A Novel Copper (II) Complex Identified as a Potent Drug Against Colorectal and Breast Cancer Cells and as a Poison Inhibitor for Human Topoisomerase IIᶐ

A novel complex, [Cu(acetylethTSC)Cl]Cl · 0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIᶐ which may account for the observed anti-cancer effects

P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored

Computational approaches to understanding reaction outcomes of organic processes in ionic liquids

This review considers how various computational methods have been applied to explain the changes in reaction outcome on moving from a molecular to an ionic liquid solvent. Initially, different conceptual approaches to modelling ionic liquids are discussed, followed by a consideration of the limitations and constraints of these approaches. A series of case studies demonstrating the utility of computational approaches to explain processes in ionic liquids are considered; some of these address the solubility of species in ionic liquids while others examine classes of reaction where the outcome in ionic liquids can be explained through the application of computational approaches. Overall, the utility of computational methods to explain, and potentially predict, the effect of ionic liquids on reaction outcome is demonstrated

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Resilience Among Urban African American Male Adolescents: A Study of the Protective Effects of Sociopolitical Control on Their Mental Health

Resilience refers to the notion that some people succeed in the face of adversity. In a risk-protective model of resilience, a protective factor interacts with a risk factor to mitigate the occurrence of a negative outcome. This study tested longitudinally the protective effects of sociopolitical control on the link between helplessness and mental health. The study included 172 urban, male, African American adolescents, who were interviewed twice, 6 months apart. Sociopolitical control was defined as the beliefs about one's capabilities and efficacy in social and political systems. Two mental health outcomes were examined—psychological symptoms and self-esteem. Regression analyses to predict psychological symptoms and self-esteem over time were conducted. High levels of sociopolitical control were found to limit the negative consequences of helplessness on mental health. The results suggest that sociopolitical control may help to protect youths from the negative consequences of feelings of helplessness. Implications for prevention strategies are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44052/1/10464_2004_Article_416735.pd

Herophilus and Erasistratus on the hēgemonikon

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.In Alexandria at some point in the early third century bc, Herophilus of Chalcedon identified the nerves as a distinct system within the body, traced their origins to the brain, and recognised their role in transmitting sensation and voluntary motion. His discovery was based on dissection and vivisection, not only of animals, but also of human beings. Herophilus’ younger contemporary Erasistratus also integrated these findings into his rather bolder physiology. The implications of this discovery were of course wide-ranging. From a modern perspective, it is now widely celebrated as having established, for the first time on something like a scientific basis, that the brain has more or less the functions that we now ascribe to it. Likewise, in antiquity, Galen relied heavily on Herophilus’ discovery in his proof that the rational soul is located in the brain. As we shall see, it also had an impact on Stoic psychology. What exactly Herophilus and Erasistratus saw as its implications, however, is a different question, and the difficulties in answering it are considerable given the state of the evidence

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A board game and a workshop for co-creating smart nature ecosystems

Younger generations from urban areas spend an increasing amount of time indoors with technology, e.g., with mobiles. GEKI is an exploratory project that investigates how to co-create with younger generations smart nature ecosystems and get them to spend time outdoors. This paper presents the design of a novel board game and a workshop with it for co-creating such an ecosystem with children