The Competition Commission Health Market Inquiry Report: An overview and key imperatives

The Competition Commission’s Health Market Inquiry (HMI) is the most systematic and comprehensive investigation carried out into the South African private health sector. The recommendations as set out in the HMI Final Report merit extensive discussion and debate, as they could – if implemented – have far-reaching consequences for the future of the healthcare system. The objective of this article is to contribute to this discussion by providing an overview of the key findings and recommendations of the HMI and highlighting the resultant key imperatives at this critical juncture of policy development

Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy

Color transform to optimize fruit ripeness discrimination in dichromats

Aim: To develop and test a color transform for red-green color defectives to enhance tomatoipeness judgements. Experimental Method: Congenital protan and deutan color defectives suffer sensitivity losses in the red-green mechanism [1] compromising performance in color-discrimination-based everyday tasks [2], which may be compensated by procedures designed to optimize image color gamuts to minimize color confusion [3]. Given that red-green defectives retain normal discrimination along the blue-yellow axis in color space [1], we propose a simple procedure to recode redgreen color differences in CIELAB color space as blue-yellow color differences, to allow red-green defectives to correctly judge the ripeness of tomatoes. An agricultural cooperative of Perelló supplied and classified by color the tomato samples in a controlled manner in four standard ripeness stages. Sample color was measured with a portable Minolta CR-300 colorimeter (Minolta Co. Ltd, Osaka, Japan). Tomatoes were photographed with a Smartphone (Samsung Galaxy S7 edge model SMG935F with a 12.2 MP camera). RGB values of the image were transformed to XYZ values using Matlab’s sRGB transform, and then to CIEL*a*b*, using as reference white a white sample illuminated as the samples. Dichromatic perception of the images was simulated by the corresponding pair algorithm [4]. The modified palette was obtained by exchanging the values of the red-green (a*) and blue-yellow (b*) descriptors (Fig. 1)

Impact of regulated and emerging pollutants and microplastics in marine ecosystems (IMPACTA project)

Marine ecosystems are nowadays subjected to a massive input of synthetic chemicals from everywhere. Unfortunately only a small portion of them is being monitored, and it is necessary to identify which pollutants can produce adverse impacts in the marine environment. IMPACTA project (CTM2013-48194-C3) is characterizing the distribution of regulated and emerging contaminants and microplastics in marine sediments, and evaluating the biological effects that they can cause (sing sublethal embryotoxicity tests, endocrine disruption and biomarkers). Sensitive and selective analytical methods are being developed and validated for pharmaceuticals, perfluorinated compounds, organophosphorus pesticides, triazines, personal care products, nonylphenols and alkylated PAHs in sediments. Thus, relevant pollutants present in coastal and offshore areas will be identified. Furthermore potential toxic effects of the contaminants present in coastal sediments are being assessed through embryotoxicity bioassays and also the biological effects on different marine species as a consequence of their exposition to specific compounds. Another relevant contribution of this project will be the assessment of the impact of micro-plastics, first time in the Spanish coastal areas. Their potential toxic effects and their role in the transference of pollutants in the marine environment are being assessed. The concentration and composition of microplastics in sediments and demersal fish stomachs are being characterized, and their potential biological effects on marine invertebrates are also being investigated

Scientific dissemination in the Instituto Español de Oceanografía (IEO): Best practices in recent years

There is a growing interest and obligations to bring the results of scientific research closer to society. In this sense, the Instituto Español de Oceanografía (IEO, CSIC) has acquired in recent years an institutional commitment with the scientific dissemination, carrying out some projects on this topic. The objective of these projects is to visualize and value their research and results in different formats increasing the scientific culture of society that demand and financed most of public research. In the present work four successful initiatives or projects are presented. Diversimar project is a citizen science tool for the observation of the marine and fishing biodiversity of Galicia and the Cantabrian Sea. Mar interior project brings activity of IEO to society with face-to-face conferences and workshops. Planet Tuna project combines science with art through an online platform to enhance the scientific knowledge of tuna and other big pelagics for their sustainability. To end, the interactive book “45 days on the Flemish Cap Bank” spreads the technical and human effort of an oceanographic survey that remains behind the fisheries management developed by the IEO. The objective of the present study is to make visible and put in value these projects and serve as inspiration.Versión del edito

Digital messaging to support control for type 2 diabetes (StAR2D): a multicentre randomised controlled trial

Background Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. Methods StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. Results The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (− 0.08% (− 0.31 to 0.16) (IFCC − 0.82 mmol/mol (− 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was − 0.71% (− 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. Conclusions Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. Trial registration Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808

CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.Fil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Baladron, Idania. Center for Genetic Engineering and Biotechnology; CubaFil: Garcia, Yanelda. Center for Genetic Engineering and Biotechnology; CubaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Adlin. Center for Genetic Engineering and Biotechnology; CubaFil: Soriano, Jorge L.. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Batista, Noyde. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Palau, Aley. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Hernández, Ignacio. Center for Genetic Engineering and Biotechnology; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Idrian. Center for Genetic Engineering and Biotechnology; CubaFil: Gonzalez, Lidia. Center for Genetic Engineering and Biotechnology; CubaFil: Gil, Jeovanis. Center for Genetic Engineering and Biotechnology; CubaFil: Rodriguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Solares, Margarita. Center for Genetic Engineering and Biotechnology; CubaFil: Santana, Agueda. Center for Genetic Engineering and Biotechnology; CubaFil: Cruz, Marisol. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Matilde. Center for Genetic Engineering and Biotechnology; CubaFil: Valenzuela, Carmen. Center for Genetic Engineering and Biotechnology; CubaFil: Reyes, Osvaldo. Center for Genetic Engineering and Biotechnology; CubaFil: López Saura, Pedro A.. Center for Genetic Engineering and Biotechnology; CubaFil: González, Carlos A.. Center for Genetic Engineering and Biotechnology; CubaFil: Diaz, Alina. Center for Genetic Engineering and Biotechnology; CubaFil: Castellanos, Lila. Center for Genetic Engineering and Biotechnology; CubaFil: Sanchez, Aniel. Center for Genetic Engineering and Biotechnology; CubaFil: Betancourt, Lazaro. Center for Genetic Engineering and Biotechnology; CubaFil: Besada, Vladimir. Center for Genetic Engineering and Biotechnology; CubaFil: González, Luis J.. Center for Genetic Engineering and Biotechnology; CubaFil: Garay, Hilda. Center for Genetic Engineering and Biotechnology; CubaFil: Gómez, Roberto. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perrin, Phillipe. No especifíca;Fil: Renualt, Jean Yves. No especifíca;Fil: Sigman, Hugo. No especifíca;Fil: Herrera, Luis. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo, Boris. Center for Genetic Engineering and Biotechnology; Cub

The Schnitzler syndrome

The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections