New criteria for sustainable land use planning of metropolitan green infrastructures in the tropical Andes.

Context: Urbanization is rapidly increasing worldwide, with about 60% of the global population currently residing in cities and expected to reach 68% by 2050. In Latin America's tropical Andes region, managing these changes poses challenges, including biodiversity loss and vulnerability to climate change. Objectives: This study assesses urban growth and agricultural intensification impacts on the ecological functionality of metropolitan green infrastructures and their capacity to provide ecosystem services using a landscape sustainability and sociometabolic approach. Specifically, it aims to identify landscape configurations promoting socio-ecological sustainability amidst rapid urbanization. Methods: A landscape-metabolic model (IDC) was applied to evaluate the interactions between land use changes and ecosystem functions in the metropolitan region of Cali. Results: Agricultural intensification and industrialization, coupled with uncontrolled urban growth, have significantly transformed the landscape, posing threats to its sustainability. The prevailing biocultural landscapes hold a substantial potential to provide essential ecosystem services to the metropolis. The IDC offers an approach that utilizes a land cover map and agricultural production/metabolism data to calculate an indicator closely related to ecosystem services and multifunctionality. Conclusions: The IDC model stands out for efficiently capturing landscape dynamics, providing insights into landscape configuration and social metabolism without extensive resource requirements. This research highlights the importance of adopting a landscape-metabolic and green infrastructure framework to guide territorial policies in the tropical Andes and similar regions. It stresses the need for informed land use planning to address challenges and leverage opportunities presented by biocultural landscapes for regional sustainability amidst rapid urbanization and agricultural expansion.

Relationship between oral microbiota and colorectal cancer: A systematic review.

This systematic review aims to investigate the microbial basis underlying the association between oral microbiota and colorectal cancer. A comprehensive search was conducted across four databases, encompassing potentially relevant studies published up to April 2024 related to the PECO question: "Is there a differentiation in oral microbial composition between adult patients diagnosed with colorectal cancer compared to healthy patients?". The Newcastle-Ottawa Scale was used to evaluate the quality of the studies included. The level of evidence was assessed through the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool. Sixteen studies fulfilled the eligibility criteria. Based on low to moderate evidence profile, high levels of certain subspecies within Firmicutes (such as Streptococcus anginosus, Peptostreptococcus stomatis, S. koreensis, and S. gallolyticus), Prevotella intermedia, Fusobacterium nucleatum, and Neisseria oralis were found to be associated with colorectal cancer. Conversely, certain bacteria (e.g., Lachnospiraceae, F. periodonticum, and P. melaninogenica) could exert a symbiotic protective effect against colorectal cancer. Based on existing evidence, it appears that variations in oral microbiota composition exist among individuals with and without colorectal cancer. However, further research is necessary to determine the mechanisms of oral dysbiosis in colorectal carcinogenesis.

Follow-up of Immune Response in Patients with Common Variable Immunodeficiency following SARS-CoV-2 Vaccination.

The COVID-19 pandemic highlighted the importance of effective vaccination strategies in controlling the spread of infectious diseases. SARS-CoV-2 vaccine has demonstrated high efficacy in preventing COVID-19 infection in the general population. However, the efficacy of this vaccine in patients with predominantly antibody deficiencies, such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA), should be closely monitored. CVID and XLA are rare genetic disorders that impair the immune system's ability to produce antibodies, which are crucial for fighting infections. Patients with these disorders have a higher risk of severe disease and mortality from COVID-19 due to their compromised immune systems. In this study, we evaluated the humoral and cellular immune responses after four doses of mRNA-1273 and one BNT162b2 bivalent vaccine in a cohort of patients with CVID and XLA. The response in this population was lower than in the control group. However, the administration of the third dose improved the number of patients with seroconversion and the intensity of the humoral response, as well as the number of patients with a positive cellular response. Finally, the administration of the fourth and fifth doses improves the antibody titer and neutralization against wild type variant, but not against the prevalent XBB1.5 variant.

Assessment of Standardized Care Plans for People with Chronic Diseases in Primary Care Settings.

BACKGROUND: Aging populations are driving a shift in emphasis toward enhancing chronic disease care, reflected in Catalonia's regional plan which prioritizes standardized nursing care plans in primary care settings. To achieve this, the ARES-AP program was established with a focus on harmonizing standards and supporting routine nursing clinical decision-making. This study evaluates nurses' perceptions of ARES-AP's standardized care plans for chronic diseases. METHODS: A mixed-methods approach based on an ad hoc questionnaire (n = 141) and a focus group (n = 14) was used. Quantitative data were statistically analysed, setting significance at p < 0.05. Qualitative data were explored via content analysis. RESULTS: ARES-AP training was assessed positively. The resources for motivational interviewing and care plans for the most prevalent chronic diseases were rated very positively. This study identified key factors influencing program implementation, including facilitators such as structured information and nursing autonomy, barriers such as resistance to change, motivators such as managerial support, and suggested improvements such as technological improvements and time management strategies. CONCLUSIONS: This study identifies areas for improvement in implementing standardized nursing care plans, including additional time, motivation, enhanced IT infrastructure, and collaboration among primary care professionals. It enhances understanding of these plans in primary care, especially in managing chronic diseases in aging populations. Further research should assess the program's long-term impact on chronic patients. This study was not registered.

Preserving the spots: Jaguar (Panthera onca) distribution and priority conservation areas in Colombia.

The jaguar (Panthera onca) is a charismatic species considered Vulnerable in Colombia but yet largely unknown in the country. The species is mostly threatened by the continuous decline in its habitats, mostly derived from deforestation and habitat loss, additional to hunting and conflicts with humans. Thus, the future of jaguars in Colombia depends on protecting and recovering existing habitats. The aims of this study were to 1) evaluate jaguar distribution and identify the remnant patches of habitat in Colombia, 2) define an ecological connectivity network within the country, and 3) propose a priority areas portfolio for the conservation and recovery of jaguars. We used a presence background model for estimating species potential distribution and subsequently identified remaining habitat patches across the country based on land cover and species-specific ecological attributes. We then created an ecological connectivity network based on circuit theory and following a multi-criteria approach identified jaguar priority areas for conservation (JPCA) and recovery (JPRA). Jaguar potential distribution comprises 1103122.43 km2, from which 56.71% maintain suitable patches of potential habitat. We identified 960 corridors between remnant patches of natural or semi-natural vegetation. Based on the criteria, JPCAs with greater importance were identified in each of the five Colombian regions. JPRAs were located mainly towards the Andean and Caribbean regions. These JPCAs and JPRAs could serve as a guide for designing and implementing management strategies for the long-term conservation and recovery of the species in Colombia.

Bone metabolism and inflammatory biomarkers in radiographic and non-radiographic axial spondyloarthritis patients: a comprehensive evaluation.

Introduction: Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. Methods: A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. Results: R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Conclusion: Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

Diversity of oncopharmacogenetic profile within Spanish population.

Consensus guidelines for genotype-guided fluoropyrimidine dosing based on variation in the dihydropyrimidine dehydrogenase (DPYD) gene before treatment have been firmly established. The prior pharmacogenetic report avoids the serious toxicity that inevitably occurred in a non-negligible percentage of the treated patients. The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.

Economical Evaluation of Reduced Herbicide Doses Application Rates to Control Phalaris brachystachys (Short-Spiked Canary Grass) in a Biennial Wheat-Sunflower Rotation in Mediterranean Dryland: A Modelling Approach.

Phalaris brachystachys (short-spiked canary grass) is considered to be among the most troublesome cereal weeds in Mediterranean areas. A bioeconomic model, based on population dynamics, competition and economic sub-models, was developed to simulate the long-term economic consequence of using herbicide-based strategies: no herbicide application, full herbicide dose (standard rate) and two reduced dose rates (75 and 50% of the standard rate) to control P. brachystachys in a biennial wheat-sunflower rotation. Simulation results indicated that only herbicide application at a full dose (90% control) and 3/4 dose (80% control) produced positive economic results, with the full dose being the best strategy (EUR 98.65 ha-1 year-1). A sensitivity analysis showed that the economic outcome, in terms of annualized net return, was strongly influenced by changes in yield, price, and fixed costs. In addition, the annualized net return was more sensitive to parameter changes at reduced herbicide doses than at full rate. In the wheat-sunflower rotation system, the application of the full dose of herbicide was the most economical and stable strategy in the long-term. Reduced doses are not a recommended option from an economic point of view. Bioeconomic models provide practical insight into different management approaches for effective weed control.

Mechanistic manifold in a hemoprotein-catalyzed cyclopropanation reaction with diazoketone.

Hemoproteins have recently emerged as promising biocatalysts for new-to-nature carbene transfer reactions. However, mechanistic understanding of the interplay between productive and unproductive pathways in these processes is limited. Using spectroscopic, structural, and computational methods, we investigate the mechanism of a myoglobin-catalyzed cyclopropanation reaction with diazoketones. These studies shed light on the nature and kinetics of key catalytic steps in this reaction, including the formation of an early heme-bound diazo complex intermediate, the rate-determining nature of carbene formation, and the cyclopropanation mechanism. Our analyses further reveal the existence of a complex mechanistic manifold for this reaction that includes a competing pathway resulting in the formation of an N-bound carbene adduct of the heme cofactor, which was isolated and characterized by X-ray crystallography, UV-Vis, and Mössbauer spectroscopy. This species can regenerate the active biocatalyst, constituting a non-productive, yet non-destructive detour from the main catalytic cycle. These findings offer a valuable framework for both mechanistic analysis and design of hemoprotein-catalyzed carbene transfer reactions.

Violencia urbana y salud mental de adultos jóvenes de Paraguay / Urban violence and mental health of young adults in Paraguay

A nivel mundial, la violencia urbana se ha convertido en una preocupación importante para la salud pública. Investigaciones resaltan que la violencia es un factor de riesgo significativo para la salud mental de los individuos. La exposición a eventos traumáticos relacionados con la violencia urbana, como asaltos, robos o violencia interpersonal, puede tener consecuencias graves para la salud mental. En el contexto continental, América Latina se ha visto especialmente afectada por la violencia urbana. Estudios epidemiológicos en países latinoamericanos han demostrado que la violencia urbana está asociada con un mayor riesgo de trastornos de ansiedad, estrés y depresión en la población joven y adulta. A nivel nacional, el Paraguay enfrenta desafíos significativos en términos de violencia urbana. Aunque la situación ha mejorado en los últimos años, persisten altos índices de violencia relacionada con el crimen, pandillas y conflictos socioeconómicos. La población joven se encuentra particularmente expuesta a estos eventos traumáticos, lo que plantea preocupaciones sobre el impacto en su salud mental.

Comprehensive Analysis of CdS Ultrathin Films Modified by the Substrate Position inside the Reactor Container Using the CBD Technique.

The cadmium sulfide (CdS) n-type semiconductor is one of the most used as a window layer in thin-film solar cells, such as CdTe, CIS, CIGS, and CZTS. Optoelectronic properties are the most important characteristics for window materials. CdS thin films obtained using the chemical bath deposition technique (CBD) have been reported; however, large amounts of precursor solutions are used, which generate considerable amounts of toxic waste. The aim of this work is to reduce the amount of precursor solutions used for CdS growth; for this, it is necessary to consider an efficient position for the substrate inside the reactor container and at the same time allow obtaining CdS thin films with adequate physical properties to be applied in the photovoltaic solar cell development. CdS thin films were deposited on soda-lime/SnO2:F substrates (FTO) using the CBD technique; the substrates were placed in three different arrangements [rack system, step system (up), and step system (down)]. CdS samples with areas of 4 cm2 and a thickness of 27-48 nm were obtained; the X-ray diffraction patterns show CdS thin films with different polycrystalline structures. The morphological measurements reveal different surface formations depending on the substrate position, and resistivity values of around 105 Ω*cm were measured. UV-vis spectra show transmittance values of around 45-94% in the visible region with band gap energy values of around 2.1-2.36 eV. The best physical properties of CdS thin films and an efficient CBD process were obtained when the FTO substrates were located near the bottom of the reactor container with the FTO side down, leading to an optimal configuration that allows reducing the amount of precursor solutions and in this way reduces the toxic waste generated. These results are important in the photovoltaic technology process and environmental impact.

Insight into Radical Initiation, Solvent Effects, and Biphenyl Production in Iron-Bisphosphine Cross-Couplings.

Iron-bisphosphines have attracted broad interest as highly effective and versatile catalytic systems for two- and three-component cross-coupling strategies. While recent mechanistic studies have defined the role of organoiron(II)-bisphosphine species as key intermediates for selective cross-coupled product formation in these systems, mechanistic features that are essential for catalytic performance remain undefined. Specifically, key questions include the following: what is the generality of iron(II) intermediates for radical initiation in cross-couplings? What factors control reactivity toward homocoupled biaryl side-products in these systems? Finally, what are the solvent effects in these reactions that enable high catalytic performance? Herein, we address these key questions by examining the mechanism of enantioselective coupling between α-chloro- and α-bromoalkanoates and aryl Grignard reagents catalyzed by chiral bisphosphine-iron complexes. By employing freeze-trapped 57Fe Mössbauer and EPR studies combined with inorganic synthesis, X-ray crystallography, reactivity studies, and quantum mechanical calculations, we define the key in situ iron speciation as well as their catalytic roles. In contrast to iron-SciOPP aryl-alkyl couplings, where monophenylated species were found to be the predominant reactive intermediate or prior proposals of reduced iron species to initiate catalysis, the enantioselective system utilizes an iron(II)-(R,R)-BenzP* bisphenylated intermediate to initiate the catalytic cycle. A profound consequence of this radical initiation process is that halogen abstraction and subsequent reductive elimination result in considerable amounts of biphenyl side products, limiting the efficiency of this method. Overall, this study offers key insights into the broader role of iron(II)-bisphosphine species for radical initiation, factors contributing to biphenyl side product generation, and protocol effects (solvent, Grignard reagent addition rate) that are critical to minimizing biphenyl generation to obtain more selective cross-coupling methods.

Sex differences in the diagnosis, treatment and prognosis of cancer: the rationale for an individualised approach

Background Precision medicine in oncology aims to identify the most beneficial interventions based on a patient’s individual features and disease. However, disparities exist when providing cancer care to patients based on an individual’s sex. Objective To discuss how sex differences impact the epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment, with a focus on data from Spain. Results Genetic and environmental factors (social or economic inequalities, power imbalances, and discrimination) that contribute to these differences adversely affect cancer patient health outcomes. Increased health professional awareness of sex differences is essential to the success of translational research and clinical oncological care. Conclusions The Sociedad Española de Oncología Médica created a Task Force group to raise oncologists’ awareness and to implement measures to address sex differences in cancer patient management in Spain. This is a necessary and fundamental step towards optimizing precision medicine that will benefit all individuals equally and equitably (AU)

Maintenance of angiogenesis inhibition with aflibercept after progression to bevacizumab in metastatic colorectal cancer: real life study in the Valencian community

Introduction The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. Patients and methods This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. Result 122 patients with a median age of 61 years were included. 89% of patients had PS 0–1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74–6.15 months) and 10.15 (95% CI 7.47–12.82 months), respectively. Disease control rate 59.8%. The most common grade 3–4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58–17.32) in patients with hypertension vs 7.78 (95% CI 5.02–10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. Conclusions Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response (AU)

Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis.

OBJECTIVE: We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. METHODS: Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+ -related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti-tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. RESULTS: Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. CONCLUSION: RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.

Sex differences in the diagnosis, treatment and prognosis of cancer: the rationale for an individualised approach.

BACKGROUND: Precision medicine in oncology aims to identify the most beneficial interventions based on a patient's individual features and disease. However, disparities exist when providing cancer care to patients based on an individual's sex. OBJECTIVE: To discuss how sex differences impact the epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment, with a focus on data from Spain. RESULTS: Genetic and environmental factors (social or economic inequalities, power imbalances, and discrimination) that contribute to these differences adversely affect cancer patient health outcomes. Increased health professional awareness of sex differences is essential to the success of translational research and clinical oncological care. CONCLUSIONS: The Sociedad Española de Oncología Médica created a Task Force group to raise oncologists' awareness and to implement measures to address sex differences in cancer patient management in Spain. This is a necessary and fundamental step towards optimizing precision medicine that will benefit all individuals equally and equitably.

Maintenance of angiogenesis inhibition with aflibercept after progression to bevacizumab in metastatic colorectal cancer: real life study in the Valencian community.

INTRODUCTION: The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. PATIENTS AND METHODS: This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. RESULTS: 122 patients with a median age of 61 years were included. 89% of patients had PS 0-1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74-6.15 months) and 10.15 (95% CI 7.47-12.82 months), respectively. Disease control rate 59.8%. The most common grade 3-4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58-17.32) in patients with hypertension vs 7.78 (95% CI 5.02-10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. CONCLUSIONS: Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response.