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1.
Curr Biol ; 34(3): 505-518.e6, 2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-38215744

RESUMEN

Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in reproduction. Here we investigated the role of these potent signaling molecules in embryonic germ cell development, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we observed active JH signaling first within and near primordial germ cells (PGCs) as they migrate to the developing gonad. Through in vivo and in vitro assays, we determined that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were decreased or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization of the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids have many roles in development and reproduction. We found that like JHs in Drosophila, RA was sufficient to impact mouse PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration.


Asunto(s)
Drosophila melanogaster , Hormonas Juveniles , Humanos , Ratones , Animales , Células Germinativas , Drosophila , Gónadas , Terpenos , Movimiento Celular , Mamíferos
2.
Nutr Clin Pract ; 38(5): 1045-1062, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37598397

RESUMEN

BACKGROUND: We examine here the association between malnutrition risk and adverse health outcomes among older adult patients undergoing elective surgical procedures. METHODS: We conducted a retrospective study using linked clinical and administrative databases. Malnutrition risk was assessed prior to surgery, defined by unintentional weight loss and decreased food intake. We performed a logistic regression analysis of the primary outcome, a composite adverse outcome measure, including death, bleeding, pneumonia, and other surgical complications. We conducted Fine-Gray proportional hazard regression analysis of hospital length of stay (LOS). We performed a generalized linear regression analysis of in-hospital cost data. All regression analyses controlled for frailty, age, sex, surgical category, and comorbidities. RESULTS: Of a total of 3457 older adult elective surgical patients (65-102 years), 310 (9.0%) screened positive for malnutrition risk. In multivariable regression analyses, malnutrition risk was associated with an increased risk of the composite adverse outcome (odds ratio [OR] = 1.74; 95% CI = 1.25-2.39), higher hospitalization costs (relative cost = 1.84; 95% CI = 1.59-2.13), and a decreased risk of discharge from the hospital (hazard ratio = 0.67; 95% CI = 0.59-0.77) compared with those who screened negative. CONCLUSION: Older adult patients with malnutrition risk were at an increased risk of adverse surgical outcomes, had longer LOS in the hospital, and incurred higher costs of care. It is important to screen for malnutrition risk and refer older adults for dietetic consults prior to elective surgery.


Asunto(s)
Dietética , Desnutrición , Humanos , Anciano , Estudios Retrospectivos , Bases de Datos Factuales , Procedimientos Quirúrgicos Electivos/efectos adversos , Desnutrición/epidemiología
3.
Thorax ; 78(11): 1111-1117, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37173137

RESUMEN

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.


Asunto(s)
Derrame Pleural Maligno , Humanos , Derrame Pleural Maligno/terapia , Calidad de Vida , Pleura , Catéteres de Permanencia , Disnea/terapia , Drenaje
4.
Crit Care Explor ; 5(4): e0887, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36998530

RESUMEN

In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022. STUDY SELECTION: We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model. DATA SYNTHESIS: Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8-15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1-3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34-40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46-3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO. CONCLUSIONS: COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.

5.
Cult Stud Sci Educ ; 17(2): 405-438, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35663843

RESUMEN

While there are many different frameworks seeking to identify what benefits young people might derive from participation in informal STEM (Science, Technology, Engineering and Mathematics) learning (ISL), this paper argues that the sector would benefit from an approach that foregrounds equity and social justice outcomes. We propose a new model for reflecting on equitable youth outcomes from ISL that identifies five key areas: (1) Grounded fun; (2) STEM capital; (3) STEM trajectories; (4) STEM identity work; and (5) Agency+ . The model is applied to empirical data (interviews, observations and youth portfolios) collected over one year in four UK-based ISL settings with 33 young people (aged 11-14), largely from communities that are traditionally under-represented in STEM. Analysis considers the extent to which participating youth experienced equitable outcomes, or not, in relation to the five areas. The paper concludes with a discussion of implications for ISL and how the model might support ongoing efforts to reimagine ISL as vehicle for social justice.

6.
Asia Pac J Ophthalmol (Phila) ; 10(6): 553-563, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34839343

RESUMEN

PURPOSE: To report outcomes of glaucoma drainage device (GDD) surgery based on primary or secondary glaucoma diagnosis and lens status. DESIGN: Single-center, retrospective, consecutive cohort study. METHODS: University of Florida patients aged 18 to 93 years who underwent nonvalved GDD surgery between 1996 and 2015 with a minimum of 1-year follow-up were examined. Of the 186 eyes of 186 patients enrolled, 108 had a primary glaucoma and 78 a secondary glaucoma diagnosis. Excluding 13 aphakic patients, 57 eyes were phakic and 116 pseudophakic. Mean intraocular pressure (IOP), mean number of medications, visual acuity (VA), surgical complications, and failure (IOP ≥18 mm Hg, IOP <6 mm Hg, reoperation for glaucoma, or loss of light perception) were the main outcome measures. RESULTS: No significant difference was noted in mean IOP and mean medication use (12.8 ±â€Š4.5 and 13.0 ±â€Š6.6 mm Hg on 2.0 ±â€Š1.2 and 1.5 ±â€Š1.1 medication classes, respectively), mean VA (1.08 ±â€Š0.98 and 0.94 ±â€Š0.89, respectively), failure, or numbers of complications and reoperations (P > 0.05) between eyes with primary and secondary glaucomas at up to 5 years postoperatively. Comparison of phakic and pseudophakic eyes showed a statistically significant higher success rate for the pseudophakic patient group at the ≥18 mm Hg upper limit and <6 mm Hg lower limit (P = 0.01), and significantly fewer eyes required reoperation to lower IOP (6.9% vs 23%). CONCLUSIONS: GDD surgery appears equally effective for secondary glaucomas as for primary glaucomas, and has a better outcome for pseudophakic eyes than phakic eyes.


Asunto(s)
Implantes de Drenaje de Glaucoma , Glaucoma , Estudios de Cohortes , Estudios de Seguimiento , Glaucoma/cirugía , Humanos , Presión Intraocular , Estudios Retrospectivos , Resultado del Tratamiento
7.
Sci Educ ; 105(1): 166-203, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34588711

RESUMEN

Supporting more equitable participation in science, technology, engineering, and mathematics (STEM) remains a key, persistent educational challenge. This paper employs a sociological Bourdieusian lens to explore how equitable youth outcomes might be supported through informal science learning (ISL). Drawing on multimodal, ethnographic data from four case study youth aged 11-14 from two ISL programs, we identify four areas of practice that were enacted to a greater or lesser extent in the programs in support of equitable youth outcomes. We identify how the equitable potential of these practices was realized through a disruption of dominant power relations. It is argued that ISL should focus on changing the field, rather than young people. Affordances and limitations of the Bourdieusian lens are discussed.

8.
J Glaucoma ; 30(7): 585-595, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33867503

RESUMEN

PRECIS: A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without. PURPOSE: The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery. PATIENTS AND METHODS: A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review. RESULTS: No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences. CONCLUSION: Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.


Asunto(s)
Implantes de Drenaje de Glaucoma , Glaucoma , Trabeculectomía , Adolescente , Anciano , Estudios de Seguimiento , Glaucoma/cirugía , Humanos , Presión Intraocular , Implantación de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento
9.
Development ; 148(9)2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33912935

RESUMEN

In response to signals from the embryonic testis, the germ cell intrinsic factor NANOS2 coordinates a transcriptional program necessary for the differentiation of pluripotent-like primordial germ cells toward a unipotent spermatogonial stem cell fate. Emerging evidence indicates that genetic risk factors contribute to testicular germ cell tumor initiation by disrupting sex-specific differentiation. Here, using the 129.MOLF-Chr19 mouse model of testicular teratomas and a NANOS2 reporter allele, we report that the developmental phenotypes required for tumorigenesis, including failure to enter mitotic arrest, retention of pluripotency and delayed sex-specific differentiation, were exclusive to a subpopulation of germ cells failing to express NANOS2. Single-cell RNA sequencing revealed that embryonic day 15.5 NANOS2-deficient germ cells and embryonal carcinoma cells developed a transcriptional profile enriched for MYC signaling, NODAL signaling and primed pluripotency. Moreover, lineage-tracing experiments demonstrated that embryonal carcinoma cells arose exclusively from germ cells failing to express NANOS2. Our results indicate that NANOS2 is the nexus through which several genetic risk factors influence tumor susceptibility. We propose that, in the absence of sex specification, signals native to the developing testis drive germ cell transformation.


Asunto(s)
Diferenciación Celular , Neoplasias de Células Germinales y Embrionarias , Diferenciación Sexual , Neoplasias Testiculares , Animales , Diferenciación Celular/genética , Proliferación Celular , Células Madre de Carcinoma Embrionario/metabolismo , Células Germinales Embrionarias , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones , Proteínas de Unión al ARN , Transducción de Señal , Espermatogonias/metabolismo , Teratoma
10.
BMJ Open ; 11(3): e040459, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33664067

RESUMEN

OBJECTIVES: Our objectives were to review the literature to identify frailty instruments in use for transcatheter aortic valve implantation (TAVI) recipients and synthesise prognostic data from these studies, in order to inform clinical management of frail patients undergoing TAVI. METHODS: We systematically reviewed the literature published in 2006 or later. We included studies of patients with aortic stenosis, diagnosed as frail, who underwent a TAVI procedure that reported mortality or clinical outcomes. We categorised the frailty instruments and reported on the prevalence of frailty in each study. We summarised the frequency of clinical outcomes and pooled outcomes from multiple studies. We explored heterogeneity and performed subgroup analysis, where possible. We also used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to assess the overall certainty of the estimates. RESULTS: Of 49 included studies, 21 used single-dimension measures to assess frailty, 3 used administrative data-based measures, and 25 used multidimensional measures. Prevalence of frailty ranged from 5.67% to 90.07%. Albumin was the most commonly used single-dimension frailty measure and the Fried or modified Fried phenotype were the most commonly used multidimensional measures. Meta-analyses of studies that used either the Fried or modified Fried phenotype showed a 30-day mortality of 7.86% (95% CI 5.20% to 11.70%) and a 1-year mortality of 26.91% (95% CI 21.50% to 33.11%). The GRADE system suggests very low certainty of the respective estimates. CONCLUSIONS: Frailty instruments varied across studies, leading to a wide range of frailty prevalence estimates for TAVI recipients and substantial heterogeneity. The results provide clinicians, patients and healthcare administrators, with potentially useful information on the prognosis of frail patients undergoing TAVI. This review highlights the need for standardisation of frailty measurement to promote consistency. PROSPERO REGISTRATION NUMBER: CRD42018090597.


Asunto(s)
Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Estenosis de la Válvula Aórtica/cirugía , Anciano Frágil , Humanos , Pronóstico , Factores de Riesgo , Resultado del Tratamiento
11.
Pediatr Emerg Care ; 37(12): e1070-e1074, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31464879

RESUMEN

OBJECTIVE: Guidelines exist for care of pediatric sepsis, but no study has assessed the benefit of electronic learning (eLearning) in this topic area. The objective of this multicenter study was to assess knowledge acquisition and retention for pediatric sepsis across multiple health care provider roles, using an adaptive and interactive eLearning module. METHODS: The study used pretest, posttest, and 90-day delayed test scores to evaluate provider knowledge after an adaptive and interactive eLearning module intervention. The eLearning module contained conditional logic-based assessments that allowed real-time adjustments of the displayed content according to each participant's demonstrated knowledge. Physicians, nurses, and advanced practice providers, primarily emergency department based, at 9 pediatric institutions were included. Changes in test scores were stratified by provider role. RESULTS: A total of 574 participants completed the posttest, and 296 (51.6%) of those completed the delayed test. Across all providers, there was an increase in test scores of 15.7% between the pretest and posttest (P < 0.001) with a large effect size as measured by Cramer's V. Across all providers, there was an overall test score increase of 5.2% (P < 0.001) between the pretest and delayed test, with a small effect size. CONCLUSIONS: An eLearning module improved immediate and delayed pediatric sepsis knowledge in pediatric health care providers across multiple institutions and provider roles. Immediate knowledge gain was meaningful as indicated by effect sizes, although by the time of the delayed test, the effect was smaller. This module fills an important gap in currently available pediatric sepsis education.


Asunto(s)
Instrucción por Computador , Sepsis , Niño , Curriculum , Electrónica , Humanos , Aprendizaje , Sepsis/diagnóstico , Sepsis/terapia
12.
Int J STEM Educ ; 7(1): 51, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33088672

RESUMEN

BACKGROUND: Identity provides a useful conceptual lens for understanding educational inequalities in science, technology, engineering and mathematics (STEM). In this paper, we examine how paying attention to physical and digital 'materiality' enriches our understanding of identity work, by going beyond the spoken, written and embodied dimensions of identity performances that currently dominate the area of STEM identity scholarship. We draw on a multimodal ethnographic study with 36 young people aged 11-14 carried out over the course of one year at four UK-based informal STEM learning settings. Data collection included a series of interviews, observations and youth-created portfolios focused on STEM experiences. Illustrative case studies of two young men who took part in a community-based digital arts centre are discussed in detail through the theoretical lenses of Judith Butler's identity performativity and Karen Barad's intra-action. RESULTS: We argue that physical and digital materiality mattered for the performances of 'tech identity' in that (i) the focus on the material changed our understanding of tech identity performances; (ii) digital spaces supported identity performances alongside, with and beyond physical bodies, and drew attention to new forms of identity recognition; (iii) identity performances across spaces were unpredictable and contained by the limits of material possibilities; and (iv) particular identity performances associated with technology were aligned with dominant enactments of masculinity and might thus be less accessible to some young people. CONCLUSION: We conclude the paper by suggesting that accounting for materiality in STEM identity research not only guides researchers in going beyond what participants say and are observed doing (and thus engendering richer insights), but also offers more equitable ways of enacting research. Further, we argue that more needs to be done to support the translation of identity resources across spaces, such as between experiences within informal and online spaces, on the one hand, and formal education, on the other.

13.
J Opioid Manag ; 15(3): 205-212, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31343722

RESUMEN

OBJECTIVE: This study describes the incidence of neonatal abstinence syndrome (NAS) in Ontario, Canada by year and health region from 2003 to 2016. DESIGN: The incidence of NAS diagnoses per 1,000 live births was calculated for the 36 local public health agency regions in Ontario from 2003 to 2016 using retrospective hospital admissions data. Infants with a diagnosis of NAS were identified using ICD-10 code P961. Local public health agency level data were aggregated and analyzed by geographic region and by Statistics Canada 2015 Peer Groups. RESULTS: The incidence of NAS in Ontario increased from 0.99 per 1,000 live births in 2003 to 5.94 per 1,000 live births in 2016. There were major differences in NAS incidence by geography, North Western Ontario had the greatest incidence across all years. Health regions with a rural and population center mix or mostly rural population had greater incidence rate of NAS compared to health regions with high density population centers. CONCLUSIONS: The incidence of NAS has dramatically increased across Ontario in the last decade. Actions should be taken to combat the continued increase in NAS rates, especially in health regions with disproportionately high incidence of NAS.


Asunto(s)
Analgésicos Opioides/efectos adversos , Síndrome de Abstinencia Neonatal , Trastornos Relacionados con Sustancias/complicaciones , Humanos , Incidencia , Lactante , Recién Nacido , Síndrome de Abstinencia Neonatal/epidemiología , Ontario/epidemiología , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/epidemiología
14.
BMJ Open ; 9(2): e024163, 2019 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-30782896

RESUMEN

INTRODUCTION: Aortic stenosis is a significant cause of morbidity and mortality in older patients. The advent of transcatheter aortic valve implantation (TAVI) offers an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic stenosis who are at high or intermediate risk of adverse events. Existing evidence highlights the importance of frailty as a predictor of poor outcomes post-TAVI. The objective of this study is to review the operationalisation of frailty instruments for TAVI recipients and determine clinical outcomes and the change in quality of life in frail patients undergoing TAVI. METHODS AND ANALYSIS: Methods are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. We will search relevant databases to identify published, completed but unpublished and ongoing studies. We will include studies of patients with aortic stenosis, diagnosed as frail and who underwent a TAVI procedure that report mortality, clinical outcomes or health-related quality of life. Retrospective or prospective cohort studies, randomised controlled trials and non-randomised controlled trials will be eligible for inclusion. Two researchers will independently screen articles for inclusion, with disagreements resolved by a third reviewer. One researcher will extract data with audit by a second researcher. The risk of bias in studies will be evaluated using the Quality in Prognosis Studies tool. Meta-analysis of mortality, survival curve and the change in quality of life will be performed if appropriate. Subgroup analysis, sensitivity analysis and meta-regression will be performed if necessary. ETHICS AND DISSEMINATION: Due to the nature of this study, no ethical issues are foreseen. We will disseminate the results of our systematic review through a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42018090597.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Fragilidad/epidemiología , Calidad de Vida , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Estenosis de la Válvula Aórtica/epidemiología , Anciano Frágil , Humanos , Resultado del Tratamiento , Revisiones Sistemáticas como Asunto
15.
Development ; 145(6)2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29545285

RESUMEN

Testicular teratomas result from anomalies in embryonic germ cell development. In 129 inbred mice, teratoma initiation coincides with germ cell sex-specific differentiation and the mitotic-meiotic switch: XX and XY germ cells repress pluripotency, XX germ cells initiate meiosis, and XY germ cells activate male-specific differentiation and mitotic arrest. Here, we report that expression of Nanos2, a gene that is crucial to male sex specification, is delayed in teratoma-susceptible germ cells. Decreased expression of Nanos2 was found to be due, in part, to the Nanos2 allele present in 129 mice. In teratoma-susceptible germ cells, diminished expression of genes downstream of Nanos2 disrupted processes that were crucial to male germ cell differentiation. Deficiency for Nanos2 increased teratoma incidence in 129 mice and induced developmental abnormalities associated with tumor initiation in teratoma-resistant germ cells. Finally, in the absence of commitment to the male germ cell fate, we discovered that a subpopulation of teratoma-susceptible germ cells transition into embryonal carcinoma (EC) cells with primed pluripotent features. We conclude that delayed male germ cell sex-specification facilitates the transformation of germ cells with naïve pluripotent features into primed pluripotent EC cells.


Asunto(s)
Células Madre de Carcinoma Embrionario/metabolismo , Células Germinales Embrionarias/metabolismo , Teratoma/metabolismo , Neoplasias Testiculares/metabolismo , Animales , Técnicas de Cultivo de Célula , Diferenciación Celular/genética , Citometría de Flujo , Inmunohistoquímica , Masculino , Ratones , Ratones de la Cepa 129 , Polimorfismo de Nucleótido Simple , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Procesos de Determinación del Sexo/genética
16.
Public Underst Sci ; 27(7): 772-786, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29316863

RESUMEN

This article explores science communication from the perspective of those most at risk of exclusion, drawing on ethnographic fieldwork. I conducted five focus groups and 32 interviews with participants from low-income, minority ethnic backgrounds. Using theories of social reproduction and social justice, I argue that participation in science communication is marked by structural inequalities (particularly ethnicity and class) in two ways. First, participants' involvement in science communication practices was narrow (limited to science media consumption). Second, their experiences of exclusion centred on cultural imperialism (misrepresentation and 'Othering') and powerlessness (being unable to participate or change the terms of their participation). I argue that social reproduction in science communication constructs a narrow public that reflects the shape, values and practices of dominant groups, at the expense of the marginalised. The article contributes to how we might reimagine science communication's publics by taking inclusion/exclusion and the effects of structural inequalities into account.

18.
Public Health Rep ; 132(1_suppl): 106S-110S, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28692399

RESUMEN

During the summer of 2015, the Pan American and Parapan American Games took place in the Greater Toronto area of Ontario, Canada, bringing together thousands of athletes and spectators from around the world. The Acute Care Enhanced Surveillance (ACES) system-a syndromic surveillance system that captures comprehensive hospital visit triage information from acute care hospitals across Ontario-monitored distinct syndromes throughout the games. We describe the creation and use of a risk assessment tool to evaluate alerts produced by ACES during this period. During the games, ACES generated 1420 alerts, 4 of which were considered a moderate risk and were communicated to surveillance partners for further action. The risk assessment tool was useful for public health professionals responsible for surveillance activities during the games. Next steps include integrating the tool within the ACES system.


Asunto(s)
Aniversarios y Eventos Especiales , Vigilancia en Salud Pública/métodos , Medición de Riesgo/métodos , Deportes , Canadá , Brotes de Enfermedades/prevención & control , Humanos , Encuestas y Cuestionarios/estadística & datos numéricos
19.
Mol Reprod Dev ; 84(3): 200-211, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28079292

RESUMEN

Ovarian and testicular germ cell tumors of young adults are thought to arise from defects in germ cell development, but the molecular mechanisms underlying malignant transformation are poorly understood. In this review, we focus on the biology of germ cell tumor formation in the Drosophila ovary and the mouse testis, for which evidence supports common underlying mechanisms, such as blocking initiation into the differentiation pathway, impaired lineage progression, and sexual identity instability. We then discuss how these concepts inform our understanding of the disease in humans. Mol. Reprod. Dev. 84: 200-211, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Diferenciación Celular , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias Ováricas/metabolismo , Ovario/metabolismo , Neoplasias Testiculares/metabolismo , Testículo/metabolismo , Animales , Femenino , Masculino , Ratones , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/patología , Ovario/patología , Neoplasias Testiculares/patología , Testículo/patología
20.
Cell Cycle ; 15(7): 919-30, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26901436

RESUMEN

Testicular teratomas result from anomalies in embryonic germ cell development. In the 129 family of inbred mouse strains, teratomas arise during the same developmental period that male germ cells normally enter G1/G0 mitotic arrest and female germ cells initiate meiosis (the mitotic:meiotic switch). Dysregulation of this switch associates with teratoma susceptibility and involves three germ cell developmental abnormalities seemingly critical for tumor initiation: delayed G1/G0 mitotic arrest, retention of pluripotency, and misexpression of genes normally restricted to embryonic female and adult male germ cells. One misexpressed gene, cyclin D1 (Ccnd1), is a known regulator of cell cycle progression and an oncogene in many tissues. Here, we investigated whether Ccnd1 misexpression in embryonic germ cells is a determinant of teratoma susceptibility in mice. We found that CCND1 localizes to teratoma-susceptible germ cells that fail to enter G1/G0 arrest during the mitotic:meiotic switch and is the only D-type cyclin misexpressed during this critical developmental time frame. We discovered that Ccnd1 deficiency in teratoma-susceptible mice significantly reduced teratoma incidence and suppressed the germ cell proliferation and pluripotency abnormalities associated with tumor initiation. Importantly, Ccnd1 expression was dispensable for somatic cell development and male germ cell specification and maturation in tumor-susceptible mice, implying that the mechanisms by which Ccnd1 deficiency reduced teratoma incidence were germ cell autonomous and specific to tumorigenesis. We conclude that misexpression of Ccnd1 in male germ cells is a key component of a larger pro-proliferative program that disrupts the mitotic:meiotic switch and predisposes 129 inbred mice to testicular teratocarcinogenesis.


Asunto(s)
Ciclina D1/genética , Células Germinales Embrionarias/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular , Teratoma/etiología , Neoplasias Testiculares/etiología , Animales , Proliferación Celular , Ciclina D1/metabolismo , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Células Intersticiales del Testículo/metabolismo , Masculino , Meiosis , Ratones , Ratones de la Cepa 129 , Ratones Noqueados , Mitosis , Células de Sertoli/metabolismo , Teratoma/genética , Teratoma/metabolismo , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo
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