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1.
Neurooncol Adv ; 6(1): vdae126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290875

RESUMO

Background: Liquid biopsy assays that detect cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) are a promising tool for disease monitoring in pediatric patients with primary central nervous system (CNS) tumors. As a compliment to tissue-derived molecular analyses, CSF liquid biopsy has the potential to transform risk stratification, prognostication, and precision medicine approaches. Methods: In this pilot study, we evaluated a clinical pipeline to determine feasibility and sensitivity of low-pass whole genome sequencing (LP-WGS) of CSF-derived cfDNA from patients with CNS embryonal tumors. Thirty-two longitudinal CSF samples collected from 17 patients with molecularly characterized medulloblastoma (12), embryonal tumor with multilayered rosettes (2), CNS embryonal tumor, not elsewhere classified (NEC) (2), and atypical teratoid/rhabdoid tumor (1) were analyzed. Results: Adequate CSF-derived cfDNA for LP-WGS analysis was obtained in 94% of samples (30/32). Copy number variants compatible with neoplasia were detected in 90% (27/30) and included key alterations, such as isodicentric ch17, monosomy 6, and MYCN amplification, among others. Compared to tissue specimens, LP-WGS detected additional aberrations in CSF not previously identified in corresponding primary tumor specimens, suggesting a more comprehensive profile of tumor heterogeneity or evolution of cfDNA profiles over time. Among the 12 CSF samples obtained at initial staging, only 2 (17%) were cytologically positive, compared to 11 (92%) that were copy number positive by LP-WGS. Conclusions: LP-WGS of CSF-derived cfDNA is feasible using a clinical platform, with greater sensitivity for tumor detection compared to conventional CSF cytologic analysis at initial staging. Large prospective studies are needed to further evaluate LP-WGS as a predictive biomarker.

3.
Implement Sci Commun ; 5(1): 98, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285504

RESUMO

BACKGROUND: Implementation science scholars have made significant progress identifying factors that enable or obstruct the implementation of evidence-based interventions, and testing strategies that may modify those factors. However, little research sheds light on how or why strategies work, in what contexts, and for whom. Studying implementation mechanisms-the processes responsible for change-is crucial for advancing the field of implementation science and enhancing its value in facilitating equitable policy and practice change. The Agency for Healthcare Research and Quality funded a conference series to achieve two aims: (1) develop a research agenda on implementation mechanisms, and (2) actively disseminate the research agenda to research, policy, and practice audiences. This article presents the resulting research agenda, including priorities and actions to encourage its execution. METHOD: Building on prior concept mapping work, in a semi-structured, 3-day, in-person working meeting, 23 US-based researchers used a modified nominal group process to generate priorities and actions for addressing challenges to studying implementation mechanisms. During each of the three 120-min sessions, small groups responded to the prompt: "What actions need to be taken to move this research forward?" The groups brainstormed actions, which were then shared with the full group and discussed with the support of facilitators trained in structured group processes. Facilitators grouped critical and novel ideas into themes. Attendees voted on six themes they prioritized to discuss in a fourth, 120-min session, during which small groups operationalized prioritized actions. Subsequently, all ideas were collated, combined, and revised for clarity by a subset of the authorship team. RESULTS: From this multistep process, 150 actions emerged across 10 priority areas, which together constitute the research agenda. Actions included discrete activities, projects, or products, and ways to shift how research is conducted to strengthen the study of implementation mechanisms. CONCLUSIONS: This research agenda elevates actions to guide the selection, design, and evaluation of implementation mechanisms. By delineating recommended actions to address the challenges of studying implementation mechanisms, this research agenda facilitates expanding the field of implementation science, beyond studying what works to how and why strategies work, in what contexts, for whom, and with which interventions.

4.
Open Mind (Camb) ; 8: 1084-1106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229608

RESUMO

All talkers show some flexibility in their speech, and the ability to imitate an unfamiliar accent is a skill that shows vast individual differences. Yet the source of these individual differences, in particular whether they originate from perceptual, motor, or social/personality factors, is not yet clear. In the current study, we ask how individual differences in these factors predict individual differences in deliberate accent imitation. Participants imitated three accents, and attempts were rated for accuracy. A set of measures tracking individual differences in perceptual, motor, cognitive, personality, and demographic factors were also acquired. Imitation ability was related to differences in musical perception, vocal articulation, and the personality characteristic of "openness to experience," and was affected by attitudes towards the imitated talkers. Taken together, results suggest that deliberate accent imitation skill is modulated not only by core perceptual and motor skills, but also by personality and affinity to the talker, suggesting that some aspects of deliberate imitation are a function of domain-general constraints on perceptual-motor systems, while others may be modulated by social context.

5.
Cancer Epidemiol ; 93: 102663, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39255550

RESUMO

Individuals with severe mental illness (SMI) have higher mortality rates from cancer than individuals without SMI. The aim of this paper is to highlight these disparities in cancer care in individuals with SMI and suggest potential solutions. We conducted a narrative review of published papers, focusing on mortality, incidence, behavioral and provider risk factors, screening, diagnosis, treatment, and palliative care among individuals with SMI and cancer. The literature does not provide a clear consensus on whether a difference in cancer incidence exists among individuals with SMI compared to the general population. However, it is evident that individuals with SMI have higher mortality from cancer. Factors such as increased cancer related risk behavior, mental health stigma, and difficulty accessing cancer care contribute to this mortality difference. The literature also indicates lower screening rates, delayed and improper diagnosis and treatment, as well as inadequate clinical trial enrollment in individuals with SMI. While the literature is inconclusive regarding disparities in palliative care, we outline key concepts to provide the best possible end of life care to this population. We also summarize strategies to address disparities at the screening, diagnostic, and treatment levels and describe general strategic approaches to improve cancer care in individuals with SMI. We highlight patient-related, physician-related, and healthcare/systems-related factors leading to disparities in cancer care in individuals with SMI. Future research must examine the effectiveness of proposed solutions to guide evidence-based practices.

6.
HGG Adv ; : 100352, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39257002

RESUMO

The aim of this work was to identify the underlying genetic cause in a four-generation family segregating an unusual phenotype comprising a severe form of skeletal Class II malocclusion with gingival hyperplasia. SNP-array identified a copy number gain on chr1, however this chromosomal region did not segregate correctly in the extended family. Exome sequencing also failed to identify a candidate causative variant, but highlighted co-segregating genetic markers on chr17 and chr19. Short- and long-read genome sequencing allowed us to pinpoint and characterize at nucleotide-level resolution a chromothripsis-like complex rearrangement (CR) inserted into the chr17 co-segregating region at the KCNJ2-SOX9 locus. The CR involved the gain of five different regions from chr1 that are shuffled, chained and inserted as a single block (∼828 kb) at chr17q24.3. The inserted sequences contain craniofacial enhancers that are predicted to interact with KCNJ2/KCNJ16 through neo-topologically associating domain (TAD) formation to induce ectopic activation. Our findings suggest that the CR inserted at chr17q24.3 is the cause of the severe skeletal Class II malocclusion with gingival hyperplasia in this family and expands the panoply of phenotypes linked to variation at the KCNJ2-SOX9 locus. In addition, we highlight a previously overlooked potential role for misregulation of the KCNJ2/KCNJ16 genes in the pathomechanism of gingival hyperplasia associated with deletions and other rearrangements of the 17q24.2-q24.3 region (MIM 135400).

7.
PNAS Nexus ; 3(8): pgae260, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39108306

RESUMO

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.5 m) across different zones of latitude. We collated hundreds of in situ, high temporal-frequency ocean temperature time series globally to produce an intuitive measure of temperature variability, ranging in scale from quarter-diurnal to annual time spans. To estimate organismal sensitivity of ectotherms (i.e. microbes, algae, and animals whose body temperatures depend upon ocean temperature), we computed the corresponding range of biological rates (such as metabolic rate or photosynthesis) for each time span, assuming an exponential relationship. We found that subtropical regions had the broadest temperature ranges at time spans equal to or shorter than a month, while temperate and tropical systems both exhibited narrow (i.e. stable) short-term temperature range estimates. However, temperature-dependent biological rates in tropical regions displayed greater ranges than in temperate systems. Hence, our results suggest that tropical ectotherms may be relatively more sensitive to short-term thermal variability. We also highlight previously unexplained macroecological patterns that may be underpinned by short-term temperature variability.

8.
J Forensic Nurs ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111831

RESUMO

BACKGROUND: Child sexual abuse (CSA) is a preventable national public health problem that results in adverse health consequences. Research suggests youth experiencing CSA are often of school age. Screening for early detection of health issues is integral to school nurse (SN) practice. Still, there is little evidence that routine screening when CSA is suspected is occurring in schools, despite recommendations that it should be. Lack of confidence and knowledge related to screening and reporting for CSA contribute to a SN's missed opportunity for early intervention. PURPOSE: The aim of this study was to describe SNs' knowledge and self-efficacy associated with screening for and reporting suspected CSA in school settings. METHODS: A descriptive cross-sectional survey design was employed. The Child Abuse Report Intention Scale was sent to over 2,000 members of the National Association of School Nurses. RESULTS: Among SN respondents (N = 123), the main findings showed almost half reported being concerned a youth was experiencing CSA but may have missed identifying it. Self-efficacy and professional responsibility were predictors of SNs' intention to screen as well as knowledge about obvious and serious signs of abuse were predictors of SNs' intention to report in this sample. IMPLICATIONS: An educational partnership between forensic nurse examiners and SNs can facilitate improving SNs' knowledge about nonspecific physical and behavioral indicators of abuse that are not overtly obvious. The development of a screening tool specific for use by SNs can empower their confidence to screen by providing a resource for them to use as a guide when they are uncertain about the evidence.

9.
J Hand Surg Glob Online ; 6(4): 471-476, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39166206

RESUMO

Treatment of children with upper-extremity trauma, congenital hand differences, cerebral palsy, and brachial plexus birth injuries requires specialized training, given the spectrum of pathology and complexities of treating an individual who is still developing. Although a limited number of dedicated pediatric hand surgery fellowships are available, mastering the large breadth of the field should ideally begin early in training and may take several different pathways. The authors seek to provide a comprehensive list of resources for trainees interested in pediatric hand surgery, including training opportunities, educational tools, and networking organizations. By shining a light on these pediatric hand surgery resources, we hope to encourage future trainees to plan ahead, so that they are well-prepared for the care of children with complex upper limb reconstructive needs.

10.
CBE Life Sci Educ ; 23(3): ar40, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39196818

RESUMO

In this exploratory mixed-methods analysis of students' perceptions of inclusion in introductory STEM courses for STEM majors, we asked students to rate inclusion in their class and to provide an open-text explanation of their rating. Analyzing 1930 qualitative responses resulted in a codebook containing academic, identity, and nonspecific categories. The majority of responses (>80%) cited academic factors such as interactions between students and instructors or course elements and policies. Most academic responses aligned with evidence-based teaching practices fostering inclusion, describing a range of strategies and policies instructors can implement to increase students' perceptions of inclusion. A small number of student responses indicated that their perception of the required knowledge background for the course impacted course inclusivity. Few differences in frequency distributions were found between subgroups examined (gender, race and ethnicity, self-reported inclusion score, and discipline). Additionally, tracking a subset of students (135) across three courses revealed that most (80%) cited different factors influencing their perception of inclusion in each course. This suggests students' perceptions of inclusive practices are complex, and most students recognize multiple factors that influence their inclusion. Overall, our findings suggest instructors can significantly influence students' perceptions of inclusion by using multiple inclusive teaching strategies and course policies.


Assuntos
Currículo , Percepção , Estudantes , Humanos , Feminino , Masculino , Ciência/educação , Engenharia/educação , Tecnologia/educação , Matemática/educação
11.
Ann Surg ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39140603

RESUMO

OBJECTIVE: To compare the rates of unplanned procedures for access-sensitive surgical conditions among beneficiaries living in census tracts of varying social capital levels. BACKGROUND: Access-sensitive surgical conditions are conditions ideally screened for and treated in an elective setting. However, when left untreated, these conditions may result in unplanned (i.e., urgent or emergent) surgery. It is possible that social capital-the resources available to individuals through their membership in a social network-may impact the likelihood of a planned procedure occurring. METHODS: Medicare beneficiaries who underwent one of three access-sensitive procedures (abdominal aortic aneurysm repair, colectomy for cancer, and ventral hernia repair) between 2016-2020 were stratified by their census tract level of social capital, the exposure variable. Outcomes included rate of unplanned surgery, readmission, 30-day mortality, and complications which were risk-adjusted with a logistic regression model that accounted for patient age, sex, race, comorbidities, and area deprivation. RESULTS: A total of 975,048 beneficiaries were included (mean [SD] patient age, 76 [7.6] years; 443,190 were male [45.45%]). Compared to patients from census tracts in the highest overall social capital decile, those from census tracts with the least social capital were on average more likely to undergo unplanned surgery (40.67% versus 35.28%, OR=1.26 P<0.001). Additionally, beneficiaries in these communities were also more likely to experience postoperative complications (24.99% versus 22.90%, OR=1.12 P<0.001), but there was no significant difference in rates of readmission or mortality. When evaluating only elective procedures, the differences between the lowest and highest social capital decile groups reduced significantly for complications (12.77% versus 12.11%, OR=1.06 P=0.04), the differences in mortality rates collapsed, and differences in readmission rates remained insignificant. CONCLUSION: These data suggest that Medicare beneficiaries who live in communities with lower social capital are more likely to undergo unplanned surgery for access-sensitive conditions. Efforts to improve social capital in these communities may be one strategy for reducing the rate of unplanned operations.

12.
Ann Surg Oncol ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158638

RESUMO

BACKGROUND: Patients with inflammatory breast cancer (IBC) have worse survival compared with stage III non-IBC matched cohorts; however, the prognostic significance of achieving pathologic complete response (pCR) in the setting of IBC is not well described. We evaluated overall survival (OS) between IBC patients and non-IBC patients who achieved pCR. METHODS: Adult females diagnosed in 2010-2018 with clinical prognostic stage III unilateral invasive breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery were selected from the National Cancer Database. Unadjusted OS from surgery was estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Cox proportional hazard models were used to estimate the association of study groups with OS after adjustment for available covariates. RESULTS: The study included 38,390 patients; n = 4600 (12.0%) IBC and n = 33,790 (88.0%) non-IBC. Overall pCR rates were lower for IBC compared with non-IBC (20.7% vs. 23.3%; p < 0.001). Among those achieving pCR, 5-year mortality was higher for IBC patients (16.4%, 95% confidence interval [CI] 13.9-19.1%) versus non-IBC patients (9.1%, 95% CI 8.4-9.8%; log-rank p < 0.001). Among all patients achieving pCR, IBC remained associated with worse OS compared with non-IBC (hazard ratio 1.48, 95% CI 1.19-1.85; p < 0.001). CONCLUSION: We found a lower pCR rate and worse OS in IBC patients compared with non-IBC stage III patients. Despite effective systemic therapies, achieving a pCR for IBC patients may not carry the same prognostic impact compared with non-IBC stage III patients.

13.
R Soc Open Sci ; 11(6): 240308, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39100169

RESUMO

Substantial research exists on predation and its ecology. Most research has focused on durophagous fishes, brachyuran crabs, and lobsters. Data are lacking, however, on soft-bodied predators like anemones, and their contribution to overall levels of predation remains largely unevaluated. Here, we compared predation rates of the durophagous predator, the crab C. maenas and the soft-bodied predator, the anemone Actinia equina on 15 intertidal shores around Anglesey, north Wales, UK. We employed a novel approach to assess predation based on measuring faecal output from recently collected individuals and converting it to food consumed using absorption efficiencies (AEs) measured using potential prey species inhabiting the same shores. Anemone mean abundance was 8.21 (± 0.27, s.e.) individuals.m-2, whereas for C. maenas it was 0.23 (± 0.02, s.e.) individuals.m-2. AEs when fed mussel tissue, a polychaete worm, or a shrimp were 92.8-94.0% in C. maenas and 40.5-95.8% in A. equina. This difference in values reflected the different feeding modes of the two predators. Unexpectedly, A. equina consumed 3.5-7 times more prey than C. maenas. The consumption of larger amounts of prey by an anemone than the dominant durophagous predator has important consequences for calculating energy flows in food webs, understanding predation controls in assemblages, and potentially for wider predation trends.

14.
Proc Natl Acad Sci U S A ; 121(34): e2401658121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39136987

RESUMO

Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1ß, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear. While the role of microbial and cell death products has been previously described, we identified alloreactive memory CD4 T cells as the primary triggers of innate inflammation. Memory CD4 T cells engaged MHC II-mismatched dendritic cells (DCs), leading to the production of innate inflammatory cytokines. This innate inflammation was independent of several pattern recognition receptors and was primarily driven by TNF superfamily ligands expressed by alloreactive memory CD4 T cells. Blocking of CD40L and TNFα resulted in dampened inflammation, and mice genetically deficient in these molecules exhibited prolonged survival of cardiac allografts. Furthermore, myeloid cell and CD8 T cell infiltration into cardiac transplants was compromised in both CD40L- and TNFα-deficient recipients. Strikingly, we found that priming of naive alloreactive CD8 T cells was dependent on licensing of DCs by memory CD4 T cells. This study unravels the key mechanisms by which alloreactive memory CD4 T cells contribute to destructive pathology and transplant rejection.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Células Dendríticas , Rejeição de Enxerto , Transplante de Coração , Imunidade Inata , Inflamação , Animais , Rejeição de Enxerto/imunologia , Camundongos , Células Dendríticas/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Inflamação/imunologia , Imunidade Inata/imunologia , Camundongos Endogâmicos C57BL , Ligante de CD40/imunologia , Ligante de CD40/metabolismo , Células T de Memória/imunologia , Camundongos Knockout , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Citocinas/metabolismo , Citocinas/imunologia
15.
Cell Rep ; 43(8): 114607, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39126652

RESUMO

Macrophage metabolic plasticity is central to inflammatory programming, yet mechanisms of coordinating metabolic and inflammatory programs during infection are poorly defined. Here, we show that type I interferon (IFN) temporally guides metabolic control of inflammation during methicillin-resistant Staphylococcus aureus (MRSA) infection. We find that staggered Toll-like receptor and type I IFN signaling in macrophages permit a transient energetic state of combined oxidative phosphorylation (OXPHOS) and aerobic glycolysis followed by inducible nitric oxide synthase (iNOS)-mediated OXPHOS disruption. This disruption promotes type I IFN, suppressing other pro-inflammatory cytokines, notably interleukin-1ß. Upon infection, iNOS expression peaks at 24 h, followed by lactate-driven Nos2 repression via histone lactylation. Type I IFN pre-conditioning prolongs infection-induced iNOS expression, amplifying type I IFN. Cutaneous MRSA infection in mice constitutively expressing epidermal type I IFN results in elevated iNOS levels, impaired wound healing, vasculopathy, and lung infection. Thus, kinetically regulated type I IFN signaling coordinates immunometabolic checkpoints that control infection-induced inflammation.


Assuntos
Inflamação , Interferon Tipo I , Macrófagos , Staphylococcus aureus Resistente à Meticilina , Óxido Nítrico Sintase Tipo II , Transdução de Sinais , Infecções Estafilocócicas , Animais , Interferon Tipo I/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos Endogâmicos C57BL , Fosforilação Oxidativa , Glicólise , Interleucina-1beta/metabolismo
16.
ACS Chem Neurosci ; 15(18): 3354-3362, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39172951

RESUMO

One of the mechanisms accounting for the toxicity of amyloid peptides in diseases like Alzheimer's and Parkinson's is the formation of pores on the plasma membrane of neurons. Here, we perform unbiased all-atom simulations of the full membrane damaging pathway, which includes adsorption, aggregation, and perforation of the lipid bilayer accounting for pore-like structures. Simulations are performed using four peptides made with the same amino acids. Differences in the nonpolar-polar sequence pattern of these peptides prompt them to adsorb into the membrane with the extended conformations oriented either parallel [peptide labeled F1, Ac-(FKFE)2-NH2], perpendicular (F4, Ac-FFFFKKEE-NH2), or with an intermediate orientation (F2, Ac-FFKKFFEE-NH2, and F3, Ac-FFFKFEKE-NH2) in regard to the membrane surface. At the water-lipid interface, only F1 fully self-assembles into ß-sheets, and F2 peptides partially fold into an α-helical structure. The ß-sheets of F1 emerge as electrostatic interactions attract neighboring peptides to intermediate distances where nonpolar side chains can interact within the dry core of the bilayer. This complex interplay between electrostatic and nonpolar interactions is not observed for the other peptides. Although ß-sheets of F1 peptides are mostly parallel to the membrane, some of their edges penetrate deep inside the bilayer, dragging water molecules with them. This precedes pore formation, which starts with the flow of two water layers through the membrane that expand into a stable cylindrical pore delimited by polar faces of ß-sheets spanning both leaflets of the bilayer.


Assuntos
Bicamadas Lipídicas , Bicamadas Lipídicas/metabolismo , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Membrana Celular/metabolismo , Humanos , Sequência de Aminoácidos , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/metabolismo , Proteínas Amiloidogênicas/química
17.
Horm Behav ; 165: 105630, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39186858

RESUMO

Maternal behavior experienced in early life provides essential scaffolding to infant psychobiology with life-long effects on neurobiological and behavioral outcomes. However, infants are not passive recipients of caregiving. Evidence in rodents suggests that pups actively contribute to dam-pup interactions by soliciting maternal care with auditory, tactile, and hormonal cues. The limited bedding and nesting material (LBN) rearing manipulation induces changes in maternal care that have been attributed to maternal stress caused by the low-resource environment. The goal of the current study was to determine whether LBN also alters pup cues for maternal behavior, with implications for the mechanism of LBN-induced effects. Rat dams and pups were randomly assigned to LBN or Control rearing conditions on postnatal day (P) 0-6 and pups were fostered to the same or different condition on P6-13. LBN increased pup-directed maternal behaviors measured through 24 h monitoring using machine learning based automated analysis. LBN altered several pup cues known to affect maternal behavior including reducing pup core body temperature, reducing body weight, and altering pup vocalizations on P6 and P12. P6-13 LBN-exposed pups had elevated serum testosterone, which positively correlated with maternal licking and grooming. LBN reduced pup movement between nest attendance onset and the start of nursing, which was negatively related to dam nursing latency and contributed to longer nursing latency in LBN dams. P0-6 pup exposure to LBN also led to longer nest attendance bouts and shorter licking and grooming bouts on P7 and P9, suggesting lasting effects of LBN on pups. These data demonstrate that LBN changes pup behavioral and hormonal signals consistent with eliciting more maternal care, contributing to augmented pup-directed behaviors. This bidirectional interplay may be a critical mechanism involved in the lasting effects of early life environments.


Assuntos
Animais Recém-Nascidos , Sinais (Psicologia) , Comportamento Materno , Animais , Comportamento Materno/fisiologia , Feminino , Ratos , Masculino , Comportamento Animal/fisiologia , Testosterona/sangue , Ratos Long-Evans , Meio Ambiente , Ratos Sprague-Dawley , Vocalização Animal/fisiologia
18.
Autism Adulthood ; 6(2): 128-140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39144072

RESUMO

Background: The neurodiversity paradigm positions autism as a neurological difference that is disabling in the societal context, shifting away from the traditional medical view of a disorder. Several recent publications recommend use of alternative neuro-affirming language (ANL) instead of traditional medical language (TML) with the aim to increase acceptance of autistic people and reduce prejudice. Examining language use within recent autism literature, including by journal and study characteristics, may offer insight into the influence of these recommendations and current disability discourse. Methods: A systematic review was conducted using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines in autism research from 2021 (n = 2322 articles; 394 journals). Articles were coded according to topic, participants, and use of self-report. Journals were coded by topic, geographic region, and language guidelines. Terminology use was extracted using QDA Miner software. Results: Many articles primarily used TML with a smaller subset primarily using ANL. There was a positive correlation between ANL use and publication date. More ANL was associated with articles on topics of autistic traits, diversity, equity, and inclusion (DEI), or lifespan and that included autistic adults or autistic self-report. More ANL was also found in journals from Australasia or Europe or those that had identify-first language (IFL) guidelines. Less ANL (more TML) was associated with articles on biology/causes or treatment and that included autistic or non-autistic parents, autistic youth, siblings, or other clinical groups, and were published in medical journals. Conclusion: TML continues to largely dominate language choices in autism research, with an emerging shift toward ANL in recent literature. Increased ANL may be facilitated by journal and article language recommendations. Neuro-affirming language was also more likely in articles on topics prioritized by the autistic community, that included autistic adults, and may also be driven by cultural differences. Researchers and practitioners should consider the potential for their language use to impact individual and societal views of autistic people.


Why is this topic important? Language use impacts how groups of people are viewed. Historically, autism was talked about as part of the medical model, which usually focuses on autism symptoms and deficits. The recent neurodiversity paradigm views autism as a difference that could be accepted and supported. Part of this acceptance is using words that describe autism as part of someone's identity and emphasizing individualized strengths or needs. What is the purpose of this article? Several recent papers recommend using alternative neuro-affirming language (ANL) instead of traditional medical language (TML) in autism research. This article summarizes autism language use and examines how certain parts of journals and articles may impact phrasing. What did the authors do? We used guidelines for the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) to gather autism research studies published in 2021. We found 2322 articles from 594 journals. We first summarized how much ANL was in the articles relative to TML. Then, we compared this language use based on the articles' topic and types of participants, and also the journals' field, geographic region, and whether they included guidelines for language use. What were the results of the review? We found that articles primarily used TML, but more recent articles had more ANL. Articles that had more ANL were studies published more recently, were about traits or lifespan experiences (e.g., parenting, work, aging), included autistic adults as participants, from journals with language guidelines specific to disabled or autistic people, or from journals from Australasia or Europe. Articles that had more TML were those about treatments for or biological explanations of autism, included siblings as participants, or were published in medical journals. This means that certain aspects of articles and journals are related to how researchers write about autism. What do the authors recommend? Clinicians and researchers should ask autistic people their preferences surrounding language. Common language when referring to autism may differ based on the topic and participants that are being studied. More research is needed to understand how different terms impact prejudice toward and societal views of autistic people. We should also consider cultural differences in autism views, which influence researchers' terminology use. Journals that wish to accelerate use of ANL should consider adopting explicit guidelines for language use. How will these findings help autistic people now or in the future? This article summarizes how researchers talk about autism, which likely impacts how autistic people are viewed by others. Increasing use of ANL may gradually impact conceptualizations of autism and prejudice regarding autistic people.

19.
J Surg Res ; 302: 347-358, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39146842

RESUMO

INTRODUCTION: Stage III breast cancer is defined as locally advanced breast cancer and is treated with curative intent. Historically, overall survival (OS) did not differ based on treatment sequence (neoadjuvant chemotherapy [NAC] followed by surgery versus surgery followed by chemotherapy). Given recent advancements, we examined if treatment sequence may be associated with improved OS in a contemporary cohort of patients with stage III breast cancer. METHODS: Patients aged 18-80 years with prognostic stage III breast cancer who received chemotherapy and surgery were selected from the Surveillance, Epidemiology, and End Results database. Patients were stratified by treatment sequence (NAC versus surgery first). Unadjusted OS and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and compared with log-rank tests. Cox proportional hazards models were used to estimate the association of treatment sequence with OS and BCSS after adjustment for selected covariates. RESULTS: The study included 26,573 patients; median follow-up was 62.0 months (95% confidence interval [CI] 61.0-63.0). Patients receiving NAC had a worse OS and BCSS compared to those who underwent surgery first (5-year OS rates 0.66 versus 0.73; 5-year BCSS rates 0.70 versus 0.77; both log-rank P < 0.001). After adjustment for tumor subtype, receipt of NAC (versus surgery first) remained associated with a worse OS (hazard ratio 1.27, 95% CI 1.2-1.34, P < 0.001) and BCSS (hazard ratio 1.35, 95% CI 1.27-1.43, P < 0.001). CONCLUSIONS: Based on data from patients treated largely before 2020, undergoing surgery first may be associated with improved survival, even after adjustment for known covariates including tumor subtype. These findings may inform treatment when caring for patients with operable, locally advanced breast cancer.

20.
Med Sci Sports Exerc ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39160762

RESUMO

INTRODUCTION: To evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared to an eumenorrheic (EUM) cycle, on maximal strength and power between hormone phases. METHODS: One repetition max (1RM) leg press and bench press, peak force (PF) from knee extension and upright row isometric dynamometry, and power from vertical jump height (VJH) and reactive strength index (RSI; cm/s) were measured in 60 healthy, active women (mean ± standard deviation [SD]; Age: 26.5 ± 7.0 yrs, BMI: 22.5 ± 3.7 kg/m2) who were monophasic OC users for ≥6 months (n = 21), had a H-IUD for ≥6 months (n = 20), or had regularly naturally occurring menstrual cycle for ≥3 months or were using a non-hormonal IUD (EUM; n = 19). Participants were randomly assigned to begin in the follicular phase/placebo pill (low hormone phase; LHP) or in the luteal phase/active pill (high hormone phase; HHP) and were tested once in each phase. Estimates of total lean mass (LM), leg LM, and arm LM were measured via dual energy x-ray absorptiometry. Separate univariate ANCOVAs were used to assess the change from HHP to LHP between groups, with LM and progesterone as covariates. RESULTS: Leg press 1RM was significantly different across phases between groups (p = 0.027), with higher leg press 1RM in the HHP for the OC group (mean difference[∆HHP-LHP] ± standard error: ∆7.4 ± 15.9 kg; p = 0.043) compared to the H-IUD group (∆-8.9 ± 23.8 kg; p = 0.043). All groups demonstrated similar bench press 1RM, PF, VJH, and RSI between phases (p > 0.05). CONCLUSIONS: Lower body strength was greater in the HHP for OC users (5.6% increase) suggesting lower body maximal strength outcomes may be influenced by hormonal contraception type.

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