Community-based care models for arterial hypertension management in non-pregnant adults in sub-Saharan Africa: a literature scoping review and framework for designing chronic services

BACKGROUND: Arterial hypertension (aHT) is the leading cardiovascular disease (CVD) risk factor in sub-Saharan Africa; it remains, however, underdiagnosed, and undertreated. Community-based care services could potentially expand access to aHT diagnosis and treatment in underserved communities. In this scoping review, we catalogued, described, and appraised community-based care models for aHT in sub-Saharan Africa, considering their acceptability, engagement in care and clinical outcomes. Additionally, we developed a framework to design and describe service delivery models for long-term aHT care. METHODS: We searched relevant references in Embase Elsevier, MEDLINE Ovid, CINAHL EBSCOhost and Scopus. Included studies described models where substantial care occurred outside a formal health facility and reported on acceptability, blood pressure (BP) control, engagement in care, or end-organ damage. We summarized the interventions' characteristics, effectiveness, and evaluated the quality of included studies. Considering the common integrating elements of aHT care services, we conceptualized a general framework to guide the design of service models for aHT. RESULTS: We identified 18,695 records, screened 4,954 and included twelve studies. Four types of aHT care models were identified: services provided at community pharmacies, out-of-facility, household services, and aHT treatment groups. Two studies reported on acceptability, eleven on BP control, ten on engagement in care and one on end-organ damage. Most studies reported significant reductions in BP values and improved access to comprehensive CVDs services through task-sharing. Major reported shortcomings included high attrition rates and their nature as parallel, non-integrated models of care. The overall quality of the studies was low, with high risk of bias, and most of the studies did not include comparisons with routine facility-based care. CONCLUSIONS: The overall quality of available evidence on community-based aHT care is low. Published models of care are very heterogeneous and available evidence is insufficient to recommend or refute further scale up in sub-Sahara Africa. We propose that future projects and studies implementing and assessing community-based models for aHT care are designed and described according to six building blocks: providers, target groups, components, location, time of service delivery, and their use of information systems

Hyperpolarized13c mri of tumor metabolism demonstrates early metabolic response to neoadjuvant chemotherapy in breast cancer

Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material–enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board–approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent13C MRI after injection of hyperpolarized [1–carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized13C MRI and the pharmacokinetic parameters transfer constant (Ktrans) and washout parameter (kep ) derived from DCE MRI were compared before and after treatment. Results: Exchange of the13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI

Hyperpolarized 13C-MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

Purpose: To compare hyperpolarized carbon-13 (13C)-MRI with dynamic contrast-enhanced MRI (DCE-MRI) for detecting early treatment response in breast cancer. Materials and Methods: In this institutional review board-approved prospective study, one woman with triple-negative breast cancer (age 49) underwent 13C-MRI following injection of hyperpolarized [1-13C]pyruvate and DCE-MRI at 3 T at baseline and after a single cycle of neoadjuvant therapy. The 13C-lactate/13C-pyruvate ratio derived from hyperpolarized 13C-MRI and the pharmacokinetic parameters Ktrans and kep derived from DCE-MRI were compared, before and after treatment. Results: Exchange of the 13C-label between injected hyperpolarized [1-13C]pyruvate and the endogenous lactate pool was demonstrated, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-lactate/13C-pyruvate ratio was shown to correctly identify the patient as a responder to therapy, which was subsequently confirmed by a complete pathologic response. However, DCE-MRI showed an increase in the pharmacokinetic parameters Ktrans (132%) and kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized 13C-MRI successfully identified response in breast cancer after a single cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.This work was supported by a Wellcome Trust Strategic Award, Cancer Research UK (CRUK; Grants C8742/A18097, C19212/ A16628, C19212/A911376, and C197/A16465), the Austrian Science Fund (Grant J4025-B26), the CRUK Cambridge Centre, the CRUK & Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, the Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre (Grant C9685/A25177), CRUK National Cancer Imaging Translational Accelerator Award, Addenbrooke’s Charitable Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, and Cambridge University Hospitals National Health Service Foundation Trust

Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors.

BACKGROUND:Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established. METHODS:Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine. RESULTS:Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings. CONCLUSIONS:These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches

Methods to Study Centrosomes and Cilia in Drosophila

The deposited item is a book chapter and is part of the series " Methods in Molecular Biology book series ([MIMB, volume 1454]) published by the publisher Humana Press.The deposited book chapter is a pre-print version and hasn't been submitted to peer reviewing.There is no public supplementary material available for this publication.This publication hasn't any creative commons license associated.Centrioles and cilia are highly conserved eukaryotic organelles. Drosophila melanogaster is a powerful genetic and cell biology model organism, extensively used to discover underlying mechanisms of centrosome and cilia biogenesis and function. Defects in centrosomes and cilia reduce fertility and affect different sensory functions, such as proprioception, olfaction, and hearing. The fly possesses a large diversity of ciliary structures and assembly modes, such as motile, immotile, and intraflagellar transport (IFT)-independent or IFT-dependent assembly. Moreover, all the diverse ciliated cells harbor centrioles at the base of the cilia, called basal bodies, making the fly an attractive model to better understand the biology of this organelle. This chapter describes protocols to visualize centrosomes and cilia by fluorescence and electron microscopy.Fundação Portuguesa para a Ciência e Tecnologia grants: (SFRH/BPD/87479/2012, SFRH/BD/52176/2013); EMBO installation grant; ERC starting grant.info:eu-repo/semantics/publishedVersio

Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia