The purpose of this study was to explore the effect of vocalic behavior in resolving high-conflict situations. A quantitative study was employed using 277 university students from California and ...Florida. We experimentally tested a vocal coding system using passive, aggressive, and assertive audio clips presented to research subjects, which included volume, pitch, rate, pausing, and vocal variety. Participants rated these audio clips based on vocal qualities, relational outcomes, appropriateness, and resolving conflict. Results revealed that the assertive vocal style was associated with higher ratings to resolve conflict and perceptions of verbal assertiveness and appropriateness than were passive or aggressive vocal styles. Implications and applications are discussed to stimulate future research among researchers and practitioners when addressing conflict situations.
Public Significance Statement
This study tested the effects of different vocal qualities on perceptions of conflict. The results found that the assertive vocal style (as opposed to aggressive or passive) was most conducive to resolving conflict and wanting to work with a partner in the future.
A goal in precision medicine is to use patient-derived material to predict disease course and intervention outcomes. Here, we use mechanistic observations in a preclinical animal model to design an ...ex vivo platform that recreates genetic susceptibility to T-cell–mediated damage. Intestinal graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation. We found that intestinal GVHD in mice deficient in Atg16L1, an autophagy gene that is polymorphic in humans, is reversed by inhibiting necroptosis. We further show that cocultured allogeneic T cells kill Atg16L1-mutant intestinal organoids from mice, which was associated with an aberrant epithelial interferon signature. Using this information, we demonstrate that pharmacologically inhibiting necroptosis or interferon signaling protects human organoids derived from individuals harboring a common ATG16L1 variant from allogeneic T-cell attack. Our study provides a roadmap for applying findings in animal models to individualized therapy that targets affected tissues.
•Intestinal GVHD in Atg16L1-deficient mice was reversed by inhibiting necroptosis.•An ex vivo platform incorporating organoids and T cells can recreate susceptibility to tissue injury and be applied to drug testing.
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Lower limb biomechanics, including asymmetry, are frequently monitored to determine sport performance level and injury risk. However, contributing factors extend beyond biomechanical and asymmetry ...measures to include psychological, sociological, and environmental factors. Unfortunately, inadequate research has been conducted using holistic biopsychosocial models to characterize sport performance and injury risk. Therefore, this scoping review summarized the research landscape of studies concurrently assessing measures of lower limb biomechanics, asymmetry, and introspective psychological state (e.g., pain, fatigue, perceived exertion, stress, etc.) in healthy, competitive athletes.
A systematic search of MEDLINE, Embase, CINAHL, SPORTDiscus, and Web of Science Core Collections was designed and conducted in accordance with PRISMA guidelines. Fifty-one articles were included in this review.
Significant relationships between biomechanics (k = 22 studies) or asymmetry (k = 20 studies) and introspective state were found. Increased self-reported pain was associated with decreased range of motion, strength, and increased lower limb asymmetry. Higher ratings of perceived exertion were related to increased lower limb asymmetry, self-reported muscle soreness, and worse jump performance. Few studies (k = 4) monitored athletes longitudinally throughout one or more competitive season(s).
This review highlights the need for concurrent analysis of introspective, psychological state, and biomechanical asymmetry measures along with longitudinal research to understand the contributing factors to sport performance and injury risk from biopsychosocial modeling. In doing so, this framework of biopsychosocial preventive and prognostic patient-centered practices may provide an actionable means of optimizing health, well-being, and sport performance in competitive athletes.
Socioeconomic status (SES) is associated with white matter hyperintensities (WMHs) and contributes to racial and ethnic health disparities. However, traditional measures of SES may not accurately ...represent individual financial circumstances among non-Latinx Black and Latinx older adults due to longstanding structural inequities. This study examined associations between multiple SES indicators (education, income, subjective financial worry) and WMHs across non-Latinx Black, Latinx, and non-Latinx White older adults in the Washington Heights-Inwood Columbia Aging Project (N = 662). Latinx participants reported the lowest SES and greatest financial worry, while Black participants evidenced the most WMHs. Greater financial worry was associated with higher WMHs volume above and beyond education and income, which were not associated with WMHs. However, this association was only evident among Latinx older adults. These results provide evidence for the minority poverty hypothesis and highlight the need for systemic socioeconomic interventions to alleviate brain health disparities in older adulthood.
•HHV-6 reactivation in plasma occurred in 6% and possible HHV-6 encephalitis in 0.2% of patients within 12 weeks after CARTx.•HHV-6 reactivation and disease are infrequent after CARTx, and routine ...HHV-6 monitoring is not warranted.
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Human herpesvirus 6B (HHV-6B) reactivation and disease are increasingly reported after chimeric antigen receptor (CAR) T-cell therapy (CARTx). HHV-6 reactivation in the CAR T-cell product was recently reported, raising questions about product and patient management. Because of overlapping manifestations with immune effector cell–associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging. We provide 2 lines of evidence assessing the incidence and outcomes of HHV-6B after CARTx. First, in a prospective study with weekly HHV-6B testing for up to 12 weeks after infusion, HHV-6B reactivation occurred in 8 of 89 participants; 3 had chromosomally integrated HHV-6 and were excluded, resulting in a cumulative incidence of HHV-6B reactivation of 6% (95% confidence interval CI, 2.2-12.5). HHV-6B detection was low level (median peak, 435 copies per mL; interquartile range, 164-979) and did not require therapy. Second, we retrospectively analyzed HHV-6B detection in the blood and/or cerebrospinal fluid (CSF) within 12 weeks after infusion in CARTx recipients. Of 626 patients, 24 had symptom-driven plasma testing, with detection in 1. Among 34 patients with CSF HHV-6 testing, 1 patient had possible HHV-6 encephalitis for a cumulative incidence of 0.17% (95% CI, 0.02-0.94), although symptoms improved without treatment. Our data demonstrate that HHV-6B reactivation and disease are infrequent after CARTx. Routine HHV-6 monitoring is not warranted.
Kampouri and colleagues report on human herpesvirus 6B (HHV-6B) reactivation and disease following chimeric antigen receptor (CAR) T-cell therapy. A prospective study of 89 patients tested weekly revealed reactivation in 6%, with low-level detection requiring no therapy. In a retrospective study of 626 patients, 24 had symptom-driven plasma testing, with 1 patient testing positive; in 34 patients receiving symptom-driven cerebrospinal fluid testing, 1 patient had HHV-6 that resolved without therapy, with a cumulative incidence of 0.17%. HHV-6B reactivation is infrequent following CAR T-cell therapy, suggesting routine testing is not indicated.
Abstract Objective White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association ...between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship. The purpose of this study was to test the reserve hypothesis in the association between WMH severity and cognition. We hypothesized that individuals with higher amounts of reserve would be able to tolerate greater amounts of pathology than those with lower reserve. Methods Neurologically healthy older adults ( n = 717) from a community-based study received structural MRI, neuropsychological assessment, and evaluation of reserve. WMH volume was quantified algorithmically. We derived latent constructs representing four neuropsychological domains, a measure of cognitive reserve, and a measure of brain reserve. Measures of cognitive and brain reserve consisted of psychosocial (e.g., education) and anthropometric (e.g., craniometry) variables, respectively. Results Increased WMH volume was associated with poorer cognition and higher cognitive and brain reserve were associated with better cognition. Controlling for speed/executive function or for language function, those with higher estimates of cognitive reserve had significantly greater degrees of WMH volume, particularly among women. Controlling for cognitive functioning across all domains, individuals with higher estimates of brain reserve had significantly greater WMH volume. Conclusions For any given level of cognitive function, those with higher reserve had more pathology in the form of WMH, suggesting that they are better able to cope with pathology than those with lower reserve. Both brain reserve and cognitive reserve appear to mitigate the impact of pathology on cognition.
In 2014, Vietnam was the first Southeast Asian country to commit to achieving the World Health Organization's 90-90-90 global HIV targets (90% know their HIV status, 90% on sustained treatment, and ...90% virally suppressed) by 2020. This pledge represented further confirmation of Vietnam's efforts to respond to the HIV epidemic, one feature of which has been close collaboration with the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Starting in 2004, PEPFAR supported community outreach programs targeting high-risk populations (people who inject drugs, men who have sex with men, and sex workers). To provide early evidence on program impact, in 2007-2008 we conducted a nationwide evaluation of PEPFAR-supported outreach programs in Vietnam. The evaluation focused on assessing program effect on HIV knowledge, high-risk behaviors, and HIV testing among high-risk populations-results relevant to Vietnam's push to meet global HIV goals.
We used a mixed-methods cross-sectional evaluation design. Data collection encompassed a quantitative survey of 2199 individuals, supplemented by 125 in-depth interviews. Participants were members of high-risk populations who reported recent contact with an outreach worker (intervention group) or no recent contact (comparison group). We assessed differences in HIV knowledge, risky behaviors, and HIV testing between groups, and between high-risk populations.
Intervention participants knew significantly more about transmission, prevention, and treatment than comparison participants. We found low levels of injection drug-use-related risk behaviors and little evidence of program impact on such behaviors. In contrast, a significantly smaller proportion of intervention than comparison participants reported risky sexual behaviors generally and within each high-risk population. Intervention participants were also more likely to have undergone HIV testing (76.1% vs. 47.0%, p < 0.0001) and to have received pre-test (78.0% vs. 33.7%, p < 0.0001) and post-test counseling (80.9% vs. 60.5%, p < 0.0001). Interviews supported evidence of high impact of outreach among all high-risk populations.
Outreach programs appear to have reduced risky sexual behaviors and increased use of HIV testing services among high-risk populations in Vietnam. These programs can play a key role in reducing gaps in the HIV care cascade, achieving the global 90-90-90 goals, and creating an AIDS-free generation.
Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites ...separated by 0-13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (n = 0-13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi-in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical (1/2)-(a single decamer) and (3/4)-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of (1/2)- and (3/4)-site REs greatly expands the p53 master regulatory network.
Premature ovarian insufficiency (POI) is the loss of normal hormonal and reproductive function of ovaries in women before age 40 as the result of premature depletion of oocytes. The incidence of POI ...increases with age in reproductive-aged women, and it is highest in women by the age of 40 years. Reproductive function and the ability to have children is a defining factor in quality of life for many women. There are several methods of fertility preservation available to women with POI. Procreative management and preventive strategies for women with or at risk for POI are reviewed.
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