Metabolic syndrome in rural Peruvian adults living at high altitudes using different cookstoves

This study determined the prevalence of metabolic syndrome (MetS) in open fire stoves and improved cookstoves users (ICS) in the rural Peruvian Andes. Participants answered a socioeconomic questionnaire, one 24-hour food recall and underwent a physical examination. We analysed data from 385 participants, 190 (112 women and 78 men) were ICS users and 195 (123 women and 72 men) were open fire stove users. The prevalence of MetS was 21.3, 26.4% in women and 13.3% in men. We found no statistically significant association between the type of cookstove and MetS. Body mass index and altitude were important determinants of MetS. Research on cardiometabolic diseases and open fire stove use contributes to understanding the effect of household air pollution on health in high altitude populations

Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration-UV-vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K (1)' = 5.3-5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event

Magnetospheric ULF waves with increasing amplitude related to solar wind dynamic pressure changes: The Time History of Events and Macroscale Interactions during Substorms (THEMIS) observations

Ultralow frequency (ULF) waves play an important role in transferring energy by buffeting the magnetosphere with solar wind pressure impulses. The amplitudes of magnetospheric ULF waves, which are induced by solar wind dynamic pressure enhancements or shocks, are thought to damp in one half a wave cycle or an entire wave cycle. We report in situ observations of solar wind dynamic pressure impulse‐induced magnetospheric ULF waves with increasing amplitudes. We found six ULF wave events induced by solar wind dynamic pressure enhancements with slow but clear wave amplitude increase. During three or four wave cycles, the amplitudes of ion velocities and electric field of these waves increased continuously by 1.3–4.4 times. Two significant events were selected to further study the characteristics of these ULF waves. We found that the wave amplitude growth is mainly contributed by the toroidal mode wave. Three possible mechanisms of causing the wave amplitude increase are discussed. First, solar wind dynamic pressure perturbations, which are observed in a duration of 20–30 min, might transfer energy to the magnetospheric ULF waves continually. Second, the wave amplitude increase in the radial electric field may be caused by superposition of two wave modes, a standing wave excited by the solar wind dynamic impulse and a propagating compressional wave directly induced by solar wind oscillations. When superposed, the two wave modes fit observations as does a calculation that superposes electric fields from two wave sources. Third, the normal of the solar wind discontinuity is at an angle to the Sun‐Earth line. Thus, the discontinuity will affect the dayside magnetopause continuously for a long time.Key PointsSix Psw enhancement‐induced ULF waves with increasing amplitudes were observedThe wave amplitude could increase four times in several wave periodsSuperposition of two wave modes could cause the wave amplitude increasePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115986/1/jgra52015_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115986/2/jgra52015.pd

Identifying gaps on health impacts, exposures, and vulnerabilities to climate change on human health and wellbeing in South America: a scoping review

There is an important gap in regional information on climate change and health, limiting the development of science-based climate policies in South American countries. This study aims to identify the main gaps in the existing scientific literature on the impacts, exposure, and vulnerabilities of climate change on population health. A scoping review was performed guided by four sub-questions focused on the impacts of climate change on physical and mental health, exposure and vulnerability factors of population to climate hazards. The main findings showed that physical impacts mainly included infectious diseases, while mental health impacts included trauma, depression, and anxiety. Evidence on population exposure to climate hazards is limited, and social determinants of health and individual factors were identified as vulnerability factors. Overall, evidence on the intersection between climate change and health is limited in South America and has been generated in silos, with limited transdisciplinary research. More formal and systematic information should be generated to inform public policy

Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Conjugation of Organoruthenium(II) 3-(1H-Benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and Indolo[3,2-d]benzazepines to Recombinant Human Serum Albumin: a Strategy To Enhance Cytotoxicity in Cancer Cells

Five organoruthenium complexes [RuCl(η6-arene)(L)]Cl with a modified arene ligand, namely, 4-formylphenoxyacetyl-η6-benzylamide, and L = 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines or indolo[3,2-d]benzazepines were synthesized and conjugated to recombinant human serum albumin in order to improve their drug targeting and delivery to cancer cells, and a marked increase in cytotoxicity was observed

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides

Importance of Polaronic Effects for Charge Transport in CdSe Quantum Dot Solids

We developed an accurate model accounting for electron-phonon interaction in colloidal quantum dot supercrystals that allowed us to identify the nature of charge carriers and the electrical transport regime. We find that in experimentally analyzed CdSe nanocrystal solids the electron-phonon interaction is sufficiently strong that small polarons localized to single dots are formed. Charge-carrier transport occurs by small polaron hopping between the dots, with mobility that decreases with increasing temperature. While such a temperature dependence of mobility is usually considered as a proof of band transport, we show that the same type of dependence occurs in the system where transport is dominated by small polaron hopping