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PURPOSE: Co-creation of a citizen-science research initiative with a collaborative team of community members and university-based scientists to address regional disparities in maternal and fetal health outcomes for Black birthing people. DESCRIPTION: Citizen scientist-led projects, where community members actively contribute to each discovery step, from setting a research agenda to collecting data and disseminating results, can extend community participatory research initiatives and help reconceptualize traditional research processes. The Pregnancy Collaborative is a citizen-science research initiative and one of nine scientific committees of The Pittsburgh Study-a longitudinal, community-partnered study designed to bring together collaborators to improve child thriving. ASSESSMENT: Ten community members and five university-based scientists participated during all phases of developing a citizen-scientist collaboration over an initial two-and-a-half-year period. Phases include forming the Pregnancy Collaborative and group research ethics training; co-creating a research agenda grounded in shared principles; and community-partnered data collection, analysis, and dissemination. These phases produced three key co-designed products: (1) a mission and vision statement of the Pregnancy Collaborative, (2) a Collaborative-endorsed research agenda, and (3) a citizen-scientist-executed research survey. CONCLUSION: Lessons learned from the formation of the Pregnancy Collaborative highlight the importance of equitable power distribution through bidirectional knowledge sharing and by centering intellectual effort, lived experience, and tools and resources of those affected by health inequities. Using a citizen science approach to co-designing and executing research helps us move maternal health inequity work from "research on" to "research with."
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BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders (SSD) are associated with face perception impairments. It is unclear whether impairments are equal across aspects of face perception or larger-indicating a differential impairment-for perceiving emotions relative to other characteristics (eg, identity, age). While many studies have attempted to compare emotion and non-emotion face perception in SSD, they have varied in design and produced conflicting findings. Additionally, prior meta-analyses on this topic were not designed to disentangle differential emotion impairments from broader impairments in face perception or cognition. We hypothesize that SSD-related impairments are larger for emotion than non-emotion face perception, but study characteristics moderate this differential impairment. STUDY DESIGN: We meta-analyzed 313 effect sizes from 104 articles to investigate if SSD-related impairments are significantly greater for emotion than non-emotion face perception. We tested whether key study characteristics moderated these impairments, including SSD severity, sample intelligence matching, task difficulty, and task memory dependency. STUDY RESULTS: We found significantly greater impairments for emotion (Cohen's dâ =â 0.74) than non-emotion face perception (dâ =â 0.55) in SSD relative to control samples, regardless of SSD severity, intelligence matching, or task difficulty. Importantly, this effect was obscured when non-emotion tasks used a memory-dependent design. CONCLUSIONS: This is the first meta-analysis to demonstrate a differential emotion impairment in SSD that cannot be explained by broader impairments in face perception or cognition. The findings also underscore the critical role of task matching in studies of face perception impairments; to prevent confounding influences from memory-dependent task designs.
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Antimicrobial resistance is a global health concern. As such, there have been increased efforts to monitor and standardize antimicrobial prescribing practices in humans and domestic animals. In contrast, there is relatively little known about specific prescribing practices in wild animals despite the wide use of antimicrobials and other microbial interventions, such as probiotics to treat captive wildlife. Therefore, the goal of this study was to examine current antimicrobial and probiotic use from a cross-section of wildlife rehabilitation facilities in the United States. An anonymous electronic survey was sent to 105 United States permitted wildlife facilities to collect information about admissions, current antimicrobial and probiotic use practices, and current staff knowledge and attitudes surrounding antimicrobial resistance and probiotic effectiveness. Respondents from over 50% of facilities participated in the survey (54/105), including 45 facilities that treated birds. All facilities reported using antimicrobials, including some from groups considered critically important for human medicine, for a wide range of medical conditions and prophylaxis. Among antibiotics, enrofloxacin and amoxicillin-clavulanic acid were the most commonly used. Antifungals were not as widespread, but itraconazole was the most commonly used. Over 75% of respondents said that their facilities would benefit from having standardized antimicrobial guidelines in place. Probiotics were also used in more than 50% of facilities, but there was notable disparity in opinions regarding their efficacy. The results of this survey are a first step towards understanding antimicrobial and probiotic use practices in the treatment of captive wildlife and developing an antimicrobial stewardship program for wildlife rehabilitation.
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Animales Salvajes , Probióticos , Animales , Estados Unidos , Encuestas y Cuestionarios , Humanos , Antiinfecciosos/uso terapéutico , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Aged Care Assessment Teams are the assessment component of the Australian aged care system. Their purpose is to undertake needs-based assessments to determine an older person's eligibility for, and access to Commonwealth-funded aged care services. There are no measures that tell us if the aged care assessment service is of high quality from the perspective of the person being assessed. Quality measures have been developed and introduced in Australian residential aged care facilities. These however, have not considered the perspectives of those living in this setting. Quality measures for home care services have also been recommended. This research aims to address the gap in person-centred quality measures by asking current and future service users of aged care assessment services to vote on the importance of 24 person-centred quality indicators (PC-QIs), that were developed in a previous study using a modified Delphi method approach supported by engagement with a consumer led Advisory Board. METHODS: This mixed methods study used the RAND/UCLA Appropriateness Method to reach consensus on a final set of PC-QIs. Twenty-five community-dwelling older people in Brisbane, Australia, voted on the importance of 24 PC-QIs using a five-point Likert scale. A consensus statement for PC-QI elimination was determined prior to participants voting. Voting was undertaken with participants individually either face-to-face or via telephone, in their homes. To capture any narrative provided by participants regarding each PC-QI, participant voting sessions were audio-recorded and subsequently transcribed verbatim. Quantitative data from participant votes for each PC-QI were calculated and statistically described by median, interquartile range, consensus met, percentile, percentile rank, rank order, median and standard deviation. PC-QIs were then assessed against the consensus statement for elimination and rank ordered according to importance to participants. Content analysis of qualitative data from audio transcriptions was conducted to determine the presence of certain words supporting participant votes for each PC-QI. RESULTS: No PC-QIs were eliminated during voting. Variation existed among participants' ratings of importance for each PC-QI. Final quality domains, their respective title, quality indicator descriptor and supporting qualitative data are presented. Five PC-QIs had a median of five, no votes recorded below four, an interquartile range of zero, and a rank order score of one, two and four, out of a possible ten, indicating they were of highest importance to participants. CONCLUSION: Participants reached consensus on 24 evidence-based PC-QIs that represent measures of quality of aged care assessment services from the perspectives of current and future service users.
In Australia, people 65 years or over, and Aboriginal and Torres Strait Islander Peoples 50 years or over, can apply to access aged care services funded by the Australian government (Australian Government, Department of Health and Aged Care. 2021-2022 Report on the Operation of the Aged Care Act 1997, 2022). Services the government funds include supporting older people to live at home, residential aged care if the person can't live at home, and short-term rehabilitation (Australian Government, Department of Health and Aged Care. 2021-2022 Report on the Operation of the Aged Care Act 1997, 2022). To access these services, a person needs to fill out an application form and undergo an aged care assessment. Another person can help complete the application. The purpose of the aged care assessment is to assess the person's needs to determine what aged care services they are eligible to access. There are no measures that tell us if the aged care assessment service is of high quality from the perspective of the person being assessed. Twenty-four measures of quality were developed in a previous study with support from a consumer Advisory Board (Smith S, Travers C, Roberts N, MartinKhan M. Health Expect, 2024). This study asked 25 older people living in Brisbane, the importance of the 24 measures, to decide if any should be eliminated. People were asked to vote using a number scale where number one meant it 'wasn't important', and five meant it was 'extremely important.' A consensus statement was agreed to decide if a measure would be eliminated. All measures were voted as being important with no measure eliminated. Quality Measures voted as being important included receiving assessments from knowledgeable health care staff, who treated them with dignity and respect, adopted a person-centred approach, established a collaborative relationship, and communicated clearly.
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PURPOSE: Sexual and gender diverse youth (SGDY) are at greater risk for adolescent relationship abuse (ARA) than cisgender heterosexual youth, but there are not enough evidence-based interventions for reducing ARA among SGDY. We piloted online human-centered design (HCD) methodology to engage SGDY in generating ARA intervention ideas. This study evaluated the acceptability, appropriateness, and feasibility of the online methods and identified SGDY-derived intervention ideas for reducing ARA. METHODS: From August 2020 through March 2021, we conducted a longitudinal online HCD study with 46 SGDY (aged 14-18 years) recruited via social media from across the United States. SGDY completed HCD activities using MURAL (collaborative digital whiteboard) in four group-based sessions (1.5 hours each) and a follow-up survey with validated measures of acceptability, appropriateness, and feasibility (a priori success benchmarks: means > 3.75 on each five-point scale). RESULTS: SGDY in the sample were 41% racial/ethnic minorities. SGDY rated the online HCD methods as highly acceptable, appropriate, and feasible (means ≥ 4.29). SGDY co-created a breadth of ARA intervention concepts across all social-ecological levels, including commonplace ideas (e.g., curriculum for schools) and novel ideas, such as social media-based interventions to foster healthy relationships, incentivization interventions for performing social justice work, and school plays with SGDY storylines. DISCUSSION: Online HCD methods are acceptable, appropriate, and feasible for designing ARA intervention ideas. The intervention ideas generated in this study can help catalyze ARA intervention research for SGDY. Our method can be transported to other populations and health topics to help advance adolescent health and equity.
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The coronavirus disease 2019 pandemic was a public health emergency that impacted adolescents across the United States and disproportionately affected youth experiencing marginalization due to less access to resources and supports. This study reviews the increases in intimate partner and youth violence during the pandemic, mechanisms contributing to these increases, and the overarching health impacts on adolescents. Pediatric health professionals have a vital role to play in implementing healing-centered practices and prevention efforts that mitigate impacts of trauma and violence and that support youth and families in pathways to healing and recovery.
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COVID-19 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Adolescente , Estados Unidos/epidemiología , Violencia/prevención & control , SARS-CoV-2 , Violencia de Pareja/prevención & control , Pandemias/prevención & controlRESUMEN
Introduction: Economic abuse is one form of intimate partner violence (IPV) intended to control a survivor's ability to make, save, or spend money to gain power over them. Perinatal people may be more vulnerable to economic abuse due to changes in employment and finances. This study's aims were to explore how economic abuse manifests among pregnant and parenting survivors and how best to support pregnant and parenting survivors of economic abuse. Methods: We conducted virtual semistructured interviews with IPV survivors and IPV advocates. Participants were recruited through an online recruitment registry, national IPV organizations, and local domestic violence agencies. Interview audiorecordings were transcribed. We used a deductive-inductive thematic analysis approach. Two research team members individually coded each transcript and met to resolve discrepancies in coding. Results: We completed interviews with 18 advocates and 20 survivors. Participants described experiences of financial control, exploitation, and employment sabotage. Partners leveraged the criminal-legal, child welfare, and health care systems and cultural norms about pregnancy, including those related to gender and religion to financially harm survivors. Advocates described how economic abuse impacts marginalized survivors. Dream resources described include cash assistance, healthy relationship and financial education, and employer policies. Discussion: Survivors and advocates reported a variety of experiences with economic abuse during the perinatal period. Future interventions should focus on providing unrestricted cash transfers to survivors, developing education on economic abuse, and creating supportive policies in health care and employment settings. This study highlights the ways that economic abuse specifically impacts perinatal survivors and their children.
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BACKGROUND: This study assessed feasibility constructs of adolescent contraceptive care in the pediatric emergency department (PED), including contraception initiation. METHODS: We conducted a randomized trial in two PEDs with pregnancy-capable adolescents aged 15-18 years who were assigned to enhanced usual care (usual) or same-day initiation (same day). All received counseling and clinic referral, but same-day participants could also receive contraception in the PED. We trained PED clinicians in counseling and prescribing. Adolescents and clinicians rated feasibility using five Likert-type items (1 = strongly disagree to 5 = strongly agree) after the session. We assessed PED medication initiation and appropriateness via medical record review and contraception use and side effects at 30 days via adolescent survey. To further explore feasibility, we conducted clinician interviews at study completion; these were audio-recorded, transcribed, and analyzed. We hypothesized contraceptive care would be feasible (defined as average score ≥ 4 across five survey items). RESULTS: We enrolled 37 adolescents (12 in usual and 25 in same-day), mean age was 16.6 years, 73% were Black, and 19% were Hispanic. We trained 27 clinicians. Average feasibility scores were 4.6 ± 0.4 (adolescents) and 4.1 ± 0.8 (clinicians). Eleven (44%) same-day participants initiated contraception in the PED. One adolescent with migraines initially received estrogen-containing pills; this was corrected after discharge. At 30 days, same-day participants were more likely to report contraception use (78% vs. 13%; p = 0.007). One adolescent reported bloating as a side effect. Clinicians enjoyed delivering contraceptive care, found study resource materials useful, and identified staffing shortages as a barrier to care delivery. CONCLUSIONS: We are among the first to report on PED-based adolescent contraception initiation to prevent unintended pregnancy. Adolescents and clinicians reported that contraceptive care was feasible. Initiation was common and medications were largely appropriate and tolerated. Future efforts should explore integrating contraceptive care into routine PED care.
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Sexual minority (e.g., gay/lesbian, bisexual, and queer) students are more likely than their heterosexual peers to experience sexual violence (SV) during college. Interventions that prevent SV and improve SV care-seeking behaviors for sexual minority students are lacking. Giving Information for Trauma Support and Safety (GIFTSS) is an evidence-based universal SV intervention implemented by providers during college health and counseling visits. Compared to controls, GIFTSS participants reported greater self-efficacy to use SV harm reduction strategies and SV disclosure during clinical visits. However, GIFTSS' effectiveness for sexual minority participants is unknown. The current study examines whether sexual orientation moderates GIFTSS' effects on numerous SV-related outcomes (i.e., to test whether intervention effects at 4 and 12 months differed based on sexual orientation). Across 28 college campuses in Pennsylvania and West Virginia, 2,291 students participated in a two-arm cluster-randomized controlled trial. We used mixed models with two- and three-way interaction terms to test whether sexual orientation modified GIFTSS' effects at 4- and 12-month follow-up on participants': SV recognition; knowledge of and self-efficacy to enact SV harm reduction strategies; intentions to intervene; knowledge of and self-efficacy to use SV-related services; SV disclosure during visits; and recent SV exposure. Overall, 22.1% of participants were sexual minorities (n = 507). Sexual orientation moderated GIFTSS effectiveness as indicated by significant three-way interaction (p = .01) at 12-month follow-up, and knowledge of SV services decreased for heterosexual participants (ß = -.23) but increased for sexual minority participants (ß = .23). Our study indicates that universal provider-based education may promote greater knowledge of SV services among sexual minority than heterosexual participants, and population-specific interventions are needed that reduce sexual minority students' SV exposure, service utilization, and other critical aspects of SV prevention on university campuses.Clinical Trial Registration: Registry name: College Health Center-based Alcohol and Sexual Violence Intervention (GIFTSS), Registration number: NCT02355470, Web link: https://clinicaltrials.gov/ct2/show/NCT02355470, Deidentified individual participant data will not be made available.
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Black adolescent males are disproportionally impacted by violence exposure and violent loss. The primary aim of this study was to explore the bereavement experiences of Black adolescent males who have lost a friend or family member to murder. Participants were Black adolescent males between the ages of 14-19 years. This was a purposive sample recruited from a community-based study that took place in urban neighborhoods in Pittsburgh, Pennsylvania. Participants who completed their final survey for the parent study were recruited from January to June 2017. Participants completed a brief computerized survey and those who responded affirmatively to a screening question about losing a friend or family member to murder were invited to a qualitative interview. Interviews were audio recorded, transcribed, and coded to identify key themes. Among the 31 youth interviewed, 30 had lost more than one person to murder. Four primary themes emerged from their narratives: (1) self-preservation through isolation, (2) finding sanctuary through shared narratives of loss, (3) freedom from the mind, and (4) post-traumatic growth (i.e., motivation, healing, resilience). Findings suggest that interventions that provide sanctuary for youth that are culturally relevant and create opportunities for youth to process violent loss may aid in promoting opportunities for youth to grieve and heal from violent loss.
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Aflicción , Negro o Afroamericano , Homicidio , Investigación Cualitativa , Humanos , Masculino , Adolescente , Homicidio/psicología , Homicidio/etnología , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Pennsylvania , Adulto Joven , Víctimas de Crimen/psicología , Víctimas de Crimen/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Introduction: Children and adolescents with elevated internalizing symptoms are at increased risk for depression, anxiety, and other psychopathology later in life. The present study examined the predictive links between two bioecological factors in early childhood-parental hostility and socioeconomic stress-and children's internalizing symptom class outcomes, while considering the effects of child sex assigned at birth on internalizing symptom development from childhood to adolescence. Materials and Methods: The study used a sample of 1,534 children to test the predictive effects of socioeconomic stress at ages 18 and 27 months; hostile parenting measured at child ages 4-5; and sex assigned at birth on children's internalizing symptom latent class outcomes at child ages 7-9, 10-12, 13-15, and 16-19. Analyses also tested the mediating effect of parenting on the relationship between socioeconomic stress and children's symptom classes. Other covariates included parent depressive symptoms at child ages 4-5 and child race and ethnicity. Results: Analyses identified three distinct heterogenous internalizing symptom classes characterized by relative symptom levels and progression: low (35%); moderate and increasing (41%); and higher and increasing (24%). As anticipated, higher levels of parental hostility in early childhood predicted membership in the higher and increasing symptom class, compared with the low symptom class (odds ratio (OR) = .61, 95% confidence interval (CI) [.48,.77]). Higher levels of early childhood socioeconomic stress were also associated with the likelihood of belonging to the higher-increasing symptom class compared to the low and moderate-increasing classes (OR = .46, 95% CI [.35,.60] and OR = .56, 95% CI [.44,.72], respectively). The total (c = .61) and direct (c' = .57) effects of socioeconomic stress on children's symptom class membership in the mediation analysis were significant (p <.001). Discussion: Study findings suggest that intervening on modifiable bioecological stressors-including parenting behaviors and socioeconomic stressors-may provide important protective influences on children's internalizing symptom trajectories.
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Salmonella enterica serovar Typhimurium is one of the top Salmonella serovars annually linked to poultry production and corresponding human illnesses. Because of this, vaccination of commercial poultry against Salmonella Typhimurium has been a focal point in recent years. There are several commercially available Salmonella Typhimurium vaccines available for use in poultry production. Among these are modified live vaccines, including Poulvac ST (Zoetis), Megan Egg (AviPro), and Megan Vac 1 (AviPro). In this study, analyses of 27 field isolates of Salmonella Typhimurium from poultry sources indicated evidence for the persistence of some vaccine-origin strains through the commercial production cycle. Further analyses of 26,812 database isolates indicated vaccine-origin isolates are persisting frequently through processing, are present on retail meat products, and are even occasionally found in human patients. A novel polymerase chain reaction (PCR) was created and validated which enables simultaneous identification of Salmonella enterica sp., the Salmonella Typhimurium serovar, and differentiation of wild type Salmonella Typhimurium from live attenuated vaccines involving mutations in the cya/crp or aroA genes. The PCR was developed considering whole genome differences between the vaccines and wild type field isolates and was validated using different field isolates and recovered vaccine strains. This method enables poultry producers to rapidly determine if recovered field isolates have a vaccine origin.
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Pollos , Enfermedades de las Aves de Corral , Salmonelosis Animal , Vacunas contra la Salmonella , Salmonella typhimurium , Animales , Salmonella typhimurium/aislamiento & purificación , Salmonelosis Animal/prevención & control , Salmonelosis Animal/microbiología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/prevención & control , Vacunas contra la Salmonella/inmunología , Reacción en Cadena de la Polimerasa/veterinaria , Vacunas Atenuadas , SerogrupoRESUMEN
Persons with amyotrophic lateral sclerosis (PALS) are at risk of developing cognitive impairments and frontotemporal dementia (FTD). This study examined the relationship between performance of the ALS-Cognitive Behavioral Screen (ALS-CBS) and the demographic parameters of sex, education, time post-ALS diagnosis, and severity of symptoms. Data were collected retrospectively from 69 participants seen at the Mayo Clinic. Correlations were conducted on the ALS-CBS total scores and subsection scores and the above listed parameters; t-tests were conducted between participant subgroups. No statistically significant relationships or differences occurred between the ALS-CBS or its subsections and the variables measured with exception of age and the attention subsection. Older participants had lower ALS-CBS attention subsection scores. Based on the ALS-CBS scores, most participants had some degree of cognitive impairments: 43 had suspected cognitive impairment, 8 had suspected FTD; 18 fell within the normal range of cognitive function. Overall, the variables of sex, education, time post-diagnosis, and severity of symptoms do not appear to influence ALS-CBS scores. It is recommended cognitive screenings be completed for all PALS due to the high risk for developing cognitive impairments and FTD. Such knowledge can help clinicians develop assessment and treatment plans.
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Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Disfunción Cognitiva/diagnóstico , Pruebas Neuropsicológicas , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/psicología , Adulto , Anciano de 80 o más AñosRESUMEN
Importance: Youths with type 2 diabetes are at higher risk for complications compared with peers with type 1 diabetes, though few studies have evaluated differences in access to specialty care. Objective: To compare claims with diabetes specialists for youths with type 1 vs type 2 diabetes and the association between specialist claims with multidisciplinary and acute care utilization. Design, Setting, and Participants: This cross-sectional study used Optum Clinformatics Data Mart commercial claims. Individuals included in the study were youths younger than 19 years with type 1 or 2 diabetes as determined by a validated algorithm and prescription claims. Data were collected for youths with at least 80% enrollment in a commercial health plan from December 1, 2018, to December 31, 2019. Statistical analysis was performed from September 2022 to January 2024. Main Outcomes and Measures: The primary outcome was the number of ambulatory claims from an endocrine and/or diabetes physician or advanced practice clinician associated with a diabetes diagnosis code; secondary outcomes included multidisciplinary and acute care claims. Results: Claims were analyzed for 4772 youths (mean [SD] age, 13.6 [3.7] years; 4300 [90.1%] type 1 diabetes; 472 [9.9%] type 2 diabetes; 2465 [51.7%] male; 128 [2.7%] Asian, 303 [6.4] Black or African American, 429 [9.0%] Hispanic or Latino, 3366 [70.5%] non-Hispanic White, and 546 [11.4%] unknown race and ethnicity). Specialist claims were lower in type 2 compared with type 1 diabetes (incidence rate ratio [IRR], 0.61 [95% CI, 0.52-0.72]; P < .001) in propensity score-weighted analyses. The presence of a comorbidity was associated with increased specialist claims for type 1 diabetes (IRR, 1.07 [95% CI, 1.03-1.10]) and decreased claims for type 2 diabetes (IRR, 0.77 [95% CI, 0.67-0.87]). Pooling diagnosis groups and adjusted for covariates, each additional specialist claim was associated with increased odds of a claim with a diabetes care and education specialist (odds ratio [OR], 1.31 [95% CI, 1.25-1.36]), dietitian (OR, 1.14 [95% CI, 1.09-1.19]), and behavioral health clinician (OR, 1.16 [95% CI, 1.12-1.20]). For acute care claims, each additional specialist claim was associated with increased odds of admission (OR, 1.17 [95% CI, 1.11-1.24]) but not for emergency claims (OR, 1.03 [95% CI, 0.98-1.82]). Conclusions and Relevance: This cross-sectional study found that youths with type 2 diabetes were significantly less likely to have specialist claims despite insurance coverage, indicating other barriers to care, which may include medical complexity. Access to diabetes specialists influences engagement with multidisciplinary services. The association between increasing ambulatory clinician services and admissions suggests high utilization by a subgroup of patients at greater risk for poor outcomes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Adolescente , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicaciones , Estudios Transversales , Estudios Retrospectivos , EtnicidadRESUMEN
The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes. Membrane binding is required for relief of Sly1 autoinhibition and also allows Sly1 to directly tether incoming vesicles to the Qa-SNARE on the target organelle. The SLY1-20 mutation bypasses requirements for diverse tethering factors but loses this ability if the tethering activity is impaired. We propose that long-range tethers, including Golgins and multisubunit tethering complexes, hand off vesicles to Sly1, which then tethers at close range to initiate trans-SNARE complex assembly and fusion in the early secretory pathway.
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Vesículas Citoplasmáticas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Animales , Aparato de Golgi/genética , Aparato de Golgi/metabolismo , Mamíferos/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas Munc18/análisis , Proteínas Munc18/genética , Proteínas Munc18/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Vesículas Citoplasmáticas/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismoRESUMEN
PURPOSE: The purpose of this study was to identify factors affecting contraceptive intention and behavior among adolescent females in the pediatric Emergency Department. METHODS: We conducted a qualitative interview study nested within a larger prospective cohort study examining adolescent contraceptive counseling for females ages 15-18 years at-risk of unintended pregnancy presenting to the pediatric Emergency Department. Interviews were conducted in a subset of participants. The ecologically expanded Theory of Planned Behavior, expert opinion, and literature review informed the interview guide. Interviews were recorded, transcribed, coded and monitored for thematic saturation. RESULTS: Twenty-eight interviews were analyzed. Mean age was 17.1 years. Themes were mapped to ecologically expanded Theory of Planned Behavior constructs. Within health system influences, prior contraceptive experiences and patient-clinician interactions were described. Within community influences, contraceptive education, knowledge and misinformation, teen pregnancy norms, and social media impacts were described. Within attitudes influences, side-effect and safety concerns, contraceptive motivations and teen pregnancy beliefs were described. Within subjective norm influences, peer and family impacts were described. Within perceived behavioral control, Emergency Department (ED) counseling intervention impacts were described. DISCUSSION: We identified factors affecting contraceptive initiation/behavior among an ED adolescent population that otherwise may not have received contraceptive education in similar detail as provided by study clinicians. Adolescents' prior contraceptive and clinician interactions, limited access to contraceptive education, knowledge and misinformation, and side-effect and safety concerns affected initiation. Peer/family sharing and social media were leading contraceptive information sources. Future studies should incorporate insights into adolescent ED intervention design to make optimal use of resources while maximizing potential benefit.
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Conducta Anticonceptiva , Servicio de Urgencia en Hospital , Embarazo en Adolescencia , Humanos , Adolescente , Femenino , Embarazo , Embarazo en Adolescencia/prevención & control , Conducta Anticonceptiva/psicología , Conocimientos, Actitudes y Práctica en Salud , Investigación Cualitativa , Estudios Prospectivos , Conducta del Adolescente/psicología , Entrevistas como Asunto , Anticoncepción/psicología , ConsejoRESUMEN
Background: Head and neck squamous cell carcinoma (HNSCC) is a lethal disease with poor survival rates, especially for cancers arising in the oral cavity or larynx. Cisplatin is a key chemotherapeutic for HNSCC; however poor survival rates may be partially due to cisplatin resistance observed in some HNSCCs. Here, we examined the utility of genome-wide CRISPR knockout profiling for nominating pivotal mechanisms of cisplatin resistance in HNSCC models. Methods: We characterized the cisplatin sensitivity of 18 HNSCC cell lines. Next, we used a genome-wide CRISPR/Cas9 library to identify genes involved in cisplatin resistance. We next performed validation assays in the UM-SCC-49 cell line model. Results: Our data prioritized 207 genes as pivotal for cisplatin resistance in HNSCC, including novel genes VGLL3, CIRHA1, NCOR1, SPANXA1, MAP2K7, ULK1, and CDK16. Gene set enrichment analysis identified several NOTCH family genes comprising the top pathway driving cisplatin resistance, which we then validated using a targeted NOTCH1 knockout model. Interestingly, we noted that HNSCC models with natural NOTCH pathway alterations including single allele mutations and/or frameshift alterations had diverse responses to cisplatin treatment suggesting that complex and multi-faceted mechanisms contribute to cisplatin resistance in HNSCC. Conclusions: Collectively, our study validates a genome-wide CRISPR/Cas9 approach for the discovery of resistance mechanisms in HNSCC, adds to the growing evidence that NOTCH1 status should be evaluated as a biomarker of cisplatin response and provides a framework for future work aimed at overcoming cisplatin resistance.
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BACKGROUND: Sexual and gender minority youths (lesbian, gay, bisexual, transgender, nonbinary, and queer individuals) face elevated risks of substance use (eg, alcohol and tobacco) and mental health issues (eg, depressive symptoms and suicidality) compared to their cisgender heterosexual peers. These inequities are hypothesized to be reduced by building supportive high school environments via the training of school staff. An intervention that trains school staff to better understand and support sexual and gender minority youths and engage in positive bystander behaviors that protect them from bullying exposure may reduce disparities in drug and alcohol use among them. Experts, school staff, and sexual and gender minority youths developed Providing LGBTQ+ Adolescents with Nurturance, Trustworthiness, and Safety (PLANTS), a web-based intervention to train school staff on how to support, affirm, and protect sexual and gender minority youths. OBJECTIVE: This paper describes the design of the PLANTS pilot trial primarily aimed at assessing its acceptability, usability, appropriateness, and feasibility. We hypothesize PLANTS will have high acceptability, usability, appropriateness, and feasibility as rated by the school staff. Secondary objectives focus on implementation, safety, and pre-post changes in high school staff outcomes, including self-efficacy and skills (eg, active-empathic listening and bullying intervention). Exploratory objectives focus on the impact of PLANTS on student health outcomes. METHODS: In a 2-arm cluster randomized controlled trial, high schools in Massachusetts are allocated to PLANTS or an active comparator group (publicly available sexual and gender minority youths resources or training). High school staff complete pretest and posttest surveys containing validated scales. Primary outcomes are validated measures of acceptability, usability, appropriateness, and feasibility of the intervention completed by staff during posttest surveys. To test our primary hypotheses for each outcome, we will calculate means and 95% CIs and P values using 1-sample 2-sided t tests against a priori thresholds or benchmarks of success. Secondary outcomes include staff's active-empathetic listening skills, self-efficacy for working with sexual and gender minority youths, bystander intervention behaviors for bullying and cyberbullying, and self-efficacy for PLANTS' change objectives completed during pretest and posttest staff surveys. Staff can also complete a posttest interview guided by the Information-Motivation-Behavior model and Consolidated Framework for Implementation Research. Exploratory outcomes include student-level data collected via the 2021 and 2023 MetroWest Adolescent Health Surveys, a health behavior surveillance system in 30 Massachusetts schools. RESULTS: School enrollment began in May 2023 and participant enrollment began in June 2023. Data collection is expected to be completed by February 2024. CONCLUSIONS: This pilot trial will yield important information about the PLANTS intervention and provide necessary information to conduct a fully powered trial of the efficacy of PLANTS for reducing the deleterious health inequities experienced by sexual and gender minority youths. TRIAL REGISTRATION: ClinicalTrials.gov NCT05897827; https://clinicaltrials.gov/study/NCT05897827. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55210.