery and (2) cultivated path in surgery for students who entered medical school not initially interested in surgery and who applied to and were successfully placed into a surgical residency at graduation. Results: Among the 5074 students who reported interest in surgery at matriculation, 2108 (41.5%) had sustained path in surgery. Compared to male students, female students were significantly less likely to have sustained path in surgery [adjusted relative risk (aRR): 0.92 (0.85-0.98)], while Asian (aRR: 0.82, 95% CI: 0.74-0.91), Hispanic (aRR: 0.70, 95% CI: 0.59-0.83), and low-income (aRR: 0.85, 95% CI: 0.78-0.92) students were less likely to have a sustained path in surgery compared to their peers. Among the 17,586 students who reported an initial interest in a nonsurgical specialty, 1869 (10.6%) were placed into a surgical residency at graduation. Female students, regardless of race/ethnic identity and income, were significantly less likely to have cultivated paths in surgery compared to male students, with underrepresented in medicine female students reporting the lowest rates. Conclusions and Relevance: This study demonstrates the significant disparity in sustained and cultivated paths in surgery during undergraduate medical education. Innovative transformation of the surgical learning environment to promote surgical identity development and belonging for females, underrepresented in medicine, and low-income students is essential to diversify the surgical workforce. [ABSTRACT FROM AUTHOR]

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.

This article presents the starting case for applying the elements of trauma-informed care (TIC) to education and outlines the authors' initial efforts to develop guidelines for what they call trauma-informed educational practice. To this end, the article starts with a literature review related to the potential for vicarious traumatization and retraumatization among students in clinical training, followed by a discussion of the TIC framework and past efforts to be trauma sensitive in social work education. The authors then describe what drew them to this perspective and inspired them to apply it to educational practice. They then present guidelines for implementing the trauma-informed principle of safety in the classroom in several domains.

Biomass from short rotation coppice (SRC) plantations has attracted widespread attention as a component of new sustainable energy concepts. Nevertheless, as yet the surface area of SRC plantations in Europe is relatively low compared to other biomass producing land-use systems. This is somewhat incomprehensible because it has been shown that SRC systems also offer distinct ecological benefits. Therefore, greater consideration of the related ecosystem services should be incorporated into land-use planning processes. Presented in this study is a conceptual framework for the integration of soil protection and nature conservation into the spatial prioritization of areas suitable for SRC. This approach includes the development of a site-specific yield model and the identification and classification of criteria and indicators for both soil protection and nature conservation. The basic concept for planning procedures was established and tested for the State of Saxony (Germany). Existing constraints were identified, and could be attributed mainly to the availability of adequate information at different spatial scales. The regional-scale study emphasized the considerable biomass potential of SRC and the related synergy effects for soil protection and nature conservation. Future work should focus on the local (district, farm) and catchment scale and attempt to integrate additional aspects such as hydrological ecosystem services and carbon sequestration.

Online patient education materials play an important role in plastic surgery, and surgeons should ensure that materials accurately reflect their patient population. This study compared the skin tone of images in online materials from the American Society of Plastic Surgeons (ASPS), academic plastic surgery programs, and private groups to the demographics of the United States (US) reduction mammaplasty population. Images within patient education materials and embedded photo galleries were assessed and skin tones were categorized using the Fitzpatrick Skin Scale (FSS). Two reviewers evaluated 616 images. Scores of 1–3 were categorized as White, while scores of 4–6 were classified as non-White. The proportion of images categorized as White and non-White were compared to the demographics of the reduction mammaplasty population in the US. Of 616 images, 82% were classified as White, while 18% were non-White. This distribution differed significantly from the racial demographic distribution of patients undergoing reduction mammaplasty in the US in 2020, where 48% identified as White and 52% as non-White (p < 0.001). There was also a statistically significant difference in the distribution of FSS scores between the materials from the ASPS, academic programs, and private surgeon groups, with private groups having a lower percentage of non-White images (p = 0.028). These findings suggest that implicit bias may impact the creation of patient education materials for reduction mammaplasty and highlights the need for improvement in distributing patient education materials that accurately represent the diverse reduction mammaplasty population. [ABSTRACT FROM AUTHOR]

A review of the marketing literature suggests that students develop personal marketing or sales plans to find their first job and subsequent career. Publishers are providing students access to online resources linked to career information. However, the person who knows most about a given career is the person who is working at that job on a daily basis (i.e., the fully employed professional). This paper builds on previous studies by providing a selling process students have used successfully to develop professional networks. (Contains 6 tables.)

The aim of this study was the preliminary development of a short 10-item version of the CiOQ. First, 10 items were selected on the basis of their high factor loadings in previously published work. Two studies are then reported. In Study 1, the 10 items were subjected to confirmatory factor analysis using data from a sample of college students (n=336) who had experienced adverse events. Study 2 involved a clinical sample (n=40) of people with posttraumatic stress disorder and examined associations of reported changes with posttraumatic stress symptoms and posttraumatic growth. Evidence is provided for a two-factor structure of the CiOQ Short Form, consisting of positive changes and negatives changes, and for the subscales' internal consistency reliability, convergent validity, and differential associations with clinically meaningful outcomes.

While deep brain stimulation (DBS) therapy can be effective at suppressing tremor in individuals with medication-refractory Essential Tremor, patient outcome variability remains a significant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract (CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to targeting parcellations within the CTT and other pathways in and around the ventral intermediate (VIM) nucleus of thalamus remain unclear. Using ultra-high field (7T) MRI, we developed high-dimensional, subject-specific pathway activation models for 23 directional DBS leads. Modeled pathway activations were compared with post-hoc analysis of clinician-optimized DBS settings, paresthesia thresholds, and dysarthria thresholds. Mixed-effect models were utilized to determine how the six parcellated regions of the CTT and how six other pathways in and around the VIM contributed to tremor suppression and induction of side effects. The lateral portion of the CTT had the highest activation at clinical settings (p < 0.05) and a significant effect on tremor suppression (p < 0.001). Activation of the medial lemniscus and posterior-medial CTT was significantly associated with severity of paresthesias (p < 0.001). Activation of the anterior-medial CTT had a significant association with dysarthria (p < 0.05). This study provides a detailed understanding of the fiber pathways responsible for therapy and side effects of DBS for Essential Tremor, and suggests a model-based programming approach will enable more selective activation of lateral fibers within the CTT. • Patient-specific pathway activation models of VIM-DBS were developed. • Activating the lateral cerebello-thalamic tract (CTT) related to tremor control. • Paresthesias occurred with medial lemniscus and posterior-medial CTT activation. • Stimulation of the anterior-medial CTT was associated with dysarthria. • These results provide guidance on how to optimize DBS for Essential Tremor. [ABSTRACT FROM AUTHOR]