RESUMEN
Variants in MYH7 cause cardiomyopathies as well as myosin storage myopathy and Laing early-onset distal myopathy (MPD1). MPD1 is characterized by muscle weakness and atrophy usually beginning in the lower legs. Here, we generated iPSC lines from lymphoblastoid cells of three unrelated individuals heterozygous for the most common MPD1-causing variant; p.Lys1617del. iPSC lines showed typical morphology, expressed pluripotency markers, demonstrated trilineage differentiation potential, and had a normal karyotype. These lines represent the first iPSCs derived from MPD1 patients and complement existing MPD1 animal models. They can provide in vitro platforms to better understand and model MPD1 pathomechanisms and test therapies.
RESUMEN
RYR1 variants are a common cause of congenital myopathies, including multi-minicore disease (MmD) and central core disease (CCD). Here, we generated iPSC lines from two CCD patients with dominant RYR1 missense variants that affect the transmembrane (pore) and SPRY3 protein domains (p.His4813Tyr and p.Asn1346Lys, respectively). Both lines had typical iPSC morphology, expressed canonical pluripotency markers, exhibited trilineage differentiation potential, and had normal karyotypes. Together with existing RYR1 iPSC lines, these represent important tools to study and develop treatments for RYR1-related myopathies.
Asunto(s)
Células Madre Pluripotentes Inducidas , Mutación Missense , Canal Liberador de Calcio Receptor de Rianodina , Humanos , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Miopatía del Núcleo Central/genética , Miopatía del Núcleo Central/patología , Miopatía del Núcleo Central/metabolismo , Adulto , Línea Celular , Masculino , Diferenciación Celular , FemeninoRESUMEN
RYR1 variants are the most common genetic cause of congenital myopathies, and typically cause central core disease (CCD) and/or malignant hyperthermia (MH). Here, we generated iPSC lines from two patients with CCD and MH caused by dominant RYR1 variants within the central region of the protein (p.Val2168Met and p.Arg2508Cys). Both lines displayed typical iPSC morphology, uniform expression of pluripotency markers, trilineage differentiation potential, and had normal karyotypes. These are the first RYR1 iPSC lines from patients with both CCD and MH. As these are common CCD/MH variants, these lines should be useful to study these conditions and test therapeutics.
Asunto(s)
Células Madre Pluripotentes Inducidas , Hipertermia Maligna , Mutación Missense , Canal Liberador de Calcio Receptor de Rianodina , Humanos , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Hipertermia Maligna/genética , Células Madre Pluripotentes Inducidas/metabolismo , Miopatía del Núcleo Central/genética , Miopatía del Núcleo Central/patología , Masculino , Femenino , Línea Celular , Diferenciación CelularRESUMEN
Central core disease (CCD) is a congenital disorder that results in hypotonia, delayed motor development, and areas of reduced oxidative activity in the muscle fibre. Two induced pluripotent stem cell (iPSC) lines were generated from the lymphoblastoid cells of a 33-year-old male with CCD, caused by a previously unreported dominant c.14145_14156delCTACTGGGACA (p.Asn4715_Asp4718del) deletion in the RYR1 gene. Both lines demonstrated typical morphology, pluripotency, trilineage differentiation, and had a normal karyotype. As the first published iPSC model of CCD caused by an RYR1 variant these lines are a potential resource for further investigation of RYR1-related myopathies in a human context.
Asunto(s)
Células Madre Pluripotentes Inducidas , Miopatía del Núcleo Central , Masculino , Humanos , Adulto , Miopatía del Núcleo Central/genética , Miopatía del Núcleo Central/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , MutaciónRESUMEN
Importance: The perioperative environment is hazardous, but patients remain safe with a successful outcome during their care due to staff adaptability and resiliency. The behaviors that support this adaptability and resilience have yet to be defined or analyzed. One Safe Act (OSA), a tool and activity developed to capture self-reported proactive safety behaviors that staff use in their daily practice to promote individual and team-based safe patient care, may allow for improved definition and analysis of these behaviors. Objective: To thematically analyze staff behaviors using OSA to understand what may serve as the basis for proactive safety in the perioperative environment. Design, Setting, and Participants: This qualitative thematic analysis included a convenience sample of perioperative staff at a single-center, tertiary care academic medical center who participated in an OSA activity during a 6-month period in 2021. All perioperative staff were eligible for inclusion. A combined deductive approach, based on a human factor analysis and classification framework, as well as an inductive approach was used to develop themes and analyze the self-reported staff safety behaviors. Exposures: Those selected to participate were asked to join an OSA activity, which was conducted in-person by a facilitator. Participants were to self-reflect about their OSA (proactive safety behavior) and record their experience as free text in an online survey tool. Main Outcome and Measures: The primary outcome was the development and application of a set of themes to describe proactive safety behaviors in the perioperative environment. Results: A total of 140 participants (33 nurses [23.6%] and 18 trainee physicians [12.9%]), which represented 21.3% of the 657 total perioperative department full-time staff, described 147 behaviors. A total of 8 non-mutually exclusive themes emerged with the following categories and frequency of behaviors: (1) routine-based adaptations (46 responses [31%]); (2) resource availability and assessment adaptations (31 responses [21%]); (3) communication and coordination adaptation (23 responses [16%]); (4) environmental ergonomics adaptation (17 responses [12%]); (5) situational awareness adaptation (12 responses [8%]); (6) personal or team readiness adaptation (8 responses [5%]); (7) education adaptation (5 responses [3%]); and (8) social awareness adaptation (5 responses [3%]). Conclusions and Relevance: The OSA activity elicited and captured proactive safety behaviors performed by staff. A set of behavioral themes were identified that may serve as the basis for individual practices of resilience and adaptability that promote patient safety.
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Seguridad del Paciente , Médicos , Humanos , Pacientes , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Adverse events in the perioperative environment, a potential risk to patients, may be mitigated by nurturing staff adaptability and resiliency. An activity called "One Safe Act" (OSA) was developed to capture and highlight proactive safety behaviors that staff use in their daily practice to promote safe patient care. METHODS: One Safe Act is conducted in-person in the perioperative environment by a facilitator. The facilitator gathers an ad hoc group of perioperative staff in the work unit. The activity is run as follows: staff introductions, purpose/instructions of the activity, participants self-reflect about their OSA (proactive safety behavior) and record it as free text in an online survey tool, the group debriefs with each person sharing their OSA, and the activity is concluded by summarizing behavioral themes. Each participant completed an attitudinal assessment to understand changes in safety culture perception. RESULTS: From December 2020 to July 2021, a total of 140 perioperative staff participated (21%, 140/657) over 28 OSA sessions with 136 (97%, 140/136) completing the attitudinal assessment. A total of 82% (112/136), 88% (120/136), and 90% (122/136) agreed that this activity would change their practices related to patient safety, improve their work unit's ability to deliver safe care, and demonstrated their colleagues' commitment to patient safety, respectively. CONCLUSIONS: The OSA activity is participatory and collaborative to build shared, new knowledge, and community practices focused on proactive safety behaviors. The OSA activity achieved this goal with a near universal acceptance of the activity in promoting an intent to change personal practice and increasing engagement and commitment to safety culture.
Asunto(s)
Seguridad del Paciente , Atención Perioperativa , Humanos , Encuestas y CuestionariosRESUMEN
Variants in the ACTA1 gene are a common cause of nemaline myopathy (NM); a muscle disease that typically presents at birth or early childhood with hypotonia and muscle weakness. Here, we generated an induced pluripotent stem cell line (iPSC) from lymphoblastoid cells of a 3-month-old female patient with intermediate NM caused by a dominant ACTA1 variant (c.515C > A (p.Ala172Glu)). iPSCs showed typical morphology, expressed pluripotency markers, demonstrated trilineage differentiation potential, and had a normal karyotype. This line complements our previously published ACTA1 iPSC lines derived from patients with typical and severe NM.
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Células Madre Pluripotentes Inducidas , Miopatías Nemalínicas , Actinas/genética , Actinas/metabolismo , Preescolar , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Lactante , Recién Nacido , Músculo Esquelético/metabolismo , Mutación , Miopatías Nemalínicas/genéticaRESUMEN
Nemaline myopathy (NM) is a congenital skeletal muscle disorder that typically results in muscle weakness and the presence of rod-like structures (nemaline bodies) in the sarcoplasma and/or in the nuclei of myofibres. Two induced pluripotent stem cell (iPSC) lines were generated from the lymphoblastoid cells of a 1-month-old male with severe NM caused by a homozygous recessive mutation in the ACTA1 gene (c.121C > T, p.Arg39Ter). The iPSC lines demonstrated typical morphology, expressed pluripotency markers, exhibited trilineage differentiation potential and displayed a normal karyotype. These isogenic lines represent a potential resource to investigate and model recessive ACTA1 disease in a human context.
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Células Madre Pluripotentes Inducidas , Miopatías Nemalínicas , Actinas/genética , Actinas/metabolismo , Homocigoto , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Lactante , Masculino , Músculo Esquelético/metabolismo , Mutación , Miopatías Nemalínicas/genética , Miopatías Nemalínicas/metabolismoRESUMEN
This article provides a background of hepatic encephalopathy, its relation to liver disease as well as its prevalence in the United States. A literature review provides an overview of HE discussing the pathophysiology, evidence-based diagnosis, and grading of the disease severity as well as treatment options and interventions. A large emphasis of the article is placed on nursing's role of identifying and managing hepatic encephalopathy. The authors hope to provide clinical nurses with the tools and information needed to provide evidence-based care to this patient population. Pharmacologic therapies, as well as nutrition for these patients, are other topics reviewed. Education for nurses on the management of hepatic encephalopathy is important, as well as education needed for patients and families to support them through the treatment and follow-up care needed to manage hepatic encephalopathy. The authors also hope to provide nurses with education tips to provide the patients and families they care for during their hospitalization with HE, as well as on discharge from the hospital to prevent reoccurrence of symptoms.
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Encefalopatía Hepática/enfermería , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , HumanosRESUMEN
BACKGROUND AND PURPOSE: The flipped teaching method was implemented through a series of multiple condensed videos for pharmaceutical calculations with student perceptions and academic performance assessed post-intervention. EDUCATIONAL ACTIVITY AND SETTING: Student perceptions from the intervention group were assessed via an online survey. Pharmaceutical exam scores of the intervention group were compared to the control group. The intervention group spent a greater amount of class time on active learning. FINDINGS: The majority of students (68.2%) thought that the flipped teaching method was more effective to learn pharmaceutical calculations than the traditional method. The mean exam scores of the intervention group were not significantly different than the control group (80.5 ± 15.8% vs 77.8 ± 16.8%; p = 0.253). DISCUSSION: Previous studies on the flipped teaching method have shown mixed results in regards to student perceptions and exam scores, where either student satisfaction increased or exam scores improved, but rarely both. SUMMARY: The flipped teaching method was rated favorably by a majority of students. The flipped teaching method resulted in similar outcomes in pharmaceutical calculations exam scores, and it appears to be an acceptable and effective option to deliver pharmaceutical calculations in a Doctor of Pharmacy program.
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Rendimiento Académico , Actitud , Instrucción por Computador , Cálculo de Dosificación de Drogas , Educación en Farmacia/métodos , Aprendizaje Basado en Problemas , Estudiantes de Farmacia , Curriculum , Evaluación Educacional , Humanos , Percepción , Satisfacción Personal , Encuestas y Cuestionarios , Grabación de Cinta de VideoRESUMEN
Male courtship behavior in Drosophila melanogaster is controlled by two main regulators, fruitless (fru) and doublesex (dsx). Their sex-specific expression in brain neurons has been characterized in detail, but little is known about the downstream targets of the sex-specific FRU and DSX proteins and how they specify the function of these neurons. While sexual dimorphism in the number and connections of fru and dsx expressing neurons has been observed, a majority of the neurons that express the two regulators are present in both sexes. This poses the question which molecules define the sex-specific function of these neurons. Signaling molecules are likely to play a significant role. We have identified a predicted G-protein coupled receptor (GPCR), CG4395, that is required for male courtship behavior. The courtship defect in the mutants can be rescued by expression of the wildtype protein in fru neurons of adult males. The GPCR is expressed in a subset of fru-positive antennal glomeruli that have previously been shown to be essential for male courtship. Expression of 4395-RNAi in GH146 projection neurons lowers courtship. This suggests that signaling through the CG4395 GPCR in this subset of fru neurons is critical for male courtship behavior.