Eosinophils in Colorectal Cancer: Emerging Insights into Anti-Tumoral Mechanisms and Clinical Implications.

Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.

Assessing individual and population variability in degenerative joint disease prevalence using generalized linear mixed models.

OBJECTIVES: In this paper, we introduce the use of generalized linear mixed models (GLMM) as a better alternative to traditional statistical methods for studying factors associated to the prevalence of degenerative joint disease (DJD) in bioarchaeological contexts. MATERIALS AND METHODS: DJD prevalence was assessed for the appendicular joints and the spine of a Spanish population dated from the 15th to the 18th century. Data were analyzed using contingency tables, logistic regression models, and logistic GLMM. RESULTS: In general, results from GLMMs find agreement in other methods. However, by being able to analyze the data at the level of individual bones instead of aggregated joints or limbs, GLMMs are capable of revealing associations that are not evident in other frameworks. DISCUSSION: Currently widely available in statistical analysis software, GLMMs can accommodate a wide array of data distributions, account for hierarchical correlations, and return estimates of DJD prevalence within individuals and skeletal locations that are unbiased by the effect of covariates. This gives clear advantages for the analysis of bioarchaeological datasets which can lead to more robust and comparable analyses across populations.

Use of Computing Devices as Sensors to Measure Their Impact on Primary and Secondary Students' Performance.

The constant innovation in new technologies and the increase in the use of computing devices in different areas of the society have contributed to a digital transformation in almost every sector. This digital transformation has also reached the world of education, making it possible for members of the educational community to adopt Learning Management Systems (LMS), where the digital contents replacing the traditional textbooks are exploited and managed. This article aims to study the relationship between the type of computing device from which students access the LMS and how affects their performance. To achieve this, the LMS accesses of students in a school comprising from elementary to bachelor's degree stages have been monitored by means of different computing devices acting as sensors to gather data such as the type of device and operating system used by the students.The main conclusion is that students who access the LMS improve significantly their performance and that the type of device and the operating system has an influence in the number of passed subjects. Moreover, a predictive model has been generated to predict the number of passed subjects according to these factors, showing promising results.

High-Level Modeling and Simulation Tool for Sensor Conditioning Circuit Based on Artificial Neural Networks.

For current microelectronic integrated systems, the design methodology involves different steps that end up in the full system simulation by means of electrical and physical models prior to its manufacture. However, the higher the circuit complexity, the more time is required to complete these simulations, jeopardizing the convergence of the numerical methods and, hence, meaning that the reliability of the results are not guaranteed. This paper shows the use of a high-level tool based on Matlab to simulate the operation of an artificial neural network implemented in a mixed analog-digital CMOS process, intended for sensor calibration purposes. The proposed standard tool enables modification of the neural model architecture to adapt its characteristics to those of the electronic system, resulting in accurate behavioral models that predict the complete microelectronic IC system behavior under different operation conditions before its physical implementation with a simple, time-efficient, and reliable solution.

Evaluation of formaldehyde as an ocular irritant: a systematic review and Meta-analysis.

OBJECTIVE: The aim of this study was to use meta-regression to evaluate the safety of the maximum allowable dose of formaldehyde in terms of eye irritation symptoms. METHODS: We performed a systematic review of literature published in the PubMed, Embase, Lilacs, Web of Science, and Cochrane Library databases. We selected clinical trials, cohort studies, and case-control studies that compared eye irritation between patients exposed and not exposed to formaldehyde. Eighteen of the 2561 studies retrieved met the inclusion criteria. Data were extracted using structured forms and study quality was analyzed using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist. Odds ratios (ORs) were calculated using a random effects model with stratification by airborne dose and subsequent meta-regression analysis. RESULTS: The random effects model yielded an OR of 8.11 (95% CI: 5.85-10.37), with an I2 statistic of 99.8% and p < 0.00001. In the meta-regression analysis, we observed an I2 of 87.29% with an R2 of 23.96; the regression line for exposure had a slope of 1.466 (95% CI: 0.096-2.836) in relation to the Napierian log of the OR. Considering a safety level based on an OR of 2 relative to the unexposed group, an airborne concentration of formaldehyde of less than 0.001 mg/m3 can be considered safe. CONCLUSION: Although current formaldehyde exposure concentrations are relatively safe in terms of cancer risk, they continue to cause eye irritation.

Early Transthoracic Echocardiography after Cardiac Surgery Predicts Postoperative Atrial Fibrillation.

PURPOSE: Postoperative atrial fibrillation (POAF) is frequent after cardiac surgery. We aimed to establish a predictive model of POAF based on postoperative transthoracic echocardiography (TTE) findings. METHODS: This study included 147 patients (aged 67 ± 11 years; 109 men) undergoing coronary artery bypass grafting and/or aortic valve replacement. TTE and Doppler tissue imaging were performed on intensive care unit arrival after surgery. All patients were continuously monitored during hospitalization. The end point was the appearance of POAF. RESULTS: POAF appeared in 37 patients (25.2%). These patients were older (69 ± 16 vs. 65 ± 12 years; P < 0.001) and had increased long axis of the left atrium (LA) dimension (5.4 ± 1 vs. 4.8 ± 0.9 cm, P = 0.02), lower early diastolic velocity of the mitral annulus (e') (6.9 ± 2.1 vs. 8 ± 1.8 cm/sec; P < 0.01), and higher early diastolic pulsed Doppler mitral ratio (E)/e' (E/e') (17.4 ± 6.8 vs. 13.8 ± 6; P = 0.01). Left ventricle diastolic dysfunction grade (DFG) of 2 or 3 relative to grade 0 was significant: odds ratio (OR) 22.5, 95% confidence interval (CI) 4.52-57.2; P < 0.001, and OR: 23.6, 95% CI: 3.57-60.1; P = 0.001), respectively. On multivariate analysis, the independent predictors of POAF were age (OR: 1.10, 95% CI: 1.01-1.18; P < 0.05), long-axis LA dimension (OR: 6.24, 95% CI: 1.97-8.23; P = 0.0017), DFG-2 (OR: 4.1, 95% CI: 1.57-15.81; P < 0.001), and DFG-3 (OR: 8.3, 95% CI: 4.11-25.37; P < 0.001). CONCLUSIONS: Apart from age, the simple determination by postoperative TTE of long-axis LA dimension and DFG after cardiac surgery proved to be powerful independent predictors of POAF and may be useful for risk stratification of these patients.

PAP/HIP protein is an obesogenic factor.

In this article we report the obesogenic role of the acute phase protein PAP/HIP. We found that the transgenic TgPAP/HIP mice develop spontaneous obesity under standard nutritional conditions, with high levels of glucose, leptin, and LDL and low levels of triglycerides and HDL in blood. Accordingly, PAP/HIP-deficient mice are skinny under standard nutritional conditions. We also found that expression of PAP/HIP is induced in intestinal epithelial cells in response to gavage with olive oil and this induction is AG490 sensitive. We demonstrated that incubation of 3T3-L1 preadipocytes with a low concentration as 1 ng/ml of recombinant PAP/HIP results in accelerated BrdU incorporation in vitro. PAP/HIP-dependent adipocytes growth is sensitive to the MEK inhibitor U0126. Finally, patients with severe obesity present higher blood levels of PAP/HIP than non-obese control individuals. Altogether our data suggest that PAP/HIP could be a mediator of fat tissue development, released by the intestine and induced by the presence of food into the gut.

Evaluation of large-scale genetic structure in complex demographic and historical scenarios: the mitochondrial DNA and Y-chromosome pools of the Iberian Atlantic façade.

Genetic structural patterns of human populations are usually a combination of long-term evolutionary forces and short-term social, cultural, and demographic processes. Recently, using mitochondrial DNA and Y-chromosome loci, various studies in northern Spain have found evidence that the geographical distribution of Iron Age tribal peoples might have influenced current patterns of genetic structuring in several autochthonous populations. Using the wealth of data that are currently available from the whole territory of the Iberian Peninsula, we have evaluated its genetic structuring in the spatial scale of the Atlantic façade. Hierarchical tree modeling procedures, combined with a classic analysis of molecular variance (AMOVA), were used to model known sociocultural divisions from the third century BCE to the eighth century CE, contrasting them with uniparental marker data. Our results show that, while mountainous and abrupt areas of the Iberian North bear the signals of long-term isolation in their maternal and paternal gene pools, the makeup of the Atlantic façade as a whole can be related to tribal population groups that predate the Roman conquest of the Peninsula. The maintenance through time of such a structure can be related to the numerous geographic barriers of the Iberian mainland, which have historically conditioned its settlement patterns and the occurrence of genetic drift processes.

Over the sands and far away: interpreting an Iberian mitochondrial lineage with ancient Western African origins.

OBJECTIVES: There is an ongoing effort to characterize the genetic links between Africa and Europe, mostly using lineages and haplotypes that are specific to one continent but had an ancient origin in the other. Mitochondrial DNA has been proven to be a very useful tool for this purpose since a high number of putatively European-specific variants of the African L* lineages have been defined over the years. Due to their geographic locations, Spain and Portugal seem to be ideal places for searching for these lineages. METHODS: Five members of a minor branch of haplogroup L3f were found in recent DNA samplings in the region of Asturias (Northern Spain), which is known for its historical isolation. The frequency of L3f in this population (≈1%) is unexpectedly high in comparison with other related lineages in Europe. Complete mitochondrial DNA sequencing of these L3f lineages, as well phylogenetic and phylogeographic comparative analyses have been performed. RESULTS: The L3f variant found in Asturias seems to constitute an Iberian-specific haplogroup, distantly related to lineages in Northern Africa and with a deep ancestry in Western Africa. Coalescent algorithms estimate the minimum arrival time as 8,000 years ago, and a possible route through the Gibraltar Strait. CONCLUSIONS: Results are concordant with a previously proposed Neolithic connection between Southern Europe and Western Africa, which might be key to the proper understanding of the ancient links between these two continents.

An integrated low-power lock-in amplifier and its application to gas detection.

This paper presents a new micropower analog lock-in amplifier (LIA) suitable for battery-operated applications thanks to its reduced size and power consumption as well as its operation with single-supply voltage. The proposed LIA was designed in a 0.18 µm CMOS process with a single supply voltage of 1.8 V. Experimental results show a variable DC gain ranging from 24.7 to 42 dB, power consumption of 417 µW and integration area of 0.013 mm2. The LIA performance was demonstrated by measuring carbon monoxide concentrations as low as 1 ppm in dry N2. The experimental results show that the response to CO of the sensing system can be considerably improved by means of the proposed LIA.

Design and Evaluation of a Collective Preventive Program for Musical Performance Anxiety (ConfiDance).

Musical performance anxiety (MPA) is considered a subtype of social phobia and affects musicians who must face musical exposure in public, potentially severely affecting their emotional stability and significantly impairing the quality of their performance. This research has utilized previous scientific knowledge on the issue and a qualitative approach to musicians' needs through focus groups in order to design a collective preventive program for MPA that could be implemented within the training curriculum of professional musicians. To evaluate the adequacy of the preventive program 'ConfiDance', a pilot test was conducted with a sample of 17 professional musicians in training, all post-graduate students in classical music performance. For the pilot test, a quasi-experimental model with a repeated measures methodology (pre-post and one-year follow-up after application) was carried out. The results indicate a significant decrease in MPA after the program implementation, with a notable improvement in effect one year post-application, demonstrating an even greater positive impact over time. These data should be interpreted cautiously due to sample limitations but represent an opportunity for the future implementation of a program that can prevent and treat MPA in music education centers.

Complementary and alternative medicine in HIV care: frequency of consumption, risks and interactions with antiretroviral therapy.

OBJECTIVES: People living with HIV (PLWH) are common users of complementary and alternative medicine (CAM). The main objective of this study was to study the frequency and patterns of CAM natural products use in a large cohort of PLWH and to identify potential drug-drug interactions (DDIs) and the impact on their antiretroviral treatment (ART) adherence and efficacy. METHODS: This was a cross-sectional multicenter survey including 420 PLWH from different Spanish hospitals. Participants completed a face-to-face questionnaire on CAM consumption and different sociodemographic and clinical data were collected. DDIs between CAM and ART were identified and classified according to the Liverpool University Database and patient factors related to CAM consumption were assessed. RESULTS: 420 participants were included (82.6% male, mean age 47 years); 209 patients (49.8%) were taking at least one CAM. The most consumed CAM were green, black and red tea (n=146, 25.4%), ginger (n=26, 4.5%), fish oil (n=25, 4.4%) and cannabis (n=24, 4.2%). An ART based on integrase inhibitors was the only factor independently associated with CAM consumption (OR 1.54, 95% CI 1.04 to 2.26). 50 potential CAM-ART interactions in 43 (20.6%) patients taking CAM were identified, being clinically significant in 80% of the cases. CAM products most frequently involved with a potential significant DDI were supplements containing divalent cations (n=11) and garlic (n=7). No differences in ART efficacy and adherence were observed between patients with and without CAM consumption. CONCLUSIONS: Almost 50% of patients were taking at least one CAM product and its use was associated with an integrase inhibitor based ART. One out of every six patients was at risk of presenting with an interaction between a CAM and their ART, confirming the need to review continuously the use of CAM as part of the medication review process.

[COVID-19 readmissions during the first three epidemic periods in Orihuela, Spain: incidence, risk factors and letality]. / Reingresos por la COVID-19 durante los tres primeros periodos epidémicos en Orihuela, España: incidencia, factores de riesgo y letalidad.

OBJECTIVE: Readmission for COVID-19 is associated with high mortality, saturation of health services, and high costs. This study aimed to assess the incidence and risk factors of readmissions in COVID-19 patients in a regional hospital of Spain from February 2020 to March 2021. METHODS: A retrospective cohort study describing the characteristics of adult patients readmitted within thirty days of discharge after being infected with SARS-CoV-2 was carried out. Readmission associated risk factors were analysed using a binary logistic regression model. RESULTS: Of the 967 patients who survived their first COVID-19 admission, 70 (7.2%) were readmitted within thirty days. Of these, 34.3% presented pneumonia progression, 15.7% functional deterioration, and 12.9% other infections. The mortality rate during readmission was 28.6%. There were no statistically significant differences in the cumulative incidence of readmissions between the epidemic periods (p=0.241). Factors independently associated with readmission were: diabetes mellitus (aOR 1.96, 95%CI 1.07-3.57, p=0.030); acute kidney failure (aOR 2.69, 95%CI 1.43-5.07, p=0.002); not being a candidate for intensive care (aOR 7.68, 95% CI 4.28-13.80, p<0.001); and not being prescribed corticosteroids at discharge (aOR 2.15, 95% CI 1.04-4.44; p=0.039). CONCLUSIONS: A substantial proportion of patients admitted due to COVID-19 are readmitted, and they carry a high letality. Diabetes mellitus, acute kidney failure, not being a candidate for ICU admission, and not being prescribed corticosteroids on discharge are independently associated with an increased risk of readmission.

OBJECTIVE: Los reingresos por la COVID-19 se asocian a un incremento de la mortalidad, saturación de los servicios sanitarios y elevados costes. Este estudio pretendió evaluar la incidencia y los factores de riesgo de reingreso en pacientes con COVID-19 en un hospital comarcal español entre febrero de 2020 y marzo de 2021. METHODS: Se realizó un estudio sobre una cohorte que describía las características de los pacientes adultos reingresados en los treinta días siguientes al alta tras un ingreso por la COVID-19. Se analizaron los factores de riesgo asociados a reingreso mediante un modelo de regresión de logística binaria. RESULTS: De los 967 pacientes dados de alta de un primer ingreso por la COVID-19, 70 (7,2%) reingresaron en los treinta días siguientes. De ellos, el 34,3% presentó progresión de la neumonía, el 15,7% deterioro funcional y el 12,9% otras infecciones. La letalidad en el reingreso fue del 28,6%. No hubo diferencias estadísticamente significativas en la incidencia acumulada de reingreso entre los tres periodos (p=0,241). Los factores asociados de forma independiente con el reingreso fueron: diabetes mellitus (ORa: 1,96; IC 95%:1,07-3,57; p=0,030); insuficiencia renal aguda (ORa 2,69; IC del 95%: 1,43-5,07, p=0,002); no ser candidato a cuidados intensivos (ORa 7,68, IC 95% 4,28-13,80, p<0,001); y no tener prescritos corticosteroides al alta (ORa 2,15, IC 95% 1,04- 4,44; p=0,039). CONCLUSIONS: Una proporción sustancial de los pacientes ingresados por la COVID-19 reingresan, con una elevada letalidad. La diabetes mellitus, la insuficiencia renal aguda, no ser candidato a ingreso en UCI y no tener prescritos corticoides al alta se asocian con un mayor riesgo de reingreso.

Current Trends in Music Performance Anxiety Intervention.

Music performance anxiety (MPA) is a natural, emotional, and physiological response to the stress of public performance. Debilitating forms of MPA are severe and persistent reactions that go beyond the normal adaptive response to music evaluation situations and can negatively impact the quality of musical performance and the musician's life in general. Today, it affects numerous professional performers and can result in an inability to practice their profession, posing a significant threat to their professional activity. Despite its scope, studies exploring this issue and contributing to its resolution are scarce. Thus, this review aims to compile the significant advancements made in the last five years (2018-2023) in the treatment of MPA from a scientific perspective. For this purpose, the PRISMA method was used based on the results obtained from the Web of Science, Scopus, and Google Scholar databases. Reviewed are 10 studies that have made valuable contributions to this matter in this time frame after applying the quality filters using the PRISMA method. It is concluded that, although there are methodological shortcomings and sample limitations in the current research, this field registers advancements that provide valuable information to prevent or solve this problem in professional or aspiring musicians.

Spatially resolved detection of small molecules from press-dried plant tissue using MALDI imaging.

Premise: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a chemical imaging method that can visualize spatial distributions of particular molecules. Plant tissue imaging has so far mostly used cryosectioning, which can be impractical for the preparation of large-area imaging samples, such as full flower petals. Imaging unsectioned plant tissue presents its own difficulties in extracting metabolites to the surface due to the waxy cuticle. Methods: We address this by using established delipidation techniques combined with a solvent vapor extraction prior to applying the matrix with many low-concentration sprays. Results: Using this procedure, we imaged tissue from three different plant species (two flowers and one carnivorous plant leaf). Material factorization analysis of the resulting data reveals a wide range of plant-specific small molecules with varying degrees of localization to specific portions of the tissue samples, while facilitating detection and removal of signal from background sources. Conclusions: This work demonstrates applicability of MALDI-MSI to press-dried plant samples without freezing or cryosectioning, setting the stage for spatially resolved molecule identification. Increased mass resolution and inclusion of tandem mass spectrometry are necessary next steps to allow more specific and reliable compound identification.

Premisa: Matrix­assisted laser desorption/ionization mass spectrometry imaging (MALDI­MSI) es un método de imagen química que puede visualizar distribuciones espaciales de moléculas particulares. Hasta ahora, las imágenes de tejido vegetal han utilizado principalmente la criosección, lo cual puede ser poco práctico para la preparación de muestras de imágenes con áreas grandes, tales como los pétalos completos de una flor. La obtención de imágenes de tejido vegetal no seccionado presenta sus propias dificultades durante la extracción de metabolitos a la superficie, debido a la cutícula cerosa de la planta. Métodos: Abordamos esto usando técnicas establecidas de deslipidación combinados con una extracción de vapor por solvente antes de aplicar por aspersión la matriz en bajas concentraciones. Resultados: Usando este procedimiento, obtuvimos imágenes de tejido de tres especies de plantas diferentes (dos flores y una hoja de planta carnívora). Análisis de factorización material de los datos obtenidos revelaron una amplia gama de pequeñas moléculas específicas en plantas con diversos grados de localización en porciones específicas de las muestras de tejido, al igual que facilitó la detección y remoción de las señales de fondo. Conclusión: Nuestro trabajo demuestra la aplicabilidad de MALDI­MSI hacía muestras de plantas secadas a presión sin congelación o criosección, creando el marco para la identificación de moléculas resueltas espacialmente. Aumento de la resolución de masas e inclusión de la espectrometría de masas en tándem son pasos necesarios para obtener identificación de compuestos más específica y confiable.

Constrictive pericarditis heart failure in a patient with atrial fibrillation: A diagnostic challenge.

Constrictive pericarditis is an infrequent cause of heart failure. Diagnosis is challenging and requires a high level of suspicion. Subtle echocardiographic findings, as the pericardial bounce, could be the clue to diagnosis.

A retrospective real-world study of early short-course remdesivir in non-hospitalized COVID-19 patients at high risk for progression: low rate of hospitalization or death, regardless of immunocompetence status.

Introduction: The evidence for remdesivir therapy in immunocompromised patients is scarce. To evaluate remdesivir (RDV) effectiveness and safety in COVID-19 outpatients at high risk for progression in a real-world setting, we compare the outcome in immunocompromised (IC) patients with that in non-immunocompromised patients. Methods: Two hospitals conducted a retrospective study of all adult patients with mild-to-moderate SARS-CoV-2 infection at high risk for disease progression who were treated as outpatients with a 3-day course of RDV (1st January-30th September 2022). The primary effectiveness endpoint was a composite of any cause of hospitalization or death by day 30. A multiple logistic regression model was built to explore the association between immune status and clinical outcome, estimating adjusted odds ratios [aORs (95% CI)]. Results: We have included 211 patients, of which 57% were males, with a median age of 65 years (IQR 53-77), 70.1% were vaccinated (three or four doses), and 61.1% were IC. The median duration of symptoms before RDV treatment was 3 days (IQR 2-5). During follow-up, 14 (6.6%) patients were hospitalized, of which 6 (2.8%) were hospitalized for COVID-19 progression. No patient required mechanical ventilation, and two patients died (non-COVID-19-related). After accounting for potential confounders, only anti-CD20 treatment was associated with the composed outcome [aOR 5.35 (1.02-27.5, 95% CI)], whereas the immunocompetence status was not [aOR 1.94 (0.49-7.81, 95% CI)]. Conclusion: Early COVID-19 outpatient treatment with a 3-day course of remdesivir in vaccinated patients at high risk for disease progression during the Omicron surge had a good safety profile. It was associated with a low rate of all-cause hospitalization or death, regardless of immunocompetence status.

NAC Pre-Administration Prevents Cardiac Mitochondrial Bioenergetics, Dynamics, Biogenesis, and Redox Alteration in Folic Acid-AKI-Induced Cardio-Renal Syndrome Type 3.

The incidence of kidney disease is increasing worldwide. Acute kidney injury (AKI) can strongly favor cardio-renal syndrome (CRS) type 3 development. However, the mechanism involved in CRS development is not entirely understood. In this sense, mitochondrial impairment in both organs has become a central axis in CRS physiopathology. This study aimed to elucidate the molecular mechanisms associated with cardiac mitochondrial impairment and its role in CRS development in the folic acid-induced AKI (FA-AKI) model. Our results showed that 48 h after FA-AKI, the administration of N-acetyl-cysteine (NAC), a mitochondrial glutathione regulator, prevented the early increase in inflammatory and cell death markers and oxidative stress in the heart. This was associated with the ability of NAC to protect heart mitochondrial bioenergetics, principally oxidative phosphorylation (OXPHOS) and membrane potential, through complex I activity and the preservation of glutathione balance, thus preventing mitochondrial dynamics shifting to fission and the decreases in mitochondrial biogenesis and mass. Our data show, for the first time, that mitochondrial bioenergetics impairment plays a critical role in the mechanism that leads to heart damage. Furthermore, NAC heart mitochondrial preservation during an AKI event can be a valuable strategy to prevent CRS type 3 development.

Mitochondrial diversity patterns and the Magdalenian resettlement of Europe: new insights from the edge of the Franco-Cantabrian refuge.

Phylogeography of the mitochondrial lineages commonly found in Western Europe can be interpreted in the light of a postglacial resettlement of the continent. The center of this proposal lies in the Franco-Cantabrian glacial refuge, located in the northern Iberian Peninsula and Southwestern France. Recently, this interpretation has been confronted by the unexpected patterns of diversity found in some European haplogroups. To shed new lights on this issue, research on Iberian populations is crucial if events behind the actual genetics of the European continent are to be untangled. In this regard, the region of Asturias has not been extensively studied, despite its convoluted history with prolonged periods of isolation. As mitochondrial DNA is a kind of data that has been commonly used in human population genetics, we conducted a thorough regional study in which we collected buccal swabs from 429 individuals with confirmed Asturian ancestry. The joint analysis of these sequences with a large continent-wide database and previously published diversity patterns allowed us to discuss a new explanation for the population dynamics inside the Franco-Cantabrian area, based on range expansion theory. This approximation to previously contradictory findings has made them compatible with most proposals about the postglacial resettlement of Western Europe.

Development and validation of a new multiplex for upgrading Y-STRs population databases from 12 to 23 markers and its forensic casework application.

Y chromosomal short tandem repeats (Y-STRs) are used in forensic investigations as a useful complementary tool to autosomal markers. The ongoing development of new kits with an increasing number of markers makes it necessary to update populations typed in the Y-STR Haplotype Reference Database to reach at least 23 Y-STRs. A novel Y-STR multiplex panel was developed to offer a cost-efficient alternative to update Y-STR haplotypes from 12 to 23 loci. This panel includes the eleven markers, DYS448, DYS456, DYS458, DYS635, Y-GATA H4, DYS576, DYS481, DYS549, DYS533, DYS570 and DYS643, as well as DYS385a/b for traceability purpose. Developmental validation of this panel was conducted following the recommendations of the Scientific Working Group on DNA Analysis Methods (SWGDAM), showing high sensitivity, tolerance to common inhibitors as well as high species specificity. It was efficient for degraded DNA samples and for detection of male mixtures. When applying it for extending the current data of the Ibiza population, both the discrimination capacity and the haplotype diversity increased from 0.5952 to 0.9048 and from 0.9808 to 0.9977, respectively. Together, the study demonstrates the suitability of this panel in forensic casework.