Search

Introduction: Self-reliance, emotional control, and honor ideology may prevent help-seeking when suicidal ideation emerges. Furthermore, these factors are associated with an increased likelihood of firearm ownership and unsecure storage, which could facilitate suicide attempts. The rurality of residence may impact these associations, as rural regions report increased independence, honor culture, and firearm prevalence. Therefore, this study examined how emotional control, self-reliance, and honor ideology relate to firearm storage and help-seeking for suicidal ideation, with rurality moderating these associations., Methods: Participants were 733 adults (63.6% female, 33.5% male, and 2.9% transgender/other) who reported past-month suicidal ideation. Analyses tested associations between emotional control, self-reliance, and honor ideology with help-seeking for suicidal ideation and firearm storage, with rurality moderating these associations., Results: The association of self-reliance and decreased help-seeking willingness for suicidal ideation was significant for those in non-urban areas. The association of emotional control and decreased help-seeking willingness for suicidal ideation was significant for those in urban areas. No variables predicted firearm storage., Conclusions: Self-reliance and emotional control could be barriers for help-seeking regardless of gender identity that depend on rurality. Clinicians may target emotional control/self-reliance via strengths-based approaches with an emphasis on when these constructs could be maladaptive, as this could promote help-seeking., (© 2024 American Association of Suicidology.)

Objective: Financial strain and unmet social needs are associated with greater risk for lower urinary tract symptoms. Little research has examined financial strain and unmet social needs in relation to the more holistic concept of bladder health. This study utilizes baseline data from RISE FOR HEALTH: A U.S. Study of Bladder Health to examine whether financial strain, unmet social needs, and meeting specific federal poverty level threshold levels are associated with lower urinary tract symptoms and poorer perceived bladder health, well-being, and function., Study Design: Participants were 18 years or older, born female or currently identified as a woman, and from the civilian, noninstitutionalized population residing in 50 counties in the United States that included or surrounded 9 recruitment centers. Data were collected through mailed or internet-based surveys. To address research questions, the 10-item Lower Urinary Tract Dysfunction Research Network - Symptom Index and selected Prevention of Lower Urinary Tract Symptoms Research Consortium bladder health scores were separately regressed on each financial strain, unmet social need, and federal poverty level variable, using linear regression adjusting for covariates (age, race/ethnicity, education, and vaginal parity) and robust variance estimation for confidence intervals (CI). Participants with no missing data for a given analysis were included (range of n=2564-3170). In separate sensitivity analyses, body mass index, hypertension, and diabetes were added as covariates and missing data were imputed., Results: The mean age of participants was 51.5 years (standard deviation=18.4). Not having enough money to make ends meet, housing insecurity, food insecurity, unreliable transportation, and percent federal poverty levels of 300% or less were consistently associated with more reported lower urinary tract symptoms and poorer perceived bladder health. For example, compared to food secure participants, women who worried that their food would run out at the end of the month had a Lower Urinary Tract Dysfunction Research Network - Symptom Index score that was 3.4 points higher (95% CI: 2.5, 4.3), on average. They also had lower mean scores across different bladder health measures, each assessed using a 100-point scale: global bladder health (-8.2, 95% CI: -10.8, -5.7), frequency (-10.2, 95% CI: -13.8, -6.7), sensation (-11.6, 95% CI: -15.1, -8.2), continence (-13.3, 95% CI: -16.7, -9.9), and emotional impact of bladder health status (-13.2, 95% CI: -16.5, -9.9). Across analyses, associations largely remained significant after additional adjustment for body mass index, hypertension, and diabetes. The pattern of results when imputing missing data was similar to that observed with complete case analysis; all significant associations remained significant with imputation., Conclusion: Financial strain and unmet social needs are associated with worse LUTS and poorer bladder health. Longitudinal research is needed to examine whether financial strain and unmet social needs influence the development, maintenance, and worsening of lower urinary tract symptoms; different mechanisms by which financial strain and unmet social needs may impact symptoms; and the degree to which symptoms contribute to financial strain. If supported by etiologic research, prevention research can be implemented to determine whether the amelioration of financial strain and social needs, including enhanced access to preventative care, may promote bladder health across the life course., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Background: The Centers for Disease Control and Prevention (CDC) Environmental Justice Index Social-Environmental Ranking (EJI-SER) combines a Social Vulnerability Module (SV) with an Environmental Burden Module (EB) to characterize cumulative environmental and social burden at the census tract level. This analysis evaluates the association between EJI-SER and kidney outcomes in glomerular disease (GD) patients., Methods: Cure Glomerulopathy (CureGN) is an observational cohort study of adults and children with biopsy-proven GD. EJI-SER is a percentile ranking by census tract, with a higher score indicating a more severe burden. Associations between EJI-SER and its components with kidney failure (initiation of kidney replacement therapy, transplant, or two estimated glomerular filtration rates [eGFRs] <15ml/min/1.73m2) and longitudinal eGFR were tested using multivariable Cox regression and linear mixed models, respectively, adjusted for demographics, histologic diagnosis, eGFR and urine protein to creatinine ratio at enrollment, and time from biopsy to enrollment., Results: Among 1,149 participants with census tract data, the median (IQR) follow-up was 5.4 (3.0-7.0) years, the median (IQR) age at biopsy was 24 (10-48), and self-identified racial distribution was 5% Asian, 18% Black, and 70% White. Median (IQR) EJI-SER was 0.49 (0.26-0.75). EJI-SER scores in the lowest two quartiles were associated with a lower hazard of kidney failure compared to the highest quartile (adjusted HR [95% CI] 0.62 [0.36-1.08] and 0.43 [0.25-0.76] for EJI-SER 0-25% and >25-50% vs. >75%, respectively) and higher eGFR at enrolllment (adjusted mean 90.1 vs. 87.1 ml/min/1.73m2 for 0-25% vs. >75%, p=0.08)., Conclusion: As captured by EJI-SER, higher environmental and social burdens are associated with lower eGFR and a higher risk of kidney failure in the CureGN cohort. This first use of the EJI-SER in GD demonstrates the need for additional investigation into social drivers of disparities in GD and policies and resources that address these structural inequities., (Copyright © 2025 by the American Society of Nephrology.)

Introduction: The evolution of healthcare continues to display an incongruence between delivery and outcomes. Current healthcare paradigms for patient empowerment warrants analysis. A lacking operational application for and agree upon assessment of patient empowerment contributes to healthcare's incongruence. Interchangeable psychosocial concepts and specific patient contextual factors associated with health-related behavioral change have escaped an applicable definition of empowerment. The aim of this theoretical perspective review is to support a comprehensive and contextual understanding of patient empowerment that frames a definition for future consensus research., Methods and Mechanisms: A theoretical perspective review of patient empowerment including interchangeable concepts and patient contextual factors such as personal suffering and resilience; self-determined meaning and purpose; and autonomy, competence, and self-efficacy are critically analyzed. This analysis builds on adjacent concepts including therapeutic alliance, communication, motivation, and trust. The inclusion of specific patient contextual factors that relate to behavioral change elevate the need to reinforce coping and self-management skills as mechanism for patient empowerment. Practice gaps for those experiencing chronic disease, pain, and mental health disorders in rehabilitation setting are specific populations who benefit from healthcare providers unifying the variables associated with patient empowerment., Results and Discussion: The review of associated concepts synthesized an actionable definition of patient empowerment that serves as a foundation for future research. Behavior related changes occur through the evolution in one's identity, perceptions, and abilities. Interventions that inspire autonomy, competence, and relatedness with a renewed sense of purpose establish resilience and self-efficacy. The totality of this inspired self-determined plan of care establishes the mechanisms required for behavioral change and sustainable transformation. The cumulative experience becomes patient empowerment., Competing Interests: Author AV serves as the CEO for Physical Intelligence, Fort Smith, AR, United States. The remaining 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 © 2025 Varela, Gallamore, Hansen and Martin.)

Digital health tools are positive for delivering evidence-based care. However, few studies have applied rigorous frameworks to understand their use in community settings. This study aimed to identify implementation determinants of the Automated Heart-Health Assessment (AH-HA) tool within outpatient oncology settings as part of a hybrid effectiveness-implementation trial. A mixed-methods approach informed by the Consolidated Framework for Implementation Research (CFIR) examined barriers and facilitators to AH-HA implementation in four NCI Community Oncology Research Program (NCORP) practices participating in the WF-1804CD AH-HA trial. Provider surveys were analyzed using descriptive statistics. Interviews with providers (n = 15) were coded using deductive (CFIR) and inductive codes by trained analysts. The CFIR rating tool was used to rate each quote for (i) valence, defined as a positive (+) or negative (-) influence, and (ii) strength, defined as a neutral (0), weak (1), or strong (2) influence on implementation. All providers considered discussing cardiovascular health with patients as important (61.5%, n = 8/13) or somewhat important (38.5%, n = 5/13). The tool was well-received by providers and was feasible to use in routine care among cancer survivors. Providers felt the tool was acceptable and usable, had a relative advantage over routine care, and had the potential to generate benefits for patients. Common reasons clinicians reported not using AH-HA were (i) insufficient time and (ii) the tool interfering with workflow. Systematically identifying implementation determinants from this study will guide the broader dissemination of the AH-HA tool across clinical settings and inform implementation strategies for future scale-up hybrid trials., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The Multidimensional Assessment of Interoceptive Awareness (MAIA-2) is a leading assessment of interoception. We examined the factor structure and psychometric characteristics of the MAIA-2 and its associations with psychopathology in a sample of transgender and gender-diverse (TGD) adults. Participants ( N = 301) were recruited via Prolific Academic. Regression analyses were conducted to examine the association between the MAIA-2 subscales, disordered eating, and self-injurious thoughts and behaviors. The eight-factor MAIA-2 demonstrated good model fit after removing Item 2. The MAIA-2 subscales were significantly positively associated with body appreciation and body satisfaction and negatively associated with depression, anxiety, and stress. The MAIA-2 subscales also demonstrated several significant associations with disordered eating. Only Body Trust was significantly negatively associated with participants' perceived likelihood of making a future suicide attempt. This study provided preliminary evidence that the MAIA-2 is an adequate measure of interception in TGD samples., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Discrimination disrupts sleep and contributes to race-based health inequities for Black Americans, but less is known about the psychological mechanisms underlying this relation. The current work tests whether emotion invalidation, termed Social Pain Minimization (SPM), mediates discrimination's negative effects on sleep quality. We focus on the experiences of Black Americans because of racism's disproportionate effect on the health outcomes of Black individuals in the U.S., Methods: Four studies with cross-sectional (Studies 1a-1b) and cross-lagged panel designs (Studies 2-3; N total  = 1,176) were used. Discrimination and SPM were assessed with established measures and self-reported sleep quality was assessed with three different operationalizations including the short form Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) subscale and composites of the Insomnia Severity Index (ISI)., Results: Cross-sectional (Studies 1a-1b) and longitudinal mediation analyses (Studies 2-3) indicated discrimination's negative effect on sleep quality partially operated through SPM (Study 1a, 95% CI = [-.24, -.016]); Study 1b, 95% CI = [-.22, -.03]; Study 2, 95% CI = [-.268, -.007]]; Study 3, 95% CI = [-0.043, -.002])., Conclusion: Beyond its direct negative effect on sleep, discrimination also operates through SPM to reduce sleep quality. Emotion invalidation stemming from discrimination damages sleep.

Aims: Men with lower urinary tract symptoms (LUTS) represent a heterogeneous group, and treatment decisions are often based on severity of symptoms and physical examination findings. Identification of clinically meaningful subtypes could allow for more personalized care. This study advances phenotyping efforts from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) by adding data domains to previous phenotyping using urologic symptoms alone., Methods: Two-hundred-seventeen LUTS, demographics, medical history, and physical examination datapoints from the LURN Observational Cohort study were assessed among 519 men with at least one bothersome LUTS, using weighted Tanimoto indices, semi-supervised learning, and resampling-based consensus clustering to identify distinct clusters of participants. Differentially abundant serum proteins of 220 men were compared across identified clusters., Results: Five refined male clusters (RM1-RM5) were identified. Two clusters reported mild LUTS (RM1: n = 66; RM2: n = 84). RM1 was older than RM2 (70.3 vs. 56.1 years), had more comorbidities (functional comorbidity index 2.4 vs. 1.5) and erectile dysfunction. Two benign prostatic hyperplasia-like symptom clusters were identified (RM3: n = 64; RM4: n = 188). RM3 has the largest postvoid residual volume (275 mL); RM4 reported more urinary frequency, urgency, urinary incontinence, pain, and psychosocial symptoms. RM5 (n = 119) was characterized by urgency urinary incontinence, frequency, and significant comorbidities and psychosocial symptoms. Fifteen (RM2) to 87 (RM1) differentially abundant proteins were identified within each cluster. Minimal overlap was observed between affected proteins and pathways across clusters., Conclusions: Protein signatures across newly discovered subgroups suggest identified subtypes are biochemically distinct. Findings should be validated, but may represent populations with separate pathophysiology and therapeutic needs., Clinical Trial Registration: The LURN ClinicalTrials.gov Identifier is NCT02485808., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objectives: Motivational Interviewing (MI), a client-centered approach that seeks to evoke and resolve ambivalence, and health education (HE), which provides health information and advice, may both provide some benefit to unmotivated smokers. In HE, it is possible that client language reflective of new learning, or "learning talk" (LT), and rejection of health advice, or "rejection talk," (RT), may uniquely reflect intent of subsequent behavior change., Methods: This project utilized MI and HE sessions from two randomized clinical trials (RCTs), one in a low-income, diverse community civilian sample of 255 unmotivated smokers, and the other in a sample of Veterans with mental illness who were unmotivated smokers (n = 55). Mixed methods approaches were utilized to reliably code sessions using the Motivational Interviewing Skill Code 2.5 (MISC 2.5) 1 and a refined Learning Talk coding system 2 ., Results: Reliability of LT and RT codes ranged from fair to excellent (ICCs from 0.43-0.93)., Conclusion: LT appears to be a unique construct and its impact on post-session changes in smoking is warranted., Practice Implications: This system can be used in a study to code existing interventions for smokers using both MI and HE techniques and relate in-session client LT to subsequent smoking behaviors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Introduction: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA m 6 A methylation, accounting for almost all mRNA m 6 A modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer., Areas Covered: This review provides an overview of the patent literature covering METTL3 inhibitors. A literature search was conducted in SciFinder by using 'METTL3 inhibitor' as a keyword and was refined by narrowing the criteria to patents., Expert Opinion: Efforts to develop METTL3/METTL14 inhibitors have led to the advancement of the drug candidate STC-15 to clinical trials. Preclinical studies of STC-15 show promise in inhibiting tumor growth via direct anti-tumor effects and anti-cancer immune responses. The clinical trial outcomes of STC-15 will shape future METTL3/METTL14 inhibitor development. However, critical questions remain. The role of METTL3/METTL14 in m 6 A RNA methylation is essential for cellular activity, raising concerns about the potential adverse effects of targeting this complex. Furthermore, depending on the context, METTL3/METTL14 can function as a tumor suppressor. This underscores the need for a deeper understanding of the molecular mechanisms by which RNA modifications regulate cancer.

Up to a third of service members and Veterans experience disordered eating. Disordered eating can be maintained through negative reinforcement of painful and unpleasant emotions such as guilt, shame, sadness, and hostility. Hostility is a negative emotion that may be particularly relevant for service members and Veterans, yet hostility's relation to disordered eating remains understudied. Further, variability in emotions may be particularly relevant, given that variability in emotions is often a stronger predictor of psychopathology than mean levels. Thus, the goal of the present study was to assess a potential bidirectional relationship between disordered eating symptoms and individuals' variability of hostility, stress, anxiety, sadness, and shame. Participants (N = 94, M age  = 32.2, 75.8% men; 81.8% White) completed 30 days of ecological momentary assessment (EMA) with four assessments per day along with baseline and follow-up measures including the Eating Pathology Symptom Interview (EPSI), which assessed eight disordered eating symptom domains. Hierarchical regressions revealed that higher baseline levels of Binge Eating and Excessive Exercise predicted greater intraindividual hostility variability. Further, more hostility variability predicted higher Cognitive Restraint at 1-month follow-up. Baseline disordered eating symptoms were not associated with intraindividual variability in stress, anxiety, sadness, or shame. However, greater intraindividual variability in shame predicted higher Muscle Building at 1-month follow-up. Hostility variability was the only emotion that was predicted by, and predictive of, disordered eating symptoms. These findings suggest that hostility may be a relevant treatment target for service members with disordered eating., (© 2024 Wiley Periodicals LLC.)

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders defines anorexia nervosa (AN) severity based on body mass index (BMI). However, BMI categories do not reliably differentiate the intensity of AN and comorbid symptoms. Shape/weight overvaluation has been proposed as an alternative severity specifier. The present study used structural equation model (SEM) Trees to empirically determine specific levels of BMI and/or shape/weight overvaluation that differentiate AN severity. We also compared whether the SEM Tree-derived severity groups outperformed existing AN severity definitions. Participants were 1,666 adolescents and adults with AN who were receiving eating disorder treatment at one of the three levels of care (outpatient, partial hospital program, or residential). Participants completed self-reported questionnaires assessing eating pathology and comorbid symptoms. SEM Tree analyses first specified an outcome model of AN severity, and then recursively partitioned the outcome model into subgroups based on all values of BMI and shape/weight overvaluation. One-way analyses of variance and t tests determined which severity definition explained the most variance in clinical characteristics. SEM Tree analyses yielded five severity groups, all of which were defined based on increasing intensities of shape/weight overvaluation: < 2.25, 2.25-3.24, 3.25-4.24, 4.25-5.24, and ≥ 5.25. No groups were defined based on BMI. SEM Tree-derived groupings explained more variance in clinical characteristics than existing severity definitions. Taken together, shape/weight overvaluation appears to be a more accurate marker of AN severity than BMI. The empirically determined AN severity scheme accounted for the most variance in clinical characteristics. Future research should assess the predictive value of these empirically defined AN severity indicators. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Previous studies have described two distinct vascular systems in cetacean fins. However, these studies have been limited to Delphinoidea species, with little information on their three-dimensional structures. In this study, the anatomical analysis of the caudal and dorsal fins of a dwarf sperm whale was conducted using X-ray computed tomography and gross dissection with staining, providing the first confirmation of the two vascular systems in the fins of the family Kogiidae. This finding suggested that these vascular systems are common across Odontoceti species. In addition, we observed unique three-dimensional structures in the superficial veins, which formed a reticulate pattern in both fins and converged at the centerline at the base of the dorsal fin, potentially influencing individual's heat reduction capabilities., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Self-injurious urges are arguably the clearest antecedents of engaging in self-injurious behaviors (SIBs; e.g., binge eating, self-induced vomiting, cutting, burning). However, self-injurious urges demonstrate great heterogeneity, and it is unknown which are most closely linked to SIBs. This study aims to identify latent profiles of self-injurious urges and subsequently examine associations between profiles and engagement in SIBs., Method: Adults (N = 124) who reported engaging in at least three SIBs in the past month completed six surveys a day assessing self-injurious urges for 14 days (6600 responses). Latent profiles were constructed using within-person intensity, variability, peak, duration, relative frequency, and overall stability of self-injurious urges over the EMA period., Results: Five distinct profiles were identified: "sustained," "muted," "sudden-onset," "volatile," and "virtually absent." SIB frequency differed across profiles, H(4) = 41.11, p < 0.001; η 2  = 0.31, 95% CI [0.19, 0.48], and Dunn's post-hocs indicated those in the "volatile" profile engaged in more SIBs than other profiles., Conclusion: Findings support the presence of meaningful profiles of self-injurious urges and suggest these profiles differ in levels of SIB engagement. Future work should prospectively examine associations between profile membership and engagement in SIBs and identify treatment targets to intervene on SIBs., (© 2024 American Association of Suicidology.)

Pufferfish of the genus Takifugu possess tetrodotoxin (TTX), known as "pufferfish toxin" and it is believed that pufferfish eggs and newly hatched larvae utilize TTX as a defensive substance against predators. However, the mechanism for the placement of TTX to specific cells on the larval body surface during the developmental process remains unknown. In this study, we clarify the distribution and characteristics of TTX-rich cells. We performed whole-mount immunohistochemistry (IHC) using anti-TTX monoclonal antibody on larvae of two pufferfish species, Takifugu rubripes and Takifugu alboplumbeus, just after hatching. This allowed observation of the TTX location and compared it with those of wheat germ agglutinin (WGA)-positive (periodic acid-Schiff (PAS)-positive) cells for mucous cells and IHC using anti-Na + /K + -ATPase (NKA) monoclonal antibody for ionocytes. As a result, uniformly scattered localization of TTX-rich cells was commonly observed in the epidermis of the larvae of the two Takifugu species. TTX-rich cells were WGA-negative (PAS-negative) and structurally distinct from NKA-positive cells, suggesting that TTX-rich cells are unreported small cells unique to pufferfish skin, but not mucous cells nor ionocytes., (© 2024. The Author(s).)

It is essential to provide the community with evidenced-based care to optimize healthcare outcomes; more specifically, women in underserved communities with limited access to healthcare services. The purpose of this research was to determine the effectiveness of a single virtual movement-based pelvic health education session on women's pelvic health knowledge, adherence to performing pelvic exercises and confidence in performing the exercises. Forty-two female participants were recruited in Western Arkansas. Participants completed an online pre-session (pre) questionnaire and then received a single virtual education session led by a healthcare provider trained in pelvic health. A post-session (post-1) questionnaire was completed by each participant as well as a 1-month follow-up (post-2) questionnaire. Thirty-five women completed all three questionnaires and pelvic health knowledge, adherence to pelvic floor exercises and confidence in performing pelvic floor exercises were assessed. After the participants completed the post-2 questionnaire, they were invited for a semi-structured interview and 13 women participated. Results of this study suggest pelvic health knowledge increased after a single session of movement-based education, and this was retained 1 month later. Adherence and confidence to perform the exercises did not change; however, learning about pelvic health in a virtual movement-based method was a positive experience and initiated an eagerness to learn more about pelvic health. Pelvic health education can be implemented in a virtual approach to engage women in underserved communities to learn more about pelvic health through a positive experience for an educational baseline to gain healthcare autonomy., (© The Author(s) 2024. Published by Oxford University Press.)

Weight stigma, and more specifically, anti-fat attitudes, is associated with disordered eating. Furthermore, these anti-fat attitudes influence various appearance ideals. Muscle dysmorphia (MD) is characterized by preoccupation with the muscular ideal and is a potential form of disordered eating commonly experienced by men. Despite theory suggesting that anti-fat attitudes may contribute to MD, research has yet to examine associations between anti-fat attitudes and MD symptoms. Therefore, the current study investigated longitudinal relationships between anti-fat attitudes and MD symptoms. Participants were 269 U.S. men recruited from Prolific who completed three self-report surveys each separated by one month. Primary analyses examined longitudinal relationships between specific anti-fat attitudes and MD symptoms using an adapted three-wave cross-lagged panel model. Results demonstrated that believing that fat people do not have willpower was longitudinally associated with desires to increase muscle size at multiple time points. Furthermore, MD-specific functional impairment predicted fears of becoming fat longitudinally. Practically, men may desire to increase their muscularity to demonstrate their own willpower and distance themselves from anti-fat stereotypes. Thus, clinicians may consider targeting weight stigmatizing attitudes to reduce MD symptom severity among their male clients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Perceived burdensomeness (PB) and thwarted belongingness (TB), two proximal risk factors for suicide, may rise during residential eating disorder (ED) treatment when patients are separated from support and face exorbitant costs of care. In this setting, fostering motivation for treatment is challenging, and low motivation for treatment may exacerbate feelings of PB and TB. Simultaneously, PB and TB could reduce motivation for treatment, though no studies have explored this relationship longitudinally. Accordingly, this study examined associations between interpersonal needs (TB, PB) and motivation for treatment across the first 6 weeks of residential ED treatment., Methods: Participants (n = 98) completed the Interpersonal Needs Questionnaire (INQ) and rated treatment motivation weekly. Pearson bivariate correlations examined the relationship between motivation and interpersonal needs at each timepoint. Two autoregressive cross-lagged panel models (AR-CLPMs) tested reciprocal relationships between these constructs longitudinally across the first 6 weeks of treatment., Results: Motivation was significantly negatively correlated with PB and TB at all timepoints. In AR-CLPM 1, Week 2 Motivation predicted Weeks 3 PB, then Week 3 PB predicted Week 4 Motivation. In AR-CLPM 2, Week 2 TB predicted Week 3 Motivation, but Motivation did not predict TB at any timepoint., Discussion: This study is the first to examine longitudinal relations between interpersonal needs and treatment motivation in residential ED care. PB and TB may influence one's motivation for treatment, although motivation and PB had a stronger reciprocal relationship than motivation and TB. Interpersonal needs should be addressed early in residential treatment to mitigate negative cycling., (© 2024 Wiley Periodicals LLC.)

Objective: Complex regional pain syndrome (CRPS) is a debilitating chronic condition characterized by severe, nociplastic pain along with various other symptoms. Neuromodulation, particularly electrical stimulation of the dorsal root ganglion (DRG), has emerged as a promising intervention for patients with CRPS unresponsive to conventional treatments. However, little is known about the anatomical characteristics of DRGs in patients with CRPS. This study aimed to assess DRG size in patients with CRPS compared with healthy controls., Materials and Methods: A retrospective pilot study was conducted in 12 patients with unilateral lower extremity CRPS who have a history of lumbar magnetic resonance imaging, and evaluated DRG sizes bilaterally. Patients were age-, race-, and sex-matched to patients in the control group who were asymptomatic at matched spinal level. DRG sizes were evaluated by a neuroradiologist. Statistical analyses including paired t-tests were performed to compare the difference in DRG size in contralateral sides in patients with CRPS and their matched controls., Results: Patients with CRPS exhibited a statistically significant reduction in DRG size on the affected side compared with the unaffected side (4.4 mm-4.8 mm, respectively). This difference was significant when compared with the difference observed in healthy controls (4.9 mm-5.0 mm, respectively). In addition, the mean DRG size difference between the affected and unaffected side showed a greater difference in DRG size in patients with CRPS (0.6 mm difference) than in control patients (0.2 mm difference)., Conclusions: The findings suggest that CRPS is associated with a smaller DRG size in affected dermatomes, potentially indicating neuronal atrophy. Importantly, the study offers insights for DRG stimulation therapy especially among concerns for DRG compression after placement. This pilot study reveals a significant size difference in DRGs between affected and unaffected sides in patients with CRPS compared with controls, highlighting potential implications for treating CRPS. Further research is warranted to validate these findings and explore implications for clinical practice, including optimized neuromodulation strategies., Competing Interests: Conflict of Interest Johnathan H. Goree has consulting agreements with Abbott, Saluda, and Stratus Medical, and also has funded research paid to his institution from SPR Therapeutics and Mainstay Medical. The remaining authors report no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Disease may be both a cause and a consequence of stress, and physiological responses to infectious disease may involve stress coping mechanisms that have important fitness consequences. For example, glucocorticoid and glycemic responses may affect host fitness by altering resource allocation and use in hosts, and these responses may be affected by competing stressors. To better understand the factors that affect host responses to infection, we challenged the immune system of field-acclimatized pygmy rattlesnakes, Sistrurus miliarius, with a sterile antigen, lipopolysaccharide (LPS), and measured the glucocorticoid and glycemic response in healthy non-reproductive snakes, snakes afflicted with an emerging mycosis (ophidiomycosis) and pregnant snakes. We hypothesized that LPS challenge would result in a glucocorticoid and glycemic response typical of the vertebrate acute phase response (APR), and therefore predicted that LPS challenge would result in an acute increase in plasma corticosterone (CORT) and a decline in plasma glucose in all individuals. Additionally, we hypothesized that the APR would be attenuated in individuals simultaneously coping with additional challenges to homeostasis (i.e. disease or reproduction). As predicted, the immune challenge elicited an acute increase in plasma CORT and a decrease in plasma glucose. Snakes coping with ophidiomycosis and pregnant snakes were able to mount a robust glucocorticoid and hypoglycemic response to LPS challenge, which was contrary to our hypothesis. Our findings clarify directions of causality linking infection, glucocorticoids and glucose, and emphasize the importance of future research examining the fitness consequences of interactions between stress and disease in wildlife threatened by emerging pathogens., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Etherified Carboxymethylcellulose Matrix (eCMC) is a revolutionary application of carboxymethylcellulose (CMC) in wound care, known for its potential in hemostasis and tissue regeneration. This study aims to investigate the mechanism of eCMC in tissue healing by establishing a rat burn model and administering eCMC as a treatment. The objective is to analyze cytokines and inflammatory mediators using a Cytokine Array and histochemical staining to understand the effects of eCMC on tissue regeneration. A rat burn model was created, and eCMC was applied as a treatment. Tissue samples were collected at multiple time points to assess the expression of cytokines and inflammatory mediators using a Cytokine Array. In addition, histochemical staining was performed to evaluate tissue regeneration factors. eCMC induced the expression of endogenous cytokines, particularly vascular epithelial growth factor and platelet-derived growth factor, while inhibiting inflammatory cytokines such as CINC-1, CINC-2, and MMP-8. This dual action facilitated wound healing and mitigated the risk of infection. eCMC demonstrates promising potential for enhancing skin regeneration. Further research is warranted to delve into the precise mechanism of eCMC's cytokine regulation. In vitro and in vivo studies should be conducted to comprehensively investigate the therapeutic capabilities of eCMC in wound healing., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association.)

Background: A petroleum leak into the Joint Base Pearl Harbor-Hickam water system on Oahu, Hawaii in November 2021 contaminated the drinking water of approximately 93,000 users, causing many to relocate for months. Perceptions of health and wellbeing were captured using the Centers for Disease Control/Agency for Toxic Substances and Disease Registry (CDC/ATSDR) Assessment of Chemical Exposures (ACE) cross-sectional survey in collaboration with the Hawaii Department of Health (HDOH)., Methods: Responses from the ACE online survey of community members, businesses, schools, health care and veterinary care organizations during the contamination event, containing quantitative questions and qualitative information from an open text field, were analyzed. Separately, a qualitative key informant questionnaire was administered to community establishments. Thematic content analysis was used to analyze and identify prominent themes from the ACE open text field and the key informant responses that were triangulated by the quantitative data when the themes aligned., Results: Six major themes of disruption, communication, trust, stress, support, and ongoing needs were identified. Burdensome logistics from obtaining alternate water, negative financial impacts from relocation or losing business, distrust of information, perceived lack of support from response entities and uncertainty of long-term health impact caused significant disruption, stress and mental health. Individuals reported needing water, shelter, and mental health care while establishments wanted financial reimbursement and a resolution., Conclusions: The findings show that environmental disasters have significant disruptive and mental health impacts from stress. Identified themes can inform and improve emergency response and communication strategies and increase trust with community members during and after large chemical exposure events., Competing Interests: Declarations Ethics approval and consent to participate All participants was asked to provide consent prior to starting the ACE surveys. Consent for publication No personal identifying data were used in this manuscript. Informed consent Our investigation was carried out in accordance with the project proposal approved by the NCEH/ATSDR Office of Science. All participants received an informed consent statement and agreed to participate. Disclaimer The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Competing interests One coauthor Felton, D., declared a conflict with receiving support and having leadership and a fiduciary role as a member of the EPA’s Children’s Health Protection Advisory Committee Meetings in December 2022 and May 2023 and participating in the Department of Health Data Governance Committee., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

This study explored the facilitators and barriers of community bike share use in a mid-sized city with high incidence of poverty and racial diversity using a community-based participatory action research (CBPAR) photovoice framework with the Stanford Our Voice (OV) Discovery Tool digital application. Community members participated in one of three community citizen science walks with follow up focus groups facilitated by osteopathic medical student researcher to address "What makes it easy or hard to ride a bike using the bike share?" Twenty-seven diverse community members partnered with four osteopathic medical students exploring vulnerable individuals' lived experiences, beliefs/understanding of the Social Determinants of Health (SDoH) and access to the bike share program. A total of 322 photos and narrative comments from citizen science walk audits developed deductive themes and follow up focus groups informed inductive themes. Themes addressed challenges to access, maintenance, safety in bike transit, comfort, and environment that create barriers to use and increase inequities for lower income and historically underrepresented communities. The use of OV provided photograph, narrative, and geocoded photo location. This novel approach served as an effective tool for community action with city decision makers. The narrative research identified the impact of the barriers, and the photographs and geocoding provided clear descriptions for locations to prioritize change by adding street signs for access and safety, fixing road safety issues or bike maintenance concerns. It actively engaged the community with the city to drive discussions and plans for change in repair systems and infrastructure that also addressed equity and acknowledged the SDoH supporting residents in lower income or historically underrepresented communities. Citizen science engaged community voices, supporting change in city policies and transportation initiatives to support the sustainability of the bike share program.

Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action. Despite numerous advantages, these molecules face challenges in solubility, permeability, bioavailability, and potential off-target or on-target off-tissue effects. Thus, an urgent need arises to direct the action of these degrader molecules specifically against cancer cells, leaving the proteins of non-cancerous cells intact. Recent advancements in TPD have led to innovative delivery methods that ensure the degraders are delivered in a cell- or tissue-specific manner to achieve cell/tissue-selective degradation of target proteins. Such receptor-specific active delivery or nano-based passive delivery of the PROTACs could be achieved by conjugating them with targeting ligands (antibodies, aptamers, peptides, or small molecule ligands) or nano-based carriers. These techniques help to achieve precise delivery of PROTAC payloads to the target sites. Notably, the successful entry of a Degrader Antibody Conjugate (DAC), ORM-5029, into a phase 1 clinical trial underscores the therapeutic potential of these conjugates, including LYTAC-antibody conjugates (LACs) and aptamer-based targeted protein degraders. Further, using bispecific antibody-based degraders (AbTACs) and delivering the PROTAC pre-fused with E3 ligases provides a solution for cell type-specific protein degradation. Here, we highlighted the current advancements and challenges associated with developing new tumour-specific protein degrader approaches and summarized their potential as single agents or combination therapeutics for cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered. The term "alpha-gal syndrome" (AGS) was then coined to describe allergic reactions to mammalian meat or other alpha-gal-containing products derived from mammals. Symptoms are often delayed several hours from consumption and can be urticarial and/or gastrointestinal. Medications and bioprosthetic inserts derived from mammals were also noted to cause allergic reactions in affected patients. Cardiac surgery, in particular, is considered high risk, given that unfractionated heparin has a bovine or porcine origin and is administered in large doses for cardiopulmonary bypass. Bioprosthetic valves have similar origins and risks. Awareness of AGS in cardiac surgery patients can lead to decreased risk preoperatively and inform management perioperatively and postoperatively. In this narrative review, we have reviewed the published literature relevant to AGS in patients undergoing cardiac surgery and shared our treatment approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To date, DNA methylation is the best characterized epigenetic modification in Alzheimer's disease. Involving the addition of a methyl group to the fifth carbon of the cytosine pyrimidine base, DNA methylation is generally thought to be associated with the silencing of gene expression. It has been hypothesized that epigenetics may mediate the interaction between genes and the environment in the manifestation of Alzheimer's disease, and therefore studies investigating DNA methylation could elucidate novel disease mechanisms. This chapter comprehensively reviews epigenomic studies, undertaken in human brain tissue and purified brain cell types, focusing on global methylation levels, candidate genes, epigenome wide approaches, and recent meta-analyses. We discuss key differentially methylated genes and pathways that have been highlighted to date, with a discussion on how new technologies and the integration of multiomic data may further advance the field., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Eating disorders (EDs) are associated with numerous comorbidities and deleterious outcomes (e.g. medical complications, high rates of death by suicide). The complexities of EDs are further compounded by treatment dropout, poor treatment outcomes, and relapse. One way to better understand these complexities is to investigate broad, transdiagnostic risk factors that contribute to the etiology and maintenance of EDs, such as emotion regulation (ER) difficulties. We longitudinally tested the relationship between ER difficulties and ED outcomes in a sample of 101 female ED patients in a southeastern U.S. residential ED treatment facility. Consistent with hypothesis, there were significant improvements in both ER difficulties and eating pathology from admission to discharge. Further, improvement in ER difficulties was associated with improvements in eating pathology. These findings further substantiate the role of ER difficulties in eating disorders and provide further evidence for the relationship between ER difficulties and eating pathology among residential eating disorder patients.

Background: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response., Objective: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion., Methods: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers., Results: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively., Conclusions: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Emerging evidence suggests that low socioeconomic status (SES) home environments may play a role by promoting excess energy intake through a lack of access to non-food reinforcers. Because of the deleterious effects of SES-related disparities on child health and development, feasible and culturally acceptable interventions are urgently needed. Community-based music enrichment programs may be an ideal intervention strategy., Methods: In collaboration with a local non-profit organization and music studio, we conducted a pilot randomized controlled trial to assess the effects of a music enrichment program versus a play date control in a group of 9-24-month-old healthy infants (N = 16). The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Children's Mercy Hospital Kansas City. This study is registered with clinicaltrials.gov (NCT05868811)., Results: Overall, we found some intervention effects on the relative reinforcing value of food (RRV food ) and the home environmental enrichment measures (i.e., increased music use at home and the home language environment). Our intervention demonstrated large effects on the increased use of music at home. We did not find significant group differences in the RRV food and home language environment, but some of the effect sizes were medium-to-large. Results also suggest that our intervention is feasible and acceptable. Parent feedback indicated that the intervention was well-liked and that the steps we took to help reduce barriers worked., Conclusions: Music enrichment programs may be a high-impact, low-cost strategy to address socioeconomic disparities.

Context: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels., Objective: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism., Design: Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE)., Setting: 21 sites across North America and Europe., Participants: 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52., Intervention(s): All OLE participants received TransCon PTH administered once daily., Main Outcome Measure(s): Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs)., Results: At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE., Conclusions: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: This review aims to synthesize and critically evaluate the existing literature on kratom use and its possible association with induction of psychotic and manic symptoms, in order to identify potential areas for future research that would improve our understanding of the risks of kratom consumption., Methods: An electronic search was performed using five major databases: including PubMed, Scopus, Google Scholar, Web of Science, and PsycINFO. keywords such as kratom, Mitragyna speciosa, mania, psychosis, bipolar disorder, schizophrenia, schizoaffective, case report, and case series. The retrieved articles on initial search were screened based on predefined inclusion and exclusion criteria for this study, and then data synthesis was performed to analyze relevant information from the included studies., Results: Six prior papers were found using (1 case series and 5 case reports). These included 10 cases, involving kratom use association with mania and psychosis. The ages of patients ranged from 28 to 55 years mean age was 38, and (SD 13.74), the majority were males (8 out of 11). Patients had durations of kratom use ranging from 2 wk to 15 years. Significant association was found between kratom use and the worsening of psychotic and manic symptoms in individuals with psychiatric conditions., Conclusions: Our research highlights the possibility of worsening preexisting psychiatric conditions in the context of kratom use. This study emphasizes the need for clinical evaluation of patients for kratom use. Additional research is required to gain a deeper understanding of the potential mental health implications of kratom use, especially among vulnerable populations.

Antibody-drug conjugates (ADCs) have high specificity with lesser off-target effects, thus providing improved efficacy over traditional chemotherapies. A total of 14 ADCs have been approved for use against cancer by the US Food and Drug Administration (FDA), with more than 100 ADCs currently in clinical trials. Of particular interest ADCs targeting immune antigens PD-L1, B7-H3, B7-H4 and integrins. Specifically, we describe ADCs in development along with the gene and protein expression of these immune checkpoints across a wide range of cancer types let url = window.clickTag || window.clickTag1 || window.clickTag2 || window.clickTag3 || window.clickTag4 || window.bsClickTAG || window.bsClickTAG1 || window.bsClickTAG2 || window.url || ''; if(typeof url == 'string'){ document.body.dataset['perxceptAdRedirectUrl'] = url;}., Competing Interests: Declaration of Competing Interest AR has received advisory board honoraria from AstraZeneca, Merck Sharp & Dohme, Novartis, and Pfizer; writing engagement honoraria from AstraZeneca, Merck Sharp & Dohme, and Novartis; and speaker bureau from Bristol-Myers Squibb. UM has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis, and Hedera., for work performed outside of the current study. AD has consulting/advisory role for Sanofi, Amgen, Foundation Medicine, AstraZeneca, Janssen Oncology, Merus, Daichii Sankyo, Abbvie, Regeneron, Bristol Myers Squibb, Bayer. AD has recieved research funding from Lung Cancer Research Foundation, LUNGevity Foundation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Interoception (e.g., abilities to recognize/attend to internal sensations) is robustly associated with psychopathology. One form of interoception, body trust, is relevant for the development of disordered eating and suicidal thoughts/behaviors. However, measures of body trust are narrow, despite research suggesting body trust is multifaceted. The aim of this study was to develop a comprehensive measure of body trust: The Body Trust Scale (BTS). 479 U.S. adults completed self-report surveys containing the BTS and psychopathology measures. Exploratory and confirmatory factor analyses revealed a three-factor structure: Comfort with One's Body, Physical Attractiveness, and Comfort with Internal Sensations. Factors showed strong construct, convergent, and divergent validity, as well as moderate predictive validity for suicidal thoughts/non-suicidal self-injury. Furthermore, factors showed strong internal consistency, test-retest reliability, and were invariant across the gender binary. The BTS can be used in research and clinical settings to understand how specific facets of body trust relate to psychopathology., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection., Methods: In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts., Results: We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P = 2.0 × 10 -3 ). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning = 2.47) and Parkinson's disease (hazard ratio for MCI/dementia   = 2.59)., Discussion: Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk., Highlights: We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Aims: Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy., Methods: We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation., Results: We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506 ng/mL (interquartile range (IQR) [416-750]) to 76.5 ng/mL (IQR [25.8-232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4 µg/mL (IQR [0.4-0.48]) to 8.25 µg/mL (IQR [3.7-9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72-94%], 6.7-fold increased IFX trough (95% CI = 2.4-18.7), and 76% clinical remission rescue rate (95% CI = 59-93%)., Conclusions: These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coronary artery bypass grafting (CABG) has significantly reduced the morbidity and mortality of patients suffering from ischemic heart disease over its six decades of practice. In recent years, minimally invasive techniques have been increasingly described and utilized, with the promise of providing patients with the same standard of care without the need for the traditional full sternotomy, and in select cases without cardiopulmonary bypass, and thus providing improved recovery metrics. The present systematic review and meta-analysis sought to determine the outcomes of all patients receiving robotic-assisted CABG in an Atlantic patient demographic., Methods: The methods for this systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Four databases were searched, using appropriate search terminology. Meta-analysis using proportions or means, as appropriate, were applied, and were presented as per routine practice. Kaplan-Meier curves were digitized and aggregated using previously reported, validated techniques. Quality assessment and risk of bias of each study were assessed systematically. Patient populations were subcategorized as per established technical definitions., Results: Thirty-five studies were identified through the literature search, with three studies having subgroupings appropriate for separate analysis (yielding 42 data points maximally). A total of 9,078 patients (69% male), with a mean age of 62.3 years, were identified across the study period. On actuarial assessment, survival at yearly assessment from 1-, 2-, 3-, 4- and 5-yearly intervals was determined to be 95%, 94%, 92%, 90%, and 88%, respectively., Conclusions: The present systematic review and meta-analysis demonstrated that short-term mortality, operative time, and admission [intensive care unit (ICU) and overall length of stay] outcomes were encouraging in the Atlantic demographic. Freedom from long-term mortality assessment of a smaller cohort showed encouraging results. A major caveat to the present analysis is the high degree of heterogeneity in the reporting of data. Analysis of future randomized controlled trials will be vital in establishing these procedures as commonplace., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

People share information for many reasons. For example, Berger (2011, N = 40) found that undergraduate participants manipulated to have higher physiological arousal were more likely to share a news article with others via email than people who had low arousal. Berger's research is widely cited as evidence of the causal role of arousal in sharing information and has been used to explain why information that induces high-arousal emotions is shared more than information that induces low-arousal emotions. We conducted two replications ( N = 111, N = 160) of Berger's study, using the same arousal manipulation but updating the sharing measure to reflect the rise of information sharing through social media. Both studies failed to find an impact of incidental physiological arousal on undergraduate participants' willingness to share news articles on social media. Our studies cast doubt on the idea that incidental physiological arousal-in the absence of other factors-impacts people's decisions to share information on social networking sites.

Recent work has identified fearlessness about suicide , rather than fearlessness about death , as more theoretically relevant in the assessment of capability for suicide and thus a more appropriate construct of measurement. The aim of the current project was to develop and validate a scale specifically assessing fearlessness about suicide. Across two studies, support for a 7-item, single-factor structure of the Fearlessness About Suicide Scale (FSS) emerged. The FSS factor structure demonstrated a good fit in the first study and was replicated in the second study. Measurement invariance was examined across those identifying as men and women and found to be comparable. The FSS also demonstrated test-rest reliability and good convergent and divergent validity in community and undergraduate samples. Overall, findings indicate that the FSS has a replicable factor structure that generalizes across those identifying as men and women and may better assess components of capability for suicide than existing scales., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Living donation increases the organ supply, but associated non-medical expenses can disincentivize donation. Programs aimed at increasing living donation need to better understand how financial obstacles, including lost wages, impact the decision to pursue donation. Methods/Approach: Forty-eight interviews were conducted and analyzed using a grounded theory approach. Findings: Three key themes were identified that influenced decision-making: emotional attachment, temporal flexibility, and job security. These themes emerged when dividing interview participants into 3 groups: close relationship donors, broader network donors, and non-directed donors, representing donation to a family member or friend, a specific person they do not know well or at all, or a non-specified individual, respectively. Most close relationship donors wanted to donate regardless of personal financial cost, based on emotional attachment to the recipient. Wage reimbursement did not typically affect their decision-making but could reduce stress. Since non-directed donors did not donate to a specific individual, they could wait to achieve financial stability before donating, if needed. While wage reimbursement might create more proximate stability, non-directed donors had the flexibility to postpone donations until they could independently achieve financial stability. Lacking emotional attachment and temporal flexibility, broader network donors were particularly active decision-makers and most influenced by wage reimbursement. Across all groups, donors with job security were more resolute about donating. Conclusion: The findings underscore the importance of lost wage reimbursement to facilitate donation and reduce stress, and policies to protect donor job security., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with the research, authorship, and/or publication of this article.

A primary seminal vesicle leiomyoma (PSVL) is a rare male genitourinary tract tumor. No previous reports have utilized a robotic-assisted laparoscopic posterior approach (RALPA) for surgical management. A 76-year-old man was incidentally found to have a 5cm lobulated mass posterior to the bladder in an abdominal/pelvic computed tomography scan. Biopsy confirmed leiomyoma. RALPA was utilized to excise the mass without complications. PSVLs are benign tumors with obstructive and minimal metastatic potential. Robotic-assisted surgery provides high fidelity, low risk, and an accelerated postoperative course compared to open surgery. The RALPA should be considered when surgical excision of PSVLs is required., (© 2024 The Authors.)

Context: Women outnumber men in medical school. Given the growing need for rural physicians and the underrepresentation of women in rural medicine, understanding predictors of rural practice among female students is imperative for addressing future healthcare workforce shortages in rural areas. Utilizing current evidence, medical schools should seek to admit students with a rural background and interest in pursuing a primary care specialty; however, whether this holds true for female osteopathic medical students is unknown., Objectives: This study aims to determine if a rural background, a plan to practice family medicine, and motivation toward civic duty are associated with attitudes toward eventual practice of rural medicine in female osteopathic medical students., Methods: An anonymous online survey was administered to actively enrolled female students at Arkansas Colleges of Health Education College of Osteopathic Medicine. The survey assessed the respondents' presence of a rural background, degree of civic-mindedness, intention to practice family medicine, and attitudes to rural work and life. Demographics of ethnicity and year of study in medical school were also collected. In total, 129 students responded to the survey, with 97 complete responses for analysis. Hierarchical regression was utilized to compare nested models and interpret interactions., Results: Of the 97 survey respondents, 34.0 % described themselves as first-year students, 37.1 % as second-year students, 16.5 % as third-year students, and 12.4 % as fourth-year students. Linear regression modeling indicated that for female medical students at Arkansas Colleges of Health Education, having a rural background had no relationship with their attitude toward practicing in a rural setting, β=-0.97, standard error (SE)=1.96, t =-0.49, p>0.05, CI [-4.86, 2.92]. Civic-mindedness had a positive relationship with their attitude toward practicing in a rural setting, β=0.17, SE=0.07, t =2.44, p=0.016, CI [0.03, 0.31], accounting for 4.57 % of its variance. Plan to practice family medicine was positively associated with a student's attitude toward practicing in a rural setting, β=4.38, SE=0.85, t =5.15, p<0.001, CI [2.69, 6.07], accounting for 20.25 % of its variance. Civic-mindedness appeared to moderate the relationship between planning to practice family medicine and attitudes toward practicing in a rural setting, F (1, 91) = 3.91, p=0.05, R 2 =0.31. The p value for this interaction term was 0.05, but its effect size measure and graphical representation revealed a substantive effect., Conclusions: The regression analysis showed that, for the women in this study, the greater the student's civic-mindedness, the more favorable her attitude toward practicing in a rural setting. Additionally, the stronger the student's plan to practice family medicine, the more favorable her attitude toward eventual rural practice was. Lastly, the student's civic-mindedness influenced the predictive value of having a plan to practice family medicine., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Tetrodotoxin (TTX), a pufferfish toxin, is a highly potent neurotoxin that has been found in a wide variety of animals. The TTX-bearing flatworm Planocera multitentaculata possesses a large amount of TTX and is considered responsible for the toxification of TTX-bearing animals such as pufferfish (Takifugu and Chelonodon) and the toxic goby Yongeichthys criniger. However, the mechanism underlying TTX accumulation in flatworms remains unclear. Previous studies have been limited to identifying the distribution of TTX in multiple organs, such as the digestive organs, genital parts, and the remaining tissues of flatworms. Here, we performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and immunohistochemical staining using a monoclonal anti-TTX antibody to elucidate the detailed localization of TTX in the tissues and organs of the flatworm P. multitentaculata. Immunohistochemical staining for P. multitentaculata showed that TTX-specific signals were detected not only in the ovaries and pharynx but also in many other tissues and organs, whereas no signal was detected in the brain, Lang's vesicle, and genitalia. In addition, combined with LC-MS/MS analysis, it was revealed for the first time that TTX accumulates in high concentrations in the basement membrane and epidermis. These findings robustly support the hypotheses of "TTX utilization protection from predators.", (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB)., Materials and Methods: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values., Results: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup., Conclusions: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB., Trial Registration: ClinicalTrials.gov: NCT02485808.

Objective: Investigate relationships between pediatric COVID-19 vaccination and social processes of healthcare provider recommendations and school encouragement to provide insights into social processes that may support pediatric COVID-19 vaccination among hesitant mothers., Methods: We analyzed survey data from a subsample (n = 509) of vaccine-hesitant mothers to child patients (ages 2 to 17) in regional clinics across Arkansas. Data were collected between September 16th and December 6th, 2022. Full information maximum likelihood multivariable logistic regression was conducted to evaluate associations with pediatric COVID-19 vaccination., Results: Adjusted odds of pediatric COVID-19 vaccination were more than three times greater when a child's healthcare provider recommended vaccination compared to when they did not (aOR = 3.52; 95% CI[2.06, 6.01]). Adjusted odds of pediatric COVID-19 vaccination were 85% greater when a child's school encouraged parents to vaccinate compared to when the school did not (aOR = 1.85; 95% CI[1.13, 3.03])., Conclusions: For pediatric COVID-19 vaccination, having a personal healthcare provider is not significantly different from having no personal healthcare provider if they do not recommend the child be vaccinated., Practice Implications: Clinical and public health interventions should consider social processes of healthcare provider recommendations and school encouragement., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Spinal anesthesia is the most preferred method for cesarean section (C-section). This meta-analysis was performed to determine the effect of low and high intrathecal doses of pethidine on the maternal outcomes after C-section., Methods: A systematic search of PubMed, Scopus, Cochrane Library, and Google Scholar was performed. Random-effects meta-analysis was performed to derive odds ratios (ORs) from dichotomous data., Results: Seventeen randomized controlled trials with 1304 C-section patients were included. Patients who had received intrathecal pethidine experienced decreased shivering and intensity of shivering (OR 0.13; P <0.001) and (OR 0.21; P <0.001), respectively. Moreover, vomiting (OR 2.47; P =0.002) and pruritus (OR 5.92; P <0.001) were significantly higher in the pethidine group. There was no statistically significant difference in the incidence of nausea (OR 2.55; P =0.06) and hypotension (OR 0.91; P =0.67)., Conclusions: Intrathecal pethidine can effectively decrease shivering, although it increases the risk of vomiting and pruritus. No significant difference was found both in the maternal hypotension and nausea., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Growing evidence is describing the long-term morbidity experienced by critical illness survivors, a major contributing factor being impaired physical function. Consensus is yet to be reached on which physical function measures should be included in this population. This review aimed to describe physical functioning measurement instruments used in longitudinal studies of critical illness survivors, based on the International Classification of Function (ICF)., Methods: An electronic database search of EbscoHost, Web of Science and Scopus was conducted from inception to November 2023. Two reviewers independently applied the inclusion and exclusion criteria to titles, abstracts and full text-studies. Extracted data included year of publication; country; participant age; follow-up timeframes and physical measurement instruments used. Instruments were classified according to ICF domains., Results: Eighty studies published between 1995 and November 2023 were included. Forty-four different outcome measures were identified. Most studies (68) included multiple followed-up points and were completed within a year, and few studies (12) follow-up beyond a year. Based on the ICF, 11 (25%) instruments measured impairments and 33 (75%) activity limitations. Muscle power functions were the most frequently measured impairment (65%), utilising manual muscle testing (37.3%). The six-minute walk test (6MWT) was the most frequently used instrument in the activity/participation domain (31.6%). Only one instrument addressed all five the physical activity/participation domains, while the majority focused on mobility domain., Conclusion: Multiple tools are used to report on physical deficits experienced by ICU survivors, either measuring impairments or activity/ participation limitations. Most studies report on physical function within the first year of survival. The heterogeneity and inconsistency over time of instruments used prevents synthesis of data to determine intervention efficacy. The validity, predictive value and sensitivity of the reported measures within ICU survivors needs to be established, only then can intervention studies be designed to measure effectiveness., Contribution of the Study: This scoping review contributes to the existing literature and development of standardised core outcome measure sets (COMS) for critical illness research by providing a comprehensive and systematic mapping of physical function measurement instruments utilised in longitudinal studies of critical illness survivors. By categorising these instruments according to the International Classification of Functioning, Disability and Health (ICF) framework, the review offers a novel perspective on the current state of outcome measurement in this field., (Copyright © 2024, Author(s).)

Study Design: Non-randomized clinical trial., Objectives: Examine the feasibility, physical and psychosocial effects of a high intensity functional training (HIFT) exercise program for people with spinal cord injury (pSCI) and their care partners (CPs)., Setting: Community fitness center in a Medically Underserved Area (Fort Smith, USA.) METHODS: A single-group design with three assessment points (before the program, at midpoint (13 weeks), and post-program (25 weeks) was used to examine the effects of up to 49 HIFT sessions over 25-weeks. Sessions were 60 to 75 min in duration and adapted to the abilities of participants. Feasibility measures included recruitment, retention, attendance, safety and fidelity (exercise intensity rated via session-Rating of Perceived Exertion (RPE). Physical measures included cardiovascular endurance, anaerobic power, and muscular strength. Psychosocial measures included perceived social support for exercise, exercise self-efficacy and health-related quality of life., Results: Fourteen pSCI (7 with paraplegia and 7 with tetraplegia, 2 females) and 6 CPs (4 females) were included (median age = 60) (IQR = 15.8). Recruitment rates were 40% for pSCI and 32% for CPs. On average, participants attended 73% (22%) of exercise sessions with a median session-RPE of 5 (IQR = 1). Retention rates were 83% and 67% for pSCI and CPs, respectively. For pSCI and their CPs, large effect sizes were observed for cardiovascular endurance, anaerobic power, muscular strength, and social support for exercise., Conclusions: For pSCI and their CPs, HIFT appears feasible and potentially leads to improvements in physical and psychosocial health for both groups., (© 2024. The Author(s).)

Background/aim: Fine-needle aspiration cytology (FNA) and core needle biopsy (CNB) of the thyroid gland, salivary glands, and lymph nodes are considered simple and rapid methods for minimally invasive tissue collection. We performed a postal survey to analyse the diagnostic value and complication rate of FNA and CNB in Germany., Patients and Methods: A questionnaire comprising 11 questions was sent to all 161 German ENT departments in September 2015., Results: The response rate was 45%. In 33 of the 73 responding clinics neither FNA nor CNB were carried out. Of the 26 clinics that provided detailed reasons, the majority (n=18) cited a lack of expertise among the collaborating pathologists. Overall, FNA was used more often, regardless of the anatomical region investigated. The study was based on a total of 36,684 FNAs and 9,624 CNBs. The rate of estimated meaningful and correct findings was 63% (10%-90%) for FNA, and 83% (50%-100%) for CNB. In eight cases (<0.001%) a potential tumor cell spread was reported., Conclusion: This is the first nationwide survey in Germany to investigate the utility of FNA and CNB across different localizations in the head and neck region. This study revealed comparable results to the literature regarding the diagnostic value of FNA and CNB. Cell spreading was only observed in individual cases. The appraisal of needle biopsies in the head and neck area seems to be rather inhomogeneous in Germany., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)