RESUMEN
Pericytes are multifunctional cells wrapped around capillary endothelia, essential for vascular health, development, and blood flow regulation, although their role in human placental chorionic villi has not been fully explored. The second half of normal pregnancy is characterized by a progressive decline in placental and fetal oxygen levels which, by term, comprises a substantial degree of hypoxia. We hypothesized this hypoxia would stimulate pericyte regulation of chorionic villous capillary function. This study's objective was to investigate the role of hypoxia on normal term placental pericytes (PLVP) and their signaling to endothelial cells. First, we confirmed fetoplacental hypoxia at term by a new analysis of umbilical arterial blood oxygen tension of 3,010 healthy singleton neonates sampled at caesarean section and before labor. We then measured the release of cytokines, chemokines, and small extracellular vesicles (PLVPsv), from PLVP cultured at 20%, 8% and 1% O2. As O2 levels decreased, secreted cytokines and chemokines [interleukin-6 (IL-6), interleukin-1α (IL-1α) and vascular endothelial growth factor (VEGF)], and small extracellular vesicle markers, (Alix, Syntenin and CD9) increased significantly in the culture supernatants. When primary human umbilical vein endothelial cells (HUVEC) were cultured with PLVPsv, polygon formation, number, and tube formation length was significantly increased compared to cells not treated with PLVPsv, indicating PLVPsv stimulated angiogenesis. We conclude that adding PLVPsv stimulates angiogenesis and vessel stabilization on neighboring endothelial cells in response to hypoxia in term pregnancy compared to no addition of PLVPsv. Our finding that PLVP can release angiogenic molecules via extracellular vesicles in response to hypoxia may apply to other organ systems.
Asunto(s)
Vesículas Extracelulares , Placenta , Recién Nacido , Femenino , Embarazo , Humanos , Placenta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Pericitos/metabolismo , Cesárea , Hipoxia/metabolismo , Oxígeno/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Citocinas/metabolismo , Vesículas Extracelulares/metabolismoRESUMEN
Accipiter bicolor is a widely distributed Neotropical raptor but knowledge about its ecology is poor, particularly in urban areas. In this work, we document the presence of A. bicolor in the city of Guayaquil and in nearby forested areas, in addition, we provide new records on its diet and discuss possible foraging strategies in synanthropic environments. Also, reports of this species are considered on citizen science platforms. Accipiter bicolor was observed consuming an individual of Columbina bluckeyi and another of Artibeus fraterculus; near a colony of this species of bat. Finally, we found 59 records of A. bicolor between 2007 and 2022 for Guayaquil and its surrounding areas, 14 records were in urban habitats. Observations in different urban and peri-urban habitats are discussed, as well as their feeding habits.
Accipiter bicolor es una rapaz Neotropical ampliamente distribuida pero el conocimiento sobre su ecología es escaso en particular en zonas urbanas. En este trabajo, documentamos la presencia de A. bicolor en la ciudad de Guayaquil y en áreas boscosas cercanas, además, proveemos nuevos registros sobre su dieta y discutimos posibles estrategias de forrajeo en ambientes sinantrópicas. También, se consideran reportes de esta especie en plataformas de ciencia ciudadana. Accipiter bicolor fue observada consumiendo un individuo de Columbina bluckeyi y otro de Artibeus fraterculus; cerca de una colonia de esta especie de murciélago. Finalmente, se encontraron 59 registros de A. bicolor entre el 2007 y 2022 para Guayaquil y sus áreas circundantes, 14 registros fueron en hábitat urbanos. Se discute las observaciones en diferentes hábitats urbanos y periurbanos, así como sus hábitos de alimenticios.
RESUMEN
Preeclampsia (PE) is a multisystem progressive hypertensive disorder unique to human pregnancy. The placenta is fundamental to its pathogenesis and releases placental factors as well as extracellular vesicles (small and medium/large syncytiotrophoblast extracellular vesicles (STB-EVs)) as a response to syncytiotrophoblast stress such as tissue factor and plasminogen activator inhibitors 1. Neuropilin 1 (NRP-1) is an anti-angiogenic factor involved in development, angiogenesis, arteriogenesis, and vascular permeability. NRP-1 acts as a co-receptor for growth factors such as vascular endothelial growth factor (VEGF), placenta growth factor (PLGF), and epidermal growth factor (EGF). Given the documented pro and anti-angiogenic roles of STB-EVs, we hypothesized that 1) STB-EVs might express NRP-1; and 2) the expression of NRP-1 might differ between normal and preeclampsia STB-EVs. METHODS: We isolated STB-EVs (both small and medium/large) from PE and NP placentae using the physiologic ex vivo dual lobe perfusion model. The enriched STB-EVs were characterized by Western blot, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA) according to the international society of extracellular vesicles (ISEV) guidelines. We assessed for NRP-1 expression with Western blot (placenta and STB-EVs) and immunohistochemistry (placenta). We performed co-expression analysis for placenta alkaline phosphatase (PLAP - a known STB-EV marker) and NRP-1 with immunoprecipitation followed by Western blot. RESULTS: We confirmed NRP-1 expression in NP and PE placenta. We showed that NRP-1 Expression was limited to small syncytiotrophoblast membrane extracellular vesicles (S STB-EVs) but not medium/large STB-EVs and that NRP-1 is co-expressed with PLAP. CONCLUSION: Neuropilin-1 is uniquely expressed on small syncytiotrophoblast extracellular vesicles but not on medium/large vesicles from preeclampsia and normal placentae.
Asunto(s)
Vesículas Extracelulares , Preeclampsia , Vesículas Extracelulares/metabolismo , Femenino , Humanos , Neuropilina-1/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Embarazo , Trofoblastos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Abstract Biological homochirality is modelled using chemical reaction mechanisms that include autocatalytic and inhibition reactions as well as input and output flows. From the mathematical point of view, the differential equations associated with those mechanisms have to exhibit bistability. The search for those bifurcations can be carried out using stoichiometric network analysis. This algorithm simplifies the mathematical analysis and can be implemented in a computer programme, which can help us to analyse chemical networks. However, regardless of the reduction to linear polynomials, which is made possible by this algorithm, in some cases, the complexity and length of the polynomials involved make the analysis unfeasible. This problem has been partially solved by extending the stoichiometric matrix with rows that code the duality relations between the different reactions occurring in the network given as input. All these facts allow us to analyse 28 different network models, highlighting the basic requirements needed by a chemical mechanism to have spontaneous mirror symmetry breaking.
Resumen El origen de la homoquiralidad biológica se ha modelado usando mecanismos de reacción con pasos autocatalíticos, de inhibición y flujos de entrada y salida. Desde el punto de vista de las matemáticas, las ecuaciones diferenciales asociadas a tales mecanismos deben exhibir biestabilidad. La búsqueda de tales bifurcaciones se puede hacer usando el análisis de redes estequiométricas. Tal algoritmo facilita el trabajo matemático y se puede implementar en un programa de computadora, con lo que se simplifica el análisis y ayuda a entender y mejorar los mecanismos de reacción. No obstante, y a pesar de la reducción en la complejidad que es alcanzada usando el análisis de redes estequiométricas, la dificultad y la longitud de los polinomios involucrados hacen que, en los casos más difíciles y de mayor envergadura, la solución de estos no sea posible. En este trabajo se ha superado parcialmente el problema, adicionando a la matriz estequiométrica un conjunto de filas que codifican la relación de dualidad entre las diferentes reacciones presentes en la red química dada como entrada al programa. Así, hemos logrado analizar 28 modelos diferentes de homoquiralidad biológica, extrayendo de ellos el conjunto de requisitos necesarios para tener un modelo cinética y termodinámicamente consistente.
Resumo A origem da homoquiralidade biológica foi modelada usando mecanismos de reação com etapas autocatalíticas, de inibição e fluxos de entrada e saída. Do ponto de vista da matemática, as equações diferenciais associadas a tais mecanismos devem ser instáveis. A instabilidade pode ser estudada usando o algoritmo de análise de redes estequiométricas. Tal algoritmo facilita o trabalho matemático e pode ser implementado num programa de computador, o que simplifica a análise e ajuda a entender e melhorar os mecanismos de reação. No entanto, e apesar da redução na complexidade que é alcançada usando a análise de redes estequiométricas, a complexidade e comprimento dos polinômios envolvidos fazem que, nos casos mais complexos e de maior envergadura, a solução dos mesmos não seja possível. Neste trabalho, o problema foi superado, parcialmente, adicionando à matriz estequiométrica um conjunto de linhas que codificam a relação de dualidade entre as diferentes reações presentes na rede química dada como entrada ao programa. Desta forma foi possível analisar 28 modelos diferentes de homoquiralidade biológica, extraindo deles o conjunto de requisitos necessários para ter um modelo cinético e termodinamicamente consistente.
RESUMEN
This cross-sectional study evaluated epidemiologic characteristics of persons living with HIV (PWH) coinfected with Trypanosoma cruzi in Cochabamba, Bolivia, and estimated T. cruzi parasitemia by real-time quantitative polymerase chain reaction (qPCR) in patients with and without evidence of reactivation by direct microscopy. Thirty-two of the 116 HIV patients evaluated had positive serology for T. cruzi indicative of chronic Chagas disease (27.6%). Sixteen of the 32 (50%) patients with positive serology were positive by quantitative polymerase chain reaction (qPCR), and four of the 32 (12.5%) were positive by direct microscopy. The median parasite load by qPCR in those with CD4+ < 200 was 168 parasites/mL (73-9951) compared with 28.5 parasites/mL (15-1,528) in those with CD4+ ≥ 200 (P = 0.89). There was a significant inverse relationship between the degree of parasitemia estimated by qPCR from blood clot and CD4+ count on the logarithmic scale (rsBC= -0.70, P = 0.007). The correlation between T. cruzi estimated by qPCR+ blood clot and HIV viral load was statistically significant with rsBC = 0.61, P = 0.047. Given the significant mortality of PWH and Chagas reactivation and that 57% of our patients with CD4+ counts < 200 cells/mm3 showed evidence of reactivation, we propose that screening for chronic Chagas disease be considered in PWH in regions endemic for Chagas disease and in the immigrant populations in nonendemic regions. Additionally, our study showed that PWH with advancing immunosuppression have higher levels of estimated parasitemia measured by qPCR and suggests a role for active surveillance for Chagas reactivation with consideration of treatment with antitrypanosomal therapy until immune reconstitution can be achieved.
Asunto(s)
Enfermedad de Chagas/sangre , Infecciones por VIH/sangre , Infección Latente/sangre , Parasitemia/sangre , Adulto , Anticuerpos Antiprotozoarios/inmunología , Bolivia , Recuento de Linfocito CD4 , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/tratamiento farmacológico , Coinfección , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Humanos , Infección Latente/complicaciones , Infección Latente/diagnóstico , Infección Latente/tratamiento farmacológico , Masculino , Microscopía , Persona de Mediana Edad , Nitroimidazoles/uso terapéutico , Carga de Parásitos , Parasitemia/complicaciones , Parasitemia/diagnóstico , Parasitemia/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Tripanocidas/uso terapéutico , Trypanosoma cruzi , Carga ViralRESUMEN
Syncytiotrophoblast derived Extracellular Vesicles (STBEV) from normal pregnancy (NP) have previously been shown to interact with circulating monocytes and B cells and induce pro-inflammatory cytokine release. Early-onset preeclampsia (EOPE) is associated with an exacerbated inflammatory response, yet there is little data regarding late-onset PE (LOPE) and immune function. Here, using a macrophage/monocyte cell line THP-1, we investigated the inflammatory potential of STBEV, comprising medium/large-STBEV (>200nm) and small-STBEV (<200nm), isolated from LOPE (n=6) and normal (NP) (n=6) placentae via dual-lobe ex-vivo placental perfusion and differential centrifugation. THP-1 cells bound and internalised STBEV isolated from NP and LOPE placentae, as revealed by flow cytometry, confocal microscopy, and ELISA. STBEV-treated THP-1 cells were examined for cytokine gene expression by RT-qPCR and the cell culture media examined for secreted cytokines/chemokines. As expected, NP medium/large-STBEV significantly upregulated the transcriptional expression of TNF-α, IL-10, IL-6, IL-12, IL-8 and TGF-ß compared to PE medium/large-STBEV. However, there was no significant difference in the small STBEV population between the two groups, although in general, NP small STBEVs slightly upregulated the same cytokines. In contrast, LOPE STBEV (medium and large) did not induce pro-inflammatory responses by differentiated THP-1 macrophages. This decreased effect of LOPE STBEV was echoed in cytokine/chemokine release. Our results appear to suggest that STBEV from LOPE placentae do not have a major immune-modulatory effect on macrophages. In contrast, NP STBEV caused THP-1 cells to release pro-inflammatory cytokines. Thus, syncytiotrophoblast extracellular vesicles from LOPE dampen immune functions of THP-1 macrophages, suggesting an alternative mechanism leading to the pro-inflammatory environment observed in LOPE.
Asunto(s)
Vesículas Extracelulares/fisiología , Macrófagos/inmunología , Placenta/inmunología , Preeclampsia/inmunología , Trofoblastos/ultraestructura , Adulto , Citocinas/biosíntesis , Citocinas/genética , Femenino , Citometría de Flujo , Humanos , Microscopía Confocal , Microscopía Electrónica de Transmisión , Embarazo , Células THP-1RESUMEN
INTRODUCTION: Genital necrosis (GN) is a rare complication of cytoreductive surgery with hyperthermic intraoperative chemotherapy (CRS/HIPEC) which can be confused with necrotizing fasciitis. We present an analysis of GN after CRS/HIPEC to define its natural history. METHODS: We identified patients with GN after CRS/HIPEC at two peritoneal surface malignancy institutions. Patient demographic, surgical, and postoperative data were extracted from prospective databases. RESULTS: Of 1597 CRS/HIPECs performed, 13 patients (0.8%) had GN. The median age was 57 years (IQR: 49-64) and 77% (n = 10) were male. Mitomycin-C was the perfusion agent in all cases of GN (100%). The median time to GN onset after CRS/HIPEC was 64 days (IQR: 60-108) and 2 (15%) patients were receiving systemic chemotherapy at the time of GN onset. Symptoms included severe pain (100%), edema (100%), labial or scrotal skin ulceration (92%), signs of infection (39%), and fever (15%). Seven (54%) patients had thrombocytosis >400 ∗109/L, whereas coagulation tests were within normal reference range in 100% cases. All patients initially underwent conservative treatment, with antibiotic therapy administered in 62% (n = 8). Surgical debridement was performed in 9 (70%) cases with median time after GN onset of 57 (IQR: 8-180). CONCLUSION: GN is a debilitating complication after CRS/HIPEC with delayed onset and a protracted clinical course. Optimal treatment results could be achieved with initial conservative management until complete lesion demarcation followed by surgical debridement. The pathophysiology of GN is unclear, and we call for other researchers attention to better understand the complication and prevention.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Genitales Femeninos/patología , Genitales Masculinos/patología , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Neoplasias Peritoneales/terapia , Antibacterianos/uso terapéutico , Antibióticos Antineoplásicos/administración & dosificación , Terapia Combinada , Desbridamiento , Edema/etiología , Femenino , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Necrosis/diagnóstico , Necrosis/etiología , Necrosis/terapia , Dolor/etiología , Neoplasias Peritoneales/patología , Estudios Retrospectivos , Úlcera Cutánea/etiología , Factores de TiempoRESUMEN
We present the first case of isolated peritoneal carcinomatosis (PC) from prostate cancer carrying a previously unreported pathogenic BRCA2 mutation without other organ involvement. CT showed PC with no extra-peritoneal metastases. Treatment included neoadjuvant chemotherapy, cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant chemotherapy. Patient is disease-free after 30-months. Germline genetic testing showed BRCA2 c.1813dupA (p.I605Nfs*11) mutation, reported in breast and ovarian cancers. Tumor genomic testing also revealed TMPRSS2, TBX3, and TP53 mutations. Given the comparable presentation and BRCA-mutation profile to ovarian cancer, BRCA2 mutations may contribute to disease phenotypes. CRS/HIPEC may provide long-term outcomes for this unique metastatic pattern.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/terapia , Terapia Combinada , Genes BRCA2 , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/secundario , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patologíaRESUMEN
Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae are increasingly common; however, predicting which patients are likely to be infected with an ESBL pathogen is challenging, leading to increased use of carbapenems. To date, five prediction models have been developed to distinguish between patients infected with ESBL pathogens. The aim of this study was to validate and compare each of these models to better inform antimicrobial stewardship. This was a retrospective cohort study of patients with Gram-negative bacteremia treated at the South Texas Veterans Health Care System over 3 months from 2018 to 2019. We evaluated isolate, clinical syndrome, and score variables for the five published prediction models/scores: Italian "Tumbarello," Duke, University of South Carolina (USC), Hopkins clinical decision tree, and modified Hopkins. Each model was assessed using the area under the receiver operating characteristic curve (AUROC) and Pearson correlation. One hundred forty-five patients were included for analysis, of which 20 (13.8%) were infected with an ESBL Escherichiacoli or Klebsiella spp. The most common sources of infection were genitourinary (55.8%) and gastrointestinal/intraabdominal (24.1%), and the most common pathogen was E. coli (75.2%). The prediction model with the strongest discriminatory ability (AUROC) was Tumbarello (0.7556). The correlation between prediction model score and percent ESBL was strongest with the modified Hopkins model (R2 = 0.74). In this veteran population, the modified Hopkins and Duke prediction models were most accurate in discriminating between Gram-negative bacteremia patients when considering both AUROC and correlation. However, given the moderate discriminatory ability, many patients with ESBL Enterobacteriaceae (at least 25%) may still be missed empirically.
Asunto(s)
Bacteriemia , Infecciones por Escherichia coli , Infecciones por Klebsiella , Veteranos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Atención a la Salud , Resistencia a Medicamentos , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Estudios Retrospectivos , Texas , beta-Lactamasas/genéticaRESUMEN
BACKGROUND: Although potentially curable with early detection and timely treatment, breast cancer (BC) and cervical cancer (CC) remain leading causes of death for Colombian women. Lack of education, complicated administrative processes, and geographic limitations hinder early cancer detection. Today, technological tools permeate the society and could assess user risk, deliver customized information, and provide care coordination. We evaluated the effectiveness of a free mobile application (mApp) to reach women, understand misconceptions, identify users at risk for BC and/or CC, and coordinate screening tests in Cali, Colombia. METHODS: The mApp was developed and advertised in four healthcare facility waiting rooms. It used educational, evaluative, and risk factor questions followed by brief explanations to assess the population's knowledge, educate on BC and/or CC, and identify users in need of screening test(s). Women who required screening were navigated and enrolled in the national cancer program. RESULTS: From August 2017 to August 2019, 1,043 women downloaded the mApp. BC misconceptions included beliefs that BC can be prevented (87%), obesity does not increase the risk of BC (49%), and deodorant causes BC (17%). CC misconceptions included that pap smears should not be performed while sexually active (64%), vaginal pain is an early sign of CC (44%), and only women contract human papilloma virus (33%). Overall, 29% (303) were identified as at risk and needed a screening test, with 32% (98) successfully screened. DISCUSSION: mApps can identify women at risk for BC and/or CC, detect barriers to early cancer detection, and help coordinate screening test(s). This technology has widespread applications and may be useful in other underserved communities.
Asunto(s)
Neoplasias del Cuello Uterino , Colombia , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Neoplasias del Cuello Uterino/diagnóstico , Frotis VaginalRESUMEN
INTRODUCTION: Preeclampsia (PE) is associated with an exaggerated maternal systemic inflammatory response. Throughout gestation, the placenta releases extracellular vesicles through the syncytiotrophoblast layer (STB) into the maternal circulation and this is increased in PE. Expression of Siglec-6, a transmembrane receptor of molecular weight 50 KDa, is upregulated in PE placental tissue. METHODS: Here we investigated respective abundance of Siglec-6 in PE -and normal pregnancy- (NP) derived placental lysates (PL) and syncytiotrophoblast-derived extracellular vesicles (STBEV). STBEV from PE and NP placentas were isolated through dual-lobe placental perfusion and serial ultracentrifugation. Siglec-6 was characterized by immunohistochemistry, immunoblotting, mass spectrometry (MS), and deglycosylation. RESULTS: Immunoblotting revealed the expected Siglec-6 (50 KDa) band present in both PE and NP PL, however an additional heavier band was observed at 70 KDa only in PE PL, but not in NP. When interrogating STBEV we saw an absence of the expected 50 KDa band but the 70 KDa was present predominantly only in the PE STBEV. Deglycosylation of PL and STBEV from PE showed that the 70 KDa and the 50 KDa bands were reduced to 48 KDa, suggesting glycosylation. Both 48 KDa and 70 KDa bands were subjected to MS, confirming Siglec-6 expression in both. DISCUSSION: Our data shows that the inability to detect Siglec-6 in circulation might be due to the placenta secreting STBEV carrying a modified glycosylated form of Siglec-6 with a 70 KDa molecular weight, significantly and uniquely upregulated in PE STBEV.
Asunto(s)
Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Vesículas Extracelulares/metabolismo , Lectinas/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Trofoblastos/metabolismo , Adulto , Femenino , Glicosilación , Humanos , Embarazo , Regulación hacia ArribaRESUMEN
A hibernoma is an uncommon benign soft tissue tumor composed of brown adipose cells; the mediastinal location as presentation is scarce, with only six cases previously reported. The diagnosis of hibernoma is challenging and must be made based on the clinical, radiographic, and cytologic features. Here we present a 33-year-old woman without any relevant medical history presented for outpatient evaluation of a dry cough persisting for three months, and the X-rays revealed a dense well-defined mass with smooth borders in the left upper posterior mediastinum. Posterior mediastinal lesions represent a relatively small proportion of patient loads in thoracic surgery and account for a total of 25% of the cases, with neurogenic tumors among the most frequently seen in adults. Of these, the nerve sheath tumors (schwannoma, neurofibroma, paraspinal ganglioneuroma) are the most seen. Other differential diagnoses of paravertebral masses are the paraspinal abscess, metastases, hematoma, descending aortic aneurysm, among others. The patient underwent surgical resection via left posterolateral thoracotomy, without complications.
RESUMEN
After the biomass pretreatment and fermentation processes, the purification step constitutes a major task in bioethanol production processes. The use of membranes provides an interesting choice to achieve high-purity bioethanol. Membrane separation processes are generally characterized by low energy requirements, but a high capital investment. Some major design aspects for membrane processes and their application to the ethanol dehydration problem are addressed in this work. The analysis includes pervaporation and vapor permeation methods, and considers using two types of membranes, A-type zeolite and amorphous silica membrane. The results identify the best combination of membrane separation method and type of membrane needed for bioethanol purification.
Asunto(s)
Carcinoma , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Piodermia Gangrenosa/etiología , Neoplasias del Recto , Carcinoma/complicaciones , Carcinoma/terapia , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Recto/complicaciones , Neoplasias del Recto/terapiaRESUMEN
The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EV) into the maternal circulation throughout gestation. STB-EV dependent signalling is believed to contribute to the widespread maternal adaptive physiological changes seen in pregnancy. Transfer RNA (tRNA) halves have been identified in vesicles released from other human and murine organ systems, which alter gene expression in target cells. Here, we characterise tRNA-half expression in STB-EV and demonstrate biological activity of a highly abundant tRNA-half. Short RNA from ex-vivo, dual-lobe placental perfusion STB-EV was sequenced, showing that most (>95%) comprised tRNA species. Whole placental tissue contained <50% tRNA species, suggesting selective packaging and export of tRNA into STB-EV. Most tRNA within STB-EV were 5'-tRNA halves cleaved at 30-32 nucleotides. The pattern of tRNA expression differed depending on the size/origin of the STB-EV; this was confirmed by qPCR. Protein synthesis was suppressed in human fibroblasts when they were cultured with a 5'-tRNA half identified from STB-EV sequencing. This study is the first to evaluate tRNA species in STB-EV. The presence of biologically active 5'-tRNA halves, specific to a vesicular origin, suggests a novel mechanism for maternal-fetal signalling in normal pregnancy.
Asunto(s)
Vesículas Extracelulares/metabolismo , ARN de Transferencia/metabolismo , Trofoblastos/metabolismo , Vesículas Extracelulares/ultraestructura , Femenino , Fibroblastos/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Conformación de Ácido Nucleico , Perfusión , Embarazo , ARN de Transferencia/químicaRESUMEN
Background: Male engagement is becoming more common in family planning (FP) strategies and interventions, yet effective monitoring and evaluation (M&E) of this approach lags. This review sought to understand how male engagement in FP is defined, identify gaps in M&E of male engagement and make recommendations. Methods: We conducted key informant interviews and a desk review of peer-reviewed articles and gray literature, including national FP strategies and policies. We then facilitated an online forum with experts in the field of male engagement in FP to provide feedback on our proposed indicators for male engagement in FP to reach consensus on and validate key indicators. Results: Although there is no universal definition of male engagement in FP, the most common definition is the inclusion of men in FP programming as FP clients, supportive partners, and agents of change. The most common approach was engaging men as clients exclusively, followed by engaging men as partners. Few papers reported on programs that engaged men across the full spectrum of the definition. There's significant variation in the degree to which male engagement in FP is included in M&E, planning, and approaches. Few programs reported findings disaggregated by sex and by contraceptive method, making it difficult to determine the effect of programming on male use of methods. There is a dearth of indicators for measuring male engagement in FP in national strategies and policies. Other gaps are a lack of core indicators for male engagement, qualitative indicators, and indicator reference sheets for many commonly used indicators. Among over 100 indicators being used to monitor and evaluate male engagement in FP, 15 key indicators were identified and validated, with accompanying guidance. Conclusions: As programming for male engagement in FP increases, coordinated efforts should be made to improve the systems that collect, analyze, and use data.
RESUMEN
Breast and cervical cancers are leading causes of mortality among women in Latin America. Colombia has universal health care and a government-sponsored 10-year cancer control plan focused on prevention, early detection, and treatment. However, many administrative and social barriers have hindered its success, and a majority of patients are diagnosed at a late stage. Established in 2012, Partners for Cancer Care and Prevention (PFCCAP) works to decrease the burden of these cancers by mitigating the obstacles women face during their cancer diagnosis and treatment. Through community outreach meetings with medical personnel, hospital directors, and government officials, PFCCAP identified major barriers, including lack of trained health care personnel, few centers with adequate screening equipment, and a fragmented health system with significant administrative delays and poor continuity of care. Its solution included monthly teleconferences, biannual on-site training, quality control programs, and improved access to screening equipment. PFCCAP also initiated a patient navigation project. After implementation of the PFCCAP plan of action, from 2012 to 2018, the average time from initial consult to biopsy decreased from 65 to 20 days; from biopsy to diagnosis, 33 to 4 days; and from diagnosis to surgery, 121 to 60 days. To date, more than 1,500 women have benefited from this initiative, which has expanded to other regions. Overall, PFCCAP is creating centers of excellence in strategically located hospitals and promoting the implementation of national guidelines. Although several barriers still exist, PFCCAP is helping to implement an efficient health care model that can be replicated in other underserved populations.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Tamizaje Masivo/métodos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Neoplasias de la Mama/prevención & control , Colombia , Relaciones Comunidad-Institución , Detección Precoz del Cáncer , Femenino , Humanos , Área sin Atención Médica , Navegación de Pacientes , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Telecomunicaciones , Tiempo de Tratamiento , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EVs) into the maternal circulation, which is enhanced in GDM. Dipeptidyl peptidase IV (DPPIV) is known to play a role in type 2 diabetes by breaking down GLP-1, which in turn regulates glucose-dependent insulin secretion. STB-EVs from control and GDM women were analysed. We show that normal human placenta releases DPPIV-positive STB-EVs and that they are higher in uterine than paired peripheral blood, confirming placental origin. DPPIV-bound STB-EVs from normal perfused placentae are dose dependently inhibited with vildagliptin. DPPIV-bound STB-EVs from perfused placentae are able to breakdown GLP-1 in vitro. STB-EVs from GDM perfused placentae show greater DPPIV activity. Importantly, DPPIV-bound STB-EVs increase eightfold in the circulation of women with GDM. This is the first report of STB-EVs carrying a biologically active molecule that has the potential to regulate maternal insulin secretion.
RESUMEN
BACKGROUND: The integration of family planning (FP) and HIV-related services is common in sub-Saharan Africa. Little research has examined how FP quality of care differs between integrated and non-integrated facilities. Using nationally representative data from Malawi and Tanzania, we examined how HIV integration was associated with FP quality of care. METHODS: Data were drawn from Service Provision Assessments (SPAs) from Malawi (2013-2014) and Tanzania (2014-2015). The analytic sample was restricted to lower-level facilities in Malawi (n = 305) and Tanzania (n = 750) that offered FP services. We matched SPA measures to FP quality of care indicators in the Quick Investigation of Quality (QIQ). We conducted bivariate and multivariate analyses of 22 QIQ indicators to examine how integration status was related to individual QIQ indicators and overall FP quality of care at the facility- and client-level. RESULTS: The prevalence of HIV integration in Malawi (39%) and Tanzania (38%) was similar. Integration of HIV services was significantly associated (p < 0.05) with QIQ indicators in Malawi (n = 3) and Tanzania (n = 4). Except for one negative association in Tanzania, all other associations were positive. At the facility-level, HIV integration was associated with increased odds of being at or above the median in FP quality of care in Malawi (adjusted odd ratio (OR) = 2.24; 95% confidence interval (CI) = 1.32, 3.79) and Tanzania (adjusted OR = 2.10; 95% CI = 1.37, 3.22). At the client-level, HIV integration was not associated with FP quality of care in either country. CONCLUSION: Based on samples in Malawi and Tanzania, HIV integration appears to be beneficially associated with FP quality of care. Using a spectrum of FP quality of care indicators, we found little evidence to support concerns that HIV integration may strain facilities and providers, and adversely impact quality outcomes. Rather, it appears to strengthen FP service delivery by increasing the likelihood of stocked FP commodities and achievement of other facility-level quality indicators, potentially through HIV-related supply chains. Further research is needed to assess FP quality of care outcomes across the various platforms of FP integration found in sub-Saharan Africa.
Asunto(s)
Prestación Integrada de Atención de Salud , Servicios de Planificación Familiar/normas , Infecciones por VIH/prevención & control , Instituciones de Salud/normas , Calidad de la Atención de Salud , Estudios Transversales , Femenino , VIH/aislamiento & purificación , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Malaui/epidemiología , Estudios Retrospectivos , Tanzanía/epidemiologíaRESUMEN
NEP (neprilysin) is a widely expressed membrane-bound metalloprotease, which binds and cleaves a variety of peptides including vasodilators, natriuretics, and diuretics. Higher levels of NEP result in hypertension-a cardinal feature of the placental disease preeclampsia. Syncytiotrophoblast-derived extracellular vesicles (EVs), comprising microvesicles and exosomes, are released into the peripheral circulation in pregnancy and are postulated as a key mechanism coupling placental dysfunction and maternal phenotype in preeclampsia. We aimed to determine whether higher levels of active NEP are found in syncytiotrophoblast-derived EVs in preeclampsia compared with normal pregnancy. Using immunostaining and Western blotting, we first demonstrated that NEP levels are greater not only in preeclampsia placental tissue but also in syncytiotrophoblast-derived microvesicles and exosomes isolated from preeclampsia placentas ( P<0.05, n=5). We confirmed placental origin using antibody-coated magnetic beads to isolate NEP-bound vesicles, finding that they stain for placental alkaline phosphatase. NEP on syncytiotrophoblast-derived EVs is active and inhibited by thiorphan ( P<0.01, n=3; specific inhibitor). Syncytiotrophoblast-derived microvesicles, isolated from peripheral plasma, demonstrated higher NEP expression in preeclampsia using flow cytometry ( P<0.05, n=8). We isolated plasma exosomes using size-exclusion chromatography and showed greater NEP activity in preeclampsia ( P<0.05, n=8). These findings show that the placenta releases active NEP into the maternal circulation on syncytiotrophoblast-derived EVs, at significantly greater levels in preeclampsia. NEP has pathological roles in hypertension, heart failure, and amyloid deposition, all of which are features of preeclampsia. Circulating syncytiotrophoblast-derived EV-bound NEP thus may contribute to the pathogenesis of this disease.