Survival Bias and Crosstalk between Chronological and Behavioral Age: Age- and Genotype-Sensitivity Tests Define Behavioral Signatures in Middle-Aged, Old, and Long-Lived Mice with Normal and AD-Associated Aging

Malaltia d'Alzheimer; Envelliment; SupervivènciaAlzheimer’s disease; Aging; SurvivalEnfermedad de Alzheimer; Envejecimiento; SupervivenciaNew evidence refers to a high degree of heterogeneity in normal but also Alzheimer’s disease (AD) clinical and temporal patterns, increased mortality, and the need to find specific end-of-life prognosticators. This heterogeneity is scarcely explored in very old male AD mice models due to their reduced survival. In the present work, using 915 (432 APP23 and 483 C57BL/6 littermates) mice, we confirmed the better survival curves in male than female APP23 mice and respective wildtypes, providing the chance to characterize behavioral signatures in middle-aged, old, and long-lived male animals. The sensitivity of a battery of seven paradigms for comprehensive screening of motor (activity and gait analysis), neuropsychiatric and cognitive symptoms was analyzed using a cohort of 56 animals, composed of 12-, 18- and 24-month-old male APP23 mice and wildtype littermates. Most variables analyzed detected age-related differences. However, variables related to coping with stress, thigmotaxis, frailty, gait, and poor cognition better discriminated the behavioral phenotype of male APP23 mice through the three old ages compared with controls. Most importantly, non-linear age- and genotype-dependent behavioral signatures were found in long-lived animals, suggesting crosstalk between chronological and biological/behavioral ages useful to study underlying mechanisms and distinct compensations through physiological and AD-associated aging.This work was funded by the BrightFocus Foundation, US (A2017243S). The Neurovascular Research Laboratory is part of the INVICTUS+network, Instituto de Salud Carlos III (ISCIII), Spain [RD16/0019/0021], co-financed by the European Regional Development Fund FEDER. P.M. held a predoctoral fellowship from the Vall d’Hebron Research Institute

Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study

Microhemorragias cerebrales; Beta-amiloidosis cerebral; Resonancia magnética preclínicaCerebral microbleeds; Cerebral beta-amyloidosis; Preclinical MRIMicrohemorràgies cerebrals; Beta-amiloidosi cerebral; Ressonància magnètica preclínicaThe pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic.This work was funded by the Instituto de Salud Carlos III (ISCIII), (PI20/00465) and co-financed by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the RICORS-ICTUS-Enfermedades Vasculares Cerebrales network, ISCIII, Spain (RD21/0006/0007)

Coordinated inflammation and immune response transcriptional regulation in breast cancer molecular subtypes

Breast cancer, characterized by its complexity and diversity, presents significant challenges in understanding its underlying biology. In this study, we employed gene co-expression network analysis to investigate the gene composition and functional patterns in breast cancer subtypes and normal breast tissue. Our objective was to elucidate the detailed immunological features distinguishing these tumors at the transcriptional level and to explore their implications for diagnosis and treatment. The analysis identified nine distinct gene module clusters, each representing unique transcriptional signatures within breast cancer subtypes and normal tissue. Interestingly, while some clusters exhibited high similarity in gene composition between normal tissue and certain subtypes, others showed lower similarity and shared traits. These clusters provided insights into the immune responses within breast cancer subtypes, revealing diverse immunological functions, including innate and adaptive immune responses. Our findings contribute to a deeper understanding of the molecular mechanisms underlying breast cancer subtypes and highlight their unique characteristics. The immunological signatures identified in this study hold potential implications for diagnostic and therapeutic strategies. Additionally, the network-based approach introduced herein presents a valuable framework for understanding the complexities of other diseases and elucidating their underlying biology

Implementación de la metodología 5S para incrementar la productividad en el taller de confección textil de un establecimiento penal - 2022

La presente investigación tiene como objetivo principal implementar la metodología 5s para incrementar la productividad en el taller de confección textil de un Establecimiento Penal, evaluando como la organización, orden y limpieza de los espacios y materiales influye en la eficiencia de este Taller y comprobando si los procesos estandarizados de actividades se relacionan con la eficacia del mismo. Para la explicación del presente proyecto se abordó el concepto de manufactura esbelta, dentro de la cual se encuentra la Metodología 5s; y por otra parte los conceptos de productividad, definiendo los términos de eficiencia y eficacia dentro de una Empresa. Asimismo, se realizó un diagnóstico de la situación actual del Taller, en el cual se identificaron las principales causas de la baja productividad dentro del Taller, las cuales fueron principalmente los procesos y tareas no estandarizadas y la deficiencia en la organización de materiales y orden de los espacios. La presente investigación fue de tipo aplicada, con un diseño experimental de corte preexperimental. Utilizando un muestreo no probabilístico, tomando como población y muestra la producción de polos durante los meses de junio y agosto. Se emplearon técnicas de observación directa y análisis documental para recabar la información, mediante instrumentos tales como guía de información, fichas de recolección de datos y listas de verificación; se procedió a implementar la propuesta de mejora, mediante la cual se evaluó los resultados obtenidos después de la misma; concluyendo que la implementación de la Metodología 5s incrementó en 31.36% la productividad, además de incrementar la eficiencia y eficacia del Taller de confección textil en un 11.87 %, y 33.05% respectivamente

Use of time-of-flight mass spectrometry for large screening of organic pollutants in surface waters and soils from a rice production area in Colombia

The irrigate district of Usosaldaña, an important agricultural area in Colombia mainly devoted to rice crop production, is subjected to an intensive use of pesticides. Monitoring these compounds is necessary to know the impact of phytosanitary products in the different environmental compartments. In this work, surface water and soil samples from different sites of this area have been analyzed by applying an analytical methodology for large screening based on the use of time-of-flight mass spectrometry (TOF MS) hyphenated to liquid chromatography (LC) and gas chromatography (GC). Several pesticides were detected and unequivocally identified, such as the herbicides atrazine, diuron or clomazone. Some of their main metabolites and/or transformation products (TPs) like deethylatrazine (DEA), deisopropylatrazine (DIA) and 3,4-dichloroaniline were also identified in the samples. Among fungicides, carbendazim, azoxystrobin, propiconazole and epoxiconazole were the most frequently detected. Insecticides such as thiacloprid, or p,p′-DDT metabolites (p,p′-DDD and p,p′-DDE) were also found. Thanks to the accurate-mass full-spectrum acquisition in TOF MS it was feasible to widen the number of compounds to be investigated to other families of contaminants. This allowed the detection of emerging contaminants, such as the antioxidant 3,5-di-tertbutyl-4-hydroxy-toluene (BHT), its metabolite 3,5-di-tert-butyl-4-hydroxy-benzaldehyde (BHT-CHO), or the solar filter benzophenone, among other

Oceanic and Neritic Ichthyoplankton at the Edge of the Continental Shelf in the Southern Gulf of Mexico

Oceanic and neritic ichthyoplankton were examined at a single sampling site at the edge of the continental shelf in the southern Gulf of Mexico. Double oblique tows were made with a 60 cm Bongo net fitted with 505 µm mesh netting. Collections were taken every 2 hours over a 24 h period during spring, summer and fall of 1992. Fish larvae were described as either oceanic or neritic depending upon adult lifestage habitat. The larvae of 59 taxa were collected in spring (50 oceanic, 9 neritic), 53 in summer (26 oceanic, 27 neritic) and 55 in fall (22 oceanic, 33 neritic). Larvae were least abundant during spring and most abundant in fall, for both oceanic and neritic taxa. Highest abundances of larvae were collected at night indicating increased gear avoidance during daylight

Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail

IP-10; Tuberculosis; MailIP-10; Tuberculosi; CorreuIP-10; Tuberculosis; CorreoThe aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management

Occurrence of antibiotics and bacterial resistance in wastewater and sea water from the Antarctic

The potential presence of introduced antibiotics in the aquatic environment is a hot topic of concern, particularly in the Antarctic, a highly vulnerable area protected under the Madrid protocol. The increasing presence of human population, especially during summer, might led to the appearance of pharmaceuticals in wastewater. The previous discovery of Escherichia coli strains resistant to antibiotics in sea water and wastewater collected in King George Island motivated our investigation on antibiotics occurrence in these samples. The application of a multi-residue LCMS/MS method for 20 antibiotics, revealed the presence of 8 compounds in treated wastewater, mainly the quinolones ciprofloxacin and norfloxacin (92% and 54% of the samples analyzed, average concentrations 0.89 μg/L and 0.75 μg/L, respectively) and the macrolides azithromycin and clarithromycin (15% positive samples, and average concentrations near 0.4 μg/L), and erythromycin (38% positive samples, average concentration 0.003 μg/L). Metronidazole and clindamycin were found in one sample, at 0.17 and 0.1 μg/L, respectively; and trimethoprim in two samples, at 0.001 μg/L. Analysis of sea water collected near the outfall of the wastewater discharges also showed the sporadic presence of 3 antibiotics (ciprofloxacin, clindamycin, trimethoprim) at low ng/L level, illustrating the impact of pharmaceuticals consumption and the poor removal of these compounds in conventional WWTPs. The most widespread antibiotic in sea water was ciprofloxacin, which was found in 15 out of 34 sea water samples analyzed, at concentrations ranging from 4 to 218 ng/L. Bacteria resistance was observed for some antibiotics identified in the samples (e.g. trimetropim and nalidixic acid –a first generation quinolone). However, resistance to some groups of antibiotics could not be correlated to their presence in the water samples due to analytical limitations (penicillins, tetraciclines). On the contrary, for some groups of antibiotics detected in samples (macrolides), the antibacterial activity against E. Coli was not investigated because these antibiotics do not include this bacterial species in their spectrum of activity. Our preliminary data demonstrate that antibiotics occurrence in the Antarctic aquatic environment is an issue that needs to be properly addressed. Periodical monitoring of water samples and the implementation of additional treatments in the WWTPs are recommended as a first step to prevent potential problems related to the presence of antibiotics and other emerging contaminants in the near future in Antarctica