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1.
Nat Commun ; 15(1): 6213, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043652

RESUMEN

Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.


Asunto(s)
Daño del ADN , Reparación del ADN , Inestabilidad Genómica , Ratones Transgénicos , Mutación , Obesidad , Animales , Obesidad/genética , Humanos , Ratones , Reparación del ADN/genética , Daño del ADN/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Masculino , Ratones Endogámicos C57BL , Femenino , Linfoma de Burkitt/genética , ADN/genética , ADN/metabolismo
2.
An Bras Dermatol ; 90(3 Suppl 1): 156-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26312702

RESUMEN

Neurothekeoma is an uncommon, benign neoplasm presenting in young adults, primarily on the head and neck. It was initially related to nerve sheath myxoma but with the advent of immunohistochemistry, new insights into its cellular differentiation and origin have emerged, unlinking Neurothekeoma and nerve sheath myxoma. Herein we describe a 19-year-old male who had had a frontal, flesh-colored, asymptomatic papule for 2 years. Histology showed a dermal fusocellular-spindle cell tumor, including an eosinophilic cytoplasm with mild cellular pleomorphism and moderately dense fibrous stroma. IHQ was positive for CD10 and negative for S100 and Claudin-1. These findings were compatible with cellular Neurothekeoma. The lesion was completely extirpated and at the 6-month follow-up, the patient was asymptomatic and had experienced no recurrences.


Asunto(s)
Neoplasias de la Vaina del Nervio/patología , Neurotecoma/patología , Neoplasias Cutáneas/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Masculino , Adulto Joven
3.
An. bras. dermatol ; An. bras. dermatol;90(3,supl.1): 156-159, May-June 2015. tab, ilus
Artículo en Inglés | LILACS | ID: lil-755756

RESUMEN

Abstract

Neurothekeoma is an uncommon, benign neoplasm presenting in young adults, primarily on the head and neck. It was initially related to nerve sheath myxoma but with the advent of immunohistochemistry, new insights into its cellular differentiation and origin have emerged, unlinking Neurothekeoma and nerve sheath myxoma. Herein we describe a 19-year-old male who had had a frontal, fl esh-colored, asymptomatic papule for 2 years. Histology showed a dermal fusocellular-spindle cell tumor, including an eosinophilic cytoplasm with mild cellular pleomorphism and moderately dense fi brous stroma. IHQ was positive for CD10 and negative for S100 and Claudin-1. These fi ndings were compatible with cellular Neurothekeoma. The lesion was completely extirpated and at the 6-month follow-up, the patient was asymptomatic and had experienced no recurrences.

.


Asunto(s)
Humanos , Masculino , Adulto Joven , Neoplasias de la Vaina del Nervio/patología , Neurotecoma/patología , Neoplasias Cutáneas/patología , Diagnóstico Diferencial , Inmunohistoquímica
4.
Malar J ; 12: 342, 2013 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-24059757

RESUMEN

BACKGROUND: Malaria during pregnancy is dangerous to both mother and foetus. Intermittent preventive treatment of malaria in pregnancy (IPTp) is a strategy where pregnant women in malaria-endemic countries receive full doses of sulphadoxine-pyrimethamine (SP), whether or not they have malaria. The Nigerian government adopted IPTp as a national strategy in 2005; however, major gaps affecting perception, uptake, adherence, and scale-up remain. METHODS: A cross-sectional study was conducted in peri-urban and rural communities in Nasarawa and Cross River States in Nigeria. Study instruments were based on the socio-ecological model and its multiple levels of influences, taking into account individual, community, societal, and environmental contexts of behaviour and social change. Women of reproductive age, their front-line care providers, and (in Nasarawa only) their spouses participated in focus group discussions and in-depth individual interviews. Facility sampling was purposive to include tertiary, secondary and primary health facilities. RESULTS: The study found that systems-based challenges (stockouts; lack of provider knowledge of IPTp protocols) coupled with individual women's beliefs and lack of understanding of IPT contribute to low uptake and adherence. Many pregnant women are reluctant to seek care for an illness they do not have. Those with malaria often prefer to self-medicate through drug shops or herbs, though those who seek clinic-based treatment trust their providers and willingly accept medicine prescribed. CONCLUSIONS: Failing to deliver complete IPTp to women attending antenatal care is a missed opportunity. While many obstacles are structural, programmes can target women, their communities and the health environment with specific interventions to increase IPTp uptake and adherence.


Asunto(s)
Antimaláricos/administración & dosificación , Quimioprevención/métodos , Conocimientos, Actitudes y Práctica en Salud , Malaria/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Pirimetamina/administración & dosificación , Sulfadoxina/administración & dosificación , Adolescente , Adulto , Estudios Transversales , Combinación de Medicamentos , Femenino , Humanos , Entrevistas como Asunto , Masculino , Nigeria , Embarazo , Población Rural , Población Suburbana , Adulto Joven
5.
Health Policy Plan ; 22(4): 234-45, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17475627

RESUMEN

This article reviews 44 operations research projects aiming to improve reproductive health services in Guatemala, conducted by the Population Council from 1988 to 2001. It documents the experience of the research programme, traces the extent to which research results are identifiable in existing programmes, and analyses factors influencing utilization. Utilization of research results occurs as a gradual process of information sharing, where researchers influence decision-makers through a continual stream of information rather than a single set of findings. Utilization depends on leadership, collaborative planning and implementation, close monitoring, and feasible research designs, among other factors. To influence policy formulation, organizations should form enduring links among institutions and develop critical research skills among personnel who collaborate with or manage service programmes. To understand how operations research affects policy and programme change, one must consider not just individual projects, but rather the synergistic impact of multiple projects on a broad range of themes over time.


Asunto(s)
Medicina Basada en la Evidencia , Medicina Reproductiva , Investigación , Conducta de Elección , Conducta Anticonceptiva , Servicios de Planificación Familiar , Femenino , Guatemala , Humanos , Organizaciones
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