Intra-urban variability of long-term exposure to PM2.5 and NO2 in five cities in Colombia.

Rapidly urbanizing cities in Latin America experience high levels of air pollution which are known risk factors for population health. However, the estimates of long-term exposure to air pollution are scarce in the region. We developed intraurban land use regression (LUR) models to map long-term exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in the five largest cities in Colombia. We conducted air pollution measurement campaigns using gravimetric PM2.5 and passive NO2 sensors for 2 weeks during both the dry and rainy seasons in 2021 in the cities of Barranquilla, Bucaramanga, Bogotá, Cali, and Medellín, and combined these data with geospatial and meteorological variables. Annual models were developed using multivariable spatial regression models. The city annual PM2.5 mean concentrations measured ranged between 12.32 and 15.99 µg/m3 while NO2 concentrations ranged between 24.92 and 49.15 µg/m3. The PM2.5 annual models explained 82% of the variance (R2) in Medellín, 77% in Bucaramanga, 73% in Barranquilla, 70% in Cali, and 44% in Bogotá. The NO2 models explained 65% of the variance in Bucaramanga, 57% in Medellín, 44% in Cali, 40% in Bogotá, and 30% in Barranquilla. Most of the predictor variables included in the models were a combination of specific land use characteristics and roadway variables. Cross-validation suggests that PM2.5 outperformed NO2 models. The developed models can be used as exposure estimate in epidemiological studies, as input in hybrid models to improve personal exposure assessment, and for policy evaluation.

The theory of planned behavior and alcohol protective behavioral strategies: a prospective study examining the role of habit and gender invariance.

OBJECTIVES: Alcohol Protective Behavioral Strategies (PBS) have consistently shown to be effective in reducing alcohol use and its associated consequences. We aimed to examine the explanatory value of the Theory of Planned Behavior (TPB) for using five PBS, studying the role of habit, and its potential variation across genders. METHODS: Targeted sampling was used to recruit 339 young adults in the community (women = 50.7%; mean age = 2.21[SD = 2.21]), who completed baseline and 2-month follow-up questionnaires. RESULTS: The explained variance of the TPB ranged from 58-68% for intention to use PBS, and 18-50% for behavior. The inclusion of habit produced increases of 17-26% in explained variance in intention, while explained variance in behavior remained similar. Habit was the strongest predictor of intention to use PBS, followed by attitude. Except for one behavior (drinking slowly), habits did not moderate the intention-behavior relationship, and the explanatory value of the TPB did not differ across genders. CONCLUSIONS: Our findings support the utility of the TPB as an explanatory model of alcohol PBS, along with the need to include habits within the framework of dual-process models. Interventions aimed at promoting alcohol PBS could be optimized by targeting attitudes towards PBS and habits.

Antimicrobial Activity of Manganese(I) Tricarbonyl Complexes Bearing 1,2,3-Triazole Ligands.

BACKGROUND: Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation is not dealt with, we will be facing 10 million deaths due to multidrug resistant infections per year by 2050, surpassing cancer-related deaths. This alarming scenario has refocused attention into researching alternative drugs to treat multidrug-resistant infections. AIMS: In this study, the antimicrobial activities of four manganese complexes containing 1,2,3,-triazole and clotrimazole ligands have been evaluated. It is known that azole antibiotics coordinated to manganese tricarbonyl complexes display interesting antimicrobial activities against several microbes. In this work, the effect of the introduction of 1,2,3,-triazole-derived ligands in the [Mn(CO)3(clotrimazole)] fragment has been investigated against one Gram-positive bacterium and five Gram-negative bacteria. METHODS: The initial antimicrobial activity of the above-mentioned complexes was assessed by determining the minimum inhibitory and bactericidal concentrations using the broth microdilution method. Growth curves in the presence and absence of the complexes were performed to determine the effects of these complexes on the growth of the selected bacteria. A possible impact on cellular viability was determined by conducting the MTS assay on human monocytes. RESULTS: Three of the Mn complexes investigated (4-6) had good antimicrobial activities against all the bacteria tested, with values ranging from 1.79 to 61.95 µM with minimal toxicity. CONCLUSIONS: Due to the increased problem of antibiotic resistance and a lack of new antibacterial drugs with no toxicity, these results are exciting and show that these types of complexes can be an avenue to pursue in the future.

Risk Factors for Diabetic Retinopathy in Latin America (Mexico) and the World: A Systematic Review and Meta-Analysis.

Diabetic retinopathy (DR) is one of the main complications of diabetes, and the management of the main control parameters explains only an 11% reduction in the risk of progressing to DR, leaving 89% to be explained by other factors or correlations between the usual factors that are currently unknown. The objective of this systematic review and meta-analysis is to evaluate the similarities and differences between the possible risk factors for developing DR when comparing the world to Latin American populations. The search was performed first for Latin American (LA) populations and a second search for non-Latin American (Non-LA) populations. Using the PRISMA guidelines, five articles were found to be relevant for each of the groups. The patients who had elevated systolic blood pressure (SBP) developed DR more frequently than the patients without retinopathy (Z = 2.1, p = 0.03), an effect measured in the population at a global level (GL), behavior that becomes not significant when the LA and non-LA populations are grouped separately; relevant to this is that the diagnosis of hypertension (HBP) grouped globally and stratified does not present a risk factor for DR (Z = 0.79, p = 0.42). This indicates that SBP is a risk factor for the world population and that, by separating it into different regions, the omission could cause it not to be considered a possible risk factor. In conclusion, the relationship between the increase in DR associated with the risk factors present in different populations, the limited research conducted in Latin America, and the cultural, social, economic, and genetic differences makes for a complex condition, which reflects the necessity of researching in a more integrated way.

Four-decade (1977-2017) landscape tale of tourist reservoir hotspot El Piñol-Guatapé, Colombia.

Efficient management of land use/land cover (LULC) features is vital for a balanced sustainable ecosystem. Thus, this work aimed to document the LULC changes in the less studied El Peñol-Guatapé reservoir, Antioquia, Colombia, especially in the reservoir area due to the construction of a hydro-electric power plant. For this study, Landsat images of 1977, 1986, 1997, and 2017 were used and the results indicated an increase in the settlement area and road networks by 0.10 and 0.60%, respectively, while during 1986 to 2017, cropland, plantation, dense forest, and open forest areas presented an increase of 0.52, 1.06, 2.87 and 2.61%, respectively. However, the marshy vegetation, scrub forest and fallow land decreased to - 0.51, - 3.79 and - 4.29%, respectively, in the same period. The water body before and after the completion of reservoir project denoted an increase from 13.1 km2 in 1977 to 45.7 km2 in 1986. This study provides a first-hand report on LULC dynamics in this tourism dominated municipalities that will serve as a reference for ecosystem management to reconcile the conflicts between different LULC classes in ecologically enriched regions.

Drunkenness and Regretted Online Social Risk Behaviors: The Role of Social Drinking Motives and Positive Urgency.

Background: Alcohol use and the use of social media and other forms of digital communications is characteristic of young adults. The present study prospectively examined the relationship between social drinking motives and positive urgency and the engagement in regretted online social risk behaviors while drunk (having posted on social media, called or texted someone, or been visibly drunk in a photo) among a community sample of young adults. Methods: Using a targeted sampling procedure, we accessed a baseline sample of 360 young adults aged 18-25 years old from the community. Of these, 339 (mean age: 21.1 [SD = 2.21]; female = 50.7%) completed 2-month follow-up measures. Results: Social drinking motives and the tendency to act impulsively under conditions of positive affect (i.e. positive urgency) were measured at baseline, and frequency of regretted online social risk behaviors were measured at follow-up. Results showed that baseline social drinking motives were positively associated with all three regretted online social risk behaviors examined at follow-up. Higher baseline positive urgency scores were associated with a higher frequency of regretted posting on social media and calling or texting someone while drunk at follow-up. Conclusions: Our findings support the inclusion of positive urgency and social drinking motives as key components of preventive interventions aimed at reducing potential negative consequences of using social media and other forms of digital communications while under the effects of alcohol.

Half-sandwich Ru(II) N-heterocyclic carbene complexes in anticancer drug design.

The ruthenium arene fragment is a rich source for the design of anticancer drugs; in this design, the co-ligand is a critical factor for obtaining effective anticancer complexes. In comparison with other types of ligands, N-heterocyclic carbenes (NHCs) have been less explored, despite the versatility in structural modifications and the marked stabilization of metal ions, being these characteristics important for the design of metal drugs. However, notable advances have been made in the development of NHC Ruthenium arene as anticancer agents. These advances include high antitumor activities, proven both in in vitro and in in vivo models and, in some cases, with marked selectivity against tumorigenic cells. The versatility of the structure has played a fundamental role, since they have allowed a selective interaction with their molecular targets through, for example, bio-conjugation with known anticancer molecules. For this reason, the structure-activity relationship of the imidazole, benzimidazole, and abnormal NHC ruthenium (II) η6-arene complexes have been studied. Taking into account this study, several synthetic aspects are provided to contribute to the next generations of this kind of complexes. Moreover, in recent years nanotechnology has provided innovative nanomedicines, where half-sandwich Ruthenium(II) complexes are paving their way. In this review, the recent developments in nanomaterials functionalized with Ruthenium complexes for targeted drug delivery to tumors will also be highlighted.

Antifungal Potential of Marine Organisms of the Yucatan Peninsula (Mexico) against Medically Important Candida spp.

Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, partly due to the ineffectiveness of the available antifungal agents. The rampant increase in infections recalcitrant to the current antifungals has worsened this scenario and made the discovery of new and more effective antifungals a pressing health issue. In this study, 65 extracts from marine organisms of the Yucatan Peninsula, Mexico, were screened for antifungal activity against Candida albicans and Candida glabrata, two of the most prevalent fungal species that cause nosocomial invasive fungal infections worldwide. A total of 51 sponges, 13 ascidians and 1 gorgonian were collected from the coral reef and mangrove forest in the Yucatan Peninsula (Mexico) and extracted with organic solvents. Nine crude extracts showed potent antifungal activity, of which four extracts from the sponge species Aiolochroia crassa, Amphimedon compressa, Monanchora arbuscula and Agelas citrina had promising activity against Candida spp. Bioassay-guided fractionation of the M. arbuscula extract revealed the remarkable fungicidal activity of some fractions. Analysis of the chemical composition of one of the most active fractions by UHPLC-HRMS and NMR indicated the presence of mirabilin B and penaresidin B, and their contribution to the observed antifungal activity is discussed. Overall, this work highlights marine organisms of the Yucatan Peninsula as important reservoirs of natural products with promising fungicidal activity, which may greatly advance the treatment of invasive fungal infections, especially those afflicting immunosuppressed patients.

Ruthenium(II) polypyridyl complexes with benzothiophene and benzimidazole derivatives: Synthesis, antitumor activity, solution studies and biospeciation.

With the aim to incorporate pharmacophore motifs into the Ru(II)-polypyridyl framework, compounds [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzo[b]thiophene)](CF3SO3)2 (1) and [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzimidazole)](CF3SO3)2 (2) were prepared, characterized and tested for their antitumor potential. The solid-state structure of the compounds was confirmed by single-crystal X-ray diffraction analysis. The solution behavior of both complexes was investigated, namely their solubility, stability, and lipophilicity in physiological mimetic conditions, as well as an eventual uptake by passive diffusion. In vitro anticancer activity of the complexes on ovarian and different colon cancer cells and apoptosis induction by the complexes were studied. A slow transformation process was observed for complex 1 in aqueous solution when exposed to sunlight, while complex 2 undergoes deprotonation (pKa = 7.59). The lipophilicity of this latter complex depends strongly on the pH and ionic strength. In contrast, 1 is rather hydrophilic under various conditions. Complex 1 was highly cytotoxic on Colo-205 human colon (IC50 = 7.87 µM) and A2780 ovarian (IC50 = 2.2 µM) adenocarcinoma cell lines, while 2 displayed moderate anticancer activity (30.9 µM and 18.0 µM, respectively). The complexes induced late apoptosis and necrosis. Only a weak binding of the complexes to human serum albumin, the main transport protein in blood serum, was found. However, a more significant binding to calf thymus DNA was observed in UV-visible titrations and fluorometric dye displacement studies. Detailed analysis of fluorescence lifetime data collected for the latter systems reveals not only the partial intercalation of the complexes, but goes beyond the usual simplified interpretations.

In Vitro and In Vivo Biological Activity of Ruthenium 1,10-Phenanthroline-5,6-dione Arene Complexes.

Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η6-arene)Ru(L)Cl][X] X = CF3SO3 (JHOR10) and PF6 (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors.

Human Amniotic Membrane Mesenchymal Stem Cell-Synthesized PGE2 Exerts an Immunomodulatory Effect on Neutrophil Extracellular Trap in a PAD-4-Dependent Pathway through EP2 and EP4.

Human amniotic membrane mesenchymal stem cells (hAM-MSC) secrete a myriad of components with immunosuppressive activities. In the present research, we aimed to describe the effect of prostaglandin E2 (PGE2) secreted by hAM-MSCs on neutrophil extracellular trap (NET) release and to characterize the role of its receptors (EP2/EP4) in PAD-4 and NFκB activity in neutrophils. Human peripheral blood neutrophils were ionomycin-stimulated in the presence of hAM-MSC conditioned medium (CM) treated or not with the selective PGE2 inhibitor MF-63, PGE2, EP2/EP4 agonists, and the selective PAD-4 inhibitor GSK-484. NET release, PAD-4, and NFκB activation were analyzed. Ionomycin induced NET release, which was inhibited in the presence of hAM-MSC-CM, while CM from hAM-MSCs treated with MF-63 prevented NET release inhibition. PGE2 and EP2/EP4 agonists, and GSK-484 inhibited NET release. EP2/EP4 agonists and GSK-484 inhibited H3-citrullination but did not affect PAD-4 protein expression. Finally, PGE2 and EP2/EP4 agonists and GSK-484 increased NFκB phosphorylation. Taken together, these results suggest that hAM-MSC exert their immunomodulatory activities through PGE2, inhibiting NET release in a PAD-4-dependent pathway. This research proposes a new mechanism by which hAM-MSC exert their activities when modulating the innate immune response and inhibiting NET release.

Changes in the Care Activity in Addiction Centers with Dual Pathology Patients during the COVID-19 Pandemic.

BACKGROUND: Health care provision during the COVID-19 pandemic and confinement has led to significant changes in the activity of addiction centers. These changes in healthcare activity may have had a greater impact on patients with dual pathology. The aim of this study is to compare the treatment indicators of patients with dual pathology in addiction centers during the pre-confinement, confinement, and post-confinement periods. METHODS: A retrospective observational study was conducted for the period between 1 February 2019 and 30 June 2021. A total of 2785 patients treated in specialized addiction services were divided into three periods according to their time of admission: pre-confinement, confinement, and post-confinement. RESULTS: During the pre-pandemic period, the addiction centers attended to an average of 121.3 (SD = 23.58) patients, decreasing to 53 patients during confinement (SD = 19.47), and 80.69 during the post-confinement period (SD = 15.33). The number of appointments scheduled monthly for each patient decreased during the confinement period, although this number increased after confinement. There was a reduction in the number of toxicological tests carried out both during and after confinement (except for alcohol). CONCLUSIONS: The results show a reduction in the number of patients seen and the care activity delivered to dual diagnosis patients. These results, which were caused by the COVID-preventive measures, may affect the progress and recovery of dual patients. A greater investment is needed to bring the care activity up to the standards of the years prior to confinement.

An agent-based simulation model to compare different reproductive strategies in cow-calf operations: Economic performance.

In a companion paper, Ojeda-Rojas et al. (2021) [1] describe a stochastic agent-based simulation (ABS) model of a cow-calf operation on a commercial farm in São Paulo, Brazil. The model's parameterization was based on data collected from two sources: a real beef cattle herd and related scientific literature. Based on the mentioned simulation model, this study aims to assess the economic outcome of 10 different reproductive scenarios: Natural mating only (ONM); one timed artificial insemination (TAI) plus natural mating (NM) (1TAI + NM); two TAI plus NM, with 24, 32, and 40 days between TAI (2TAI/24 + NM, 2TAI/32 + NM, and 2TAI/40 + NM, respectively); three TAI without NM, with 24, 32, and 40 days between TAI (3TAI/24, 3TAI/32, and 3TAI/40, respectively); and three TAI plus NM, with an interval between TAI of 24 (3TAI/24 + NM) and 32 days (3TAI/32 + NM). The simulation was performed on an animal-by-animal basis over a time horizon of 5000 days. Each scenario had 32 farms, and each farm kept up to 400 adult females. According to the scenario, a bull population was composed of 0, 7, or 15 individuals. The outcomes, represented as means ± standard deviations, were assessed after reaching a steady-state (1825 days). The model outcomes showed that the 3TAI/24 + NM scenario resulted in higher incomes (US$ 96,479.19 ± 709.81), whereas the ONM scenario had the lowest incomes (US$ 79,753.37 ± 741.87). The 3TAI/24 + NM (US$ 101.720.63 ± 79.21) and ONM (US$ 90.898.58 ± 59.17) scenarios presented the highest and lowest total operating costs (TOC), respectively. However, when TOC was evaluated per kg of the weaned calf, the highest and lowest costs were associated with the ONM (US$ 2.81 ± 0.03/kg) and 2TAI/24 + NM (US$ 2.17 ± 0,04/kg) scenarios, respectively. Our model suggests that reproductive strategies that use TAI have a better economic performance than those under NM. However, when performing three TAI with an interval of 40 days, the benefit was lower; in some cases, it was even worse than the ONM. Combining TAI with early pregnancy diagnosis resulted in better economic performance than other TAI programs and NM. The 2TAI/24 + NM scenario outperformed the others due to the contrast between its high income and moderate costs. Beef cattle production is a highly complex system. Simulations models, specifically ABS models, could make the decision-making process on complex systems straightforward and effective. Furthermore, ABS models can overcome the limitations of conventional research approaches, such as high costs and long experimentation periods.

Bridge Nodes between Personality Traits and Alcohol-Use Disorder Criteria: The Relevance of Externalizing Traits of Risk Taking, Callousness, and Irresponsibility.

BACKGROUND: Personality disorders show strong comorbidities with alcohol-use disorder (AUD), and several personality traits have been found to be more frequent in people with AUD. This study analyzes which personality facets of those proposed in the Alternative Model of Personality Disorder (AMPD) of DSM-5 are associated with the diagnostic criteria of AUD. METHODS: The sample was composed of 742 participants randomly selected from the Spanish population, and 243 patients attending mental health services. All participants were of legal age and signed an informed consent form. The instruments were administered to the community sample in an online format, and a psychologist conducted individual face-to-face interviews with the patients. AMPD facets were assessed through the Personality Inventory of DSM-5 Short-Form, and the AUD criteria through the Substance Dependence Severity Scale. A network analysis was applied to identify the personality facets mostly associated with the AUD criteria. RESULTS: The network analysis showed the existence of three communities, grouping the AUD criteria, externalizing spectrum facets, and internalizing spectrum facets, respectively. Risk taking, callousness, and irresponsibility facets showed the strongest association with the AUD criteria, bridging externalizing personality traits with AUD criteria. CONCLUSIONS: The facets of risk taking, callousness, and irresponsibility should be accurately assessed in patients with AUD to differentiate between a possible primary personality disorder and a syndrome induced by alcohol addiction.

Methylation of Subtelomeric Chromatin Modifies the Expression of the lncRNA TERRA, Disturbing Telomere Homeostasis.

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.

Harm Reduction Strategies among University Students Who Use Alcohol and Cannabis, and Related Psychological Variables: A Systematic Review.

This systematic review identifies the psychological variables associated with the use of harm reduction strategies (HRS) among university students who use alcohol or cannabis. The reviewed studies are categorized according to the psychological variables studied and the different analytic approaches used (direct effects, mediation, and moderation). Among the empirical peer-reviewed studies identified (n = 76), most (94.7%) were cross-sectional studies conducted in the US (90.8%) with samples of alcohol-using university students (86.8%). Five categories were identified: mental health, motives/expectancies, personality, social cognition, and self-efficacy. The most studied constructs were motives, anxiety and depression, impulsivity, and social norms. Most studies conducted mediation or moderation analyses including psychological variables, HRS and alcohol outcomes. Social, enhancement and coping motives, impulsivity, and social norms of alcohol use were associated with lower use of HRS, which, in turn, was associated with a higher number of alcohol/cannabis outcomes. The results of moderation studies consistently suggest that HRS use was more protective for students with poor mental health, high impulsivity, and low self-regulation. The synthesis of evidence provided in this review could be useful for guiding future research and informing the design of interventions aimed at promoting the use of HRS among university students who use alcohol and/or cannabis.

Polyvalent human immunoglobulin for infectious diseases: Potential to circumvent antimicrobial resistance.

Antimicrobial resistance (AMR) is a global health problem that causes more than 1.27 million deaths annually; therefore, it is urgent to focus efforts on solving or reducing this problem. The major causes of AMR are the misuse of antibiotics and antimicrobials in agriculture, veterinary medicine, and human medicine, which favors the selection of drug-resistant microbes. One of the strategies proposed to overcome the problem of AMR is to use polyvalent human immunoglobulin or IVIG. The main advantage of this classic form of passive immunization is its capacity to enhance natural immunity mechanisms to eliminate bacteria, viruses, or fungi safely and physiologically. Experimental data suggest that, for some infections, local administration of IVIG may produce better results with a lower dose than intravenous application. This review presents evidence supporting the use of polyvalent human immunoglobulin in AMR, and the potential and challenges associated with its proposed usage.

Manganese(I) tricarbonyl complexes as potential anticancer agents.

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).

Water quality in the Lachuá Ecoregion Landscape: Comparing streams from Forest, Milpa, and an Oil Palm plantation / Calidad del agua en el paisaje de la Ecorregión Lachuá: Comparando arroyos en bosques, milpa y palma africana

The hydrological network in the Lachuá Ecoregion (EL), Alta Verapaz, Guatemala, hosts high levels of biodiversity and supplies water to 44 Mayan communities. Despite this critical fact, this network has been threatened by scarcely monitored industrial activities including the rapidly expanding oil palm monoculture (Elaeis guineensisJacq). Regardless of Lachua's freshwaters importance, there is little information on how this monoculture impacts them. We compared water-quality properties from streams in oil palm plantations (P), paddock and milpa systems (M), and primary forests (F) in the EL. During 2015-2016, 13 rivers were sampled (5 times) for water temperature, pH, dissolved oxygen (DO), conductivity, hardness, chemical and biochemical oxygen demand (COD and BOD), and concentration of silica, nitrates, phosphates, and ammonia. Several parameters showed significant differences. P were 2.7 ºC and 1.8 ºC warmer than M and F and carried 1.4 mg/L more nitrates than F. F carried 10.8 mg/L and 11.8 mg/L more silica than M and P. M showed intermediate temperatures and silica concentrations, as well as 14.8 µS/cm and 8.9 µS/cm lower conductivities than P and F, respectively. Additionally, COD in M was 9.9 mg/L and 4.6 mg/L lower than P and F, respectively. We believe higher temperatures and lower silica in P are due to the loss of riparian forest and their role in buffering temperatures and recycling silicon. In addition, the existence of secondary forest (guamil) in M might explain the intermediate temperatures and silica concentrations. Our results highlight the contributions of forests to waterways and suggest potential water-quality depletion from the oil palm expansion in the EL.

La red hídrica en la Ecorregión Lachuá (EL), Alta Verapaz, Guatemala, alberga una alta biodiversidad y abastece de agua a 44 comunidades mayas. Sin embargo, recientemente se ha visto amenazada por actividades industriales escasamente monitoreadas, incluido el creciente monocultivo de palma africana (Elaeis guineensis Jacq) del cual se desconocen sus impactos en la EL. Este estudio explora la calidad del agua de arroyos en plantaciones de palma africana (P), bosques primarios (B), y sistemas de potrero y milpa (M) en Lachuá. Durante 2015-2016, se tomaron muestras de 13 ríos (5 veces) para medir la temperatura del agua, pH, oxígeno disuelto (OD), conductividad, dureza, demanda química y bioquímica de oxígeno (DQO y DBO) y la concentración de sílice, nitratos, fosfatos, y amoníaco. Varios parámetros mostraron diferencias significativas. P fue 2.7 ºC y 1.8 ºC más calientes que M y F y portó 1.4 mg/L más nitrato que F. F portó 10.8 mg/L y 11.8 mg/L más sílice que M y P. M mostró temperaturas y concentraciones de sílice intermedias y conductividades 14.8 µS/cm y 8.9 µS/cm menores que P y F. La DQO en M fue 9.9 mg/L y 4.6 mg/L menor que P y F. El aumento de temperatura y la disminución de sílice en P podría deberse a la pérdida de bosques ribereños los cuales amortiguan la tempe-ratura y reciclan el silicio. La presencia de bosque secundarios (guamil) en M podría explicar las temperaturas y las concentraciones de sílice intermedias resaltando la importancia de los bosques en la red hídrica. Se predice un posible deterioro en el agua resultado de la expansión de palma africana en la EL.

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation.

Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.