Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 81
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
PLoS Pathog ; 19(1): e1011081, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36701396

RESUMEN

Fasciola hepatica infection is responsible for substantial economic losses in livestock worldwide and poses a threat to human health in endemic areas. The mainstay of control in livestock and the only drug licenced for use in humans is triclabendazole (TCBZ). TCBZ resistance has been reported on every continent and threatens effective control of fasciolosis in many parts of the world. To date, understanding the genetic mechanisms underlying TCBZ resistance has been limited to studies of candidate genes, based on assumptions of their role in drug action. Taking an alternative approach, we combined a genetic cross with whole-genome sequencing to localise a ~3.2Mbp locus within the 1.2Gbp F. hepatica genome that confers TCBZ resistance. We validated this locus independently using bulk segregant analysis of F. hepatica populations and showed that it is the target of drug selection in the field. We genotyped individual parasites and tracked segregation and reassortment of SNPs to show that TCBZ resistance exhibits Mendelian inheritance and is conferred by a dominant allele. We defined gene content within this locus to pinpoint genes involved in membrane transport, (e.g. ATP-binding cassette family B, ABCB1), transmembrane signalling and signal transduction (e.g. GTP-Ras-adenylyl cyclase and EGF-like protein), DNA/RNA binding and transcriptional regulation (e.g. SANT/Myb-like DNA-binding domain protein) and drug storage and sequestration (e.g. fatty acid binding protein, FABP) as prime candidates for conferring TCBZ resistance. This study constitutes the first experimental cross and genome-wide approach for any heritable trait in F. hepatica and is key to understanding the evolution of drug resistance in Fasciola spp. to inform deployment of efficacious anthelmintic treatments in the field.


Asunto(s)
Antihelmínticos , Fasciola hepatica , Fascioliasis , Animales , Humanos , Triclabendazol/metabolismo , Triclabendazol/farmacología , Triclabendazol/uso terapéutico , Bencimidazoles/farmacología , Antihelmínticos/farmacología , Fascioliasis/tratamiento farmacológico , Fascioliasis/parasitología , Resistencia a Medicamentos
2.
Plant Cell ; 32(9): 2742-2762, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32699170

RESUMEN

While root diseases are among the most devastating stresses in global crop production, our understanding of root immunity is still limited relative to our knowledge of immune responses in leaves. Considering that root performance is based on the concerted functions of its different cell types, we undertook a cell type-specific transcriptome analysis to identify gene networks activated in epidermis, cortex, and pericycle cells of Arabidopsis (Arabidopsis thaliana) roots challenged with two immunity elicitors, the bacterial flagellin-derived flg22 and the endogenous Pep1 peptide. Our analyses revealed distinct immunity gene networks in each cell type. To further substantiate our understanding of regulatory patterns underlying these cell type-specific immunity networks, we developed a tool to analyze paired transcription factor binding motifs in the promoters of cell type-specific genes. Our study points toward a connection between cell identity and cell type-specific immunity networks that might guide cell types in launching immune response according to the functional capabilities of each cell type.


Asunto(s)
Arabidopsis/citología , Arabidopsis/inmunología , Redes Reguladoras de Genes/inmunología , Raíces de Plantas/inmunología , Arabidopsis/fisiología , Proteínas de Arabidopsis , Basidiomycota , Sitios de Unión , Regulación de la Expresión Génica de las Plantas , Células Vegetales/inmunología , Inmunidad de la Planta/genética , Inmunidad de la Planta/fisiología , Raíces de Plantas/citología , Raíces de Plantas/microbiología , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Transducción de Señal , Transactivadores
3.
Pediatr Blood Cancer ; 69(3): e29550, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34971076

RESUMEN

Chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect of pediatric cancer therapy, can be challenging to diagnose. We estimated the prevalence of newly identified and previously diagnosed CIPN in the regional HEROS Childhood Cancer Survivorship Clinic. From 2016 to 2018, 148 survivors (45.3% female, age 17.1 [SD 7.7] years, 81.8% in ongoing routine oncology follow-up) had their initial survivorship evaluation at an average of 7.4 (SD 6.6) years from diagnosis. Fifty-six survivors (37.8%) had CIPN, of these 46 (82.1%) were newly identified. Our findings demonstrate CIPN may be missed in routine oncology care, and new methods are needed to screen for CIPN.


Asunto(s)
Antineoplásicos , Supervivientes de Cáncer , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Adolescente , Antineoplásicos/efectos adversos , Niño , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/epidemiología , Supervivencia
4.
J Fam Nurs ; 28(4): 368-380, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35491764

RESUMEN

Reproductive loss, which includes miscarriage and nongestational loss, such as adoption loss, is rarely recognized as part of the family-building journey. Such loss tends to be even more invisible among LGBTQ individuals. The current study examines the experiences of 80 LGBTQ individuals who experienced adoption-related losses (i.e., failed adoption matches, child removals, disrupted child placements), with attention to how these losses impacted them and what enabled them to move forward. Participants who pursued private domestic adoption experienced failed matches (i.e., birth parents deciding to parent or choosing another family) both before (n = 21) and/or after (n = 24) a child was born. Participants who pursued public domestic adoption experienced child removals involving reunification with birth parents (n = 14) and other birth relatives (n = 18), as well as disrupted placements initiated by parents (n = 10) and children (n = 7). Failed matches, child removals, and disrupted placements were typically experienced as "crushing" and invisible losses. They were often followed by a period of grieving, and sometimes prompted adjustments to the type of matches or placements participants would consider (e.g., to mitigate the likelihood of future similar losses). Moving forward from adoption losses was facilitated by support from partners and those who experienced similar losses, knowledge or hope regarding the children once in their care, and finally being placed with the child(ren) whom they ultimately legally adopted.


Asunto(s)
Adopción , Minorías Sexuales y de Género , Niño , Pesar , Humanos , Padres
5.
J Fam Nurs ; 28(4): 381-395, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36221248

RESUMEN

Lesbian, gay, bisexual, transgender, and queer (LGBTQ) families have expanded our understanding of who counts as family, to include legal as well as chosen ties. Yet, nonbiological parents in LGBTQ families are vulnerable to invalidation and erasure in social institutions, including health care, legal, and educational settings, where genetic and gestational linkages are privileged. The current study was guided by a queer phenomenological perspective to examine how LGBTQ parents experience and respond to dominant norms related to family relatedness and membership and thus queer the family. This mixed-methods study sampled 250 LGBTQ parents (including cisgender women and trans/nonbinary participants) to examine the question: In what ways does genetic asymmetry matter for families? The qualitative and quantitative analyses yielded three primary findings that revealed experiences of erasure and discrimination, as well as proactive strategies and active resistance used to counteract these difficulties. Themes were organized by (a) encountering marginalization and invalidation: health care, schools, and beyond; (b) strategic actions and discursive practices toward parental equality; and (c) confronting and resisting the need for legal, symbolic, and parenting strategies. This study documents ways in which nonbiological LGBTQ parents, in particular, embrace and resist societal norms for biological connectedness. Implications for nursing professionals include our finding that reproductive and perinatal contexts were particular sites of invalidation, necessitating education about the range of queer, nonbiological, and trans/nonbinary parents so that all parents are included in professional health care encounters.


Asunto(s)
Minorías Sexuales y de Género , Bisexualidad , Femenino , Identidad de Género , Humanos , Padres , Embarazo , Conducta Sexual
6.
J Women Aging ; 34(6): 692-705, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33896403

RESUMEN

This study explored experiences of 23 Black women owners and operators of Adult Foster Care (AFC) homes for midlife and older adults. Semi-structured interview data focusing on multiple dimensions of the care context were analyzed using grounded theory methods. Women leveraged their resources as they invested their expertise, time, and relationships to support their residents and embraced the value of residents for their contribution to the success of AFC settings. The findings underline the critical roles of these AFC providers in maintaining safe and home-like care contexts for aging adults, in the face of systemic challenges.


Asunto(s)
Cuidados en el Hogar de Adopción , Servicios de Atención de Salud a Domicilio , Anciano , Envejecimiento , Femenino , Teoría Fundamentada , Humanos , Negociación
7.
Fam Process ; 60(3): 866-887, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34227099

RESUMEN

The COVID-19 pandemic has caused significant stress for individuals, couples, and families. Divorced and separated couples with children face unique stresses amid the pandemic. This mixed-methods study explored these challenges among 296 divorced and separated parents: namely 204 women formerly partnered with men, 34 men formerly partnered with women, and 58 women formerly partnered with women, who were surveyed during Summer/Fall of 2020. Participants described legal, financial, and coparenting challenges. Those who were not yet divorced described difficulties filing for or finalizing their divorce because of court closures and lack of responsiveness from legal professionals. Those who were already divorced also faced legal challenges, such as being unable to obtain a court date to modify custody arrangements. Financial challenges included renegotiating financial support obligations in the context of job loss. Salient coparenting conflicts, explored through closed- and open-ended questions, included communication issues, different views on virus risk mitigation behaviors, financial issues (especially for those not yet divorced), and transitioning between households and handling remote schooling (especially for those with shared physical custody). Participants elaborated on COVID-19-specific challenges, revealing that (a) lack of communication or agreement regarding shared strategies for risk mitigation reflected and exacerbated challenging dynamics between coparents, (b) remote schooling was often the site of disagreement when one parent felt that they were doing more than their fair share of coordination and oversight, and (c) different perspectives on science were expected to lead to future contention when making a joint decision about whether to vaccinate children. Findings have implications for family and legal professionals working with divorced, divorcing, and separated parents.


La pandemia de la COVID-19 ha generado mucho estrés en las personas, las parejas y las familias. Las parejas separadas y divorciadas que tienen niños enfrentan tensiones únicas en medio de la pandemia. En este estudio de métodos combinados se analizaron estas dificultades entre 296 padres divorciados y separados, por ejemplo, 204 mujeres que antes estaban en pareja con hombres, 34 hombres que antes estaban en pareja con mujeres y 58 mujeres que antes estaban en pareja con mujeres, a quienes se los encuestó durante el verano/otoño de 2020. Los participantes describieron las dificultades legales, económicas y de cocrianza. Aquellos que aún no estaban divorciados describieron dificultades para presentar la demanda de divorcio o para finalizar su divorcio debido a los cierres de los juzgados y a la falta de respuesta de los abogados. Los que ya estaban divorciados también enfrentaron dificultades legales, como no poder obtener una cita en el juzgado para modificar los acuerdos de tenencia. Entre las dificultades económicas se encontraron la renegociación de las obligaciones de ayuda económica en el contexto de la pérdida del empleo. Los conflictos de cocrianza más destacados, analizados mediante preguntas cerradas y abiertas, fueron los problemas de comunicación, los diferentes puntos de vista sobre las conductas de disminución del riesgo de contagio del virus, los problemas económicos (especialmente para aquellos que aún no estaban divorciados) y la transición entre hogares y el manejo de las clases virtuales (especialmente para aquellos con tenencia compartida). Los participantes explicaron en profundidad las dificultades específicas de la COVID-19, y revelaron que (a) la falta de comunicación o de acuerdo con respecto a las estrategias compartidas para la reducción de riesgos reflejaron y exacerbaron la dinámica compleja entre los copadres, (b) las clases virtuales fueron generalmente el punto de desacuerdo cuando uno de los padres sentía que estaba haciendo más de lo que le correspondía con respecto a la coordinación y la supervisión, y (c) se esperó que los diferentes puntos de vista sobre la ciencia condujeran a futuras disputas a la hora de tomar una decisión conjunta acerca de si vacunar o no a los niños. Los resultados tienen consecuencias para los especialistas en familia y en leyes que trabajan con padres divorciados, que se están divorciando y separados.


Asunto(s)
COVID-19 , Divorcio , Responsabilidad Parental , Padres , Niño , Custodia del Niño , Divorcio/economía , Divorcio/legislación & jurisprudencia , Relaciones Familiares , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Estados Unidos
8.
J Women Aging ; 33(2): 184-200, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33164694

RESUMEN

Relational dissolution is often characterized by heightened feelings, especially around co-parenting and child custody. Lesbian mothers may experience their emotions in uniquely nuanced ways due to intersections among female gender, minority sexual orientation, and family structural change. Framed by a critical feminist perspective, we conducted a qualitative analysis of telephone interview and online survey responses by 17 lesbian adoptive mothers whose relationship ended. Four emotional response patterns emerged - mostly positive, mixed feelings, mostly negative, very negative - corresponding to four adaptation patterns: adapted, improving, stalled, and stuck. We provide implications for individuals, families, and societal change related to LGBTQ divorcing families.


Asunto(s)
Adopción , Divorcio , Emociones , Homosexualidad Femenina/psicología , Madres/psicología , Adulto , Ajuste Emocional , Femenino , Humanos , Relaciones Interpersonales , Persona de Mediana Edad , Responsabilidad Parental/psicología , Minorías Sexuales y de Género
9.
Ann Emerg Med ; 76(3): 318-327, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32241746

RESUMEN

Despite consensus recommendations from the American College of Emergency Physicians (ACEP), the Centers for Disease Control and Prevention, and the surgeon general to dispense naloxone to discharged ED patients at risk for opioid overdose, there remain numerous logistic, financial, and administrative barriers to implementing "take-home naloxone" programs at individual hospitals. This article describes the recent collective experience of 7 Chicago-area hospitals in implementing take-home naloxone programs. We highlight key barriers, such as hesitancy from hospital administrators, lack of familiarity with relevant rules and regulations in regard to medication dispensing, and inability to secure a supply of naloxone for dispensing. We also highlight common facilitators of success, such as early identification of a "C-suite" champion and the formation of a multidisciplinary team of program leaders. Finally, we provide recommendations that will assist emergency departments planning to implement their own take-home naloxone programs and will inform policymakers of specific needs that may facilitate dissemination of naloxone to the public.


Asunto(s)
Sobredosis de Droga/prevención & control , Servicio de Urgencia en Hospital/legislación & jurisprudencia , Implementación de Plan de Salud/legislación & jurisprudencia , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Trastornos Relacionados con Opioides/prevención & control , Alta del Paciente , Chicago , Humanos , Gobierno Estatal
10.
J Am Pharm Assoc (2003) ; 60(6): e324-e331, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32690447

RESUMEN

OBJECTIVE: To describe the development of an ED-based take-home naloxone (THN) program in which naloxone kits are dispensed directly to patients during ED discharge. PRACTICE DESCRIPTION: Our THN program was carried out at an urban academic hospital in downtown Chicago, IL. The THN kits consisted of 3 vials of 0.4-mg naloxone and 3 sterile syringes and needles for intramuscular delivery. Any member of the ED team (e.g., physician, pharmacist, or nurse) could recommend naloxone dispensing for a patient; however only the treating ED physician served as the prescriber for record. The ED pharmacist provided bedside education on recognizing opioid overdose and administering naloxone. The naloxone kit was dispensed to the patient at no cost. PRACTICE INNOVATION: This ED pharmacist-led naloxone dispensing model bypasses barriers to naloxone filling and ensures that patients walk out of the emergency department with naloxone in hand. EVALUATION METHODS: We report key metrics from the first 16 months of program implementation, including the number of ED visits for opioid overdose and THN kits dispensed. We further describe the key facilitators and barriers to program development. RESULTS: Over 16 months, our emergency department had 669 unique visits for opioid overdose, and we dispensed 168 THN kits (10.5 per month). We are aware of at least 3 cases in which our THN kits were used to reverse opioid overdose. We faced key informational barriers to program development, such as a lack of knowledge regarding the allowability of ED medication dispensing, as well as financial barriers, such as the need to obtain a supply of naloxone. We also recognized the key facilitators of success, such as early engagement with hospital leadership. CONCLUSION: Implementing a successful THN program is possible in the ED setting, and individual hospital emergency departments seeking to build their own program may benefit from our report.


Asunto(s)
Sobredosis de Droga , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Chicago , Sobredosis de Droga/tratamiento farmacológico , Servicio de Urgencia en Hospital , Humanos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Desarrollo de Programa
11.
J Lesbian Stud ; 24(1): 12-24, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31131737

RESUMEN

Despite shifts in societal attitudes, lesbian women who separate and divorce still must cope with recriminating societal messages that blame and condemn them for not conforming to the gendered heteronormative dictate of married motherhood. Guided by feminist theory, we conducted a qualitative analysis of narratives from 17 adoptive lesbian mothers who had dissolved their relationship. The women's narratives revealed five cultural discourses that they variously embraced, resisted, or disrupted: (1) the ideology of the good mother; (2) divorce is bad for children; (3) marriage is the ideal way to live; (4) couples should stay together for the children; and (5) lesbian ex-lovers should be lifelong friends. All women embraced the cultural belief in "the good mother," which is the linchpin of gendered oppression, but they were much more disruptive regarding the remaining four discourses surrounding marriage, divorce, and lesbian relationships. Their assessments of life after separation revealed that divorce can actually be better than marriage for their children; marriage is often overrated; having children can complicate a marriage; and remaining friends with one's ex-partner is not always desirable. The feminist tenet that oppression and agency coexist was revealed as the women both engaged and resisted dominant cultural narratives in order to navigate the dilemmas of crafting a new life for themselves and their children post-divorce.


Asunto(s)
Divorcio , Homosexualidad Femenina , Matrimonio , Madres , Minorías Sexuales y de Género , Adulto , Divorcio/psicología , Femenino , Homosexualidad Femenina/psicología , Humanos , Matrimonio/psicología , Persona de Mediana Edad , Madres/psicología , Minorías Sexuales y de Género/psicología , Normas Sociales
12.
J Women Aging ; 31(3): 192-212, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29452052

RESUMEN

Researchers consider older women in rural Appalachia to have low levels of agency and high levels of fatalism regarding decision making about cancer treatment. Using the life course perspective, we examined older women's agency with information seeking about gynecological cancer. Semistructured interviews with 20 White women living in central Appalachia revealed four trajectories: Surrendering Control, Accepting Death, Self-Care, and Advocacy, each with its own forms of agency. Some women experienced personal transformation, increased self-efficacy, and a passion for community empowerment. Fatalism was not understood apart from placing trust in medical expertise. We implore researchers to further explore rural expressions of agency.


Asunto(s)
Neoplasias de los Genitales Femeninos/psicología , Conducta en la Búsqueda de Información , Aceptación de la Atención de Salud/psicología , Autonomía Personal , Autoeficacia , Anciano , Anciano de 80 o más Años , Región de los Apalaches , Toma de Decisiones , Femenino , Humanos , Investigación Cualitativa , Población Rural
13.
J Biol Chem ; 291(11): 5664-5675, 2016 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-26797128

RESUMEN

AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activity is inhibited in settings of insulin resistance. Exposure to a high glucose concentration has recently been shown to increase phosphorylation of AMPK at Ser(485/491) of its α1/α2 subunit; however, the mechanism by which it does so is not known. Diacylglycerol (DAG), which is also increased in muscle exposed to high glucose, activates a number of signaling molecules including protein kinase (PK)C and PKD1. We sought to determine whether PKC or PKD1 is involved in inhibition of AMPK by causing Ser(485/491) phosphorylation in skeletal muscle cells. C2C12 myotubes were treated with the PKC/D1 activator phorbol 12-myristate 13-acetate (PMA), which acts as a DAG mimetic. This caused dose- and time-dependent increases in AMPK Ser(485/491) phosphorylation, which was associated with a ∼60% decrease in AMPKα2 activity. Expression of a phosphodefective AMPKα2 mutant (S491A) prevented the PMA-induced reduction in AMPK activity. Serine phosphorylation and inhibition of AMPK activity were partially prevented by the broad PKC inhibitor Gö6983 and fully prevented by the specific PKD1 inhibitor CRT0066101. Genetic knockdown of PKD1 also prevented Ser(485/491) phosphorylation of AMPK. Inhibition of previously identified kinases that phosphorylate AMPK at this site (Akt, S6K, and ERK) did not prevent these events. PMA treatment also caused impairments in insulin-signaling through Akt, which were prevented by PKD1 inhibition. Finally, recombinant PKD1 phosphorylated AMPKα2 at Ser(491) in cell-free conditions. These results identify PKD1 as a novel upstream kinase of AMPKα2 Ser(491) that plays a negative role in insulin signaling in muscle cells.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Insulina/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Proteína Quinasa C/metabolismo , Transducción de Señal , Animales , Línea Celular , Ratones , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/metabolismo , Fosforilación , Serina/metabolismo
14.
Arch Biochem Biophys ; 623-624: 49-57, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28526426

RESUMEN

AMP-activated protein kinase (AMPK) is an enzyme crucial in cellular metabolism found to be inhibited in many metabolic diseases including type 2 diabetes. Thiazolidinediones (TZDs) are a class of anti-diabetic drug known to activate AMPK through increased phosphorylation at Thr172, however there has been no research to date on whether they have any effect on inhibition of AMPK's lesser known site of inhibition, Ser485/491. HepG2 cells were treated with troglitazone and phosphorylation of AMPK was found to increase at both Thr172 and Ser485 in a dose- and time-dependent manner. Treatment of HepG2 cells with insulin and PMA led to increases in p-AMPK Ser485 via Akt and PKD1 respectively; however these kinases were not found to be implicated in increases seen from troglitazone. Incubation with the other TZDs, rosiglitazone and pioglitazone, let to a minor increase in p-AMPK Ser485 phosphorylation as well as AMPK activity; however these findings were significantly less than those of troglitazone under equal conditions. These data suggest that the effects of troglitazone on AMPK are more complex than previously thought. Phosphorylation at sites of both activation and inhibition can occur in tandem, although the mechanism by which this occurs has not yet been elucidated.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Cromanos/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Activación Enzimática/efectos de los fármacos , Hipoglucemiantes/farmacología , Tiazolidinedionas/farmacología , Diabetes Mellitus Tipo 2/metabolismo , Células Hep G2 , Humanos , Insulina/metabolismo , Fosforilación/efectos de los fármacos , Pioglitazona , Rosiglitazona , Troglitazona
16.
Aust N Z J Psychiatry ; 50(5): 473-80, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26113745

RESUMEN

OBJECTIVE: The molecular and cellular basis of structural and functional abnormalities of the hippocampus found in schizophrenia is currently unclear. Postnatal neurogenesis contributes to hippocampal function in animal models and is correlated with hippocampal volume in primates. Reduced hippocampal cell proliferation has been previously reported in schizophrenia, which may contribute to hippocampal dysfunction. METHOD: We measured the cell proliferation marker, Ki67, in post-mortem hippocampal tissue from patients with schizophrenia (n = 10) and matched controls (n = 16). Ki67-labelled cells were counted within the dentate gyrus and hilus on sections taken from the anterior hippocampus. RESULTS: We replicated the finding of a significant reduction in Ki67+ cells/mm² in schizophrenia cases compared to controls (t24 = 2.1, p = 0.023). In our relatively small sample, we did not find a relationship between Ki67+ cells and age overall, or between Ki67 + cells and duration of illness or antipsychotic treatment in people with schizophrenia. CONCLUSION: Our results confirm that reduced hippocampal cell proliferation may be present in schizophrenia. Restoring hippocampal neurogenesis may be a potential therapeutic target for the treatment of hippocampal dysfunction in schizophrenia.


Asunto(s)
Proliferación Celular , Giro Dentado/patología , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Giro Dentado/metabolismo , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Esquizofrenia/metabolismo , Adulto Joven
17.
J Health Commun ; 21(2): 257-65, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26735927

RESUMEN

Research suggests that communications about racial health disparities may adversely affect Blacks. In this study, we varied the message content (Black-White cardiovascular-related disparities + neutral health topics vs. neutral health topics only) embedded in public service announcements given to Black and White participants (N = 86) and had them complete a purported health self-assessment. We used the number of items completed as a measure of task persistence. Our results showed that participants in the disparities condition completed fewer items on average than participants in the neutral condition (p < .01). Planned contrasts revealed that this effect was driven by the responses of Blacks who completed fewer items in the disparities condition (p < .01), though Whites evinced a comparable condition-based trend (p = .12). We found no Black-White differences in the number of items completed in either of our experimental conditions (ps ≥ .53). Although preliminary, our findings suggest that Blacks and Whites exposed to comparative racial disparities messaging about cardiovascular diseases could experience reduced task persistence. Research implications and study limitations are also discussed.


Asunto(s)
Negro o Afroamericano/psicología , Comunicación en Salud/métodos , Disparidades en el Estado de Salud , Análisis y Desempeño de Tareas , Adolescente , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etnología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Población Blanca/psicología , Población Blanca/estadística & datos numéricos , Adulto Joven
18.
BMC Neurosci ; 16: 4, 2015 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-25886766

RESUMEN

BACKGROUND: Testosterone attenuates postnatal hippocampal neurogenesis in adolescent male rhesus macaques through altering neuronal survival. While brain-derived neurotropic factor (BDNF)/ tyrosine kinase receptor B (TrkB) are critical in regulating neuronal survival, it is not known if the molecular mechanism underlying testosterone's action on postnatal neurogenesis involves changes in BDNF/TrkB levels. First, (1) we sought to localize the site of synthesis of the full length and truncated TrkB receptor in the neurogenic regions of the adolescent rhesus macaque hippocampus. Next, (2) we asked if gonadectomy or sex hormone replacement altered hippocampal BDNF and TrkB expression level in mammalian hippocampus (rhesus macaque and Sprague Dawley rat), and (3) if the relationship between BDNF/TrkB expression was altered depending on the sex steroid environment. RESULTS: We find that truncated TrkB mRNA+ cells are highly abundant in the proliferative subgranular zone (SGZ) of the primate hippocampus; in addition, there are scant and scattered full length TrkB mRNA+ cells in this region. Gonadectomy or sex steroid replacement did not alter BDNF or TrkB mRNA levels in young adult male rat or rhesus macaque hippocampus. In the monkey and rat, we find a positive correlation with cell proliferation and TrkB-TK+ mRNA expression, and this positive relationship was found only when sex steroids were present. CONCLUSIONS: We suggest that testosterone does not down-regulate neurogenesis at adolescence via overall changes in BDNF or TrkB expression. However, BDNF/TrkB mRNA appears to have a greater link to cell proliferation in the presence of circulating testosterone.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/crecimiento & desarrollo , Hipocampo/metabolismo , ARN Mensajero/metabolismo , Receptor trkB/metabolismo , Testosterona/metabolismo , Animales , Bromodesoxiuridina , Hipocampo/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Inmunohistoquímica , Hibridación in Situ , Antígeno Ki-67/metabolismo , Macaca mulatta , Masculino , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Orquiectomía , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Especificidad de la Especie , Nicho de Células Madre/efectos de los fármacos , Nicho de Células Madre/fisiología , Testosterona/administración & dosificación
19.
Horm Behav ; 70: 73-84, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25747465

RESUMEN

Although sex steroids are known to modulate brain dopamine, it is still unclear how testosterone modifies locomotor behaviour controlled, at least in part, by striatal dopamine in adolescent males. Our previous work suggests that increasing testosterone during adolescence may bias midbrain neurons to synthesise more dopamine. We hypothesised that baseline and amphetamine-induced locomotion would differ in adult males depending on testosterone exposure during adolescence. We hypothesised that concomitant stimulation of estrogen receptor signaling, through a selective estrogen receptor modulator (SERM), raloxifene, can counter testosterone effects on locomotion. Male Sprague-Dawley rats at postnatal day 45 were gonadectomised (G) or sham-operated (S) prior to the typical adolescent testosterone increase. Gonadectomised rats were either given testosterone replacement (T) or blank implants (B) for six weeks and sham-operated (i.e. intact or endogenous testosterone group) were given blank implants. Subgroups of sham-operated, gonadectomised and gonadectomised/testosterone-replaced rats were treated with raloxifene (R, 5mg/kg) or vehicle (V), daily for the final four weeks. There were six groups (SBV, GBV, GTV, SBR, GBR, GTR). Saline and amphetamine-induced (1.25mg/kg) locomotion in the open field was measured at PND85. Gonadectomy increased amphetamine-induced locomotion compared to rats with endogenous or with exogenous testosterone. Raloxifene increased amphetamine-induced locomotion in rats with either endogenous or exogenous testosterone. Amphetamine-induced locomotion was negatively correlated with testosterone and this relationship was abolished by raloxifene. Lack of testosterone during adolescence potentiates and testosterone exposure during adolescence attenuates amphetamine-induced locomotion. Treatment with raloxifene appears to potentiate amphetamine-induced locomotion and to have an opposite effect to that of testosterone in male rats.


Asunto(s)
Anfetamina/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Actividad Motora/efectos de los fármacos , Clorhidrato de Raloxifeno/antagonistas & inhibidores , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Testosterona/farmacología , Animales , Dopamina/metabolismo , Sinergismo Farmacológico , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Orquiectomía , Tamaño de los Órganos/efectos de los fármacos , Clorhidrato de Raloxifeno/farmacología , Ratas , Ratas Sprague-Dawley , Vesículas Seminales/anatomía & histología , Vesículas Seminales/efectos de los fármacos
20.
Inquiry ; 61: 469580241248130, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38785261

RESUMEN

Social care practitioners are often under-represented in research activity and output. Evidence-based practice enables social care practitioners to develop/engage the skills to evaluate evidence and be more actively involved in research. REalist Synthesis Of non-pharmacologicaL interVEntions for antipsychotic-induced weight gain (RESOLVE) is a NIHR-funded study where realist synthesis is used to understand and explain how, why, for whom, and in what contexts non-pharmacological interventions help service users, with severe mental illness, to manage antipsychotic-induced weight gain. Social care practitioners are a key part of the team providing care for people living with severe mental illness and therefore supporting antipsychotic-induced weight gain. The current study, RESOLVE 2, uses realist evaluation and RESOLVE as an illustrative example to help understand why and how social care practitioners engage (or not) with research. Semi-structured, audio-recorded interviews will be undertaken with a purposive sample of approximately 20 social care practitioners working with people who have severe mental illness, are treated with antipsychotics, and have experienced weight gain. Participants will be recruited from NHS Trusts and recruitment avenues such as social media and personal networks. Topics discussed during interviews will include barriers and facilitators to engagement in research, current, and past engagement as well as recommendations for researchers and other practitioners. Interview recordings will be transcribed verbatim and analyzed using realist evaluation which will allow in-depth causal explanations for research engagement. Better understanding of research engagement by social care practitioners will allow for evidence-based practice and better patient outcomes within these settings.


Asunto(s)
Antipsicóticos , Trastornos Mentales , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/terapia , Antipsicóticos/uso terapéutico , Investigación sobre Servicios de Salud , Aumento de Peso , Entrevistas como Asunto , Práctica Clínica Basada en la Evidencia , Servicio Social
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA