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1.
Cureus ; 16(3): e56637, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38646322

RESUMEN

Cytomegalovirus (CMV) retinitis is commonly associated with immunosuppression and can cause irreversible vision loss. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective cancer treatment option but requires immunosuppression, thereby increasing the possibility of acquiring opportunistic infections such as CMV. We present the case of a 76-year-old female with a history of hypertension and type 2 diabetes mellitus who initially presented with shortness of breath and was diagnosed with the activated B-cell subset of diffuse large B-cell lymphoma (DLBCL). She received multiple cycles of chemotherapy and experienced relapses with cardiac involvement. The patient developed vision loss in the right eye and was diagnosed with bilateral posterior vitritis. She underwent various treatments, including radiotherapy, systemic chemotherapy, cataract extraction, and vitrectomy. After CAR-T therapy, she developed bilateral CMV retinitis, confirmed through polymerase chain reaction testing and managed by valganciclovir. Overall, this case report describes the first reported case of bilateral CMV retinitis following CAR-T therapy for DLBCL. It emphasizes the need for early recognition and treatment of CMV retinitis to prevent permanent vision loss. The report also underscores the importance of regular ocular screening and consideration of prophylactic measures in patients undergoing CAR-T therapy.

2.
bioRxiv ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38559081

RESUMEN

Problem: All trainees, especially those from historically minoritized backgrounds, experience stresses that may reduce their continuation in science, technology, engineering, math, and medicine (STEMM) careers. The Johns Hopkins University School of Medicine is one of ~45 institutions with a National Institutes of Health funded Postbaccalaureate Research Education Program (PREP) that provides mentoring and a year of fulltime research to prepare students from historically excluded groups for graduate school. Having experienced the conflation of stresses during the COVID-19 pandemic and related shutdown, we realized our program lacked a component that explicitly helped PREP Scholars recognize and cope with non-academic stresses (financial, familial, social, mental) that might threaten their confidence and success as scientists and future in STEMM. Intervention: We developed an early-intervention program to help Scholars develop life-long skills to become successful and resilient scientists. We developed a year-long series comprised of 9 workshops focused on community, introspection, financial fitness, emotional intelligence, mental health, and soft-skills. We recruited and compensated a cohort of PhD students and postdoctoral fellows to serve as Peer Mentors, to provide a community and the safest 'space' for Scholars to discuss personal concerns. Peer Mentors were responsible for developing and facilitating these Community-Building Wellness Workshops (CBWW). Context: CBWW were created and exectued as part of the larger PREP program. Workshops included a PowerPoint presentation by Peer Mentors that featured several case studies that prompted discussion and provided time for small-group discussions between Scholars and Peer Mentors. We also included pre- and post-work for each workshop. These touch-points helped Scholars cultivate the habit of introspection. Impact: The CBWW exceeded our goals. Both Peer Mentors and Scholars experienced strong mutual support, and Scholars developed life-long skills. Notably, several Scholars who had been experiencing financial, mental or mentor-related stress immediately brought this to the attention of program leadership, allowing early and successful intervention. At the completion of CBWW, PREP Scholars reported implementing many workshop skills into practice, were reshaping their criteria for choosing future mentors, and evaluating career decisions. Strikingly, Peer Mentors found they also benefitted from the program as well, suggesting a potential larger scope for the role of CBWW in academia. Lessons Learned: Peer Mentors were essential in creating a safe supportive environment that facilitated discussions, self-reflection, and self-care. Providing fair compensation to Peer Mentors for their professional mentoring and teaching contributions was essential and contributed meaningfully to the positive energy and impact of this program.

3.
J Affect Disord ; 354: 302-308, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38479502

RESUMEN

BACKGROUND: Parenting stress has long been proposed as a major risk factor for child maltreatment. However, there is a lack of evidence from existing studies on the temporal sequence to establish a causal relationship. This study aims to examine bidirectional temporal relationships between parenting stress and child maltreatment. METHODS: Longitudinal data from two different sources were analysed: a pre-post study of an online parenting programme conducted across six countries - the ePLH Evaluation Study, and a prospective cohort study in the United States - LONGSCAN. Cross-lagged panel model on parenting stress and child maltreatment was used in each dataset. RESULTS: Based on repeatedly measured data of 484 caregivers in the ePLH study across five time points (every two weeks), we found that parenting stress at an earlier time point predicted later child maltreatment (IRR = 1.14, 95 % CI: 1.10,1.18). In addition, the occurrence of child maltreatment was associated with higher subsequent short-term parenting stress (IRR = 1.04, 95 % CI: 1.01,1.08) and thus could form a vicious circle. In the LONGSCAN analysis with 772 caregivers who were followed up from child age of 6 to child age of 16, we also found parenting stress at an earlier time point predicted later child maltreatment (ß = 0.11, 95 % CI: 0.01,0.20), but did not observe an association between child maltreatment and subsequent long-term parenting stress. LIMITATIONS: Potential information bias on the measurements. CONCLUSIONS: This study provides evidence for a bidirectional temporal relationship between parenting stress and child maltreatment, which should be considered in parenting intervention programmes.


Asunto(s)
Maltrato a los Niños , Responsabilidad Parental , Niño , Humanos , Estudios Prospectivos , Cuidadores
4.
J Clin Invest ; 134(5)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426503

RESUMEN

Tissue-intrinsic mechanisms that regulate severity of systemic pathogenic immune-mediated diseases, such as acute graft-versus-host disease (GVHD), remain poorly understood. Following allogeneic hematopoietic stem cell transplantation, autophagy, a cellular stress protective response, is induced in host nonhematopoietic cells. To systematically address the role of autophagy in various host nonhematopoietic tissues, both specific classical target organs of acute GVHD (intestines, liver, and skin) and organs conventionally not known to be targets of GVHD (kidneys and heart), we generated mice with organ-specific knockout of autophagy related 5 (ATG5) to specifically and exclusively inhibit autophagy in the specific organs. When compared with wild-type recipients, animals that lacked ATG5 in the gastrointestinal tract or liver showed significantly greater tissue injury and mortality, while autophagy deficiency in the skin, kidneys, or heart did not affect mortality. Treatment with the systemic autophagy inducer sirolimus only partially mitigated GVHD mortality in intestine-specific autophagy-deficient hosts. Deficiency of autophagy increased MHC class I on the target intestinal epithelial cells, resulting in greater susceptibility to damage by alloreactive T cells. Thus, autophagy is a critical cell-intrinsic protective response that promotes tissue tolerance and regulates GVHD severity.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Animales , Ratones , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/patología , Intestinos/patología , Linfocitos T/patología , Células Epiteliales/patología
5.
Acad Med ; 99(5): 493-499, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38166321

RESUMEN

ABSTRACT: Outcome data from 6 National Institutes of Health-funded Postbaccalaureate Research Education Programs (PREPs) in the Mid-Atlantic region were combined to give a multi-institutional perspective on their scholars' characteristics and progress through biomedical research training. The institutions hosting these programs were Johns Hopkins University School of Medicine, the Medical University of South Carolina, the University of Maryland School of Medicine, the University of North Carolina at Chapel Hill, Virginia Commonwealth University, and Virginia Polytechnic Institute and State University. The authors summarize the institutional pathways, demographics, undergraduate institutions, and graduate institutions for a total of 384 PREP scholars who completed the programs by June 2021. A total of 228 (59.4%) of these PREP scholars identified as Black or African American, 116 (30.2%) as Hispanic or Latinx, and 269 (70.0%) as female. The authors found that 376 of 384 scholars (97.9%) who started PREP finished their program, 319 of 376 (84.8%) who finished PREP matriculated into PhD or MD/PhD programs, and 284 of 319 (89.0%) who matriculated have obtained their PhD or are successfully making progress toward their PhD.


Asunto(s)
Investigación Biomédica , Humanos , Femenino , Masculino , Estados Unidos , Facultades de Medicina/organización & administración , Negro o Afroamericano/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , South Carolina , Adulto , Evaluación de Programas y Proyectos de Salud , Universidades
6.
Curr Opin Cell Biol ; 86: 102313, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38262116

RESUMEN

The nuclear lamina (NL) is a crucial component of the inner nuclear membrane (INM) and consists of lamin filaments and associated proteins. Lamins are type V intermediate filament proteins essential for maintaining the integrity and mechanical properties of the nucleus. In human cells, 'B-type' lamins (lamin B1 and lamin B2) are ubiquitously expressed, while 'A-type' lamins (lamin A, lamin C, and minor isoforms) are expressed in a tissue- and development-specific manner. Lamins homopolymerize to form filaments that localize primarily near the INM, but A-type lamins also localize to and function in the nucleoplasm. Lamins play central roles in the assembly, structure, positioning, and mechanics of the nucleus, modulating cell signaling and influencing development, differentiation, and other activities. This review highlights recent findings on the structure and regulation of lamin filaments, providing insights into their multifaceted functions, including their role as "mechanosensors", delving into the emerging significance of lamin filaments as vital links between cytoskeletal and nuclear structures, chromatin organization, and the genome.


Asunto(s)
Lamina Tipo B , Lámina Nuclear , Humanos , Laminas/metabolismo , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Lámina Nuclear/metabolismo , Membrana Nuclear/metabolismo , Núcleo Celular/metabolismo , Filamentos Intermedios/metabolismo , Diferenciación Celular
7.
Front Cell Dev Biol ; 11: 1240285, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37936983

RESUMEN

Clinical frailty affects ∼10% of people over age 65 and is studied in a chronically inflamed (Interleukin-10 knockout; "IL10-KO") mouse model. Frailty phenotypes overlap the spectrum of diseases ("laminopathies") caused by mutations in LMNA. LMNA encodes nuclear intermediate filament proteins lamin A and lamin C ("lamin A/C"), important for tissue-specific signaling, metabolism and chromatin regulation. We hypothesized that wildtype lamin A/C associations with tissue-specific partners are perturbed by chronic inflammation, potentially contributing to dysfunction in frailty. To test this idea we immunoprecipitated native lamin A/C and associated proteins from skeletal muscle, hearts and brains of old (21-22 months) IL10-KO versus control C57Bl/6 female mice, and labeled with Tandem Mass Tags for identification and quantitation by mass spectrometry. We identified 502 candidate lamin-binding proteins from skeletal muscle, and 340 from heart, including 62 proteins identified in both tissues. Candidates included frailty phenotype-relevant proteins Perm1 and Fam210a, and nuclear membrane protein Tmem38a, required for muscle-specific genome organization. These and most other candidates were unaffected by IL10-KO, but still important as potential lamin A/C-binding proteins in native heart or muscle. A subset of candidates (21 in skeletal muscle, 30 in heart) showed significantly different lamin A/C-association in an IL10-KO tissue (p < 0.05), including AldoA and Gins3 affected in heart, and Lmcd1 and Fabp4 affected in skeletal muscle. To screen for binding, eleven candidates plus prelamin A and emerin controls were arrayed as synthetic 20-mer peptides (7-residue stagger) and incubated with recombinant purified lamin A "tail" residues 385-646 under relatively stringent conditions. We detected strong lamin A binding to peptides solvent exposed in Lmcd1, AldoA, Perm1, and Tmem38a, and plausible binding to Csrp3 (muscle LIM protein). These results validated both proteomes as sources for native lamin A/C-binding proteins in heart and muscle, identified four candidate genes for Emery-Dreifuss muscular dystrophy (CSRP3, LMCD1, ALDOA, and PERM1), support a lamin A-interactive molecular role for Tmem38A, and supported the hypothesis that lamin A/C interactions with at least two partners (AldoA in heart, transcription factor Lmcd1 in muscle) are altered in the IL10-KO model of frailty.

8.
JAMA ; 330(17): 1694-1695, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37934224
9.
FEBS Lett ; 597(22): 2806-2822, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37953467

RESUMEN

Lamina-associated domains are large regions of heterochromatin positioned at the nuclear periphery. These domains have been implicated in gene repression, especially in the context of development. In mammals, LAD organization is dependent on nuclear lamins, inner nuclear membrane proteins, and chromatin state. In addition, chromatin readers and modifier proteins have been implicated in this organization, potentially serving as molecular tethers that interact with both nuclear envelope proteins and chromatin. More recent studies have focused on teasing apart the rules that govern dynamic LAD organization and how LAD organization, in turn, relates to gene regulation and overall 3D genome organization. This review highlights recent studies in mammalian cells uncovering factors that instruct the choreography of LAD organization, re-organization, and dynamics at the nuclear lamina, including LAD dynamics in interphase and through mitotic exit, when LAD organization is re-established, as well as intra-LAD subdomain variations.


Asunto(s)
Núcleo Celular , Lámina Nuclear , Animales , Núcleo Celular/metabolismo , Lámina Nuclear/genética , Lámina Nuclear/metabolismo , Cromatina/genética , Cromatina/metabolismo , Membrana Nuclear , Heterocromatina/genética , Heterocromatina/metabolismo , Mamíferos/genética
10.
Front Microbiol ; 14: 1282949, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37954237

RESUMEN

Introduction: The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses. Methods: A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations. Results: A 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. The fAUC/MIC or fT>MIC were calculated with a free BP fraction set at 0.4. For fAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. For fT>MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, a fT>MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L. Discussion: The PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.

11.
Int J Surg Case Rep ; 111: 108896, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37812959

RESUMEN

INTRODUCTION AND IMPORTANCE: Small bowel diverticular disease (DD) is encountered and managed much less frequently than colonic DD, leading to a significantly less developed body of evidence for managing small bowel diverticulum and its associated complications. CASE PRESENTATION: This case report discusses a rare occurrence of simultaneous perforated jejunal diverticulitis and mechanical small bowel obstruction (SBO) due to a migrating diverticular enterolith. The patient's condition was ultimately managed operatively through laparoscopically assisted small bowel resection. CLINICAL DISCUSSION: A review of the literature reveals only eight reported cases of jejunal diverticulitis with simultaneous enterolith obstruction. All cases were managed operatively, with approaches including small bowel resection encompassing both pathologies, milking the enterolith back to the diverticulitis site and resecting en bloc to avoid extensive resection, or enterotomy and enterolith retrieval. CONCLUSION: The prevalence of small bowel diverticular disease is increasing, and as a result, clinicians may encounter more complications associated with this condition in the future. This case highlights the importance of considering alternate complications of small bowel DD.

12.
Cureus ; 15(9): e45911, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37885556

RESUMEN

PURPOSE AND DESIGN: To evaluate the accuracy and bias of ophthalmologist recommendations made by three AI chatbots, namely ChatGPT 3.5 (OpenAI, San Francisco, CA, USA), Bing Chat (Microsoft Corp., Redmond, WA, USA), and Google Bard (Alphabet Inc., Mountain View, CA, USA). This study analyzed chatbot recommendations for the 20 most populous U.S. cities. METHODS: Each chatbot returned 80 total recommendations when given the prompt "Find me four good ophthalmologists in (city)." Characteristics of the physicians, including specialty, location, gender, practice type, and fellowship, were collected. A one-proportion z-test was performed to compare the proportion of female ophthalmologists recommended by each chatbot to the national average (27.2% per the Association of American Medical Colleges (AAMC)). Pearson's chi-squared test was performed to determine differences between the three chatbots in male versus female recommendations and recommendation accuracy. RESULTS: Female ophthalmologists recommended by Bing Chat (1.61%) and Bard (8.0%) were significantly less than the national proportion of 27.2% practicing female ophthalmologists (p<0.001, p<0.01, respectively). ChatGPT recommended fewer female (29.5%) than male ophthalmologists (p<0.722). ChatGPT (73.8%), Bing Chat (67.5%), and Bard (62.5%) gave high rates of inaccurate recommendations. Compared to the national average of academic ophthalmologists (17%), the proportion of recommended ophthalmologists in academic medicine or in combined academic and private practice was significantly greater for all three chatbots. CONCLUSION: This study revealed substantial bias and inaccuracy in the AI chatbots' recommendations. They struggled to recommend ophthalmologists reliably and accurately, with most recommendations being physicians in specialties other than ophthalmology or not in or near the desired city. Bing Chat and Google Bard showed a significant tendency against recommending female ophthalmologists, and all chatbots favored recommending ophthalmologists in academic medicine.

13.
Int J Surg Case Rep ; 112: 108967, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37883873

RESUMEN

INTRODUCTION AND IMPORTANCE: Lung cancer is one of the most common malignancies worldwide and common sites of metastasis are to brain, liver, adrenal glands, and bones [1]. Metastasis to the gastrointestinal (GI) tract is extremely rare (<1%) and the most common site is the small intestine [5]. CASE PRESENTATION: A 60-year-old female referred for intermittent colicky abdominal pain and diarrhoea, with cross-sectional imaging showing a distal small bowel mass with lymphadenopathy. Malignancy workup revealed an additional mediastinal mass and raised tumour marker carcinoembryonic antigen (CEA). Bronchoscopy confirmed primary lung adenocarcinoma of the mediastinal mass. Given the raised CEA, evolving obstructive symptoms, and concerns for synchronous lung and gastrointestinal primaries, the patient proceeded to have a small bowel resection leading to the diagnosis of a GI lung metastasis. CLINICAL DISCUSSION: If Symptomatic, suggested treatment of lung metastasis to the GI tract is surgical resection. Current evidence suggests that in isolated GI metastases, resection may have a therapeutic benefit and an association with overall survival rate. CONCLUSION: In patients with symptomatic or isolated GI lung metastasis, surgical resection should be considered for treatment and management of metastatic disease. The role of tumour marker CEA in primary lung adenocarcinoma is unclear.

14.
Cureus ; 15(7): e42230, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37605671

RESUMEN

Intramuscular degloving injuries (IDIs) are a rare and unique type of muscle injury where there is a dissociation between the inner and outer components of a particular muscle. This type of injury is seen exclusively within the rectus femoris (RF) muscle due to its unique muscle-within-a-muscle anatomy and represents 9% of RF injuries. Despite the significance of this injury, limited knowledge exists regarding the mechanism, management, and prognosis of IDIs, and IDIs are not currently included among the various muscle injury classifications. We present a 38-year-old active male with a one-week history of acute onset right anterior mid-thigh pain and palpable lump after playing kickball. Right thigh MRI revealed an IDI of the RF muscle, edema within the inner and outer muscular portions of the muscle, and a retraction of the torn inner indirect myotendinous complex of the RF. He was managed with physical therapy while being advised to avoid aggressive quadriceps contractions, high-intensity, or high-impact exercise. This is the first reported case of an IDI that occurred in an older recreational athlete (versus young competitive athletes), and the first case of an IDI in a kicking sport other than soccer (kickball). This case emphasizes the importance of a broader awareness of this injury, and a heightened index of suspicion is advised in assessing potential IDIs to improve patient prognosis and rehabilitation. Given the limited understanding and rarity of this injury, we also provide a comprehensive review describing the IDI to the RF.

15.
ACS Appl Mater Interfaces ; 15(35): 41992-42003, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37611072

RESUMEN

Dielectric elastomer actuators (DEAs) have been proposed as a promising technology for developing soft robotics and stretchable electronics due to their large actuation. Among available fabrication techniques, inkjet printing is a digital, mask-free, material-saving, and fast technology, making it versatile and appealing for fabricating DEA electrodes. However, there is still a lack of suitable materials for inkjet-printed electrodes. In this study, multiple carbon black (CB) inks were developed and tested as DEA electrodes inkjet-printed on acrylic membranes (VHB). Triethylene glycol monomethyl ether (TGME) and chlorobenzene (CLB) were selected to disperse CB. The inks' stability, particle size, surface tension, viscosity, electrical resistance, and printability were characterized. The DEA with Ink-TGME/CLB (mixture solvent) electrodes obtained 80.63% area strain, a new benchmark for the DEA actuation with CB powder electrodes on VHB. The novelty of this work involves the disclosure of a new ink recipe (TGME/CLB/CB) for inkjet printing that can obtain stable drop formations with a small nozzle (17 × 17 µm), high resolution (∼25 µm, approaching the limit of drop-on-demand inkjet printing), and the largest area strain of DEAs under similar conditions, distinguishing this contribution from the previous works, which is important for the fabrication and miniaturization of DEA-based soft and stretchable electronics.

16.
Brain Inj ; 37(12-14): 1310-1325, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-37553812

RESUMEN

OBJECTIVES: 1) To describe demographic factors, concussion knowledge, attitudes, subjective norms, self-efficacy and intentions to provide social support to a peer with a concussion and 2) to examine if demographic factors and concussion knowledge are associated with components of the Theory of Planned Behavior. METHODS: The survey was completed between October 2018 and February 2019 by 200 youth (M = 15.30 years, SD = 1.52). Questions were designed for athletes and non-athletes and inquired about various types of social support. Data analysis included descriptive statistics, Wilcoxon Rank Sum Tests and Spearman's Rank-Order Correlation Coefficients. RESULTS: More favorable attitudes and intentions to provide social support were observed among females (W = 2576, p ≤ 0.001; W = 2411, p ≤ 0.001), older youth (rho = 0.32, p ≤ 0.001; rho = 0.41, p ≤ 0.001) and those with higher concussion knowledge (rho = 0.29, p ≤ 0.001; rho = 0.22; p ≤ 0.001). Participating in sports with a high-risk of concussion was associated with lower attitudes and intentions to provide social support (W = 6677; p ≤ 0.001; W = 6721; p ≤ 0.001). Self-reported concussion history or knowing someone with a concussion history was not significantly associated with social support intentions. CONCLUSION: This study identified characteristics of youth who had positive intentions to provide social support. These findings identify individuals who may model providing social support to a peer, as well as opportunities for future concussion education.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Deportes , Femenino , Humanos , Adolescente , Intención , Encuestas y Cuestionarios , Atletas , Apoyo Social , Conocimientos, Actitudes y Práctica en Salud
17.
Life Sci Alliance ; 6(9)2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37438085

RESUMEN

An intronic GGGGCC repeat expansion in C9orf72 is a common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. The repeats are transcribed in both sense and antisense directions to generate distinct dipeptide repeat proteins, of which poly(GA), poly(GR), and poly(PR) have been implicated in contributing to neurodegeneration. Poly(PR) binding to RNA may contribute to toxicity, but analysis of poly(PR)-RNA binding on a transcriptome-wide scale has not yet been carried out. We therefore performed crosslinking and immunoprecipitation (CLIP) analysis in human cells to identify the RNA binding sites of poly(PR). We found that poly(PR) binds to nearly 600 RNAs, with the sequence GAAGA enriched at the binding sites. In vitro experiments showed that poly(GAAGA) RNA binds poly(PR) with higher affinity than control RNA and induces the phase separation of poly(PR) into condensates. These data indicate that poly(PR) preferentially binds to poly(GAAGA)-containing RNAs, which may have physiological consequences.


Asunto(s)
Perfilación de la Expresión Génica , Transcriptoma , Humanos , Transcriptoma/genética , Proteína C9orf72/genética , Poli A , Dipéptidos , ARN/genética
19.
NeuroRehabilitation ; 52(4): 651-662, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37125568

RESUMEN

BACKGROUND: Return-to-school processes indicate 'when' to initiate activities and 'what' activities should be accomplished, but are missing 'how' to implement the process. The SCHOOLFirst website provides the 'how' through building concussion knowledge, creating a supportive culture, and defining roles. Due to the involvement of pre-service teachers in schools during training and imminent transition to becoming teachers, it is important that pre-service teachers are trained in concussion and can optimally support current and future students. OBJECTIVE: To determine: 1) pre-service teachers' knowledge and confidence surrounding the return-to-school process before and after using the SCHOOLFirst website; 2) the usability, intended use and satisfaction of the SCHOOLFirst website from the perspective of pre-service teachers. METHODS: Thirty pre-service teachers completed the demographic survey, knowledge and confidence survey, System Usability Scale, and satisfaction and intended use survey after participating in a workshop. RESULTS: Significant increases in concussion knowledge (Z = -4.093, p < 0.001) and confidence in helping students return-to-school (Z = -4.620, p < 0.001) were measured after using the SCHOOLFirst website. Participants were satisfied with the SCHOOLFirst website (93.4%) and intend to use it in the future when supporting a student post-concussion (96.4%). CONCLUSION: The SCHOOLFirst website is a valuable tool for pre-service teachers to support students' return-to-school post-concussion.


Asunto(s)
Conmoción Encefálica , Humanos , Instituciones Académicas , Estudiantes , Encuestas y Cuestionarios , Satisfacción Personal
20.
Cureus ; 15(4): e37763, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37213978

RESUMEN

Subclavian artery occlusion (SAO) is a rare form of peripheral artery disease, sometimes associated with arterial thoracic outlet syndrome (ATOS). Subclavian arterial and venous occlusions are often misdiagnosed initially, and their clinical presentation can be confusing in bodybuilding athletes with increased vascularity in combination with anabolic steroid use. We present a 63-year-old male weightlifter with a history of hypertensive cardiomyopathy, renal transplant with left upper extremity arteriovenous fistula and subsequent takedown, cervical spinal stenosis, left rotator cuff surgery, and decades of testosterone injections who presented with years of left shoulder and neck pain. After having seen multiple providers and being diagnosed with various common disorders, CT angiography and conventional angiography were eventually performed and confirmed the presence of chronic SAO. The chronic occlusion was not deemed amenable to surgery or endovascular intervention and was treated medically with anticoagulation. Although anabolic steroid use is associated with arterial thrombosis, to our knowledge, this is the first reported case of SAO in a weightlifter. Initial misdiagnosis resulted in a long and costly workup. Although the patient's symptoms were consistent with occlusion (and his increased vascularity could potentially suggest chronic thrombosis of any kind), these key signs were masked given his weightlifting history, anabolic steroid use, and concurrent degenerative musculoskeletal conditions common to the weightlifting population. A thorough history, comprehensive physical examination, appropriate imaging studies, and a high index of suspicion for vascular occlusion in athletes who use steroids are critical for the timely diagnosis and treatment of SAO.

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