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1.
Nat Immunol ; 19(3): 267-278, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29358707

RESUMEN

Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation.


Asunto(s)
Linfocitos B/inmunología , Selección Clonal Mediada por Antígenos/inmunología , Centro Germinal/inmunología , Ribonucleoproteínas Nucleares Heterogéneas/inmunología , Activación de Linfocitos/inmunología , Proteína de Unión al Tracto de Polipirimidina/inmunología , Animales , Afinidad de Anticuerpos/inmunología , Diferenciación Celular/inmunología , Proliferación Celular , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
2.
Nat Immunol ; 19(8): 828-837, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29988089

RESUMEN

Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3' untranslated region (3' UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in the Ifng-3' UTR led to chronic cytokine production in memory T cells. This aberrant protein production did not result from increased expression and/or half-life of the mRNA. Instead, AREs blocked the recruitment of cytokine-encoding mRNA to ribosomes; this block depended on the ARE-binding protein ZFP36L2. Thus, AREs mediate repression of translation in mouse and human memory T cells by preventing undesirable protein production from pre-formed cytokine-encoding mRNAs in the absence of infection.


Asunto(s)
Regiones no Traducidas 3'/genética , Elementos Ricos en Adenilato y Uridilato/genética , Interferón gamma/genética , ARN Mensajero/genética , Linfocitos T/inmunología , Animales , Células Cultivadas , Represión Epigenética , Memoria Inmunológica , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Extensión de la Cadena Peptídica de Translación , Ribosomas/metabolismo , Tristetraprolina/genética , Tristetraprolina/metabolismo
3.
Nat Immunol ; 18(6): 683-693, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28394372

RESUMEN

RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RNA-binding proteins for maintaining cellular identity among closely related cell types.


Asunto(s)
Linfocitos B/inmunología , Adhesión Celular/genética , Movimiento Celular/genética , Proteínas Nucleares/genética , Proteínas de Unión al ARN/genética , Animales , Factor 1 de Respuesta al Butirato , Adhesión Celular/inmunología , Movimiento Celular/inmunología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Factores Reguladores del Interferón/genética , Factores de Transcripción de Tipo Kruppel/genética , Tejido Linfoide/citología , Tejido Linfoide/inmunología , Ratones , Proteínas Nucleares/inmunología , Fenotipo , Proteínas de Unión al ARN/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ARN , Transducción de Señal
4.
Nat Immunol ; 16(4): 415-25, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25706746

RESUMEN

Post-transcriptional regulation of mRNA by the RNA-binding protein HuR (encoded by Elavl1) is required in B cells for the germinal center reaction and for the production of class-switched antibodies in response to thymus-independent antigens. Transcriptome-wide examination of RNA isoforms and their abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interactions, revealed that HuR-dependent splicing of mRNA affected hundreds of transcripts, including that encoding dihydrolipoamide S-succinyltransferase (Dlst), a subunit of the 2-oxoglutarate dehydrogenase (α-KGDH) complex. In the absence of HuR, defective mitochondrial metabolism resulted in large amounts of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for the proliferation and differentiation of B cells.


Asunto(s)
Linfocitos B/inmunología , Proteínas ELAV/inmunología , Centro Germinal/inmunología , Inmunidad Humoral , Inmunoglobulinas/biosíntesis , ARN Mensajero/inmunología , Aciltransferasas/genética , Aciltransferasas/inmunología , Empalme Alternativo/inmunología , Animales , Antígenos/administración & dosificación , Antígenos/inmunología , Linfocitos B/citología , Linfocitos B/efectos de los fármacos , Muerte Celular , Diferenciación Celular , Proliferación Celular , Proteínas ELAV/genética , Eritrocitos/inmunología , Centro Germinal/citología , Centro Germinal/efectos de los fármacos , Inmunización , Cambio de Clase de Inmunoglobulina , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/genética , Mitocondrias/inmunología , ARN Mensajero/genética , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Ovinos
5.
PLoS Genet ; 18(3): e1010044, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35271580

RESUMEN

Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus prevent the normal transport of food into the stomach. Affected puppies regurgitate meals and water, fail to thrive, and experience complications such as aspiration pneumonia that may necessitate euthanasia. The German shepherd dog (GSD) has the highest disease incidence, indicative of a genetic predisposition. Here, we discover that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage. A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility. Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM. We describe herein the first genetic factors identified in CIM: sex and a major locus on chromosome 12, which together predict disease state in the GSD with greater than 75% accuracy.


Asunto(s)
Acalasia del Esófago , Repeticiones de Minisatélite , Animales , Perros , Acalasia del Esófago/veterinaria , Femenino , Estudio de Asociación del Genoma Completo , Intrones/genética , Masculino , Receptores de la Hormona Hipofisaria
6.
Cancer ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38567685

RESUMEN

BACKGROUND: Opioid pain management in cancer survivorship is a complex and understudied topic. METHODS: The authors conducted in-depth, qualitative interviews to understand clinician approaches to opioid pain management in chronic cancer pain and to generate ideas for improvement. They used a rigorous, inductive, qualitative, descriptive approach to examine clinician (n = 20) perspectives about opioid pain management in survivorship, including oncologists (n = 5), palliative care clinicians (n = 8), primary care clinicians (n = 5), and pain management specialists (n = 2). RESULTS: The findings indicated that no consistent medical home exists for chronic pain management in cancer survivors and that there are fundamental differences in how each subspecialty approaches chronic pain management in survivorship (e.g., "Do we think of this as noncancer pain or cancer pain?… This is in this limbo zone-this gray zone-because it's cancer-related pain, right?"). Simultaneously, clinicians are influenced by their peers' perceptions of their opioid prescribing decisions, sparking intraprofessional tension when disagreement occurs. In these instances, clinicians described overthinking and doubting their clinical decision-making as well as a sense of judgment, pressure, and/or shame. Finally, clinicians acknowledged a fear of consequences for opioid prescribing decisions. Specifically, participants cited conflict with patients, sometimes escalating to aggression and threats of violence, as well as potential disciplinary actions and/or legal consequences. CONCLUSIONS: Participants suggested that opportunities to improve chronic cancer pain care include developing clear, systematic guidance for chronic cancer pain management, facilitating clinician communication and consultation, creating tailored survivorship care plans in partnership with patients, and developing accessible, evidence-based, complementary pain treatments.

7.
Gynecol Oncol ; 186: 211-215, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38850766

RESUMEN

OBJECTIVES: Minimally invasive surgery for treatment of gynecologic malignancies is associated with decreased pain, fewer complications, earlier return to activity, lower cost, and shorter hospital stays. Patients are often discharged the day of surgery, but occasionally stay overnight due to prolonged post-anesthesia care unit (PACU) stays. The objective of this study was to identify risk factors for prolonged PACU length of stay (LOS). METHODS: This is a single institution retrospective review of patients who underwent minimally invasive hysterectomy for gynecologic cancer from 2019 to 2022 and had a hospital stay <24-h. The primary outcome was PACU LOS. Demographics, pre-operative diagnoses, and surgical characteristics were recorded. After Box-Cox transformation, linear regression was used to determine significant predictors of PACU LOS. RESULTS: For the 661 patients identified, median PACU LOS was 5.04 h (range 2.16-23.76 h). On univariate analysis, longer PACU LOS was associated with increased age (ρ = 0.106, p = 0.006), non-partnered status [mean difference (MD) = 0.019, p = 0.099], increased alcohol use (MD = 0.018, p = 0.102), increased Charlson Comorbidity Index (CCI) score (ρ = 0.065, p = 0.097), and ASA class ≥3 (MD = 0.033, p = 0.002). Using multivariate linear regression, increased age (R2 = 0.0011, p = 0.043), non-partnered status (R2 = 0.0389, p < 0.001), and ASA class ≥3 (R2 = 0.0250, p = 0.023) were associated with increased PACU LOS. CONCLUSIONS: Identifying patients at risk for prolonged PACU LOS, including patients who are older, non-partnered, and have an ASA class ≥3, may allow for interventions to improve patient experience, better utilize hospital resources, decrease PACU overcrowding, and limit postoperative admissions and complications. The relationship between non-partnered status and PACU LOS is the most novel relationship identified in this study.


Asunto(s)
Neoplasias de los Genitales Femeninos , Histerectomía , Tiempo de Internación , Humanos , Femenino , Tiempo de Internación/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias de los Genitales Femeninos/cirugía , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Estudios Retrospectivos , Anciano , Adulto , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Factores de Riesgo , Periodo de Recuperación de la Anestesia
8.
Acad Psychiatry ; 48(4): 310-319, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38291313

RESUMEN

OBJECTIVES: Psychiatric physicians may experience higher rates of assault than those in other fields. For many reasons, residents may be especially vulnerable. This study updates rates of assaults among US psychiatry residents as well as the reporting rates and emotional effects of these incidents. Little data exists to examine rates of microaggressions against psychiatry residents. METHODS: A cross-sectional online survey was distributed through a national residency database via a snowball-sampling approach between June and September of 2021. The questionnaire asked about experiences of verbal, physical, and sexual assaults, as well as microaggressions and their impact. Descriptive analyses of the obtained data were conducted. RESULTS: The survey was completed by 275 psychiatry residents from 29 states (63.6% women). At least one form of assault was experienced by 78.9% of participants with 74.5% experiencing verbal, 22.2% experiencing physical, and 6.2% experiencing sexual assault. At least one type of microaggression was experienced by 86.9% of trainees. Elevations in PTSD scores were seen in residents who identified as women and non-White and those physically injured or sexually assaulted. While 92.7% of residents stated their program provided training about assault, 25% of residents indicated they had no training on recognizing and responding to microaggressions. CONCLUSIONS: Psychiatric residents experience widespread assault and microaggressions in the clinical setting but often do not report them. Due to the ubiquitous nature of these events, programs should provide training about early recognition and de-escalation techniques for agitation, responding effectively to microaggressions, and the importance of reporting events.


Asunto(s)
Agresión , Internado y Residencia , Psiquiatría , Humanos , Femenino , Psiquiatría/educación , Estudios Transversales , Masculino , Estados Unidos , Agresión/psicología , Adulto , Encuestas y Cuestionarios , Violencia/estadística & datos numéricos , Violencia/psicología , Delitos Sexuales/estadística & datos numéricos , Delitos Sexuales/psicología
9.
Mamm Genome ; 34(3): 464-472, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37041421

RESUMEN

Congenital idiopathic megaesophagus (CIM) is a gastrointestinal disorder of dogs wherein the esophagus is dilated and swallowing activity is reduced, causing regurgitation of ingesta. Affected individuals experience weight loss and malnourishment and are at risk for aspiration pneumonia, intussusception, and euthanasia. Great Danes have among the highest incidences of CIM across dog breeds, suggesting a genetic predisposition. We generated low-pass sequencing data for 83 Great Danes and used variant calls to impute missing whole genome single-nucleotide variants (SNVs) for each individual based on haplotypes phased from 624 high-coverage dog genomes, including 21 Great Danes. We validated the utility of our imputed data set for genome-wide association studies (GWASs) by mapping loci known to underlie coat phenotypes with simple and complex inheritance patterns. We conducted a GWAS for CIM with 2,010,300 SNVs, identifying a novel locus on canine chromosome 1 (P-val = 2.76 × 10-10). Associated SNVs are intergenic or intronic and are found in two clusters across a 1.7-Mb region. Inspection of coding regions in high-coverage genomes from affected Great Danes did not reveal candidate causal variants, suggesting that regulatory variants underlie CIM. Further studies are necessary to assess the role of these non-coding variants.


Asunto(s)
Acalasia del Esófago , Estudio de Asociación del Genoma Completo , Animales , Perros , Acalasia del Esófago/genética , Acalasia del Esófago/veterinaria , Genoma/genética , Predisposición Genética a la Enfermedad , Fenotipo , Polimorfismo de Nucleótido Simple
10.
Semin Thromb Hemost ; 49(2): 145-161, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36318958

RESUMEN

Postpartum hemorrhage (PPH) is a common cause of significant maternal morbidity and mortality that can be associated with coagulopathy, especially hypofibrinogenemia. There is interest in point-of-care viscoelastic hemostatic assays (POC-VHA) in PPH because prompt knowledge of coagulation status can aid diagnosis, identify cases of severe coagulopathy, and allow ongoing monitoring during rapid bleeding. The incidence of coagulopathy in most cases of PPH is low because of the procoagulant state of pregnancy, including raised fibrinogen levels of around 4 to 6 g/L. A Clauss fibrinogen of >2 g/L or POC-VHA equivalent has been found to be adequate for hemostasis during PPH. POC-VHA has been used successfully to diagnose hypofibrinogenemia (Clauss fibrinogen of ≤2 g/L) and guide fibrinogen treatment which has reduced bleed size and complications of massive transfusion. There are uncertainties about the use of POC-VHA to direct fresh frozen plasma and platelet administration during PPH. Several POC-VHA algorithms have been used successfully incorporated in the management of many thousands of PPHs and clinicians report that they are easy to use, interpret, and aid decision making. Due to the relative cost of POC-VHA and lack of definitive data on improving outcomes, these devices have not been universally adopted during PPH.


Asunto(s)
Afibrinogenemia , Trastornos de la Coagulación Sanguínea , Hemostáticos , Hemorragia Posparto , Embarazo , Femenino , Humanos , Tromboelastografía , Hemorragia Posparto/diagnóstico , Hemorragia Posparto/terapia , Hemorragia Posparto/etiología , Afibrinogenemia/complicaciones , Trastornos de la Coagulación Sanguínea/diagnóstico , Fibrinógeno/uso terapéutico , Fibrinógeno/análisis
11.
Int J Gynecol Cancer ; 33(12): 1875-1881, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37903564

RESUMEN

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.


Asunto(s)
Anticoagulantes , Análisis Costo-Beneficio , Neoplasias Endometriales , Histerectomía , Tromboembolia Venosa , Femenino , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/economía , Anticoagulantes/uso terapéutico , Quimioprevención/economía , Quimioprevención/métodos , Quimioprevención/estadística & datos numéricos , Análisis de Costo-Efectividad , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Enoxaparina/administración & dosificación , Enoxaparina/economía , Enoxaparina/uso terapéutico , Histerectomía/efectos adversos , Histerectomía/economía , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/economía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Estadificación de Neoplasias , Estudios Retrospectivos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
12.
J Med Internet Res ; 25: e44528, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37343182

RESUMEN

BACKGROUND: Remote patient monitoring (RPM) is an option for continuously managing the care of patients in the comfort of their homes or locations outside hospitals and clinics. Patient engagement with RPM programs is essential for achieving successful outcomes and high quality of care. When relying on technology to facilitate monitoring and shifting disease management to the home environment, it is important to understand the patients' experiences to enable quality improvement. OBJECTIVE: This study aimed to describe patients' experiences and overall satisfaction with an RPM program for acute and chronic conditions in a multisite, multiregional health care system. METHODS: Between January 1, 2021, and August 31, 2022, a patient experience survey was delivered via email to all patients enrolled in the RPM program. The survey encompassed 19 questions across 4 categories regarding comfort, equipment, communication, and overall experience, as well as 2 open-ended questions. Descriptive analysis of the survey response data was performed using frequency distribution and percentages. RESULTS: Surveys were sent to 8535 patients. The survey response rate was 37.16% (3172/8535) and the completion rate was 95.23% (3172/3331). Survey results indicated that 88.97% (2783/3128) of participants agreed or strongly agreed that the program helped them feel comfortable managing their health from home. Furthermore, 93.58% (2873/3070) were satisfied with the RPM program and ready to graduate when meeting the program goals. In addition, patient confidence in this model of care was confirmed by 92.76% (2846/3068) of the participants who would recommend RPM to people with similar conditions. There were no differences in ease of technology use according to age. Those with high school or less education were more likely to agree that the equipment and educational materials helped them feel more informed about their care plans than those with higher education levels. CONCLUSIONS: This multisite, multiregional RPM program has become a reliable health care delivery model for the management of acute and chronic conditions outside hospitals and clinics. Program participants reported an excellent overall experience and a high level of satisfaction in managing their health from the comfort of their home environment.


Asunto(s)
Hospitales , Satisfacción del Paciente , Humanos , Enfermedad Crónica , Encuestas y Cuestionarios , Monitoreo Fisiológico
13.
Nat Immunol ; 11(8): 717-24, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20622884

RESUMEN

ZFP36L1 and ZFP36L2 are RNA-binding proteins (RBPs) that interact with AU-rich elements in the 3' untranslated region of mRNA, which leads to mRNA degradation and translational repression. Here we show that mice that lacked ZFP36L1 and ZFP36L2 during thymopoiesis developed a T cell acute lymphoblastic leukemia (T-ALL) dependent on the oncogenic transcription factor Notch1. Before the onset of T-ALL, thymic development was perturbed, with accumulation of cells that had passed through the beta-selection checkpoint without first expressing the T cell antigen receptor beta-chain (TCRbeta). Notch1 expression was higher in untransformed thymocytes in the absence of ZFP36L1 and ZFP36L2. Both RBPs interacted with evolutionarily conserved AU-rich elements in the 3' untranslated region of Notch1 and suppressed its expression. Our data establish a role for ZFP36L1 and ZFP36L2 during thymocyte development and in the prevention of malignant transformation.


Asunto(s)
Proteínas Nucleares/deficiencia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Linfocitos T/inmunología , Timo/inmunología , Tristetraprolina/deficiencia , Secuencia de Aminoácidos , Animales , Factor 1 de Respuesta al Butirato , Secuencia Conservada , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Proteínas Nucleares/genética , Proteínas Nucleares/inmunología , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , Receptor Notch1/genética , Receptor Notch1/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Alineación de Secuencia , Timo/crecimiento & desarrollo , Transcripción Genética , Tristetraprolina/genética , Tristetraprolina/inmunología
14.
Eur Arch Psychiatry Clin Neurosci ; 272(2): 273-290, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34185132

RESUMEN

Research has linked executive function (EF) deficits to many of the behavioral symptoms of attention deficit hyperactivity disorder (ADHD). Evidence of the involvement of EF impairment in ADHD is corroborated by accumulating neuroimaging studies, specifically functional magnetic resonance imaging (fMRI) studies. However, in recent years, functional near-infrared spectroscopy (fNIRS) has become increasingly popular in ADHD research due to its portability, high ecological validity, resistance to motion artifacts, and cost-effectiveness. While numerous studies throughout the past decade have used fNIRS to examine alterations in neural correlates of EF in ADHD, a qualitative review of the reliability of these findings compared with those reported using gold-standard fMRI measurements does not yet exist. The current review aims to fill this gap in the literature by comparing the results generated from a qualitative review of fNIRS studies (children and adolescents ages 6-16 years old) to a meta-analysis of comparable fMRI studies and examining the extent to which the results of these studies align in the context of EF impairment in ADHD. The qualitative analysis of fNIRS studies of ADHD shows a consistent hypoactivity in the right prefrontal cortex in multiple EF tasks. The meta-analysis of fMRI data corroborates altered activity in this region and surrounding areas during EF tasks in ADHD compared with typically developing controls. These findings indicate that fNIRS is a promising functional brain imaging technology for examining alterations in cortical activity in ADHD. We also address the disadvantages of fNIRS, including limited spatial resolution compared with fMRI.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Psicología del Desarrollo , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Niño , Humanos , Imagen por Resonancia Magnética , Metaanálisis como Asunto , Reproducibilidad de los Resultados , Espectroscopía Infrarroja Corta
15.
Cell Mol Life Sci ; 78(9): 4365-4376, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33625522

RESUMEN

The C1ORF112 gene initially drew attention when it was found to be strongly co-expressed with several genes previously associated with cancer and implicated in DNA repair and cell cycle regulation, such as RAD51 and the BRCA genes. The molecular functions of C1ORF112 remain poorly understood, yet several studies have uncovered clues as to its potential functions. Here, we review the current knowledge on C1ORF112 biology, its evolutionary history, possible functions, and its potential relevance to cancer. C1ORF112 is conserved throughout eukaryotes, from plants to humans, and is very highly conserved in primates. Protein models suggest that C1ORF112 is an alpha-helical protein. Interestingly, homozygous knockout mice are not viable, suggesting an essential role for C1ORF112 in mammalian development. Gene expression data show that, among human tissues, C1ORF112 is highly expressed in the testes and overexpressed in various cancers when compared to healthy tissues. C1ORF112 has also been shown to have altered levels of expression in some tumours with mutant TP53. Recent screens associate C1ORF112 with DNA replication and reveal possible links to DNA damage repair pathways, including the Fanconi anaemia pathway and homologous recombination. These insights provide important avenues for future research in our efforts to understand the functions and potential disease relevance of C1ORF112.


Asunto(s)
Evolución Biológica , Daño del ADN , Reparación del ADN , Replicación del ADN , Sistemas de Lectura Abierta/genética , Animales , Humanos , Masculino , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Mapas de Interacción de Proteínas , Testículo/metabolismo
16.
Prev Sci ; 23(6): 922-933, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35305231

RESUMEN

Teaching staff report poorer mental health and wellbeing than the general working population. Intervention to address this issue is imperative, as poor wellbeing is associated with burnout, presenteeism, and adverse student mental health outcomes. The Wellbeing in Secondary Education (WISE) intervention is a secondary school-based programme aimed at improving the mental health and wellbeing of teachers and students. There are three components: awareness-raising for staff; a peer support service delivered by staff trained in Mental Health First Aid (MHFA); and Schools and Colleges Mental Health First Aid (MHFA) training for teachers. A cluster randomised controlled trial with integrated process and economic evaluation was conducted with 25 secondary schools in the UK (2016-2018). The intervention was largely ineffective in improving teacher mental health and wellbeing. This paper reports process evaluation data on acceptability to help understand this outcome. It adopts a complex systems perspective, exploring how acceptability is a dynamic and contextually contingent concept. Data sources were as follows: interviews with funders (n = 3); interviews with MHFA trainers (n = 6); focus groups with peer supporters (n = 8); interviews with headteachers (n = 12); and focus groups with teachers trained in Schools and Colleges MHFA (n = 7). Results indicated that WISE intervention components were largely acceptable. Initially, the school system was responsive, as it had reached a 'tipping point' and was prepared to address teacher mental health. However, as the intervention interacted with the complexities of the school context, acceptability became more ambiguous. The intervention was seen to be largely inadequate in addressing the structural determinants of teacher mental health and wellbeing (e.g. complex student and staff needs, workload, and system culture). Future teacher mental health interventions need to focus on coupling skills training and support with whole school elements that tackle the systemic drivers of the problem.


Asunto(s)
Salud Mental , Instituciones Académicas , Humanos , Grupo Paritario , Maestros/psicología , Estudiantes/psicología
17.
Afr J Reprod Health ; 26(9): 21-30, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37585067

RESUMEN

This cross-sectional study assessed attitudes and experiences with abortion care among physician trainees in Ghana. Participants were 27 Obstetrics/Gynecology (OBGYN) residents and 138 house officers. An electronic survey evaluated attitudes, training, clinical experience, and technical skills with abortion care. The majority of participants believe that women should have access to safe abortion. However, only 51.6% of OBGYN residents and 40.9% of house officers want to currently perform abortions as a trainee, primarily due to religious or ethical beliefs. Among house officers, increased likelihood of performing abortions in their future practice is associated with greater exposure to abortion training, (OR 1.40, p=0.032), fewer years practicing medicine (OR 0.26, p=0.010), and believing abortion laws should be liberalized (OR 3.62, p=0.03). Overall, we demonstrate that only two-thirds of physician trainees in Ghana are likely to perform abortion care after completing training, and greater exposure to abortion training is associated with an increased likelihood of performing abortions.


Asunto(s)
Aborto Inducido , Médicos , Embarazo , Humanos , Femenino , Ghana , Estudios Transversales , Actitud del Personal de Salud
18.
Psychiatr Q ; 93(3): 915-933, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36006571

RESUMEN

Agitation is a common and potentially dangerous condition requiring rapid recognition and treatment in acute psychiatric units. Prompt intervention can prevent a patient with agitation from harming themselves, harming others, or needing restraints or seclusion. After the review of numerous guidelines, the Modified Agitation Severity Scale (MASS) agitation treatment protocol was developed to identify and manage agitation in an inpatient adult psychiatric setting. This protocol involved modifying an existing agitation scale and pairing scores with a treatment algorithm to indicate which behavioral and medication interventions would be most appropriate. All scoring and interventions were recorded in the electronic medical record (EMR). Three months of data were collected before and after the protocol was implemented. The new, modified scale had high reliability and correlated well with another validated agitation scale. Perceived patient safety was high during both study phases. Nurses' perceptions of safety trended upward after the protocol was implemented, though these differences were not significant, likely due to insufficient power. Although there was no decrease in seclusion events after implementation of the treatment protocol, there was a 44% decrease in restraint events and average restraint minutes per incident. Despite a potential increase in workload for nursing staff, implementation of the protocol did not increase burnout scores. Physicians continued to order the protocol for 55% of patients after the study period ended. These findings suggest that including a rapid agitation assessment and protocol within the EMR potentially improves nurses' perceptions of unit safety, helps assess treatment response, reduces time patients spend restrained, and supports decision making for nurses.


Asunto(s)
Pacientes Internos , Restricción Física , Adulto , Protocolos Clínicos , Humanos , Pacientes Internos/psicología , Seguridad del Paciente , Agitación Psicomotora/tratamiento farmacológico , Reproducibilidad de los Resultados
19.
J Community Psychol ; 50(7): 3196-3209, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35233793

RESUMEN

Adults facing homelessness often perceive themselves to be at the bottom of society, which has implications for their current and future well-being. Snyder's hope theory, which posits that agency thinking and pathways thinking are necessary for achieving a hopeful outlook on life, may be helpful for understanding drivers of well-being among individuals experiencing homelessness. In this study, we examined dispositional hope, perceived goal attainment, social support, and perceived standing in society among 123 adults experiencing homelessness who were attending a support group at a daytime drop-in center in the United States. Participants completed self-report measures related to the aforementioned variables of interest. We discovered that higher levels of self-reported goal attainment, independent of the type of goal identified, were significantly associated with total hope and both its subscales, that social support was significantly associated with total hope and pathways thinking, and that perceived standing in society was significantly associated with total hope and agency thinking.


Asunto(s)
Personas con Mala Vivienda , Apoyo Social , Adulto , Actitud , Humanos , Motivación , Estados Unidos
20.
J Vet Med Educ ; 49(6): 733-739, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34469267

RESUMEN

Natural and man-made disasters lead to hundreds of millions of dollars in economic losses annually worldwide. Veterinarians are most qualified to support local, state, national, and international efforts in emergency management. However, they may lack the knowledge and advanced training to most effectively plan, prepare, and respond. Currently, only two colleges offer training embedded in their core veterinary curriculum. In this study, a survey was conducted to gain an understanding of veterinary practice and practitioner preparedness for natural and man-made disasters in the United States and Canada, with questions assessing pandemic preparedness. The participants graduated from 28 American Veterinary Medical Association (AVMA)-accredited veterinary colleges globally and 2 non-accredited veterinary colleges, represent a diverse set of veterinary practice types, and have an average of 26 years' practice experience. Overall, 63.5% of veterinary respondents had experienced a natural disaster, while only 9.6% had experienced a man-made disaster. Approximately 66% reported having a practice disaster preparedness plan, while less than 20% of those actively maintained and updated the plan. Furthermore, less than 50% of the practices and practitioners were ready to face the challenges of a global pandemic. Approximately 68% reported using some form of communication to educate clients about family and pet disaster readiness. Many felt that some advanced disaster readiness training would have been helpful in their veterinary curriculum. Our findings indicate that additional training in the veterinary curriculum, as well as continuing education, would help veterinarians and practices be better prepared for natural and man-made disasters.


Asunto(s)
COVID-19 , Educación en Veterinaria , Animales , COVID-19/epidemiología , COVID-19/veterinaria , Curriculum , Educación Continua , Universidades
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