Asunto(s)
Aborto Inducido , COVID-19 , Barreras de Comunicación , Accesibilidad a los Servicios de Salud , Tiempo de Tratamiento/estadística & datos numéricos , Aborto Inducido/economía , Aborto Inducido/métodos , Aborto Inducido/psicología , Aborto Inducido/estadística & datos numéricos , Adulto , Factores de Edad , COVID-19/epidemiología , COVID-19/prevención & control , Etnicidad , Femenino , Edad Gestacional , Accesibilidad a los Servicios de Salud/organización & administración , Accesibilidad a los Servicios de Salud/normas , Humanos , Control de Infecciones/organización & administración , Evaluación de Resultado en la Atención de Salud , Aceptación de la Atención de Salud/etnología , Aceptación de la Atención de Salud/estadística & datos numéricos , Embarazo , SARS-CoV-2 , Factores Socioeconómicos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Limited or uncertain availability of nutritionally adequate and safe food, known as food insecurity, has been associated with obesity and other adverse health outcomes, but has rarely been studied in pregnancy. Food insecurity may negatively affect behavioral and physiological changes during pregnancy and may be associated with poor perinatal outcomes including gestational weight gain. OBJECTIVE: Given the lack of information on the role of food insecurity in pregnancy and the possible relationship with perinatal outcomes such as gestational weight gain, the objective of this study was to examine the association between food insecurity and gestational weight gain in a diverse cohort of pregnant women. MATERIALS AND METHODS: This was an observational study of 299 English-speaking women who delivered live-born singleton gestations at ≥24 weeks at a single tertiary care center. During their postpartum hospitalizations, enrolled women completed a survey of food security status during pregnancy using the United States Department of Agriculture Household Food Security Survey Module. Scores were analyzed as inadequate (marginal, low, or very low) vs adequate (high) food security. Women without prepregnancy body mass index and gestational weight gain data were excluded. The primary outcome was gestational weight gain categorized as inadequate, adequate, or excessive based on 2009 National Academy of Medicine guidelines, which account for body mass index. Secondary outcomes included total gestational weight gain and other maternal and neonatal outcomes. Multivariable linear and multinomial logistic regressions were performed to assess the independent associations of food insecurity with gestational weight gain after controlling for potential confounding factors. RESULTS: Of the 299 women enrolled in the study, 11.0% (n = 33) reported inadequate food security during pregnancy. Women with inadequate food security were younger (P = .007), had a greater mean body mass index (P < .001), were more likely to be non-Hispanic black or Hispanic (P < .001) and publicly insured (P < .001), but were less likely to be employed (P < .001). Women with inadequate food security also had fewer prenatal visits (P < .001) and were less likely to have initiated prenatal care in the first trimester (P < .001). The occurrence of excessive gestational weight gain did not differ by food security status (33.3% inadequate food security vs. 43.6% adequate food security, an adjusted relative risk ratio of 0.42, 95% confidence interval 0.16 - 1.14). Median total gestational weight gain was lower for women with inadequate food security (9.2 kg, interquartile range 7.5 - 14.1) than for women with adequate food security (13.9 kg, interquartile range 10.6 - 16.7) (P < .001), and this difference persisted when controlling for potential confounders including prepregnancy body mass index (ß = -2.5, 95% confidence interval -5.0 to -0.21). CONCLUSIONS: In this diverse, urban population, more than 1 in 10 women experienced food insecurity during pregnancy. Inadequate food security was associated with lower median total gestational weight gain, but not with excessive gestational weight gain as determined by the 2009 National Academy of Medicine categories.
Asunto(s)
Ganancia de Peso Gestacional , Índice de Masa Corporal , Femenino , Inseguridad Alimentaria , Humanos , Recién Nacido , Obesidad/epidemiología , Embarazo , Estados Unidos/epidemiología , Aumento de PesoAsunto(s)
Hipertensión , Aplicaciones Móviles , Preeclampsia , Telemedicina , Femenino , Humanos , Hipertensión/diagnóstico , Preeclampsia/diagnóstico , EmbarazoRESUMEN
Recent studies have reported that the immune system significantly mediates skeletal muscle repair and regeneration. Additionally, biological scaffolds have been shown to play a role in polarizing the immune microenvironment toward pro-myogenic outcomes. Moreover, myostatin inhibitors are known to promote muscle regeneration and ameliorate fibrosis in animal models of Duchenne muscular dystrophy (DMD), a human disease characterized by chronic muscle degeneration. Biological scaffolds and myostatin inhibition can potentially influence immune-mediated regeneration in the dystrophic environment, but have not been evaluated together. Toward this end, here we created an injectable biological scaffold composed of hyaluronic acid and processed skeletal muscle extracellular matrix. This material formed a cytocompatible hydrogel at physiological temperatures in vitro When injected subfascially above the tibialis anterior muscles of both WT and dystrophic mdx-5Cv mice, a murine model of DMD, the hydrogel spreads across the entire muscle before completely degrading at 3 weeks in vivo We found that the hydrogel is associated with CD206+ pro-regenerative macrophage polarization and elevated anti-inflammatory cytokine expression in both WT and dystrophic mice. Co-injection of both hydrogel and myostatin inhibitor significantly increased FoxP3+ regulatory T cell modulation and Foxp3 gene expression in the scaffold immune microenvironment. Finally, delivery of myostatin inhibitor with the hydrogel increased its bioactivity in vivo, and transplantation of immortalized human myoblasts with the hydrogel promoted their survival in vivo This study identifies a key role for biological scaffolds and myostatin inhibitors in modulating a pro-regenerative immune microenvironment in dystrophic muscle.
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Anticuerpos Monoclonales/farmacología , Sistemas de Liberación de Medicamentos/métodos , Inmunidad Innata/efectos de los fármacos , Distrofia Muscular Animal/tratamiento farmacológico , Miostatina/antagonistas & inhibidores , Regeneración/efectos de los fármacos , Implantes Absorbibles , Animales , Matriz Extracelular/química , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Regulación de la Expresión Génica , Humanos , Ácido Hialurónico/química , Hidrogeles/química , Inmunidad Innata/genética , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Receptor de Manosa , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/inmunología , Ratones , Ratones Endogámicos mdx , Desarrollo de Músculos/efectos de los fármacos , Desarrollo de Músculos/genética , Desarrollo de Músculos/inmunología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/inmunología , Músculo Esquelético/patología , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/inmunología , Distrofia Muscular Animal/patología , Mioblastos/citología , Mioblastos/efectos de los fármacos , Mioblastos/inmunología , Miostatina/genética , Miostatina/inmunología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Regeneración/genética , Regeneración/inmunología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Andamios del TejidoRESUMEN
Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in prostate cancer cells and tumors. This isoform is transcribed from an alternative promoter and results in a protein with an amino-terminal extension. Prostate cancer cell lines and prostate tumors express more BTK-C transcript than the malignant NAMALWA B-cell line or human lymphomas. BTK protein expression is also observed in tumor tissue from prostate cancer patients. Down regulation of this protein with RNAi or inhibition with BTK-specific inhibitors, Ibrutinib, AVL-292 or CGI-1746 decrease cell survival and induce apoptosis in prostate cancer cells. Microarray results show that inhibiting BTK under these conditions increases expression of apoptosis related genes, while overexpression of BTK-C is associated with elevated expression of genes with functions related to cell adhesion, cytoskeletal structure and the extracellular matrix. These results are consistent with studies that show that BTK signaling is important for adhesion and migration of B cells and suggest that BTK-C may confer similar properties to prostate cancer cells. Since BTK-C is a survival factor for these cells, it represents both a potential biomarker and novel therapeutic target for prostate cancer.