Abstract Reactive oxygen species (ROS) are both harmful molecules sustaining the pathogenesis of several diseases and essential modulators of cell behaviours. In particular, a growing wealth of data ...suggest that ROS-dependent signalling pathways might be critical in conferring embryonic or adult stem cells their specific properties. However, how stem cells control ROS production and scavenging, and how ROS in turn contribute to stemness remain poorly understood. Using the Xenopus retina as a model system, we first investigated the redox status of retinal stem cells (RSCs). We discovered that they exhibit higher ROS levels compared to progenitors and retinal neurons and express a set of specific antioxidant genes. We next addressed the question of ROS functional involvement in these cells. Using pharmacological or genetic tools, we demonstrate that inhibition of NADPH oxidase (NOX)-dependent ROS production increases the proportion of quiescent RSCs. This is surprisingly accompanied by an apparent acceleration of the mean division speed within the remaining proliferating pool. Our data further unveil that such impact on RSC cell cycling is achieved by modulation of the Wnt/Hedgehog signalling balance. Altogether, we highlight that RSCs exhibit distinctive redox characteristics and exploit NOX signalling to limit quiescence and fine-tune their proliferation rate.
Recent research has suggested that among different relapse procedures (i.e. resurgence and renewal), an increased number of acquisition sessions contributes on observing a greater relapse. Even when ...such results seem to be consistent across studies, these can also be explained by attending to the number of scheduled reinforcers, since using different number of acquisition sessions could also result on differences in the number of scheduled reinforcers between groups. ABA renewal was assessed in four groups of rats by varying the number of acquisition sessions (12 and 4) or the number of scheduled reinforcers (240 and 720) between groups. As previous experiments, our results suggest that different number of acquisition sessions results on differences in ABA renewal; nevertheless, different number of obtained reinforcers seem to affect the degree to which renewal is observed. Therefore, it seems like renewal does not only depend upon the amount of training but also on the number of reinforcers obtained during acquisition.
Lipid droplets (LDs) are intracellular organelles found in most cell types from adipocytes to cancer cells. Although recent investigations have implicated LDs in numerous diseases, the current ...available methods to monitor them in vertebrate models rely on static imaging using fluorescent dyes, limiting the investigation of their rapid in vivo dynamics. Here, we report a fluorophore chemistry approach to enable in vivo LD dynamic monitoring using a Nernstian partitioning mechanism. Interestingly, the effect of atorvastatin and osmotic treatments toward LDs revealed an unprecedented dynamic enhancement. Then, using a designed molecular probe with an optimized response to hydration and LD dynamics applied to Zebrafish developing pericardial and yolk-sac edema, which represents a tractable model of a human cardiovascular disease, we also provide a unique dual method to detect disease evolution and recovery.
Mitochondrial voltage dynamics plays a crucial role in cell healthy and disease. Here, a new fluorescent probe to monitor mitochondrial early voltage variations is described. The slowly permeant ...probe is retained in mitochondria during measurements to avoid interferences from natural membrane potential by incorporating an hydrolizable ester function. Voltage, local polarity, pH parameters and transmembrane dynamics were found to be deeply correlated opening a approach in mitochondrial sensing.
A fluorescent probe to monitor mitochondrial voltage in live cells under conditions promoting membrane potential variations, permeability transition pore opening and under pH and redox variation.
Abstract Aims There is inconclusive evidence regarding the potential link between diabetes mellitus (DM) and colorectal cancer (CRC). Associations between type 2 DM and colorectal neoplasia (CRN; ...colorectal cancer and/or adenomas) have not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM. This study aims to assess the association between type 2 DM and CRN in Hispanics. Methods Hispanics with incident CRN and colonoscopy-negative controls from 2005 to 2009 were evaluated. Diagnosis of type 2 DM was established by previous medical diagnosis and/or use of DM treatments. Unconditional logistic regression was performed to estimate odds ratios for the association between type 2 DM and CRN. Results A total of 451 participants (mean age 61.1 ± 11.9 years, 59.6 % men) were evaluated (218 with incident CRC, 77 with colorectal adenomas, and 156 colonoscopy-negative controls). The prevalence of type 2 DM in this study was 25.1%. After adjusting for potential confounding variables, women with type 2 DM were 2.74 (95% CI: 0.94–7.99) times more likely to have CRN and 4.83 times more likely to present with proximal colonic CRN (95% CI: 1.25–18.58) than women without type 2 DM. No statistically significant associations were found between type 2 DM and CRN among men. Conclusions An increased odds for CRN and proximal location of CRN was observed among Hispanic women with type 2 DM. Since DM is a highly prevalent disease in this population, adherence to routine CRC screening is of outmost importance.
Resurgence after different number of sessions (4, 12, or 36) was studied in two experiments using a four-phase procedure –that is, target-response extinction and alternative-response reinforcement ...occurred in separate phases of the procedure (cf. three-phase procedure). For the first experiment, three groups of rats were exposed to different number of target-extinction sessions while the number of target- and alternative-reinforcement sessions was held constant; whereas, for the second experiment, target-reinforcement and -extinction sessions remained the same between phases, while alternative-reinforcement sessions varied between groups. No differences in resurgence were observed as a result of different numbers of target-extinction sessions. However, when different numbers of alternative-reinforcement sessions were arranged, greater resurgence was observed after 36 sessions. As previously reported, the current findings suggest resurgence could be mitigated or promoted by subject’s extinction or alternative-reinforcement history.
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•A sensitive fluorescent chemosensor for iodide, based-on a cationic porphyrin, 1 was synthesized and studied in pure water.•1 selectively detects I− ions in the nanomolar ...concentration range with good selectivity over common inorganic anions.•Iodide forms an very stable ion-pair complex and quenches efficiently its red fluorescence.•Iodide sensing was studied by spectroscopic experiments, fluorescence-lifetimes, crystal structure and DFT calculations.
The new tetracationic and highly luminescent triflate salt of 5,10,15,20-tetra(4-benzylpyridinium)-21H,23H-porphyrin, 1.OTf was designed and studied as a chemosensor for iodide in pure water. Under optimal conditions, the addition of inorganic anions and acetate as sodium salts to 1.OTf quench its red fluorescence with a very pronounced affinity toward iodide (K1.I− = 1.9(±0.08) x 104 M-1) accompanied by complete quenching of its emission (KSV = 1.1(±0.1) x 105) in a micromolar concentration range (0-50 μM). A rapid and direct analytical response of 1.OTf by addition of I- ions was observed in a wide range of pH (5.0–8.0) with a detection limit of 180 nmol L-1 at neutral pH and good selectivity over other biological and more basic anions such as pyrophosphate, chloride, fluoride and phosphate. The optical change by addition of iodide is attributed to a strong ion-pair binding with simultaneous formation of efficient hydrogen bonding C–H … I- interactions, these contacts are supported by 1H NMR experiments. The efficient binding and fluorescence detection is attributed to a very high positive charge of monomeric specie of 1 in combination with strong acidification of C–H donors by quaternization of pendant pyridyl groups. On the other hand, addition of bromide, common interfering anion, shows a modest spectral change but lower than those observed for iodide. On basis of multiple spectroscopic titration experiments (1H NMR, UV–vis, fluorescence), Job´s plot, crystal structure of the bromide salt of 1 and fluorescence lifetime measurements, a photoinduced electron transfer quenching mechanism with simultaneous sensor-iodide complexation both in the excited and the ground-state is proposed. From theoretical DFT studies, the binding mode of this chemosensor with iodide is markedly ionic interaction, energy calculated in 402.8 kcal/mol. The proposed method is direct, fast, accurate and of low cost for the determination of iodide ions in pure water.
Pediatric early warning systems (PEWS) aid with early identification of clinical deterioration and improve outcomes in children with cancer hospitalized in resource-limited settings; however, there ...may be barriers to implementation.
To evaluate stakeholder-reported barriers and enablers to PEWS implementation in resource-limited hospitals.
In this qualitative study, semistructured stakeholder interviews were conducted at 5 resource-limited pediatric oncology centers in 4 countries in Latin America. Hospitals participating in a multicenter collaborative to implement PEWS were purposefully sampled based on time required for implementation (fast vs slow), and stakeholders interviewed included physicians, nurses, and administrators, involved in PEWS implementation. An interview guide was developed using the Consolidated Framework for Implementation Research (CFIR). Interviews were conducted virtually in Spanish, audiorecorded, and professionally transcribed and translated into English. A codebook was developed a priori using the CFIR and supplemented with codes inductively derived from transcript review. Two coders independently analyzed all transcripts, achieving a κ of 0.8 to 0.9. The study was conducted from June 1 to August 31, 2020.
Thematic analysis was conducted based on CFIR domains (inner setting, characteristics of individuals, outer setting, intervention characteristics, and implementation process) to identify barriers and enablers to PEWS implementation.
Seventy-one staff involved in PEWS implementation were interviewed, including 32 physicians (45%), 32 nurses (45%), and 7 administrators (10%). Of these, 50 were women (70%). Components of the 5 CFIR domains were mentioned by participants as barriers and enablers to PEWS implementation at both fast- and slow-implementing centers. Participants emphasized barriers at the level of the clinical staff, hospital, external factors, and PEWS intervention. These barriers included staff resistance to change, inadequate resources, components of health systems, and the perceived origin and complexity of PEWS. At all centers, most barriers were successfully converted to enablers during the implementation process through targeted strategies, such as early stakeholder engagement and adaptation, including adapting PEWS to better fit the local context and changing the hospital setting to support ongoing use of PEWS.
To date, this is the first multicenter, multinational study describing barriers and enablers to PEWS implementation in resource-limited settings. Findings suggest that many barriers are not immutable and can be converted to enablers during the implementation process. This work can serve as a guide for clinicians looking to implement evidence-based interventions to reduce global disparities in patient outcomes.
Currently the investigation carried out in the physiology of exercise has produced new discoveries about the effect of physical activity, related to reversing the swelling process produced by ...overweight and obesity in the body, as well as, a balanced diet. Objective: Develop a nutritional and aerobic activity proposal in order to prevent and / or reverse the condition of overweight and obesity that occurs in adolescents enrolled in the Autonomous University of Hidalgo State - High School Huejutla campus. Methodology: Somatometric data was engaged in the population study which are included: Size, BMI, Waist Circumference, Arm Circumference. Subsequently, they were categorized according to the nutritional status of each individual and the proposal for a high diet in antioxidants. It was established with the purpose to reduce the level of oxidative stress and systemic inflammation to prevent future metabolic complications. Results: According to the categorization of adolescents with respect to the body mass index in percentiles, 6.6% (6) are underweight, 71.71 % (71) normal weight, 18.18 % (18) overweight, 4.4 % (4) in obesity. Conclusion: In the present study, several nutritional diets were developed, as well as an aerobic exercise plan to prevent and maintain the good development of adolescents enrolled in the ESH High school. It also emphasizes that prevention and good health of the entire population is very important, since today in Mexico and the world the main chronic degenerative diseases are caused by overweight and obesity.
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