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Abstract Background The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. Methods Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. Results Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. Conclusions This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL.

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer. Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics. Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives. Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review.

Abstract Introduction Human papillomavirus (HPV) vaccination protects against HPV-associated cancers and genital warts. Healthy People 2030 goal for HPV vaccine uptake is 80%, but as of 2021, only 58.5% of adolescents are up to date in Georgia. The purpose of the study is to assess the attitudes, vaccine practices, facilitators, and barriers to receiving the HPV vaccine in southwest Georgia. Methods We conducted 40 semi-structured interviews in the United States from May 2020-Feburary 2022 with three different audiences (young adults, parents, and providers and public health professionals) guided by the P3 (patient-, provider-, practice-levels) Model. The audiences were recruited by multiple methods including fliers, a community advisory board, Facebook ads, phone calls or emails to schools and health systems, and snowball sampling. Young adults and parents were interviewed to assess their perceived benefits, barriers, and susceptibility of the HPV vaccine. Providers and public health professionals were interviewed about facilitators and barriers of patients receiving the HPV vaccine in their communities. We used deductive coding approach using a structured codebook, two coders, analyses in MAXQDA, and matrices. Results Out of the 40 interviews: 10 young adults, 20 parents, and 10 providers and public health professionals were interviewed. Emerging facilitator themes to increase the uptake of the HPV vaccine included existing knowledge (patient level) and community outreach, providers’ approach to the HPV vaccine recommendations and use of educational materials in addition to counseling parents or young adults (provider level) and immunization reminders (practice level). Barrier themes were lack of knowledge around HPV and the HPV vaccine (patient level), need for strong provider recommendation and discussing the vaccine with patients (provider level), and limited patient reminders and health education information around HPV vaccination (practice level). Related to socio-ecology, the lack of transportation and culture of limited discussion about vaccination in rural communities and the lack of policies facilitating the uptake of the HPV vaccine (e.g., school mandates) were described as challenges. Conclusion These interviews revealed key themes around education, knowledge, importance of immunization reminders, and approaches to increasing the HPV vaccination in rural Georgia. This data can inform future interventions across all levels (patient, provider, practice, policy, etc.) to increase HPV vaccination rates in rural communities.

ObjectiveMusic strongly modulates our autonomic nervous system. This modulation is evident in musicians' beat-to-beat heart (RR) intervals, a marker of heart rate variability (HRV), and can be related to music features and structures. We present a novel approach to modeling musicians' RR interval variations, analyzing detailed components within a music piece to extract continuous music features and annotations of musicians' performance decisions.MethodsA professional ensemble (violinist, cellist, and pianist) performs Schubert's Trio No. 2, Op. 100, Andante con moto nine times during rehearsals. RR interval series are collected from each musician using wireless ECG sensors. Linear mixed models are used to predict their RR intervals based on music features (tempo, loudness, note density), interpretive choices (Interpretation Map), and a starting factor.ResultsThe models explain approximately half of the variability of the RR interval series for all musicians, with R-squared = 0.606 (violinist), 0.494 (cellist), and 0.540 (pianist). The features with the strongest predictive values were loudness, climax, moment of concern, and starting factor.ConclusionsThe method revealed the relative effects of different music features on autonomic response. For the first time, we show a strong link between an interpretation map and RR interval changes. Modeling autonomic response to music stimuli is important for developing medical and non-medical interventions. Our models can serve as a framework for estimating performers' physiological reactions using only music information that could also apply to listeners.

Objective Examine psychometric properties of frailty instruments used in adults with rheumatoid arthritis (RA) to inform selection of frailty instruments for clinical and research use. Methods A systematic review was registered in PROSPERO. Studies measuring frailty in adults with RA published before May 25, 2022, were searched in six electronic databases. Level of evidence of psychometric properties were synthesized and graded for each frailty instrument using Consensus‐Based Standards for the Selection of Health Measurement Instruments methodology. Results There were 22 articles included in the review, and psychometric properties of 16 frailty instruments were examined. RA cohorts were predominantly female with moderate RA disease activity, mean age was 60.1 years, and frailty prevalence ranged widely from 10% to 85%. Construct validity was the only psychometric property routinely examined for frailty instruments in RA, and nearly all (14/16) performed favorably in this domain. Frailty correlated most frequently with older age, higher RA disease activity, and worse physical function. Internal consistency, measurement error, and content validity were examined infrequently. Reliability and responsiveness data were not reported. Six frailty instruments were rated highest in adults with RA: three adaptations of Fried's Criteria, 32‐Item and 45‐Item Frailty Indexes, and the Comprehensive Rheumatologic Assessment of Frailty. Conclusion Six frailty instruments possessed the highest‐rated psychometric properties in RA. These instruments demonstrated construct validity of frailty with important outcomes in RA. Frailty assessment shows promise to inform risk stratification in RA, but studies are needed to evaluate reliability, responsiveness, and validity to support accuracy of frailty measurement in adults with RA who may have disease‐related features that differentially impact outcomes.

Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Some studies suggest that certain PFAS may have immunotoxic effects in humans, which could put individuals with high levels of exposure at increased risk for infectious diseases such as COVID-19. We conducted a case-control study to examine the association between COVID-19 diagnosis and PFAS serum concentrations among employees and retirees from two 3 M facilities, one of which historically generated perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS). Participants completed enrollment and follow-up study visits in the Spring of 2021. Participants were categorized as cases if they reported a COVID-19 diagnosis or became sick with at least one symptom of COVID-19 when someone else in their household was diagnosed, otherwise they were categorized as a control. COVID-19 diagnosis was modeled in relation to concentration of serum PFAS measured at enrollment after adjusting for covariates. The analytic sample comprised 573 individuals, 111 cases (19.4%) and 462 controls (80.6%). In adjusted models, the odds ratio of COVID-19 was 0.94 per interquartile range (14.3 ng/mL) increase in PFOS (95% confidence interval 0.85, 1.04). Results for PFOA, PFHxS, and perfluorononanoic acid (PFNA) were similar. Other PFAS present at lower concentrations were examined as categorical variables (above the limit of quantification [LOQ], yes vs. no [referent category]), and also showed no positive associations. In our study, which used individual-level data and included people with high occupational exposure, the serum concentrations of all PFAS examined were not associated with an increased odds ratio for COVID-19. At this point, the epidemiologic data supporting no association of COVID-19 occurrence with PFAS exposure are stronger than those suggesting a positive association.

Abstract Background As an illustrative example of COVID-19 pandemic community-based participatory research (CBPR), we describe a community-academic partnership to prioritize future research most important to people experiencing high occupational exposure to COVID-19 – food service workers. Food service workers face key challenges surrounding (1) health and safety precautions, (2) stress and mental health, and (3) the long-term pandemic impact. Method Using CBPR methodologies, academic scientists partnered with community stakeholders to develop the research aims, methods, and measures, and interpret and disseminate results. We conducted a survey, three focus groups, and a rapid qualitative assessment to understand the three areas of concern and prioritize future research. Results The survey showed that food service employers mainly supported basic droplet protections (soap, hand sanitizer, gloves), rather than comprehensive airborne protections (high-quality masks, air quality monitoring, air cleaning). Food service workers faced challenging decisions surrounding isolation, quarantine, testing, masking, vaccines, and in-home transmission, described anxiety, depression, and substance use as top mental health concerns, and described long-term physical and financial concerns. Focus groups provided qualitative examples of concerns experienced by food service workers and narrowed topic prioritization. The rapid qualitative assessment identified key needs and opportunities, with help reducing in-home COVID-19 transmission identified as a top priority. COVID-19 mitigation scientists offered recommendations for reducing in-home transmission. Conclusions The COVID-19 pandemic has forced food service workers to experience complex decisions about health and safety, stress and mental health concerns, and longer-term concerns. Challenging health decisions included attempting to avoid an airborne infectious illness when employers were mainly only concerned with droplet precautions and trying to decide protocols for testing and isolation without clear guidance, free tests, or paid sick leave. Key mental health concerns were anxiety, depression, and substance use. Longer-term challenges included Long COVID, lack of mental healthcare access, and financial instability. Food service workers suggest the need for more research aimed at reducing in-home COVID-19 transmission and supporting long-term mental health, physical health, and financial concerns. This research provides an illustrative example of how to cultivate community-based partnerships to respond to immediate and critical issues affecting populations most burdened by public health crises.

Application of polyethylene glycol (PEG) to a peripheral nerve injury at the time of primary neurorrhaphy is thought to prevent Wallerian degeneration via direct axolemma fusion. The molecular mechanisms of nerve fusion and recovery are unclear. Our study tested the hypothesis that PEG alters gene expression in neural and muscular environments as part of its restorative properties. Lewis rats underwent unilateral sciatic nerve transection with immediate primary repair. Subjects were randomly assigned to receive either PEG treatment or standard repair at the time of neurorrhaphy. Samples of sciatic nerve distal to the injury and tibialis muscle at the site of innervation were harvested at 24 hours and 4 weeks postoperatively. Total RNA sequencing and subsequent bioinformatics analyses were used to identify significant differences in differentially expressed genes (DEGs) and their related biological pathways (p

Intratumoral heterogeneity (ITH) complicates the diagnosis and treatment of glioma, partly due to the diverse metabolic profiles driven by underlying genomic alterations. While multiparametric imaging enhances the characterization of ITH by capturing both spatial and functional variations, it falls short in directly assessing the metabolic activities that underpin these phenotypic differences. This gap stems from the challenge of integrating easily accessible, colocated pathology and detailed genomic data with metabolic insights. This study presents a multifaceted approach combining stereotactic biopsy with standard clinical open-craniotomy for sample collection, voxel-wise analysis of MR images, regression-based GAM, and whole-exome sequencing. This work aims to demonstrate the potential of machine learning algorithms to predict variations in cellular and molecular tumor characteristics. This retrospective study enrolled ten treatment-naïve patients with radiologically confirmed glioma. Each patient underwent a multiparametric MR scan (T1W, T1W-CE, T2W, T2W-FLAIR, DWI) prior to surgery. During standard craniotomy, at least 1 stereotactic biopsy was collected from each patient, with screenshots of the sample locations saved for spatial registration to pre-surgical MR data. Whole-exome sequencing was performed on flash-frozen tumor samples, prioritizing the signatures of five glioma-related genes: IDH1, TP53, EGFR, PIK3CA, and NF1. Regression was implemented with a GAM using a univariate shape function for each predictor. Standard receiver operating characteristic (ROC) analyses were used to evaluate detection, with AUC (area under curve) calculated for each gene target and MR contrast combination. Mean AUC for five gene targets and 31 MR contrast combinations was 0.75 ± 0.11; individual AUCs were as high as 0.96 for both IDH1 and TP53 with T2W-FLAIR and ADC, and 0.99 for EGFR with T2W and ADC. These results suggest the possibility of predicting exome-wide mutation events from noninvasive, in vivo imaging by combining stereotactic localization of glioma samples and a semi-parametric deep learning method. The genomic alterations identified, particularly in IDH1, TP53, EGFR, PIK3CA, and NF1, are known to play pivotal roles in metabolic pathways driving glioma heterogeneity. Our methodology, therefore, indirectly sheds light on the metabolic landscape of glioma through the lens of these critical genomic markers, suggesting a complex interplay between tumor genomics and metabolism. This approach holds potential for refining targeted therapy by better addressing the genomic heterogeneity of glioma tumors.

Psychotherapy for individuals with psychosis is an effective treatment that promotes recovery in various ways. While there is strong quantitative evidence across modalities, less is known from the patient’s perspective. There are many varied forms of psychotherapy, and gaining the patient’s perspective can improve understanding of salient elements of psychotherapy and increase engagement, ultimately improving recovery rates. The purpose of this review is to identify and integrate data from published studies of patient perspectives of psychotherapy for psychosis to understand essential elements across approaches, differences between approaches, and how psychotherapy impacts recovery. We aimed to understand further: what are the perceptions about individual psychotherapy from the perspective of individuals with psychosis? The current study was a systematic review using PRISMA guidelines of studies that included qualitative interviews with persons with experiences of psychosis who participated in psychotherapy. All three authors participated in the literature search using Pubmed, APA PsycInfo, and Psychiatry Online. We identified N = 33 studies. Studies included cognitive therapies, acceptance and mindfulness approaches, trauma therapies, metacognitive therapy, and music therapy. All studies reported participants’ perceived benefit with the therapeutic relationship as especially salient. Participants described diverse aspects of objective (e.g., symptoms, functioning) and subjective (e.g., self-experience or quality of life) recovery improvements, with perceived mechanisms of change, and with music therapy having some unique benefits. Participants also reported challenges and suggestions for improvement. Study findings highlight the salient aspects of psychotherapy identified by patients that may help therapists to individualize and improve approaches to psychotherapy when working with individuals experiencing psychosis. Overall, findings support the potential for integrative psychotherapy approaches for maximal treatment personalization.

The term schizotypy refers to the latent personality organization that is thought to underpin the liability to develop schizophrenia and associated disorders. Metacognition, or the ability to understand and form increasingly complex and integrated ideas of oneself, others, and one’s community, has been proposed to be an important transdiagnostic construct across schizophrenia spectrum disorders and a range of both clinical and non-clinical manifestations of schizotypy. In this paper, we review evidence that deficits in metacognition are present in individuals with relatively high levels of schizotypy and that these deficits are related to symptomology, function, and quality of life. We address the idea that decrements in metacognition may also contribute to the progression from schizotypy to more severe manifestations, while the amelioration of these deficits may enhance aspects of recovery, including the ability to form an integrated sense of self, others, and the wider world. We also review the following two recovery-oriented psychotherapies that target metacognition to promote recovery in individuals with clinical manifestations of schizotypy: Evolutionary Systems Therapy for Schizotypy (ESTS) and Metacognitive Reflection and Insight Therapy (MERIT).

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T. cruzi. Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major, for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T. cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L. major IPCS. However, disruption of the T. cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T. cruzi IPCS null mutants are unable to establish an infection in vivo, even in immune deficient mice.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE’s 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC’s work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

KH-type splicing regulatory protein (KHSRP) regulates levels of several neuronal mRNAs linked to nervous system development and function.

The recent decline of coral health and substantial loss of coral cover along Florida’s Coral Reef (FCR) results from local stressors such as degraded water quality and disease outbreaks in addition to anthropogenically driven global stressors including ocean warming and acidification. Intervention strategies intended for the restoration of degraded reef habitats need a better understanding of the influence of ocean warming and acidification on coral health to target coral species and individual genotypes that may be more resistant or resilient to such stressors. Here, we examined a suite of physiological traits (coral host and algal symbiont) in response to experimentally elevated water temperatures and pCO2 levels, both separately and in concert, using threatened reef-building corals Pseudodiploria clivosa and Orbicella faveolata reared within a land-based coral nursery. After two months of exposure, responses differed by coral species, where P. clivosa showed declined physiology in response to combined ocean warming and acidification stress and ocean warming alone, whereas O. faveolata showed a positive response under ocean acidification. Responses to temperature could be associated with the algal symbionts harbored, as P. clivosa was dominated by the thermally sensitive Breviolum, and O. faveolata was dominated by the thermally tolerant Durusdinium. Additionally, corals were raised in well-sourced seawater that was naturally high in pCO2, which could have led to corals acclimating to acidified conditions. Of the three P. clivosa genets tested, we determined a top-performing genotype under the combined warming and acidification treatment. O. faveolata, however, displayed high genet variation by treatment and phenotypic trait, making genotype performance rankings challenging to discern. The evidence provided in this study demonstrates that high phenotypic variation in nursery-reared corals contributes to variable warming-acidification responses, suggesting that high-standing genetic variation in nursery-reared corals could support diverse coral restoration population outcomes along FCR.

Despite increased interest in K–12 online education, student engagement deficits and the resulting student attrition remain widespread issues. The Academic Communities of Engagement (ACE) framework theorizes that two groups support online student engagement: the personal community of support and the course community of support. However, more evidence is needed to understand how members of these communities, especially parents, support students in various contexts. Using insights gleaned from 14 semi-structured interviews of parents with students enrolled in online secondary school, this study adds support to the roles identified in the ACE framework by presenting real examples of parents supporting their online students’ affective, behavioral, and cognitive engagement. Findings also confirm patterns found in previous research that are not explained using the ACE framework, such as parental advocacy, communication with teachers, and self-teaching. We discuss how a systems approach to conceptualizing the ACE communities allows the framework to more accurately capture parents' perceived experiences within the personal community of support. We also discuss implications for both practitioners and members of students’ support structures.

Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Several studies have shown associations between certain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and reduced antibody concentration after vaccination against diseases such as Tetanus. Recent studies have reported associations between COVID-19 occurrence and exposure to certain types of PFAS. However, studies of antibody concentration after COVID-19 vaccination in relation to PFAS serum concentrations have not been reported. We examined COVID-19 antibody responses to vaccines and PFAS serum concentrations among employees and retirees from two 3M facilities, one of which historically manufactured PFOS, PFOA, and perfluorohexane sulfonic acid (PFHxS).Participants completed enrollment and follow-up study visits in the Spring of 2021, when vaccines were widely available. In total 415 participants with 757 observations were included in repeated measures analyses. Log-transformed concentrations of anti-spike IgG and neutralizing antibodies were modeled in relation to concentration of PFAS at enrollment after adjusting for antigenic stimulus group (9 groups determined by COVID-19 history and number and type of vaccination) and other variables. The fully adjusted IgG concentration was 3.45 percent lower (95% CI −7.03, 0.26) per 14.5 ng/mL (interquartile range) increase in PFOS; results for neutralizing antibody and PFOS were similar. For PFOA, PFHxS, and perfluorononanoic acid (PFNA), the results were comparable to those for PFOS, though of smaller magnitude. In our study data, the fully adjusted coefficients relating concentration of vaccine-induced antibodies to COVID-19 and interquartile range difference in serum concentration of PFOS, PFOA, PFHxS, and PFNA were inverse but small with confidence intervals that included zero. Our analysis showed that the coefficient for the four PFAS examined in detail was considerably affected by adjustment for antigenic stimulus group.

A Becker’s nevus typically appears as a single unilateral, well-demarcated, hyperpigmented patch over the upper trunk during adolescence. It uncommonly presents as multiple and bilateral patches and rarely involves a lower extremity. We describe the unusual case of a child with multiple, bilateral Becker’s nevi of the trunk and lower extremities present since birth.

Effective, scalable mental health programs are greatly needed for older adults. In this study, Mood Lifters—a peer-led, community-based program promoting mental well-being—was adapted to more specifically address the needs of older adults. Two groups completed the 14-week program via Zoom. A total of 24 participants enrolled ( M age = 72 years), with 20 (83%) completing the program. Compared to baseline, program completers showed significant improvements in depression symptoms ( p

Electronic cigarettes (eCig) represent a new avenue of tobacco exposure that involves heating oil-based liquids and the delivery of aerosolized flavors with or without nicotine, yet little is known about their overall health impact. The oral cavity is an anatomic gateway for exposure that can be compromised by activating myriad of signaling networks. Oral squamous cell carcinoma (OSSC) is a common malignancy affecting 30,000 people in the United States each year. Our objective was to determine the impact of eCig and nicotine on gingival OSSC invasion and their secretion of pro-inflammatory molecules. Gingiva-derived Ca9-22 cells and tongue-derived Cal27 cells were exposed to eCig vapor extract (EVE) generated from Red Hot or Green Apple (Apple) flavored eCig solution +/- nicotine for 6 hours. Isolation of protein lysates and collection conditioned media was done after treatment. Real-time cellular invasion was assessed using a RTCA DP instrument. Protein expression was determined using western blot. Compared to controls, we observed: elevated NF-kB, TNF-α, ERK, JNK, MMP-13 and cell invasion by Ca9-22 treated with Apple EVE; increased TNF-α and JNK by Ca9-22 treated with Red Hot EVE; and increased TNF-α and JNK by Cal27 cells treated with both Apple and Red Hot EVE. We conclude that eCig flavoring and nicotine orchestrated differential cell invasion and inflammatory effects. This study provides an important initial step in dissecting mechanisms of cancerous invasion and molecular avenues employed by OSCC.

Introduction: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC). Materials and methods: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs. Results: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55–69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28–89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%–89%), 77% (95% CI: 68%–86%), and 78% (95% CI: 70%–86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%–9%), 9% (95% CI: 5%–17%), and 10% (95% CI: 6%–18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4–19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p

Background:. Increased access to care and insurance coverage has led to an increase in gender-affirming surgeries performed in the United States. Gender-affirming phalloplasty has a variety of donor sites and surgical techniques including both pedicled and free flaps. Although surgical techniques and patient outcomes are well-described, no reports in the literature specifically discuss postoperative management, which plays a crucial role in the success of these operations. Here, we present a postoperative protocol based on our institution’s experience with gender-affirming phalloplasty with the hope it will serve as a standardized, reproducible reference for centers looking to offer these procedures. Methods:. Patients undergoing gender-affirming phalloplasty at our institution followed a standardized protocol from the preoperative stage through phases of postoperative recovery. Medication, laboratory, physical and occupational therapy, flap monitoring, and dressing change guidelines were extracted and compiled into a single resource detailing the postoperative protocol in full. Results:. Our institution's standardized postoperative protocol for gender-affirming phalloplasty is detailed, focusing on flap monitoring, mobilization and activity, medications, and postoperative dressing care. One hundred thirty first-stage phalloplasty procedures were performed between May 2017 and December 2021, with two patients (1.5%) experiencing partial necrosis and one incidence (0.8%) of total flap loss. Conclusions:. For optimal and safe surgical outcomes, the surgical and extended care teams need to understand flap monitoring as well as specific postoperative protocols. A systematic approach focusing on flap monitoring, mobilization and activity, medications, and postoperative dressing care decreases errors, accelerates recovery, shortens length of stay, and instills confidence in the patient.

Background:. Gender-affirming mastectomy has become one of the most frequently performed procedures for transgender and nonbinary patients. Although there are a variety of potential surgical approaches available, the impact of technique on outcomes remains unclear. Here we present our experience performing periareolar and double incision mastectomies, with a focus on comparing patient demographics, preoperative risk factors, and surgical outcomes and complication rates between techniques. Methods:. Retrospective review identified patients undergoing gender-affirming mastectomy by the senior author between 2017 and 2020. Patients were stratified according to surgical technique, with demographics and postoperative outcomes compared between groups. Results:. In total, 490 patients underwent gender-affirming mastectomy during the study period. An estimated 96 patients underwent periareolar mastectomy, whereas 390 underwent double incision mastectomy. Demographics were similar between groups, and there were no differences in rates of hematoma (3.1% versus 5.6%, respectively; P = 0.90), seroma (33.3% versus 36.4%; P = 0.52), or revision procedures (14.6% versus 15.8% P = 0.84) based on technique. Conclusions:. Our results demonstrate no difference in the rates of postoperative complications or revision procedures based on surgical technique. These results also suggest that with an experienced surgeon and proper patient selection, both techniques of gender-affirming mastectomy can be performed safely and with comparable outcomes.

While nurse staffing shortage is generally true, it is not universal, and it remains unclear the degree to which variation in local staffing markets might influence the relationship between nurse staffing and care quality. This study seeks to determine the effect of nurse staffing markets on the quality of hospital care delivered in U.S. hospitals by examining the relationship between the proximal density of nurse staffing resources to hospitals and patient-reported care quality outcomes. This examination analyzes hospital performance on (Hospital Consumer Assessment of Healthcare Providers and Systems) HCAHPS based on the proximal density of nursing schools. The analysis combines data from Centers for Medicare and Medicaid Services (CMS) Hospital Compare (N 1 = 2959) and U.S. nursing school locations from the American Association of Colleges of Nursing (N 2 = 811) via a series of binary logistic regressions to determine whether local nurse staffing availability is related to hospital’s attainment of either low or high star quality ratings. A sensitivity analysis is also offered to determine the association with 1, 3, and 5-star ratings. The findings suggest that the odds of receiving both a low-star rating and a high-star rating of HCAHPS performance increase as proximal density increases while the odds of receiving a 3-star rating decrease. Hospitals are able to achieve the highest levels of performance as high performing hospitals in high-density markets seem to be taking advantage of resource availability to establish close, strong ties with nurse staffing resources as opposed to viewing nurses as an easily replaceable resource.

Similar to trends in Europe, approaches to mental illness in colonial America and recorded in early United States history were commonly characterized by incarceration and the removal of individuals from communities. In the mid-20th century, a major shift began in which treatment was offered in the community with the aim of encouraging individuals to rejoin their communities. In this paper, we will provide a brief history of community mental health services in the United States, and the forces which have influenced its development. We will explore the early antecedents of community-based approaches to care, and then detail certain factors that led to legislative, peer and clinical efforts to create Community Mental Health Centers. We will then provide an overview of current community mental health practices and evolving challenges through to the present day, including the development of services which remain focused on recovery as the ultimate goal.

Within the Community of Inquiry (CoI) framework, cognitive presence has been central to success in higher education settings. This systematic review examined 24 articles published between 2008-2020 that empirically analyzed cognitive presence in online courses. We share the patterns that emerged regarding the interplay between teaching and cognitive presence and social and cognitive presence. We also explore how the four phases of cognitive presence—triggering event, exploration, integration, and resolution—were evident within specific instructional activities. We conclude with implications for practice that will be helpful for course instructors and designers seeking to foster greater cognitive presence within their online courses.

Introduction Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. Materials and methods Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. Results Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III–V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p

Bacteria integrate environmental signals to regulate gene expression and protein production to adapt to their surroundings. One such behavioral adaptation is the formation of a biofilm, which can promote adherence and colonization and provide protection against antimicrobials.

Circadian rhythms are nearly ubiquitous throughout nature, suggesting they are critical for survival in diverse environments. Organisms inhabiting largely arrhythmic environments, such as caves, offer a unique opportunity to study the evolution of circadian rhythms in response to changing ecological pressures. Populations of the Mexican tetra, Astyanax mexicanus, have repeatedly invaded caves from surface rivers, where individuals must contend with perpetual darkness, reduced food availability, and limited fluctuations in daily environmental cues. To investigate the molecular basis for evolved changes in circadian rhythms, we investigated rhythmic transcription across multiple independently-evolved cavefish populations. Our findings reveal that evolution in a cave environment has led to the repeated disruption of the endogenous biological clock, and its entrainment by light. The circadian transcriptome shows widespread reductions and losses of rhythmic transcription and changes to the timing of the activation/repression of core-transcriptional clock. In addition to dysregulation of the core clock, we find that rhythmic transcription of the melatonin regulator aanat2 and melatonin rhythms are disrupted in cavefish under darkness. Mutants of aanat2 and core clock gene rorca disrupt diurnal regulation of sleep in A. mexicanus, phenocopying circadian modulation of sleep and activity phenotypes of cave populations. Together, these findings reveal multiple independent mechanisms for loss of circadian rhythms in cavefish populations and provide a platform for studying how evolved changes in the biological clock can contribute to variation in sleep and circadian behavior.

Bacterial motility is critical for symbiotic colonization by Vibrio fischeri of its host, the squid Euprymna scolopes, facilitating movement from surface biofilms to spaces deep inside the symbiotic organ. While colonization has been studied traditionally using strain ES114, others, including KB2B1, can outcompete ES114 for colonization for a variety of reasons, including superior biofilm formation. We report here that KB2B1 also exhibits an unusual pattern of migration through a soft agar medium: whereas ES114 migrates rapidly and steadily, KB2B1 migrates slowly and then ceases migration. To better understand this phenomenon, we isolated and sequenced five motile KB2B1 suppressor mutants. One harbored a mutation in the gene for the cAMP receptor protein (crp); because this strain also exhibited a growth defect, it was not characterized further. Two other suppressors contained mutations in the quorum sensing pathway that controls bacterial bioluminescence in response to cell density, and two had mutations in the diguanylate cyclase (DGC) gene VF_1200. Subsequent analysis indicated that (1) the quorum sensing mutations shifted KB2B1 to a perceived low cell density state and (2) the high cell density state inhibited migration via the downstream regulator LitR. Similar to the initial point mutations, deletion of the VF_1200 DGC gene increased migration. Consistent with the possibility that production of the second messenger c-di-GMP inhibited the motility of KB2B1, reporter-based measurements of c-di-GMP revealed that KB2B1 produced higher levels of c-di-GMP than ES114, and overproduction of a c-di-GMP phosphodiesterase promoted migration of KB2B1. Finally, we assessed the role of viscosity in controlling the quorum sensing pathway using polyvinylpyrrolidone and found that viscosity increased light production of KB2B1 but not ES114. Together, our data indicate that while the two strains share regulators in common, they differ in the specifics of the regulatory control over downstream phenotypes such as motility.

Small bowel obstructions (SBO) are a commonly encountered diagnosis within emergency departments. Typically, these patients have evident risk factors including, but not limited to, prior abdominal surgery, personal or family history of gastrointestinal disorders, femoral and inguinal hernias, or neoplasm. In this case, we describe an SBO in a female, professional athlete whose swift, severe symptom onset, rapid resolution with conservative treatment, lack of identifiable risk factors, and prompt return to high level competition without recurrence are certainly unique. A female professional basketball player in her mid-20’s with no past medical history presented with a seven-hour history of worsening abdominal pain beginning in the epigastric region and migrating to the right lower quadrant. Physical exam did not reveal abdominal distension, tympany to percussion, or high-pitched bowel sounds. Initial differential diagnosis included appendicitis, ruptured ectopic pregnancy, and other genitourinary pathology. Computed tomography with contrast revealed distended loops of small bowel with wall thickening, enhancement, and decompressed loops of bowel distally, consistent with an SBO. Symptoms resolved after 24 hours with conservative treatment, including decompression with a nasogastric tube. The athlete returned to full participation five days after initial presentation without recurrence of symptoms. Outpatient gastroenterology workup was negative for predisposing conditions. This presentation is rare in the absence of bowel pathology, family history, or prior abdominal surgery. Perhaps, her profession as an athlete, with frequent air travel and extensive exercise, may have contributed to this unique presentation. This case report should serve as a reminder to all providers that SBOs can occur in young, active patients devoid of risk factors. Even in the absence of typical signs on physical examination, providers should use imaging as adjuncts based on their clinical gestalt and utilize conservative management, when appropriate, to maximize chances of recovery with minimal morbidity.

Protein hydrolysates from corn gluten meal (CGM) and distillers’- dried grains with solubles (DDGS) were prepared with Neutrase and Alcalase, and the antioxidant activity of those hydrolysates in bulk oils, ground pork, canine pet food, and pig feed were evaluated by measuring oxidation stability based on peroxide value (PV) and thiobarbituric reactive substances (TBARS) value. Alcalase-hydrolyzed CGM (CPH-A) and Neutrase-hydrolyzed CGM (CPH–N) had stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than Alcalase-hydrolyzed DDGS (DPH-A) and Neutrase-hydrolyzed DDGS (DPH-N). The CPH-N showed better prevention on lipid oxidation in both corn oil and fish oil compared with other corn antioxidants. The best oxidation prevention in ground meat was observed with 2 g/kg of CPH-N. Lipid oxidation in pet food containing 2% DPH-A was efficiently retarded by 37.8% reduction at the end of the incubation, and TBARS value of pig feed containing 2% CPH-N was reduced the most compared with other treatments. However, there was no significant difference in growth performance and plasma antioxidant concentration between broilers fed with DDGS or Alcalase-treated DDGS. Overall, CGM and DDGS protein hydrolysates could potentially be used as naturally derived antioxidant in food, pet food, and feed systems with good protection efficiency for lipid oxidation to improve product storage stability.

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient’s symptoms without radiation therapy or surgical intervention. After two courses of chemotherapy, the patient achieved complete remission in the bone marrow. Rapid administration of chemotherapy alone in this case resulted in a complete resolution of SCC. Given the rarity of this complication in adults, no standardized treatment has been established. The success of this case recommends chemotherapy as the initial management of SCC in chemotherapy-naïve ALL.

Abstract Background An essential question in evolutionary biology is whether shifts in a set of polygenic behaviors share a genetic basis across species. Such a behavioral shift is seen in the cave-dwelling Mexican tetra, Astyanax mexicanus. Relative to surface-dwelling conspecifics, cavefish do not school (asocial), are hyperactive and sleepless, adhere to a particular vibration stimulus (imbalanced attention), behave repetitively, and show elevated stress hormone levels. Interestingly, these traits largely overlap with the core symptoms of human autism spectrum disorder (ASD), raising the possibility that these behavioral traits are underpinned by a similar set of genes (i.e. a repeatedly used suite of genes). Result Here, we explored whether modification of ASD-risk genes underlies cavefish evolution. Transcriptomic analyses revealed that > 58.5% of 3152 cavefish orthologs to ASD-risk genes are significantly up- or down-regulated in the same direction as genes in postmortem brains from ASD patients. Enrichment tests suggest that ASD-risk gene orthologs in A. mexicanus have experienced more positive selection than other genes across the genome. Notably, these positively selected cavefish ASD-risk genes are enriched for pathways involved in gut function, inflammatory diseases, and lipid/energy metabolism, similar to symptoms that frequently coexist in ASD patients. Lastly, ASD drugs mitigated cavefish’s ASD-like behaviors, implying shared aspects of neural processing. Conclusion Overall, our study indicates that ASD-risk genes and associated pathways (especially digestive, immune and metabolic pathways) may be repeatedly used for shifts in polygenic behaviors across evolutionary time.

Despite increased interest in K-12 online education, student engagement deficits and the resulting student attrition remain widespread issues. The Academic Communities of Engagement (ACE) framework theorizes that two groups support online student engagement: the personal community of support and the course community of support. However, more evidence is needed to understand how members of these communities, especially parents, support students in various contexts. Using insights gleaned from 14 semistructured interviews of parents with students enrolled in online secondary school, this study adds support to the roles identified in the ACE framework by presenting real examples of parents supporting their online students' affective, behavioral, and cognitive engagement. Findings also confirm patterns found in previous research that are not explained using the ACE framework, such as parental advocacy, communication with teachers, and self-teaching. We discuss how a systems approach to conceptualizing the ACE communities allows the framework to more accurately capture parents' perceived experiences within the personal community of support. We also discuss implications for both practitioners and members of students' support structures.

Emergency department visits and healthcare expenditures for pediatric atopic dermatitis have been increasing over the last two decades. There is a paucity of replicable quality improvement initiatives addressed at educating primary care and emergency medicine clinicians on this condition. The goal of this initiative was to improve clinician knowledge and comfort in the diagnosis and management of pediatric atopic dermatitis and superinfection. Clinicians were recruited via email from academic and community settings in Travis County, Texas, in 2020. They were sent a pre-intervention survey, a series of three quizzes, and a post-intervention survey. After each quiz, participants received performance feedback and various forms of multimodal education. Differences between the first and final quiz scores and clinician confidence levels were analyzed for statistical significance. Fifty-six clinicians completed the intervention. The average overall and treatment-specific scores increased significantly by 10% and 37%, respectively. Further, confidence levels improved significantly in the majority of clinicians. Clinician qualitative feedback revealed high satisfaction. Results from this educational quality improvement project have demonstrated that this is an effective and replicable resource for educating clinicians who manage pediatric atopic dermatitis in the emergency department and outpatient setting.

This case describes a current growth opportunity for Mi Pueblo Food Center, a Hispanic grocery chain with locations throughout the Bay Area, California. The CEO of Mi Pueblo is contemplating opening a new store location in East Palo Alto, CA, which has been without a local, full-service grocery store for over 20 years. Case objectives are for students to develop an understanding of how the grocery industry operates, the risks and opportunities associated with opening a new grocery store location, and the impact on social, environmental, and economic sustainability. The SWOT (Strengths, Weaknesses, Opportunities, Threats) framework is used to analyze whether or not it is feasible for Mi Pueblo to open a new location in East Palo Alto. This case may be used with students in graduate and advanced undergraduate courses.

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease.

This examination seeks to determine the influence of proximal density to nurse education resources (nursing schools) on nursing home care quality outcomes in Alabama. Motivated by the social network theory, which highlights the influence of relational closeness on shared resources and values, we hypothesize that nursing homes that have higher levels of nursing education resources within a close proximity will exhibit significantly higher nursing home quality outcomes. As proximal density to nurse education resources increases, the opportunity for nursing homes to build closer, stronger ties increase, leading to higher quality outcomes. We examine this hypothesis via ordered logistic regressions of proximal density measures developed through geographic information systems (GIS) software, nurse education resource data from Johnson & Johnson ’s Campaign for Nursing’s Future (n = 37), and nursing home quality outcome data from Centers for Medicare and Medicaid Services’s (CMS) Nursing Home Compare from 2016 (n = 226). The results find that increases in proximal density to nurse education resources have a negative and significant association with nursing home quality outcomes in Alabama. Additional sensitivity analysis, which examines the degree to which the nature of this relationship is sensitive to health care facilities’ location in high-density areas, is offered and confirms principal findings. Because nursing programs generally have stronger ties with hospitals, the findings suggest that the nursing homes in areas with higher nurse education resources may actually face greater competition for nurses.