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1.
Cell ; 181(7): 1596-1611.e27, 2020 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-32559461

RESUMEN

Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction. VIDEO ABSTRACT.


Asunto(s)
Ácido Araquidónico/análisis , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Eicosanoides/metabolismo , Animales , Ácido Araquidónico/metabolismo , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/genética , Citosol/metabolismo , Eicosanoides/fisiología , Activación Enzimática , Femenino , Humanos , Metabolismo de los Lípidos/fisiología , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Redes y Vías Metabólicas/genética , Redes y Vías Metabólicas/fisiología , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfolipasas A2/metabolismo , Fosforilación , Proteína Quinasa C/metabolismo , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Nature ; 630(8018): 984-993, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38926615

RESUMEN

Genomic rearrangements, encompassing mutational changes in the genome such as insertions, deletions or inversions, are essential for genetic diversity. These rearrangements are typically orchestrated by enzymes that are involved in fundamental DNA repair processes, such as homologous recombination, or in the transposition of foreign genetic material by viruses and mobile genetic elements1,2. Here we report that IS110 insertion sequences, a family of minimal and autonomous mobile genetic elements, express a structured non-coding RNA that binds specifically to their encoded recombinase. This bridge RNA contains two internal loops encoding nucleotide stretches that base-pair with the target DNA and the donor DNA, which is the IS110 element itself. We demonstrate that the target-binding and donor-binding loops can be independently reprogrammed to direct sequence-specific recombination between two DNA molecules. This modularity enables the insertion of DNA into genomic target sites, as well as programmable DNA excision and inversion. The IS110 bridge recombination system expands the diversity of nucleic-acid-guided systems beyond CRISPR and RNA interference, offering a unified mechanism for the three fundamental DNA rearrangements-insertion, excision and inversion-that are required for genome design.


Asunto(s)
ADN , ARN no Traducido , Recombinación Genética , Emparejamiento Base , Secuencia de Bases , ADN/genética , ADN/metabolismo , Elementos Transponibles de ADN/genética , Mutagénesis Insercional/genética , Recombinasas/metabolismo , Recombinasas/genética , Recombinación Genética/genética , ARN no Traducido/genética , ARN no Traducido/metabolismo
3.
Nature ; 630(8018): 994-1002, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38926616

RESUMEN

Insertion sequence (IS) elements are the simplest autonomous transposable elements found in prokaryotic genomes1. We recently discovered that IS110 family elements encode a recombinase and a non-coding bridge RNA (bRNA) that confers modular specificity for target DNA and donor DNA through two programmable loops2. Here we report the cryo-electron microscopy structures of the IS110 recombinase in complex with its bRNA, target DNA and donor DNA in three different stages of the recombination reaction cycle. The IS110 synaptic complex comprises two recombinase dimers, one of which houses the target-binding loop of the bRNA and binds to target DNA, whereas the other coordinates the bRNA donor-binding loop and donor DNA. We uncovered the formation of a composite RuvC-Tnp active site that spans the two dimers, positioning the catalytic serine residues adjacent to the recombination sites in both target and donor DNA. A comparison of the three structures revealed that (1) the top strands of target and donor DNA are cleaved at the composite active sites to form covalent 5'-phosphoserine intermediates, (2) the cleaved DNA strands are exchanged and religated to create a Holliday junction intermediate, and (3) this intermediate is subsequently resolved by cleavage of the bottom strands. Overall, this study reveals the mechanism by which a bispecific RNA confers target and donor DNA specificity to IS110 recombinases for programmable DNA recombination.


Asunto(s)
ADN , ARN no Traducido , Recombinación Genética , Dominio Catalítico , Microscopía por Crioelectrón , ADN/química , ADN/metabolismo , ADN/ultraestructura , Elementos Transponibles de ADN/genética , Modelos Moleculares , Conformación de Ácido Nucleico , Multimerización de Proteína , Recombinasas/química , Recombinasas/genética , Recombinasas/metabolismo , ARN no Traducido/química , ARN no Traducido/genética , ARN no Traducido/metabolismo , ARN no Traducido/ultraestructura , Especificidad por Sustrato
4.
Nat Methods ; 18(9): 1075-1081, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34354266

RESUMEN

Epigenetic editing is an emerging technology that uses artificial transcription factors (aTFs) to regulate expression of a target gene. Although human genes can be robustly upregulated by targeting aTFs to promoters, the activation induced by directing aTFs to distal transcriptional enhancers is substantially less robust and consistent. Here we show that long-range activation using CRISPR-based aTFs in human cells can be made more efficient and reliable by concurrently targeting an aTF to the target gene promoter. We used this strategy to direct target gene choice for enhancers capable of regulating more than one promoter and to achieve allele-selective activation of human genes by targeting aTFs to single-nucleotide polymorphisms embedded in distally located sequences. Our results broaden the potential applications of the epigenetic editing toolbox for research and therapeutics.


Asunto(s)
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Marcación de Gen/métodos , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Alelos , Apolipoproteína C-III/genética , Apolipoproteínas A/genética , Línea Celular , Elementos de Facilitación Genéticos , Humanos , Subunidad alfa del Receptor de Interleucina-2/genética , Proteína MioD/genética , Polimorfismo de Nucleótido Simple , Activación Transcripcional , Globinas beta/genética
5.
Arthroscopy ; 40(1): 55-57, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38123273

RESUMEN

Although many surgeons discard the long head of the biceps (LHB) tendon during arthroscopic rotator cuff repairs, several authors have argued that the LHB tendon may serve as a biologic and structural augment for massive repairs. There are multiple benefits of incorporating the LHB tendon autograft in difficult-to-repair massive rotator cuff tears. First, by maintaining the glenoid origin, the tendon likely retains a significant native blood supply, as well as tenocytes, which may support the healing process. In addition, there are several biomechanical benefits. The LHB may act as a dynamic humeral head depressor since it is still attached to the muscular unit distally. The tendon could also serve as a convergence post, while proving robust tissue for the repair. Also, the LHB tendon may decrease undue tension on the repair, bringing us closer to a tension-free repair. Finally, this may be a cost-conscious technique. One concern, requiring additional investigation, is that some surgeons believe the LHB may be a pain generator in patients with rotator cuff tears. One surgeon's trash is another surgeon's treasure.


Asunto(s)
Lesiones del Manguito de los Rotadores , Humanos , Lesiones del Manguito de los Rotadores/cirugía , Hombro , Tenotomía , Manguito de los Rotadores/cirugía , Tendones/cirugía , Rotura , Artroscopía/métodos
6.
Arthroscopy ; 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38537727

RESUMEN

Diminished hip labral size and tissue quality may be a predictor of poor patient outcomes when a non-augmented primary labral repair is performed. Labral augmentation is an option for patients with hypoplastic or degenerative labral tissue. The optimal graft for augmentation has yet to be identified, and biomechanical research shows no difference in force to suction-seal disruption between dermal allograft and iliotibial band allograft when used to augment the labrum. However, time-zero biomechanical studies do not reflect the biological ability of the graft to heal to surrounding structures, revascularization of the graft, durability of the graft, hip capsular status, and response to functional demands of the patient.

7.
J Pediatr ; 257: 113355, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36822509

RESUMEN

OBJECTIVES: To examine fluidity in sexual orientation identity and behavior among cisgender youth. STUDY DESIGN: Data were analyzed from 5 survey waves of the longitudinal US Growing Up with Media Study (2010-2019). Participants were 989 cisgender youth, aged 13-20 years at baseline, who completed online surveys assessing sexual orientation identity and behavior (gender of sexual partners). Amount of change (mobility) and patterns of change across waves were assessed for identity and behavior. RESULTS: Consistently heterosexual was the most common sexual orientation identity (89%-97% for boys, 80%-90% for girls), followed by gay (3%) for boys, and bisexual (8%) for girls. Sexual minority identities increased (3%-11% for boys, 10%-20% for girls) over time, same-gender sexual behavior also increased. Girls had more identity mobility than boys; no gender difference was found for behavior mobility. Movement from heterosexual to a sexual minority identity occurred for 9% of girls and 6% of boys; movement from different-gender sexual behavior to same-gender sexual behavior occurred for 2% of girls and boys. CONCLUSIONS: Findings highlight the need to assess multiple dimensions and patterns of change of youth sexual orientation in research and clinical care. Recognizing and creating space for conversations about changes in sexual identity and behavior over time will help providers accurately and effectively address the health needs of all patients.


Asunto(s)
Conducta Sexual , Minorías Sexuales y de Género , Humanos , Masculino , Adolescente , Femenino , Heterosexualidad , Parejas Sexuales , Identidad de Género
8.
J Immunol ; 206(2): 446-451, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33277386

RESUMEN

Human regulatory T cells (Tregs) have been implicated in cancer immunotherapy and are also an emerging cellular therapeutic for the treatment of multiple indications. Although Treg stability during ex vivo culture has improved, methods to assess Treg stability such as bisulfite Sanger sequencing to determine the methylation status of the Treg-specific demethylated region (TSDR) have remained unchanged. Bisulfite Sanger sequencing is not only costly and cumbersome to perform, it is inaccurate because of relatively low read counts. Bisulfite next-generation sequencing, although more accurate, is a less accessible method. In this study, we describe the application of methylation-sensitive restriction enzymes (MSRE) and quantitative PCR (qPCR) to determine the methylation status of the TSDR. Using known ratios of Tregs and non-Tregs, we show that MSRE-qPCR can distinguish the methylation status of the TSDR in populations of cells containing increasing proportions of Tregs from 0 to 100%. In a comparison with values obtained from an established bisulfite next-generation sequencing approach for determining the methylation status of the TSDR, our MSRE-qPCR results were within 5% on average for all samples with a high percentage (>70%) of Tregs, reinforcing that MSRE-qPCR can be completed in less time than other methods with the same level of accuracy. The value of this assay was further demonstrated by quantifying differences in TSDR methylation status of Tregs treated with and without rapamycin during an ex vivo expansion culture. Together, we show that our novel application of the MSRE-qPCR to the TSDR is an optimal assay for accurate assessment of Treg purity.


Asunto(s)
Islas de CpG/genética , Enzimas de Restricción del ADN/metabolismo , Reacción en Cadena de la Polimerasa/métodos , Linfocitos T Reguladores/inmunología , Células Cultivadas , Metilación de ADN , Desmetilación , Factores de Transcripción Forkhead/metabolismo , Regulación de la Expresión Génica , Humanos , Inmunofenotipificación , Especificidad de Órganos , Cultivo Primario de Células
9.
Arthroscopy ; 39(1): 29-31, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36543419

RESUMEN

Optimal treatment of irreparable rotator cuff tears is still debated. Proponents of the superior capsule reconstruction (SCR) have previously used fascia lata autograft and acellular dermal allograft. Interest is growing in using fascia lata allograft as a new graft material. Well-designed biomechanical studies are important to understand the mechanical properties of the superior capsular tissue and fascia lata allograft. Recent biomechanical research shows that fascia lata allograft has similar initial stiffness (over the first 2 mm) and ultimate load compared to the native superior capsule. That said, ultimate load is the load at which a construct fails, whereas the yield point is the load on the stress-strain curve at which a material transitions from elastic to plastic deformation. In the shoulder where the SCR, for example, is going to be repetitively loaded, it is potentially more meaningful to talk about the yield point in order to stay within the elastic range. Using this framework, the yield point for fascia lata allograft is approximately one third the yield point of native capsular tissue. Additionally, "initial" stiffness is not the entire story. At greater loads, fascia lata allograft has higher displacement compared to native tissue. Of importance, fascia lata allograft failed by sutures slowly cutting through the allograft tissue; this may represent a limitation of the construct that could be addressed using stitch configurations resistant to cut through. Fascia lata allograft is a promising solution for SCR. Biomechanical studies require nuanced interpretation, and most of all, do not evaluate clinical healing.


Asunto(s)
Lesiones del Manguito de los Rotadores , Articulación del Hombro , Humanos , Lesiones del Manguito de los Rotadores/cirugía , Hombro , Fascia Lata/trasplante , Articulación del Hombro/cirugía , Rango del Movimiento Articular , Aloinjertos
10.
Aging Ment Health ; 27(8): 1609-1618, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36415908

RESUMEN

Objectives: Mental health concerns (e.g. depression, anxiety) that negatively impact gay, bisexual, and other men who have sex with men (GBMSM) persist over the life course and into old age, but less is known about potential contributors to GBMSM's mental health. Close relationships can be a source of risk or resilience from stress, exerting direct relationships on mental health, and may mediate well-established associations between minority stress and mental health. This study examined whether primary partner relationship support and strain were uniquely associated with, and mediated the association between internalized homophobia, and mental health among older GBMSM.Methods: GBMSM (N = 517, M age = 60) from the Multicenter AIDS Cohort Study, who were in primary relationships with men, provided self-report data at four timepoints. We used multilevel modeling to examine longitudinal associations among relationship support and strain and internalized homophobia with depression and anxiety.Results: Relationship strain, but not support, was positively associated with mental health concerns longitudinally. There was a significant, positive indirect effect of internalized homophobia on depression and anxiety through strain, but no support. Internalized homophobia was positively associated with relationship strain, which was positively associated with mental health symptoms longitudinally.Conclusions: Relationship strain was associated with depression and anxiety longitudinally among middle-aged and older GBMSM and mediated associations of internalized homophobia with mental health. The role of partner support warrants further investigation. Mental health interventions are critically needed for older GBMSM and, for partnered GBMSM, should include strategies for reducing relationship strain to foster well-being.

11.
J Sex Med ; 19(3): 521-528, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35090838

RESUMEN

INTRODUCTION: Knowledge about sexual health is a key determinant of sexual behavior among adolescent sexual minority males (ASMM). No measures exist to assess anal sex knowledge, even though anal sex is the primary route by which ASMM acquire sexually transmitted infections (STIs), including a disproportionate burden of human immunodeficiency virus (HIV). AIM: We developed a new measure as a first step toward assessing the prevalence and correlates of anal sex knowledge and potential effects of interventions to improve knowledge. METHODS: Two coders independently outlined domains of knowledge within 2 sex education videos designed to address anal sex knowledge among ASMM. An initial set of 56 items, some duplicative, encompassed all domains. A larger team, including a psychometrician, then iteratively revised and reduced the set of items, and assessed construct validity via cognitive testing among ASMM (N = 4, aged 16-17 years old, 75% identifying as racial/ethnic minorities). For the final set of 10 items, factor structure and convergent and divergent validity were assessed using baseline responses to an online survey within a randomized controlled pilot trial among 154 ASMM. Open-ended questions assessed their comprehension and the acceptability of items. OUTCOMES: We examined correlates that we anticipated would be theoretically related (ie, the HIV Knowledge Questionnaire [HIV-KQ-18] and the STD-Knowledge Questionnaire [STD-KQ]) and theoretically distinct (ie, the Patient Health Questionnaire [PHQ-2], Generalized Anxiety Disorder scale [GAD-2], and employment status). RESULTS: The one-factor model explained 42% of the items' common variance and demonstrated acceptable internal reliability (Cronbach's alpha = 0.72). The measure withstood tests of convergent and divergent validity when compared to current measures (HIV knowledge, r = 0.35 and STI knowledge, r = 0.24, both P < .05; internalizing mental health symptoms, r = -0.07 and employment status, r = 0.13, both P > .05). Few respondents found words unfamiliar or uncomfortable. CLINICAL IMPLICATIONS: A method for assessing anal sex knowledge may offer opportunities to intervene to lessen harmful sequelae of a lack of knowledge. STRENGTH & LIMITATIONS: We developed a brief, psychometrically valid measure of anal sex knowledge. The measure may neither generalize to all anal health knowledge nor to more sexually experienced, older SMM. CONCLUSION: The resulting 10-item, single-factor measure, the Inventory of Anal Sex Knowledge (iASK), is psychometrically sound and addresses the lack of anal sex knowledge measures among ASMM. The iASK can function to assess the prevalence and sequelae of anal sex knowledge among ASMM as well as the impact of interventions targeting anal sex knowledge. Kutner BA, Perry N, Stout C, et al. The Inventory of Anal Sex Knowledge (iASK): A New Measure of Sexual Health Knowledge Among Adolescent Sexual Minority Males. J Sex Med 2022;19:521-528.


Asunto(s)
Infecciones por VIH , Salud Sexual , Minorías Sexuales y de Género , Adolescente , Infecciones por VIH/epidemiología , Humanos , Masculino , Reproducibilidad de los Resultados , Conducta Sexual/psicología
12.
AIDS Behav ; 26(2): 569-583, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34342742

RESUMEN

The Young Men and Media study developed and pilot tested a community-informed, online HIV prevention program for adolescent sexual minority males (ASMM) in the United States. The developed intervention uses nine interactive modules to increase sexual health knowledge, promote critical examination of pornography, and decrease sexual risk among ASMM. Participants (N = 154, age 14-17 years) were recruited online in Spring 2020 and randomized to the intervention (n = 77) or other existing HIV websites (n = 77). Of the 65 intervention participants who logged in to the website, most completed all nine modules and found the content useful (average module score 4.3 out of 5 stars). The intervention also showed improved HIV/STI knowledge, increased pornography knowledge, and reduced beliefs that pornography is an accurate depiction of male-male sex. Results indicate that the Young Men and Media intervention is feasible, acceptable, and may positively impact sexual health outcomes.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Adolescente , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Proyectos Piloto , Conducta Sexual , Estados Unidos/epidemiología
14.
Bioorg Med Chem ; 28(1): 115195, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31761726

RESUMEN

N-acylethanolamine acid amidase (NAAA) inhibition represents an exciting novel approach to treat inflammation and pain. NAAA is a cysteine amidase which preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA is an endogenous agonist of the nuclear peroxisome proliferator-activated receptor-α (PPAR-α), which is a key regulator of inflammation and pain. Thus, blocking the degradation of PEA with NAAA inhibitors results in augmentation of the PEA/PPAR-α signaling pathway and regulation of inflammatory and pain processes. We have prepared a new series of NAAA inhibitors exploring the azetidine-nitrile (cyanamide) pharmacophore that led to the discovery of highly potent and selective compounds. Key analogs demonstrated single-digit nanomolar potency for hNAAA and showed >100-fold selectivity against serine hydrolases FAAH, MGL and ABHD6, and cysteine protease cathepsin K. Additionally, we have identified potent and selective dual NAAA-FAAH inhibitors to investigate a potential synergism between two distinct anti-inflammatory molecular pathways, the PEA/PPAR-α anti-inflammatory signaling pathway,1-4 and the cannabinoid receptors CB1 and CB2 pathways which are known for their antiinflammatory and antinociceptive properties.5-8 Our ligand design strategy followed a traditional structure-activity relationship (SAR) approach and was supported by molecular modeling studies of reported X-ray structures of hNAAA. Several inhibitors were evaluated in stability assays and demonstrated very good plasma stability (t1/2 > 2 h; human and rodents). The disclosed cyanamides represent promising new pharmacological tools to investigate the potential role of NAAA inhibitors and dual NAAA-FAAH inhibitors as therapeutic agents for the treatment of inflammation and pain.


Asunto(s)
Amidohidrolasas/antagonistas & inhibidores , Cianamida/farmacología , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Amidohidrolasas/metabolismo , Animales , Cianamida/síntesis química , Cianamida/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Ratones , Modelos Moleculares , Estructura Molecular , Ratas , Relación Estructura-Actividad
15.
Arch Sex Behav ; 48(8): 2345-2355, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31506866

RESUMEN

Adolescent sexual minority males (ASMM; < 18 years old) do not typically receive sexual education that addresses male-male relationships from traditional sources (i.e., school, parents). Therefore, many rely on sexually explicit online media (SEOM; i.e., pornography) to find sexual health information. The current study describes SEOM use by ASMM in the U.S. and examined the association between exposure to condomless anal sex (CAS) in SEOM and engagement in CAS. In 2017, ASMM (N = 206; M age = 16, range: 14-17; 51% racial/ethnic minorities) from across the U.S. completed an online sexual health survey, including questions about SEOM use and sexual behaviors. Most (86%) reported that they had viewed SEOM. Engagement with SEOM was frequent (86% reported viewing ≥ one time per week) and lengthy (70% reported viewing for ≥ 15 min per session). Youth perceived that SEOM influenced how they, and other ASMM, think and behave sexually. Further, exposure to risky sexual behavior in SEOM appeared to be associated with youths' dyadic sexual behavior. To support the healthy sexual development of ASMM, it is important to acknowledge the near-universal use of SEOM by ASMM, to identify ways to maximize its potential value, and to minimize potential harms.


Asunto(s)
Homosexualidad Masculina/psicología , Conducta Sexual/psicología , Minorías Sexuales y de Género/psicología , Medios de Comunicación Sociales/normas , Adolescente , Humanos , Masculino , Encuestas y Cuestionarios , Estados Unidos
16.
Scand J Med Sci Sports ; 29(3): 469-475, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30468537

RESUMEN

Training and competition loads have emerged as valuable injury risk factors but very few studies have explored injury outcomes in adolescent athletes. The aims of this study were to describe injuries and to explore the relationship between training and match load volumes and injury in adolescent athletes participating in multiple contact team sports. One hundred and three male youth rugby athletes aged 14-16 years from 8 rugby union teams were prospectively monitored during a season for weekly training and match volumes and injuries. The relationship between volume and injury was explored by comparing the weekly volume in the week prior to an injury vs weeks without injury. There were 83 time-loss injuries in 58 athletes (62%). Overall injury incidence was 18.5 per 1000 player-hours. Mean weekly injury prevalence was 27% (95% CI 25-30). Average weekly volume was 5.4 (2.2) hours comprising 1.4 (1) match hours and 4 (2.6) training hours. Compared with weeks without injury, weeks prior to an injury had higher match volumes (110 [57] min vs 83 [59] min, P < 0.001). Poisson regression demonstrated that match volume was a predictor of injury with an odds ratio of 1.41 (P = 0.001). The contribution of match volumes to injury risk and the relatively high injury burden in these athletes may be profound. Very high match volumes are unlikely to be in the best interests of young athletes and could be avoided with a systematic approach to load management and athlete development.


Asunto(s)
Traumatismos en Atletas/epidemiología , Fútbol Americano/lesiones , Carga de Trabajo , Adolescente , Humanos , Incidencia , Masculino , Acondicionamiento Físico Humano , Prevalencia , Estudios Prospectivos , Factores de Riesgo
17.
J Strength Cond Res ; 33(6): 1463-1466, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30985524

RESUMEN

Delaney, JA, Wileman, TM, Perry, NJ, Thornton, HR, Moresi, MP, and Duthie, GM. The validity of a global navigation satellite system for quantifying small-area team-sport movements. J Strength Cond Res 33(6): 1463-1466, 2019-The recent development of global navigation satellite systems (GNSS) has improved the availability and signal strength of surrounding satellites compared with traditional global positioning systems, although their ability to quantify rapid changes in speed may still be limited. This study aimed to evaluate the validity of GNSS to quantify the mean speed (m·s) and acceleration (m·s) of movements typical to team sports. One participant completed 9 periods of 4 minutes of activity, separated by 2-minute rest periods, which involved walking, jogging, and running in a variety of directions and patterns, aimed to simulate a team-sport movement profile. Speed and acceleration were quantified from a 10-Hz GNSS unit and compared with a 10-camera, 3-dimensional motion capture system (VICON), from which the movement of both the participant's center of mass (COM) and the location of the GNSS unit (e.g., C7 vertebrae) were calculated. Practical estimates of speed were associated with small differences from both the criterion COM (effect size; ±90% confidence limits = 0.19-0.25; ± ∼0.21) and criterion C7 (0.14-0.22; ± ∼0.13). The corresponding estimates of acceleration derived from raw data were classified as small (0.16-0.22; ± ∼0.15) and small to moderate (0.25-0.35; ± ∼0.24) for the COM and C7, respectively. Software-exported acceleration values exhibited very large mean bias compared with both criterion measures (-3.81 to -3.77; ± ∼0.24). This study demonstrates that 10-Hz GNSS possess acceptable validity for assessing the average demands of movements typical of team-sports training and competition, although caution is recommended when using software-exported measures of acceleration.


Asunto(s)
Aceleración , Sistemas de Información Geográfica , Movimiento , Adulto , Humanos , Trote , Masculino , Grabación en Video , Caminata
18.
Psychother Res ; 29(4): 492-502, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-28990883

RESUMEN

OBJECTIVE: The mental health burden among people living with HIV/AIDS (PLWHA) is high and often involves multiple comorbid psychological and substance use-related psychosocial problems. These co-occurring problems, or syndemics, additively impair engagement in HIV disease management. Existing psychotherapies for mental health and HIV health have generally focused on a single psychosocial problem and little research exists to guide future psychotherapies that address multiple mental health issues. METHOD: To address this gap in understanding, we conducted qualitative interviews with multiply comorbid PLWHA (N = 30) who completed cognitive-behavioural therapy (CBT) for depression and medication adherence. RESULTS: Themes emerged regarding participants' perspectives on how overlapping substance use and mood disorders interacted to reduce the benefit of CBT. Substance use was a dominant theme compared to other syndemics, highlighting the need for integrated mental health and substance use interventions. Interviews also suggested modifications of which psychosocial concerns participants felt should be prioritized in treatment delivery. Finally, participants described content they would want in a psychotherapy intervention, including intimacy and sexual health. CONCLUSIONS: Future psychotherapeutic interventions for syndemic problems and HIV self-care will need to comprehensively address complex concerns, including issues salient to the overall well-being of PLWHA. This may improve client engagement and, ultimately, mental, and physical health outcomes. Clinical or methodological significance of this article: Although mental health comorbidity is common and often complex among clients living with HIV, little research exists to guide psychotherapy for such intricate mental health concerns. The current study used content analysis of in-depth qualitative interviews with clients living with HIV and multiple mental health comorbidities who had recently completed cognitive-behavioural therapy. Recommendations based on these findings suggest strategies for clinicians working with similar clients to consider and offers suggestions for future treatment development research.


Asunto(s)
Terapia Cognitivo-Conductual/métodos , Infecciones por VIH/psicología , Cumplimiento de la Medicación/psicología , Trastornos del Humor/terapia , Evaluación de Resultado en la Atención de Salud , Prioridad del Paciente/psicología , Sindémico , Adulto , Comorbilidad , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/epidemiología , Investigación Cualitativa , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapia
19.
Ann Behav Med ; 52(5): 406-411, 2018 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-29684134

RESUMEN

Background: Executive functioning (EF) describes a set of neurocognitive processes critical to enacting complex health behaviors. However, theoretical frameworks for understanding sexual risk behavior have generally neglected neurocognitive constructs, and beyond a few studies of individuals selected for high substance use, the literature contains virtually no research on this topic with other adults at risk for HIV infection, such as men who have sex with men (MSM). Purpose: This study tested whether EF was associated with condomless anal intercourse (CAI) among MSM. Methods: Seventy MSM completed cognitive tests assessing EF at two time points-baseline, and approximately 30 min later after engaging in a stressful interpersonal task. Men also reported their sexual behaviors over the past 3 months, including the frequency of CAI. Results: Baseline EF was unrelated to CAI. However, CAI was associated with the degree to which performance improved from baseline to post-stressor administration. Compared with norms for practice effects, men who reported CAI improved less than expected from baseline to post-stressor EF performance, whereas men who reported no CAI exhibited a more normative practice effect. Conclusions: MSM with histories of greater sexual risk improved less than anticipated from baseline to post-stressor on tests of EF, suggesting that they might be more cognitively depleted by the stressful interpersonal task they engaged in between administrations. It is possible that certain individuals struggle to maintain executive control in stressful interpersonal situations, a finding that could contribute to the difficulty some individuals face executing precautionary behaviors during a sexual encounter.


Asunto(s)
Condones , Función Ejecutiva/fisiología , Homosexualidad Masculina , Relaciones Interpersonales , Asunción de Riesgos , Estrés Psicológico/fisiopatología , Sexo Inseguro/fisiología , Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Fam Process ; 57(2): 308-323, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28328086

RESUMEN

Low-SES couples have limited resources to manage the chronic and acute stressors with which they are disproportionately faced. Although these couples are at greater risk for negative individual and relationship outcomes, evaluations of the impact of couple relationship education (CRE) in low-SES couples have been plagued by methodological problems, most notably challenges associated with recruitment and retention. We review the literature on challenges couples face associated with low-SES, as well as on recruitment, retention, and CRE in low-SES, ethnic minority populations. We illustrate some of these challenges in a case study of CRE for low-SES couples transitioning to parenthood. In this pilot study, 21 couples were recruited from a community health clinic and randomized to either an experimental treatment condition (EXP; N = 11) or a treatment-as-usual control condition (TAU; N = 10). This study sought to mitigate documented challenges with recruitment and retention: We leveraged community partnerships, attempted to build and maintain strong relationships with study participants, provided incentives for assessments as well as intervention meetings, and attempted to reduce potential barriers to enrollment and retention. Nonetheless, we had low rates of recruitment and retention. We integrate these findings and experiences with our review of previous work in this area. We make recommendations for future CRE research and practice that have potential implications for public policy in this area.


Asunto(s)
Composición Familiar/etnología , Grupos Minoritarios/psicología , Selección de Paciente , Pobreza/psicología , Sujetos de Investigación/psicología , Adulto , Etnicidad/psicología , Femenino , Humanos , Los Angeles , Masculino , Responsabilidad Parental/psicología , Proyectos Piloto , Adulto Joven
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