Systematic review of the role of high intensity focused ultrasound (HIFU) in treating malignant lesions of the hepatobiliary system

BACKGROUND: High Intensity Focused Ultrasound (HIFU) is an emerging non-invasive, targeted treatment of malignancy. The aim of this review was to assess the efficacy, safety and optimal technical parameters of HIFU to treat malignant lesions of the hepatobiliary system. METHODS: A systematic search of the English literature was performed until March 2020, interrogating Pubmed, Embase and Cochrane Library databases. The following key-words were input in various combinations: 'HIFU', 'High intensity focussed ultrasound', 'Hepatobiliary', 'Liver', 'Cancer' and 'Carcinoma'. Extracted content included: Application type, Exposure parameters, Patient demographics, and Treatment outcomes. RESULTS: Twenty-four articles reported on the clinical use of HIFU in 940 individuals to treat malignant liver lesions. Twenty-one studies detailed the use of HIFU to treat hepatocellular carcinoma only. Mean tumour size was 5.1 cm. Across all studies, HIFU resulted in complete tumour ablation in 55% of patients. Data on technical parameters and the procedural structure was very heterogeneous. Ten studies (n = 537 (57%) patients) described the use of HIFU alongside other modalities including TACE, RFA and PEI; 66% of which resulted in complete tumour ablation. Most common complications were skin burns (15%), local pain (5%) and fever (2%). CONCLUSION: HIFU has demonstrated benefit as a treatment modality for malignant lesions of the hepatobiliary system. Combining HIFU with other ablative therapies, particularly TACE, increases the efficacy without increasing complications. Future human clinical studies are required to determine the optimal treatment parameters, better define outcomes and explore the risks and benefits of combination therapies

Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways

Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells.This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação da Universidade Federal Fluminense (PROPPI/UFF). TGE, ID, and NAO were recipients of graduate student fellowships from CAPES. RPC is a research fellow from CNPq and FAPERJ. CCP and RS hold employment contracts financed by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., in the context of the program-contract described in paragraphs 4, 5 and 6 of art. 23 of Law no. 57/2016, of August 29, as amended by Law no. 57/2017 of July 19

Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

Sociodemographic characteristics determine dietary pattern adherence during pregnancy

OBJECTIVE:Sociodemographic factors may affect adherence to specific dietary patterns during pregnancy. The present study aimed to identify dietary patterns during pregnancy and associated factors among Brazilian pregnant women. DESIGN:A cross-sectional analysis. Dietary intake was evaluated with a semi-quantitative FFQ during the first postpartum week; the time frame included the second and third gestational trimesters. Principal component analysis was used to identify dietary patterns during pregnancy. Sociodemographic data were obtained using a structured questionnaire. Multiple linear regressions were applied to test the associations between the sociodemographic factors and dietary patterns. SETTING:Mesquita, Rio de Janeiro, Brazil, 2011. SUBJECTS:Postpartum women (n 327) who were 18-45 years of age and Mesquita residents. RESULTS:Three different dietary patterns were identified: 'healthy' (mainly comprising legumes, vegetables and fruits), 'mixed' (mainly comprising candy, butter and margarine, and snacks) and 'traditional' (mainly comprising beans and rice). Women with a higher monthly per capita family income (β=0·0006; 95% CI 0·0001, 0·001; P=0·011) and women of older age (β=0·021; 95% CI -0·001, 0·042; P=0·058) were more likely to adhere to the 'healthy' dietary pattern. Women with higher parity were less likely to adhere to the 'healthy' pattern (β=-0·097; 95% CI -0·184, -0·009; P=0·030) and were more likely to adhere to the 'traditional' pattern (β=0·098; 95% CI 0·021, 0·175; P=0·012). Although not statistically significant, older women were less likely to adhere to the 'mixed' (β=-0·017; 95% CI -0·037, 0·003; P=0·075) and 'traditional' (β=-0·018; 95% CI -0·037, 0·001; P=0·061) dietary patterns. CONCLUSIONS:Monthly per capita family income, parity and maternal age were factors associated with adherence to a healthy diet during pregnancy