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tandard, as well as considerations for developing countries, are presented.The resistance of Rhipicephalus microplus to acaricides is a serious control problem, so its early diagnosis by a molecular technique is important. This study aims to develop a multiplex allele-specific polymerase chain reaction (PCR) for single-nucleotide polymorphisms (SNPs) in the para-sodium channel gene and in the GABA-Cl gene, associated with pyrethroids (cypermethrin and flumethrin) and fipronil resistance, respectively. We used 22 tick field isolates from farms with tick control problems (sampling convenience). These farms are located in departments of northern Uruguay. Three mutations in the sodium channel gene (Domain II S4-5 C190A and G215T; domain III S6 T2134A) and one in the GABA-Cl gene (A286S/L CG856CC/TG) were studied. Mutations G215T and T213A were not detected. In all field isolates, the resistant allele (R) for C190A mutation (knockdown resistance, kdr) was detected, mainly in heterozygous individuals (SR) (11.1% to 86.7%). The highest incidence of the kdr mutant allele occurred in the Taceir frequency varied between 0.06% and 60%. Genotypic analysis shows that tick resistance to both acaricides, especially pyrethroids, is a serious problem. It is important to monitor the resistance using molecular techniques to plan efficient control measures. This is the first report describing kdr and rdl detection in R. microplus in Uruguay.Ferroptosis is a programmed iron-dependent cell death associated with peroxidation of lipids particularly, phospholipids. Several studies suggested a possible contribution of mitochondria to ferroptosis although the mechanisms underlying mitochondria-mediated ferroptotic pathways remain elusive. Reduced glutathione (GSH) is a central player in ferroptosis that is required for glutathione peroxidase 4 to eliminate oxidized phospholipids. Mitochondria do not produce GSH, and although the transport of GSH to mitochondria is not fully understood, two carrier proteins, the dicarboxylate carrier (DIC, SLC25A10) and the oxoglutarate carrier (OGC, SLC25A11) have been suggested to participate in GSH transport. Here, we elucidated the role of DIC and OGC as well as mitochondrial bioenergetics in ferroptosis in H9c2 cardioblasts. Results showed that mitochondria are highly sensitive to ferroptotic stimuli displaying fragmentation, and lipid peroxidation shortly after the onset of ferroptotic stimulus. Inhibition of electron transport chain complexes and oxidative phosphorylation worsened RSL3-induced ferroptosis. LC-MS/MS analysis revealed a dramatic increase in the levels of pro-ferroptotic oxygenated phosphatidylethanolamine species in mitochondria in response to RSL3 (ferroptosis inducer) and cardiac ischemia-reperfusion. Inhibition of DIC and OGC aggravated ferroptosis and increased mitochondrial ROS, membrane depolarization, and GSH depletion. Dihydrolipoic acid, an essential cofactor for several mitochondrial multienzyme complexes, attenuated ferroptosis and induced direct reduction of pro-ferroptotic peroxidized phospholipids to hydroxy-phospholipids in vitro. In conclusion, we suggest that ferroptotic stimuli diminishes mitochondrial bioenergetics and stimulates GSH depletion and glutathione peroxidase 4 inactivation leading to ferroptosis.Exposure to toxic levels of fatty acids (lipotoxicity) leads to cell damage and death and is involved in the pathogenesis of the metabolic syndrome. Since the metabolic consequences of lipotoxicity are still poorly understood, we studied the bioenergetic effects of the saturated fatty acid palmitate, quantifying changes in mitochondrial morphology, real-time oxygen consumption, ATP production sources, and extracellular acidification in hepatoma cells. Surprisingly, glycolysis was enhanced by the presence of palmitate as soon as 1 h after stimulus, while oxygen consumption and oxidative phosphorylation were unchanged, despite overt mitochondrial fragmentation. Palmitate only induced mitochondrial fragmentation if glucose and glutamine were available, while glycolytic enhancement did not require glutamine, showing it is independent of mitochondrial morphological changes. Redox state was altered by palmitate, as indicated by NAD(P)H quantification. Furthermore, the mitochondrial antioxidant mitoquinone, or a selective inhibitor of complex I electron leakage (S1QEL) further enhanced palmitate-induced glycolysis. find more Our results demonstrate that palmitate overload and lipotoxicity involves an unexpected and early increase in glycolytic flux, while, surprisingly, no changes in oxidative phosphorylation are observed. Interestingly, enhanced glycolysis involves signaling by mitochondrially-generated oxidants, uncovering a novel regulatory mechanism for this pathway.Today, urban and transport planners face considerable challenges in designing and retrofitting cities that are prepared for increasing urban populations, and their service and mobility needs. When it comes to health-promoting urban and transport developments, there is also a lack of standardized, quantitative indicators to guide the integration of health components right from the outset, i.e. in the formal planning or zoning phase. We narratively reviewed the literature and organized stakeholder workshops to identify and tailor planning principles and indicators that can be linked to health outcomes. We defined four core planning objectives that previous authoritative studies have suggested to result in positive health outcomes among city dwellers, which are I) development of compact cities, II) reduction of private motorized transport, III) promotion of active (i.e. walking and cycling) and public transport, IV) development of green and public open space. Built on the review and stakeholder consensus, we identified 10 urban and transport planning principles that work towards achieving the four core objectives thought to provide health benefits for European city dwellers. These 10 planning principles are 1) land use mix, 2) street connectivity, 3) density, 4) motorized transport reductions, 5) walking, 6) cycling, 7) public transport, 8) multi-modality, 9) green and public open space, and 10) integration of all planning principles. A set of indicators was developed and tailored for each planning principle. The final output of this work is a checklist ready to be applied by urban and transport professionals to integrate health into urban and transport developments in urban environments right from the outset.