Childhood opportunity and appropriate use of child safety restraints in motor vehicle collisions.

Objectives: Safety restraints reduce injuries from motor vehicle collisions (MVCs) but are often improperly applied or not used. The Childhood Opportunity Index (COI) reflects social determinants of health and its study in pediatric trauma is limited. We hypothesized that MVC patients from low-opportunity neighborhoods are less likely to be appropriately restrained. Methods: A retrospective cross-sectional study was performed on children/adolescents ≤18 years old in MVCs between January 1, 2011 and December 31, 2021. Patients were identified from the Children's Hospital Los Angeles trauma registry. The outcome was safety restraint use (appropriately restrained, not appropriately restrained). COI levels by home zip codes were stratified as very low, low, moderate, high, and very high. Multivariable regression controlling for age identified factors associated with safety restraint use. Results: Of 337 patients, 73.9% were appropriately restrained and 26.1% were not appropriately restrained. Compared with appropriately restrained patients, more not appropriately restrained patients were from low-COI (26.1% vs 20.9%), high-COI (14.8% vs 10.8%) and very high-COI (10.2% vs 3.6%) neighborhoods. Multivariable analysis demonstrated no significant associations in appropriate restraint use and COI. There was a non-significant trend that children/adolescents from moderate-COI neighborhoods were more likely than those from very low-COI neighborhoods to be appropriately restrained (OR=1.82, 95% CI 0.78, 4.28). Conclusion: Injury prevention initiatives focused on safety restraints should target families of children from all neighborhood types. Level of evidence: III.

Severe hurricanes increase recruitment and gene flow in the clonal sponge Aplysina cauliformis.

Upright branching sponges, such as Aplysina cauliformis, provide critical three-dimensional habitat for other organisms and assist in stabilizing coral reef substrata, but are highly susceptible to breakage during storms. Breakage can increase sponge fragmentation, contributing to population clonality and inbreeding. Conversely, storms could provide opportunities for new genotypes to enter populations via larval recruitment, resulting in greater genetic diversity in locations with frequent storms. The unprecedented occurrence of two Category 5 hurricanes in close succession during 2017 in the U.S. Virgin Islands (USVI) provided a unique opportunity to evaluate whether recolonization of newly available substrata on coral reefs was due to local (e.g. re-growth of remnants, fragmentation, larval recruitment) or remote (e.g. larval transport and immigration) sponge genotypes. We sampled A. cauliformis adults and juveniles from four reefs around St. Thomas and two in St. Croix (USVI). Using a 2bRAD protocol, all samples were genotyped for single-nucleotide polymorphisms (SNPs). Results showed that these major storm events favoured sponge larval recruitment but did not increase the genetic diversity of A. cauliformis populations. Recolonization of substratum post-storms via clonality was lower (15%) than expected and instead was mainly due to sexual reproduction (85%) via local larval recruitment. Storms did enhance gene flow among and within reef sites located south of St. Thomas and north of St. Croix. Therefore, populations of clonal marine species with low pelagic dispersion, such as A. cauliformis, may benefit from increased frequency and magnitude of hurricanes for the maintenance of genetic diversity and to combat inbreeding, enhancing the resilience of Caribbean sponge communities to extreme storm events.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged adults.

AIMS: Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. METHODS: A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrollment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed, and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). RESULTS: On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 (OR for 3rd tertile, 8.31; 95% CI 2.85-24.2; p<0.001; and 2.77; 95% CI, 1.02-7.51; p=0.045, respectively) and provided significant incremental diagnostic value over SCORE2. CONCLUSIONS: In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures.

Сopper nanoparticles supported on charcoal and betacellulin - Two novel stimulators of ovarian granulosa cell functions and their functional interrelationships.

The present experiments are aimed to examine the effect of copper nanoparticles supported on charcoal (CuNPs/C), growth factor betacellulin (BTC) and their interrelationships in the control of ovarian cell functions. Porcine ovarian granulosa cells were cultured in the presence of CuNPs/C (0, 1, 10 or 100 ng/ml), BTC (100 ng/ml) and the combination of both, CuNPs/C + BTC. Markers of cell proliferation (BrDU incorporation), of the S-phase (PCNA) and G-phase (cyclin B1) of the cell cycle, markers of extrinsic (nuclear DNA fragmentation) and cytoplasmic/mitochondrial apoptosis (bax and caspase 3), and the release of progesterone and estradiol were assessed by BrDU test, TUNEL, quantitative immunocytochemistry and ELISA. Both CuNPs/C and BTC, when added alone, increased the expression of all the markers of cell proliferation, reduced the expression of all apoptosis markers and stimulated progesterone and estradiol release. Moreover, BTC was able to promote the CuNPs/C action on the accumulation of PCNA, cyclin B1, bax and estradiol output. These observations demonstrate the stimulatory action of both CuNPs/C and BTC on ovarian cell functions, as well as the ability of BTC to promote the action of CuNPs/C on ovarian cell functions.

Seasonality and temporal variation of pediatric trauma in Southern California.

INTRODUCTION: Seasonality of pediatric trauma has been previously described, although the association of season with hour of presentation is less understood. Both factors have potential implications for resource allocation and team preparedness. METHODS: A multicenter retrospective study was conducted to analyze the records of injured children <18 years-old who presented to one of the 15 trauma centers within Los Angeles County. Data from the County Trauma and Emergency Medicine Information System Registry was abstracted from 1/1/10 to 12/31/21. Patient demographics, mechanism of injury (MOI) and time of presentation by season were analyzed using Kruskal Wallis tests and chi-square tests. RESULTS: A total of 30,444 pediatric trauma presentations were included. Both the time of presentation and the MOI differed significantly by season with p < 0.001. Autumn had a higher incidence of pedestrian injuries during hours of 08:00 and 15:0020:00, and sports injuries from 16:00 to 21:00. In the Summer there were more burns between 17:00 and 23:00 and falls from greater than 10 ft after 13:00. The mode of transport used was also different across seasons (p = 0.03), with the use of both air and ground EMS greatest during summer and least during winter. The hours of greatest utilization remained relatively constant for all seasons for air transport (18:00-19:00 h) and ground transport (19:00-20:00 h). CONCLUSION: These data demonstrate the significant seasonal and temporal variation within pediatric trauma. These findings could be used to inform improvements in emergency response, and resource allocation in particular.

[Efectividad de la suspensión bacteriana sublingual en la prevención de infecciones de vías aéreas de repetición en pediatría].

Background: Upper respiratory tract infections (URIs) are very common in the pediatric population. Most of these infections are mild, but due to their chronicity they affect quality of life (QoL), in addition to high costs for medical care. The use of bacterial extracts (BE) that stimulate general immunity can reduce its frequency and improve the QoL of the patient. Objective: Evaluate the effectiveness of a BE in the prevention of ARVI in children from 1 to 6 years of age. Methods: Children between the ages of 1 and 6 years, with a diagnosis of RAVI, were randomized into 3 different groups, with medical follow-up at 6 and 12 weeks after the start. The EB was administered with different doses to each group. An ANOVA test with a Tukey post hoc is used for multiple comparisons (maximum type I error of 0.05). Results: 33 children (12 girls) with a mean age of 3.11 years were included. The average frequency of RAVI prior to treatment was 2.2 events/month and 0.9 and 0.4 events/month at 6 and 12 weeks, respectively. The IVARS were reduced by 76.9% at 3 months of treatment. (Graph). No adverse effects were reported. Conclusions: BE is safe and effective in reducing the frequency of RAVI in children, in agreement with the literature. There is not enough published scientific evidence, but the BE seems to have an application in the prevention and treatment of RAVI. Sublingual administration is comfortable in this age group.

Antecedentes: Las infecciones de vías aéreas superiores (IVASR) son muy frecuentes en la población pediátrica. La mayoría de estas infecciones son leves, pero por la cronicidad afectan la calidad de vida (CdV), además de elevados costos por la atención médica. El uso de extractos bacterianos (EB) que estimulen la inmunidad general pueden reducir su frecuencia y mejorar la CdV del paciente. Objetivo: Evaluar la efectividad de un EB en la prevención de IVASR en niños de 1 a 6 años. Métodos: Se aleatorizaron niños entre 1 y 6 años, con diagnóstico IVASR en 3 grupos distintos, seguimiento médico a las 6 y 12 semanas tras el inicio. El EB se administró con dosis distintas a cada grupo. Se utiliza una prueba de ANOVA con un post hoc Tukey para comparaciones múltiples (error tipo I máximo de 0.05). Resultados: Se incluyeron 33 niños (12 niñas) con una media de edad de 3.11 años. La frecuencia de IVASR previo al tratamiento en promedio fue de 2.2 eventos/mes y de 0.9 y de 0.4 eventos/mes a las 6 y 12 semanas respectivamente. La IVARS se redujeron un 76.9% a los 3 meses de tratamiento. (Gráfica). No se reportaron efectos adversos. Conclusiones: El EB es seguro y efectivo en disminuir la frecuencia de IVASR en niños en concordancia con la literatura. No hay suficiente evidencia científica publicada pero el EB parece tener aplicación en la prevención y tratamiento de las IVASR. La administración sublingual es cómoda en este grupo etario.

Extracellular vesicles from Mycobacterium tuberculosis-infected neutrophils induce maturation of monocyte-derived dendritic cells and activation of antigen-specific Th1 cells.

Tuberculosis remains one of the leading public health problems in the world. The mechanisms that lead to the activation of the immune response against Mycobacterium tuberculosis have been extensively studied, with a focus on the role of cytokines as the main signals for immune cell communication. However, less is known about the role of other signals, such as extracellular vesicles, in the communication between immune cells, particularly during the activation of the adaptive immune response. In this study, we determined that extracellular vesicles released by human neutrophils infected with M. tuberculosis contained several host proteins that are ectosome markers. In addition, we demonstrated that extracellular vesicles released by human neutrophils infected with M. tuberculosis released after only 30 min of infection carried mycobacterial antigens and pathogen-associated molecular patterns, and we identified 15 mycobacterial proteins that were consistently found in high concentrations in extracellular vesicles released by human neutrophils infected with M. tuberculosis; these proteins contain epitopes for CD4 T-cell activation. We found that extracellular vesicles released by human neutrophils infected with M. tuberculosis increased the expression of the costimulatory molecule CD80 and of the coinhibitory molecule PD-L1 on immature monocyte-derived dendritic cells. We also found that immature and mature dendritic cells treated with extracellular vesicles released by human neutrophils infected with M. tuberculosis were able to induce IFN-γ production by autologous M. tuberculosis antigen-specific CD4 T cells, indicating that these extracellular vesicles acted as antigen carriers and transferred mycobacterial proteins to the antigen-presenting cells. Our results provide evidence that extracellular vesicles released by human neutrophils infected with M. tuberculosis participate in the activation of the adaptive immune response against M. tuberculosis.

Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions.

INTRODUCTION: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. METHODS: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). RESULTS: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response (p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL (p = 0.039). CONCLUSIONS: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Valorization of CO2 through the Synthesis of Cyclic Carbonates Catalyzed by ZIFs.

One way to exploit CO2 is to use it as a feedstock for the production of cyclic carbonates via its reaction with organic epoxides. As far as we know, there is still no heterogeneous catalyst that accelerates the reaction in a selective, efficient and industrially usable way. Cobalt and zinc-based zeolitic imidazole frameworks (ZIFs) have been explored as heterogeneous catalysts for this reaction. In particular, we have prepared ZIF-8 and ZIF-67 catalysts, which have been modified by partial replacement of 2-methylimidazole by 1,2,4-triazole, in order to introduce uncoordinated nitrogen groups with the metal. The catalysts have shown very good catalytic performance, within the best of the heterogeneous catalysts tested in the cycloaddition of CO2 with epichlorohydrin. The catalytic activity is due ultimately to defects on the outer surface of the crystal, and varies in the order of ZIF-67-m > ZIF-67 > ZiF-8-m = ZIF-8. Notably, reactions take place under mild reaction conditions and without the use of co-catalysts.

Differential activation of innate and adaptive lymphocytes during latent or active infection with Mycobacterium tuberculosis.

Most individuals infected with Mycobacterium tuberculosis (Mtb) have latent tuberculosis (TB), which can be diagnosed with tests (such as the QuantiFERON-TB Gold test [QFT]) that detect the production of IFN-γ by memory T cells in response to the Mtb-specific antigens 6 kDa early secretory antigenic target EsxA (Rv3875) (ESAT-6), 10 kDa culture filtrate antigen EsxB (Rv3874) (CFP-10), and Mtb antigen of 7.7 kDa (Rv2654c) (TB7.7). However, the immunological mechanisms that determine if an individual will develop latent or active TB remain incompletely understood. Here we compared the response of innate and adaptive peripheral blood lymphocytes from healthy individuals without Mtb infection (QFT negative) and from individuals with latent (QFT positive) or active TB infection, to determine the characteristics of these cells that correlate with each condition. In active TB patients, the levels of IFN-γ that were produced in response to Mtb-specific antigens had high positive correlations with IL-1ß, TNF-α, MCP-1, IL-6, IL-12p70, and IL-23, while the proinflammatory cytokines had high positive correlations between themselves and with IL-12p70 and IL-23. These correlations were not observed in QFT-negative or QFT-positive healthy volunteers. Activation with Mtb-soluble extract (a mixture of Mtb antigens and pathogen-associated molecular patterns [PAMPs]) increased the percentage of IFN-γ-/IL-17-producing NK cells and of IL-17-producing innate lymphoid cell 3 (ILC3) in the peripheral blood of active TB patients, but not of QFT-negative or QFT-positive healthy volunteers. Thus, active TB patients have both adaptive and innate lymphocyte subsets that produce characteristic cytokine profiles in response to Mtb-specific antigens or PAMPs. These profiles are not observed in uninfected individuals or in individuals with latent TB, suggesting that they are a response to active TB infection.

Photosensitized selective semi-oxidation of tetrahydroisoquinoline: a singlet oxygen path.

Selective semi-oxidation of tetrahydroisoquinoline (THIQ) leads to a valuable dihydroisoquinoline (DHIQ) derivative via singlet oxygen photooxidation process. Typical photosensitisers (i.e., Ru complexes) can activate the reaction even under heterogeneous conditions that facilitate catalyst separation and reusability. In contrast to DHIQ, THIQ acts as an efficient singlet oxygen quencher driving the reaction selectivity. The reaction can also be facilitated by semiconductor catalysts such as MoCo@GW, a glass wool-based catalyst that is easy to separate and reuse and compatible with flow photochemistry. Its role is to mediate the formation of isoquinoline (IQ) and thus an in situ-generated singlet oxygen catalyst. Laser flash photolysis with NIR detection provides proof of the singlet oxygen mechanism proposed and rate constants for the key steps that mediate the oxidation.

Mechanical bull riding in early childhood: a preventable cause of serious injury.

Our institution saw three cases of moderate to severe injury in children under 7 years of age caused by falls from mechanical bulls at private parties. Injuries sustained included long bone fracture, skull fracture and intracranial haemorrhage. The circumstances of these injuries led our institution's injury prevention team to investigate the safety protocols of local vendors, revealing limited regulation of safety equipment, rider age or height minimums and training for the operation of mechanical bulls. This information was reported to the US Consumer Product Safety Commission in order to reduce instances of these serious injuries in young children.

A novel yeast-based high-throughput method for the identification of protein palmitoylation inhibitors.

Protein S-acylation or palmitoylation is a widespread post-translational modification that consists of the addition of a lipid molecule to cysteine residues of proteins through a thioester bond. Palmitoylation and palmitoyltransferases (PATs) have been linked to several types of cancers, diseases of the central nervous system and many infectious diseases where pathogens use the host cell machinery to palmitoylate their effectors. Despite the central importance of palmitoylation in cell physiology and disease, progress in the field has been hampered by the lack of potent-specific inhibitors of palmitoylation in general, and of individual PATs in particular. Herein, we present a yeast-based method for the high-throughput identification of small molecules that inhibit protein palmitoylation. The system is based on a reporter gene that responds to the acylation status of a palmitoylation substrate fused to a transcription factor. The method can be applied to heterologous PATs such as human DHHC20, mouse DHHC21 and also a PAT from the parasite Giardia lamblia. As a proof-of-principle, we screened for molecules that inhibit the palmitoylation of Yck2, a substrate of the yeast PAT Akr1. We tested 3200 compounds and were able to identify a candidate molecule, supporting the validity of our method.

Genetic composition of queen conch (Lobatus gigas) population on Pedro Bank, Jamaica and its use in fisheries management.

The queen conch fishery in Jamaica is sustained by Pedro Bank, which is the main harvesting site located approximately 80 km south-west from Kingston. Due to its relative size, Pedro Bank has been subdivided into zones for management purposes by the Fisheries Division and the Veterinary Services Division. Understanding whether these sub-divisions reflect different sub-populations is critical for managing exploitation levels because fisheries management must demonstrate that harvesting does not endanger the future viability of the population as queen conch are on Appendix II of the Convention in Trade in Endangered Species of Wild Fauna and Flora (CITES). This determination is essential for the continued export to international markets such as the European Union. Two hundred and eight samples were collected across the entire Pedro Bank and were genetically characterized using nine polymorphic microsatellite loci. Population structure analysis for Lobatus gigas from Pedro Bank yielded low but significant values (FST = 0.009: p = 0.006) and suggested a high magnitude of gene flow indicative of a fit and viable population throughout the bank. Analysis of molecular variance (AMOVA) indicated a 100% variation within individual samples with little variation (0.9%) between populations. In contrast pairwise genetic comparisons identified significant differences between populations located to the south eastern and eastern region of the bank to those in the central and western locations. Bayesian clustering analysis also indicated the likelihood of two population sub-divisions (K = 2) on Pedro Bank. The results provided evidence of a weak but significant population structure which has crucial implications for the fishing industry as it suggests the use of ecosystem based management (EBM) in setting quotas to promote sustainable harvesting of L. gigas within each monitoring zone on Pedro Bank.

Valproic acid inhibits interferon-γ production by NK cells and increases susceptibility to Listeria monocytogenes infection.

Valproic acid (VPA) is a drug commonly used for epileptic seizure control. Recently, it has been shown that VPA alters the activation of several immune cells, including Natural Killer (NK) cells, which play an important role in the containment of viruses and intracellular bacteria. Although VPA can increase susceptibility to extracellular pathogens, it is unknown whether the suppressor effect of VPA could affect the course of intracellular bacterial infection. This study aimed to evaluate the role of VPA during Listeria monocytogenes (L.m) infection, and whether NK cell activation was affected. We found that VPA significantly augmented mortality in L.m infected mice. This effect was associated with increased bacterial load in the spleen, liver, and blood. Concurrently, decreased levels of IFN-γ in serum and lower splenic indexes were observed. Moreover, in vitro analysis showed that VPA treatment decreased the frequency of IFN-γ-producing NK cells within L.m infected splenocytes. Similarly, VPA inhibited the production of IFN-γ by NK cells stimulated with IL-12 and IL-18, which is a crucial system for early IFN-γ production in listeriosis. Finally, VPA decreased the phosphorylation of STAT4, p65, and p38, without affecting the expression of IL-12 and IL-18 receptors. Altogether, our results indicate that VPA increases the susceptibility to Listeria monocytogenes infection and suggest that NK cell is one of the main targets of VPA, but further work is needed to ascertain this effect.

Abatement of the Stimulatory Effect of Copper Nanoparticles Supported on Titania on Ovarian Cell Functions by Some Plants and Phytochemicals.

The application of nanoparticles has experienced a vertiginous growth, but their interaction with food and medicinal plants in organisms, especially in the control of reproduction, remains unresolved. We examined the influence of copper nanoparticles supported on titania (CuNPs/TiO2), plant extracts (buckwheat (Fagopyrum esculentum) and vitex (Vitex agnus-castus)), phytochemicals (rutin and apigenin), and their combination with CuNPs/TiO2 on ovarian cell functions, using cultured porcine ovarian granulosa cells. Cell viability, proliferation (PCNA accumulation), apoptosis (accumulation of bax), and hormones release (progesterone, testosterone, and 17ß-estradiol) were analyzed by the Trypan blue test, quantitative immunocytochemistry, and ELISA, respectively. CuNPs/TiO2 increased cell viability, proliferation, apoptosis, and testosterone but not progesterone release, and reduced the 17ß-estradiol output. Plant extracts and components have similar stimulatory action on ovarian cell functions as CuNPs/TiO2, but abated the majority of the CuNPs/TiO2 effects. This study concludes that (1) CuNPs/TiO2 can directly stimulate ovarian cell functions, promoting ovarian cell proliferation, apoptosis, turnover, viability, and steroid hormones release; (2) the plants buckwheat and vitex, as well as rutin and apigenin, can promote some of these ovarian functions too; and (3) these plant additives mitigate the CuNPs/TiO2's activity, something that must be considered when applied together.

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation.

Mast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate.

Linkage between Fluorescence and Electrochemical Properties of Imidazolium Compounds in Acetonitrile Solution.

The fluorescence properties of some imidazolium derivatives are relevant in photosensing and therefore, the structural analysis of them is a key point for its rational design, which would be useful to prepare new systems with novel applications. Herein we report a multidisciplinary study of the fluorescence and voltammetric properties of three imidazolium compounds {1,3-bis[(R,R)-1'-chloro-1'-phenylpropan-2'-yl]-imidazolium chloride (1), 1,3-bis[(Z)-1'-phenylprop-1'-en-2'-yl]imidazolium chloride (2) 1,3-bis[(R)-1'-chlorobutan-2'-yl]-imidazolium chloride (3)}. Electronic structure calculations and Bader analyses were used to correlate both fluorescence and the capability of the molecules to be reduced through a heterogeneous electron transfer process. Both properties are strongly dependent on the proton in position two of the imidazolium ring, where the electron transfer as well as the excitation of the electrons are carried out. The reactivity in this position is controlled by the N-substituents on the imidazolium ring and is due to single contacts H⋅⋅⋅Cl- , tricentric contacts Cl⋅⋅⋅Cl- ⋅⋅⋅Cl, π-electronic delocalization and π-stacking interactions.

Therapeutic opportunities for PLK1 inhibitors: Spotlight on BRCA1-deficiency and triple negative breast cancers.

Polo-Like Kinases (PLKs) are central players of mitotic progression in Eukaryotes. Given the intimate relationship between cell cycle progression and cancer development, PLKs in general and PLK1 in particular have been thoroughly studied as biomarkers and potential therapeutic targets in oncology. The oncogenic properties of PLK1 overexpression across different types of human cancers are attributed to its roles in promoting mitotic entry, centrosome maturation, spindle assembly and cytokinesis. While several academic labs and pharmaceutical companies were able to develop potent and selective inhibitors of PLK1 (PLK1i) for preclinical research, such compounds have reached only limited success in clinical trials despite their great pharmacokinetics. Even though this could be attributed to multiple causes, the housekeeping roles of PLK1 in both normal and cancer cells are most likely the main reason for clinical trials failure and withdraw due to toxicities issues. Therefore, great efforts are being invested to position PLK1i in the treatment of specific types of cancers with revised dosages schemes. In this mini review we focus on two potential niches for PLK1i that are supported by recent evidence: triple negative breast cancers (TNBCs) and BRCA1-deficient cancers. On the one hand, we recollect several lines of strong evidence indicating that TNBCs are among the cancers with highest PLK1 expression and sensitivity to PLK1i. These findings are encouraging because of the limited therapeutics options available for TNBC patients, which rely mainly on classic chemotherapy. On the other hand, we discuss recent evidence that unveils synthetic lethality induction by PLK1 inhibition in BRCA1-deficient cancers cells. This previously unforeseen therapeutic link between PLK1 and BRCA1 is promising because it defines novel therapeutic opportunities for PLK1i not only for breast cancer (i.e. TNBCs with BRCA1 deficiencies), but also for other types of cancers with BRCA1-deficiencies, such as pancreatic and prostate cancers.