Sustainable water management should consider climate change effects to ensure its future availability. Hydrological modeling is a supportive tool for this analysis, which has been used in this work to assess the climate change impacts on the water resources of three basins under Mediterranean climate (Ompólveda and Salado River basins, in Spain, and Guadalupe River basin, in Mexico). The outcomes of previous climate change scenarios simulation addressed with the Soil and Water Assessment Tool (SWAT) have been compiled, evaluating the impacts on the water balance, and focusing on the streamflow components. The potential implications of these effects on energy production have been discussed. The results point to a streamflow reduction by the end of the century around 50%–60% in the worst scenarios, with varying effects for each of the streamflow components. In the Spanish catchments, where groundwater contribution dominates in baseline conditions, a noticeable decrease of this component is expected (up to -74%), becoming lateral flow the main streamflow component. In the Mexican basin, lateral flow, which is already predominant (69%), will experience the largest absolute decrease, but the highest relative decrease might be experienced by groundwater flow, up to -92%. Absolute variations in the surface component are small and the different ways to simulate the climate change scenarios might hinder their interpretation. This work shows that water resources will be even more scarce in these regions, being especially worrying the groundwater component reduction, which currently maintains the streamflow during dry periods. This situation would limit energy production both from sources that directly use water, such as hydropower, and others that require water for cooling. Higher atmospheric and water temperatures will increase demands for irrigation and for cooling systems. Therefore, competition for water will rise among key sectors, and an accurate planning considering these factors must be a priority.
Understanding how Mediterranean forests respond to the increasing frequency of extreme droughts and forest densification is crucial for effective land management in the present context of climate change and land abandonment. We study the responses of Iberian holm oak (Quercus ilex L.) woodlands to recent extreme droughts during 2000-2019 along broad gradients of climate aridity and forest structure. To this purpose, we apply large-scale remote-sensing using MODIS EVI as a primary production proxy in 5274 Q. ilex sites distributed within a 100,000 km2 region in eastern Spain. These woodlands were extensively affected by two extreme drought events in 2005 and 2012. Resistance, assessed as the capacity of the ecosystems to maintain primary production during drought, was significantly lower for semi-arid than for sub-humid and dry-transition conditions. Holm oak woodlands located in semi-arid areas of the region showed also poorer resilience to drought, characterized by low capacity to fully recover to their pre-drought production levels. Further, drought intensity and both pre- and post-drought hydric conditions controlled the variations of resistance, recovery and resilience between the two analyzed extreme drought events. Drought effects were particularly negative for dense Q. ilex stands under semi-arid climate conditions, where strong competition for scarce water resources reduced drought resistance. The observed drought vulnerability of semi-arid holm oak woodlands may affect the long-term stability of these dry forests. Adaptive management strategies, such as selective forest thinning, may be useful for improving drought responses in these more vulnerable semi-arid woodlands. Conversely, natural rewilding may more appropriately guide management actions for more humid areas, where densely developed Q. ilex woodlands show in general a high ability to maintain ecosystem primary production during drought.
IMPACT: For policy-makers, statisticians, public accountants, social security actuaries, public finance economists and other stakeholders, the regulation introduced by the EU regarding the disclosure of an accrued-to-date liability (ADL) table (Table 29) is a valuable first step in reporting pension liabilities. However, the information disclosed is incomplete and does not provide an indicator of solvency or sustainability. In addition, pensioners and those making contributions to pensions have no information regarding the security of their future benefits. In this timely article, the authors present a methodology to easily transform Table 29 into an actuarial balance sheet (ABS) and compile its associated income statement (IS). The ABS can be used to assess the solvency of pension schemes, whereas Table 29 cannot. ABSTRACT: This article develops a methodology to (easily) transform the EU’s Table 29 into an actuarial balance sheet (ABS) and compile its associated income statement (IS). The article contains a study based on data from the most recently published Table 29 for Spain to understand its functioning for other jurisdictions. With the new method, the authors found that the Spanish pension system is partially insolvent because only part of the pension entitlements are backed up by assets—showing a deterioration in sustainability from 2015 to 2018. The idea of transforming Table 29 into an ABS and compiling its associated IS has not been previously explored and it could improve people’s understanding of the public pension system and make this public indicator more useful and transparent.
Fractures of the shoulder affect both young, active individuals and older adults. The clavicle is the most common broken bone in the body. Simple radiological imaging is often enough to ascertain the type of fracture. Nondisplaced fractures should be managed conservatively, but the management of displaced clavicle fractures is controversial. Scapula fractures are rare, are most commonly seen in young and middle-aged patients involved in high-energy trauma and are frequently associated with other relevant injuries. Nondisplaced fractures can be managed conservatively. Displaced fractures might require open reduction and internal fixation. Fractures of the proximal humerus are common injuries. Clinical examination reveals pain, swelling and decreased range of motion. Simple X-rays will allow for initial diagnosis, but a CT scan is often needed. Proximal humerus fracture treatment is one of the most controversial topics in shoulder surgery. For nondisplaced or minimally displaced (<5 mm) fracture patterns, conservative management is the norm. Fracture-dislocations almost always require surgical treatment. For the rest of the fracture patterns, there is considerable controversy over the best treatment option. Surgical alternatives include closed reduction and percutaneous pinning, open reduction and fixation with plates and screws, endomedullary nailing and arthroplasty.
Adhesive capsulitis of the shoulder, also known as frozen shoulder, is an idiopathic condition that presents with pain and stiffness. It is characterized by initial inflammation followed by fibrotic alterations in the glenohumeral capsule without previous injury. Its prevalence is 3–5%, affecting adults between the fifth and sixth decades of life. The association with diabetes mellitus is strong. The clinical course has three phases: the initial freezing phase, lasting 2–9 months, courses with intense shoulder pain and progressive development of stiffness. Later, in the frozen phase (4–12 months), the pain progressively disappears, and stiffness persists. Finally, in the thawing phase (5–26 months), the stiffness slowly disappears, but 30% of cases will have persistent stiffness. The diagnosis is fundamentally clinical. On physical exam, there is loss of passive range of motion, with preserved strength. Magnetic resonance imaging will show inflammatory changes and capsular thickening and will help exclude osteoarthritis, rotator cuff disease, or calcifying tendinitis. Oral NSAIDs and intra-articular steroid injections can provide short-term pain relief. Physical therapy is recommended, but intensive therapy has poorer outcomes than self-administered, home-based, exercises. When symptoms persist for 3–6 months without improvement, arthroscopic capsular release should be considered.
Plant material culture can offer unique insights into the ways of life of prehistoric societies; however, its perishable nature has prevented a thorough understanding of its diverse and complex uses. Sites with exceptional preservation of organic materials provide a unique opportunity for further research. The burial site of Cueva de los Murciélagos in southern Iberia, uncovered during 19th-century mining activities, contained the best-preserved hunter-gatherer basketry in southern Europe, together with other unique organic artifacts associated with the first farming communities, such as sandals and a wooden hammer. We present 14 14 C dates for the perishable artifacts (N = 76), situating the assemblage between the Early and Middle Holocene (c. 7500 to 4200 cal BCE). Our integrated analysis includes raw material determination and technological and chrono-cultural contextualization of this unique and important set of materials.
Bayesian network (BN) models are increasingly used as tools to support probabilistic environmental risk assessments (ERA), as they can better account for uncertainty compared to the simpler approaches commonly used in traditional ERA. We used BNs as meta‐models to link various sources of information in a probabilistic framework, to predict the risk of pesticides to aquatic communities under given scenarios. The research focused on rice fields surrounding a Spanish Natural Park Albufera, considering three selected pesticides: acetamiprid (insecticide), MCPA (herbicide), and azoxystrobin (fungicide). The developed BN linked the inputs and outputs of two pesticide models: a process‐based exposure model (RICEWQ), and probabilistic effects model (PERPEST) using case‐based reasoning with data from microcosm and mesocosm experiments. The model characterised risk at three levels in a hierarchy: biological endpoints (e.g., molluscs, zooplankton, insects, etc.), endpoint groups (plants, invertebrates, vertebrates, and community processes), and community. The pesticide risk to a biological endpoint was characterised as the probability of an effect for a given pesticide concentration interval. The risk to an endpoint group was calculated as the joint probability of effect on any of the endpoints in the group. Likewise, community‐level risk was calculated as the joint probability of any of the endpoint groups being affected. This approach enabled comparison of risk to endpoint groups across different pesticide types. For example, in a scenario for year 2050, the predicted risk of the insecticide to the community (40% probability of effect) was dominated by the risk to invertebrates (36% risk). In contrast, herbicide‐related risk to the community (63%) was resulting from risk to both plants (35%) and invertebrates (38%); the latter might here represent indirect effects of toxicity through the food chain. This novel approach combines the quantification of spatial variability of exposure with probabilistic risk prediction for different components of aquatic ecosystems.
Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.
Aim To monitor prospectively the occurrence of colorectal anastomotic leakage (CAL) in patients with colon cancer undergoing resectional surgery, characterizing the microbiota in both faeces and mucosal biopsies of anastomosis. In a second stage, we investigated the ability to predict CAL using machine learning models based on clinical data and microbiota composition. Method A total of 111 patients were included, from whom a faecal sample was obtained, as well as biopsy samples from proximal and distal sites in the healthy margins of the tumour piece. The microorganisms present in the samples were investigated using microbial culture and 16S rDNA massive sequencing. Collagenase and protease production was determined, as well as the presence of genes responsible for expressing enzymes with these activities. Machine learning analyses were developed using clinical and microbiological data. Results The incidence of CAL was 9.0%, and CAL was associated with collagenase/protease‐producing Enterococcus . Significant differences were found in the microbiota composition of proximal and distal biopsy samples, but not in faecal samples, among patients who developed CAL. Clinical predictors of CAL were 5‐day C‐reactive protein and heart disease, whereas 3‐day C‐reactive protein and diabetes were negative predictors. Conclusion Biopsy samples from surgical margins, rather than faecal samples, are the most appropriate samples for exploring the contribution of the intestinal microbiota to CAL. Enterococci are only enriched in the anastomosis after surgery, and their collagenases and proteases are involved in the degradation of the anastomotic scar.
Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.
Resumen Objetivo Describir las experiencias y las necesidades de atención médica de un grupo de progenitores de niños con encefalopatías epilépticas y del desarrollo (EED) causadas por las variantes SCN1A , KCNQ2 , CDKL5 , PCDH19 y GNAO1 . Método Se realizó un estudio cualitativo descriptivo. Los participantes fueron reclutados mediante un muestreo intencional. Los criterios de inclusión consistieron en progenitores de niños con EED causadas por las variantes SCN1A , KCNQ2 , CDKL5 , PCDH19 o GNAO1 , con edades comprendidas entre los 4 y los 10 años. En total, se incluyeron 21 progenitores. Los datos se obtuvieron mediante entrevistas en profundidad y notas de campo del investigador. Se realizó un análisis temático. Resultados Se identificaron tres temas principales: (1) Manejando los síntomas, las crisis epilépticas se viven con gran incertidumbre, y se acompañan de síntomas cognitivos, conductuales y motores que limitan la vida del niño; b) Aceptando el tratamiento, la pauta de la medicación idónea es un reto, la decisión de retirar o comenzar una nueva terapia recae en los progenitores; y c) Relación terapéutica y atención médica, existen comportamientos y acciones del profesional que facilitan o dificultan la relación terapéutica con los progenitores. Acudir al servicio de urgencias es vivido con recelo por los progenitores. Interpretación Los profesionales de los servicios de urgencias deben conocer mejor las EED, acoger a los progenitores y mejorar el tratamiento de los niños. Los resultados de este estudio pueden servir como punto de partida para una hoja de ruta de los resultados relevantes reportados por los cuidadores de las EED, a implementar nuevos ensayos clínicos y terapias dirigidas a la etiología.
One of the justifications for promoting tourism development is the capacity that it has to generate spillover effects on traditional economic activities. However, the strength of these spillover effects depends, largely, on the complementary or competitive nature of the traditional sector with respect to the resources used by tourism. Using time series analysis techniques, this paper examines the relationship existing between tourism development and the local fisheries sector. The results suggest that fisheries have been benefiting from growth in tourism, not so much in terms of an increase in the volume of catches but rather due to an increase in their value.
In recent years, the issue of sexual consent in relationships influenced by alcohol and other substances has come under scrutiny and analysis within both the sociopolitical and academic spheres. To comprehend the moral validity attributed by Spanish youth to sexual consent in nightlife settings, in-depth group and individual interviews were conducted with a total of 53 university students. The findings reveal how the moral discussion surrounding consent validity becomes complex depending on the level of intoxication of those involved. It is concluded that three key ideas govern this discussion: (a) the ability to discern the level of intoxication of the other person, (b) the prior relationship between the victim and the perpetrator, and (c) the relationship between the person judging the validity of that consent and the aggressor. Thus, depending on how the mentioned key factors are resolved, the morality regarding the same act varies. The findings of this research contribute to the scientific literature with yet another piece of evidence highlighting the intricacies inherent in a profound understanding of sexual consent.
Background The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the-art proton nuclear magnetic resonance spectrometry ( ¹ H-NMRS) metabolomics profiling, that androgen excess in women induces a certain masculinization of postprandial metabolism that is modulated by obesity. Materials and methods Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected to be similar in terms of age and body mass index (BMI). Half of the subjects had obesity. Patients were submitted to isocaloric separate glucose, lipid and protein oral challenges in alternate days and fasting and postprandial serum samples were submitted to ¹ H-NMRS metabolomics profiling for quantification of 36 low-molecular-weight polar metabolites. Results The largest postprandial changes were observed after glucose and protein intake, with lipid ingestion inducing smaller differences. Changes after glucose intake consisted of a marked increase in carbohydrates and byproducts of glycolysis, and an overall decrease in byproducts of proteolysis, lipolysis and ketogenesis. After the protein load, most amino acids and derivatives increased markedly, in parallel to an increase in pyruvate and a decrease in 3-hydroxybutyric acid and glycerol. Obesity increased β- and d -glucose and pyruvate levels, with this effect being observed mostly after glucose ingestion in women with PCOS. Regardless of the type of macronutrient, men presented increased lysine and decreased 3-hydroxybutyric acid. In addition, non-obese men showed increased postprandial β-glucose and decreased pyroglutamic acid, compared with non-obese control women. We observed a common pattern of postprandial changes in branched-chain and aromatic amino acids, where men showed greater amino acids increases after protein intake than control women and patients with PCOS but only within the non-obese participants. Conversely, this increase was blunted in obese men but not in obese women, who even presented a larger increase in some amino acids compared with their non-obese counterparts. Interestingly, regardless of the type of macronutrient, only obese women with PCOS showed increased leucine, lysine, phenylalanine and tryptophan levels compared with non-obese patients. Conclusions Serum ¹ H-NMRS metabolomics profiling indicated sexual dimorphism in the responses to oral macronutrient challenges, which were apparently driven by the central role of postprandial insulin effects with obesity, and to a lesser extent PCOS, exerting modifying roles derived from insulin resistance. Hence, obesity impaired metabolic flexibility in young adults, yet sex and sex hormones also influenced the regulation of postprandial metabolism. Graphical abstract
During the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOCs) of particular relevance emerged. Early detection of VOCs entering a country is essential to control spread. The alert triggered by the first suspected case of the Omicron variant in Spain in a traveler arriving from South Africa in November 2021 provided a unique opportunity to evaluate four different methodological strategies tailored to rapid identification of Omicron. The different approaches were designed to respond to the different technical resources available in different settings. First, we used melting probes in RT-PCR to determine the presence of four Omicron signatures (K417N, E484A, P681H, and absence of L452R): three probes showed deviations in temperature (Tm) values relative to the reference codons (E484K-15.8°C, P681H-5.2°C, and L452R-7.2°C) and one maintained the reference value (K417N). The deviation in Tm of P681H suggested the presence of the characteristic Omicron N679K mutation in the probe hybridization region; these data pointed to the presence of Omicron alleles. Second, the presence of 29 of the 33 characteristic single nucleotide polymorphisms (SNPs) in the Omicron variant S-gene was identified by Sanger sequencing of nine amplicons. The final two strategies involved identification of 47 of the 50 non-synonymous and indel mutations attributed to Omicron by rapid nanopore whole genome sequencing (WGS) and by Illumina WGS technology. These strategies enabled us to pre-assign the first Omicron case in Spain with high certainty 2 h after receipt of RNA and to confirm it genomically 3 h later, so that the Public Health authorities could be rapidly notified. IMPORTANCE The study presents different experimental alternatives to identify new variants of concern (VOCs) of SARS-CoV-2 entering a certain population. Early detection of a new VOC is crucial for surveillance and control of spread. The objective is to provide laboratories with tools adapted to their resource capabilities that offer a sufficient level of resolution to rule out, confirm, or pre-assign the presence of a suspected VOC. The study describes four different techniques that were applied simultaneously to the first suspected Omicron case in Spain, highlighting the level of resolution and response time achieved in each case. These techniques are based on the detection of mutations in the S-gene of the virus that can easily adapt to potential emerging variants. The results of the study allow any laboratory to prepare for new alerts of SARS-CoV-2 VOCs.
The aim of this work is to compare the Corvis ST stress–strain index (SSI) and highest concavity (HC) parameters at baseline and 1 month after initiating monotherapy with prostaglandin analogues (PGs) in eyes showing visual field (VF) progression or stability. In this prospective, single-center, observational study, newly diagnosed and treatment-naïve OAG patients were examined at baseline and 1 month after beginning monotherapy with topical PGs monotherapy. Goldmann applanation tonometry pressure readings, Corneal Hysteresis (ORA-CH), and the Corvis ST measurements were obtained at both visits. VF progression (Humphrey) was evaluated based on data from 6 years of follow-up after the baseline visit. Stress–strain index (SSI) and HC parameters in progressing (P) and non-progressing (NP) eyes were the main outcome measures. Sixty-three eyes were analyzed; mean age was 64.63 ± 11.26 years; 47 eyes were NP and 16 eyes were P according to the event analysis performed by the Humphrey device. There were no significant differences in IOP, CCT, or Corvis parameters between NP and P groups at baseline. Nevertheless, at 1 month, the SSI index was 1.60 ± 0.34 vs. 1.80 ± 0.34 (p = 0.003) in NP vs. P eyes, respectively. HC parameters were different between the groups at 1 month (p < 0.05) suggesting an increased scleral rigidity in the P group. There was no significant difference in IOP between groups at 1 month. The Corvis ST provides a corneal rigidity index (SSI) that seems to be related to VF progression when measured 1 month after initiating PGs monotherapy. Differences in HC parameters, indicative of increased scleral stiffness, are also evident at 1 month on latanoprost in the P eyes.
Although typically used to measure dynamic strain from seismic and acoustic waves, Rayleigh‐based distributed acoustic sensing (DAS) is also sensitive to temperature, offering longer range and higher sensitivity to small temperature perturbations than conventional Raman‐based distributed temperature sensing. Here, we demonstrate that ocean‐bottom DAS can be employed to study internal wave and tide dynamics in the bottom boundary layer, a region of enhanced ocean mixing but scarce observations. First, we show temperature transients up to about 4 K from a power cable in the Strait of Gibraltar south of Spain, associated with passing trains of internal solitary waves in water depth <200 m. Second, we show the propagation of thermal fronts associated with the nonlinear internal tide on the near‐critical slope of the island of Gran Canaria, off the coast of West Africa, with perturbations up to about 2 K at 1‐km depth and 0.2 K at 2.5‐km depth. With spatial averaging, we also recover a signal proportional to the barotropic tidal pressure, including the lunar fortnightly variation. In addition to applications in observational physical oceanography, our results suggest that contemporary chirped‐pulse DAS possesses sufficient long‐period sensitivity for seafloor geodesy and tsunami monitoring if ocean temperature variations can be separated.
Aim To construct and validate a scale to measure the degree of acceptance of the population towards drug-facilitated sexual assault. Subject and methods The drug-facilitated sexual assault acceptance scale was validated in a sample of secondary school students (n = 485). For this purpose, the sample was divided into two subsamples (n1 = 240; n2 = 245), and exploratory factor analysis and confirmatory factor analysis were applied to each of them. In addition, the reliability of the developed scale was analyzed using Cronbach's α. Results In the exploratory factor analysis, a scale of 15 items was obtained, divided into three factors: (a) Sexual Duty, (b) Drunken Effervescence, and (c) Sexual Success. Confirmatory factor analysis confirmed the results. In measuring the reliability of the scale, a Cronbach's α of 0.877 was obtained for the whole sample. Conclusion These results confirm the adequacy of the scale and its component items, reflecting its suitability for measuring the acceptability of drug-facilitated sexual assaults. Thus, the drug-facilitated sexual assault acceptance scale provides a valid and reliable instrument specifically designed to measure the acceptability of drug-facilitated sexual violence.
Background The long-standing underrepresentation of women in leadership positions in medicine is well-known, but poorly documented globally. There is some evidence of the gender gap in academia, medical society leadership, or specific problems in some specialties. However, there are no investigations analyzing all medical specialties together and reporting the glass ceiling from a 360º perspective that includes positions in academia, research, professional organizations, and clinical activity. Additionally, the majority of studies have a US perspective, and we wonder if the perspective of a European country might be different. The WOmen in MEDicine in Spain (WOMEDS) project (https://womeds.es) aims to describe and characterize, in a systematic and detailed way, the gender bias in the medical profession in Spain in order to monitor its evolution over time and contribute to prioritizing gender policies. Methods We retrieved data for the calendar years 2019–2021 from several sources and selected surveys. We built four groups of indicators to describe leadership positions in the medical profession: (i) leadership in healthcare according to specialty and region; (ii) leadership in scientific and professional bodies; (iii) academic career; and (iv) leadership in clinical research activity. As a summary measure, we reported the women ratios, calculated as the percentage of women in specific top positions divided by the percentage of women in the relevant population. Results We found gender inequity in leadership positions in all four settings. During the observed period, only 27.6% of the heads of departments in hospitals were women compared to 61.1% of women in medical staff. Ten of the 46 medical societies grouped in the Spanish Federation of Medical Societies (FACME) (21.7%) had a women president at some point during the study period, and only 4 annual congresses had ratios of women speakers higher than 1. Women were over-represented in the lower positions and underrepresented in the top academic ones. Only 26% and 27%, respectively, of the heads of departments and deans were women. The applications for public funding for research projects are led by women only in 45% of the cases, and the budget granted to women in public calls was 24.3% lower than that of men. Conclusion In all the areas analyzed, the leadership positions are still mostly occupied by men despite the feminization of medicine in Spain. The severe gender inequity found calls for urgent interventions within a defined time horizon. Such measures must concern all levels, from national or regional regulation to changes in organizational culture or incentives in specific organizations.
The IRS (insulin receptor substrate) family of scaffold proteins includes insulin receptor substrate-4 (IRS4), which is expressed only in a few cell lines, including human kidney, brain, liver, and thymus and some cell lines. Its N-terminus carries a phosphotyrosine-binding (PTB) domain and a pleckstrin homology domain (PH), which distinguishes it as a member of this family. In this paper, we collected data about the molecular mechanisms that explain the relevance of IRS4 in the development of cancer and identify IRS4 differences that distinguish it from IRS1 and IRS2. Search engines and different databases, such as PubMed, UniProt, ENSEMBL and SCANSITE 4.0, were used. We used the name of the protein that it encodes “(IRS-4 or IRS4)”, or the combination of these terms with the word “(cancer)” or “(human)”, for searches. Terms related to specific tumor pathologies (“breast”, “ovary”, “colon”, “lung”, “lymphoma”, etc.) were also used. Despite the lack of knowledge on IRS4, it has been reported that some cancers and benign tumors are characterized by high levels of IRS-4 expression. Specifically, the role of IRS-4 in different types of digestive tract neoplasms, gynecological tumors, lung cancers, melanomas, hematological tumors, and other less common types of cancers has been shown. IRS4 differs from IRS1 and IRS2 in that can activate several oncogenes that regulate the PI3K/Akt cascade, such as BRK and FER, which are characterized by tyrosine kinase-like activity without regulation via extracellular ligands. In addition, IRS4 can activate the CRKL oncogene, which is an adapter protein that regulates the MAP kinase cascade. Knowledge of the role played by IRS4 in cancers at the molecular level, specifically as a platform for oncogenes, may enable the identification and validation of new therapeutic targets.
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