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Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein.

The overlapping circulation of influenza (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SC2), and respiratory syncytial virus (RSV) continues to challenge clinical laboratories, particularly in settings with limited automation and fragmented healthcare coverage. This study expanded the CDC Flu-SC2 assay by incorporating a laboratory-developed test (LDT) for RSV A/B detection into a fully automated quadruplex RT-qPCR (LDRA) on the Panther Fusion® Open Access™ system. The design, based on more than 8000 RSV genomic sequences targeting the conserved M gene, achieved optimal amplification efficiencies (97–105%) and full multiplex compatibility. Analytical assessment established limits of detection between 9.6 and 37.8 copies per reaction, absence of cross-reactivity with 30 respiratory pathogens, and inclusivity for 32 viral variants. Commutability and diagnostic performance among the LDRA, CE IVD-marked Allplex™ SARS-CoV-2/FluA/FluB/RSV, and US IVD-marked Panther Fusion® SARS-CoV-2/Flu A/B/RSV Assays were evaluated using 405 nasopharyngeal UTM-preserved swabs. The LDRA demonstrated excellent concordance (overall agreement ≥ 98%, κ > 0.95), strong diagnostic accuracy, and reliable detection of mixed infections. This quadruplex provides a fully automated, rapid, and accurate solution for the simultaneous detection of influenza A, influenza B, SARS-CoV-2, and RSV viruses, enhancing molecular diagnostic capacity and supporting equitable, timely clinical decision-making in middle-income healthcare systems such as that of the Dominican Republic.

Purpose: To compare image quality and radiation dose among different protocols in patients who underwent a 128-slice dual source computed tomography coronary angiography (DSCT-CTCA). Methods: Ninety patients were retrospectively grouped according to heart rate (HR): 26 patients (group A) with stable HR ≤60 bpm were acquired using high pitch spiral mode (FLASH); 48 patients (group B) with irregular HR ≤60 bpm or stable HR between 60 and 70 bpm using step and shoot mode; and 16 patients (group C) with irregular HR >60 bpm or stable HR ≥70 bpm by retrospective electrocardiogram pulsing acquisition. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were measured for the main vascular structures. Moreover, the dose-length product and the effective dose were assessed. Results: Both SNR and CNR were higher in group A compared to group C (18.27 ± 0.32 vs 11.22 ± 0.50 and 16.75 ± 0.32 vs 10.17 ± 0.50; P = .001). The effective dose was lower in groups A and B (2.09 ± 1.27 mSv and 4.60 ± 2.78 mSv, respectively) compared to group C (9.61 ± 5.95 mSv) P < .0001. Conclusion: The correct selection of a low-dose, HR-matched CTCA scan protocol with a DSCT scanner provides substantial reduction of radiation exposure and better SNR and CNR.

La neumonía se define clínicamente como la presencia aguda de fiebre acompañada de síntomas y signos respiratorios que pueden estar o no acompañados de hallazgos radiográficos. Sin embargo, los signos y síntomas que acompañan la enfermedad en la edad pediátrica son inespecíficos.

Background Senescence in stem cells and progenitor cells can be particularly detrimental because these cells are essential for tissue renewal and overall organismal homeostasis. In mesenchymal stromal cells (MSCs), which comprise a heterogeneous mix of stem cells, progenitors, fibroblasts, and other stromal cells, senescence poses a significant challenge, as it impairs their ability to support tissue repair and maintenance. This decline in regenerative capacity can contribute to aging-related diseases, impaired wound healing, and degenerative disorders. One hallmark of senescence is resistance to apoptosis, mediated by activation of anti-apoptotic pathways. Consequently, senotherapeutics have emerged as a promising strategy to selectively eliminate senescent cells and promote healthy aging. Plant secondary metabolites, notably polyphenols and terpenes, exhibit diverse effects on living organisms and have served as medicinal agents. Methods In this study, we investigated four terpenes—carvacrol, thymol, eugenol, and lycopene—for their senolytic potential in human senescent MSCs. Results We found that these compounds induce apoptosis through both caspase-dependent and caspase-independent mechanisms, involving the activation of BAX, cytochrome c release, and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei. Importantly, terpene-induced apoptosis was associated with a significant increase in reactive oxygen species, and pre-incubation with glutathione partially rescued cell viability, confirming oxidative stress as a central trigger. Moreover, we identified SRC pathway modulation as a critical determinant of the senescence-to-apoptosis shift, highlighting a key regulatory switch in terpene action. Conclusions These findings provide a detailed mechanistic dissection of terpene-induced senolysis and underscore their potential as promising candidates for senotherapeutics targeting senescent cells.

Multicellular eukaryotes demonstrate nongenetic, heritable phenotypic versatility in their adaptation to environmental changes. This inclusive inheritance is composed of interacting epigenetic, maternal, and environmental factors. Yet-unidentified maternal effects can have a pronounced influence on plant phenotypic adaptation to changing environmental conditions. To explore the control of phenotypy in higher plants, we examined the effect of a single plant nuclear gene on the expression and transmission of phenotypic variability in Arabidopsis (Arabidopsis thaliana). MutS HOMOLOG1 (MSH1) is a plant-specific nuclear gene product that functions in both mitochondria and plastids to maintain genome stability. RNA interference suppression of the gene elicits strikingly similar programmed changes in plant growth pattern in six different plant species, changes subsequently heritable independent of the RNA interference transgene. The altered phenotypes reflect multiple pathways that are known to participate in adaptation, including altered phytohormone effects for dwarfed growth and reduced internode elongation, enhanced branching, reduced stomatal density, altered leaf morphology, delayed flowering, and extended juvenility, with conversion to perennial growth pattern in short days. Some of these effects are partially reversed with the application of gibberellic acid. Genetic hemicomplementation experiments show that this phenotypic plasticity derives from changes in chloroplast state. Our results suggest that suppression of MSH1, which occurs under several forms of abiotic stress, triggers a plastidial response process that involves nongenetic inheritance.

MutS Homolog 1 (MSH1) encodes a plant-specific protein that functions in mitochondria and chloroplasts. We showed previously that disruption or suppression of the MSH1 gene results in a process of developmental reprogramming that is heritable and non-genetic in subsequent generations. In Arabidopsis, this developmental reprogramming process is accompanied by striking changes in gene expression of organellar and stress response genes. This developmentally reprogrammed state, when used in crossing, results in a range of variation for plant growth potential. Here we investigate the implications of MSH1 modulation in a crop species. We found that MSH1-mediated phenotypic variation in Sorghum bicolor is heritable and potentially valuable for crop breeding. We observed phenotypic variation for grain yield, plant height, flowering time, panicle architecture, and above-ground biomass. Focusing on grain yield and plant height, we found some lines that appeared to respond to selection. Based on amenability of this system to implementation in a range of crops, and the scope of phenotypic variation that is derived, our results suggest that MSH1 suppression provides a novel approach for breeding in crops.

Background Hypertension is common among patients with type 2 diabetes mellitus (T2DM) and represents a major contributor to cardiovascular and renal morbidity. Real-world data from primary care are essential to characterise associated clinical profiles and cardiometabolic multimorbidity patterns in routine clinical practice. Objective To assess the prevalence of hypertension among patients with T2DM managed in primary care, to characterise associated clinical profiles, and to explore sex-related differences using real-world data. Methods A cross-sectional study was conducted including 680 adults with T2DM receiving routine care in primary care settings. Clinical, sociodemographic and laboratory data were obtained from electronic health records, direct clinical assessment, and structured patient interviews. Hypertension was defined as a previously recorded clinical diagnosis, current antihypertensive treatment, or blood pressure ≥ 140/90 mmHg. Comparisons were performed according to sex. Factors independently associated with hypertension were analysed using bivariate analyses and multivariable logistic regression models adjusted for age, sex, duration of T2DM, pharmacologically treated dyslipidaemia, and established cardiovascular disease. Results The mean age of participants was 69.8 ± 13.3 years and the mean duration of diabetes was 9.9 ± 4.6 years; 52.1% were men. Overall hypertension prevalence was 84.3%, with no significant difference between men (85.9%) and women (82.5%). Hypertension prevalence increased with age in both sexes. Women had lower educational and socioeconomic levels, higher abdominal obesity, and higher lipid concentrations, whereas men showed higher fasting glucose, serum creatinine, and markers of renal damage. In multivariable analysis, hypertension was independently associated with older age (OR 1.04 per year; 95% CI 1.02–1.06), pharmacologically treated dyslipidaemia (OR 1.83; 95% CI 1.17–2.86), established cardiovascular disease (OR 2.03; 95% CI 1.16–3.55), and longer duration of T2DM (OR 1.06 per year; 95% CI 1.00–1.12). Sex was not independently associated with hypertension after adjustment. Conclusions Hypertension was common among patients with T2DM in primary care and was associated with older age, longer diabetes duration, and established cardiovascular disease. Sex-related differences in clinical profiles were observed but should be interpreted as descriptive. This cross-sectional secondary analysis has limitations, including the lack of blood pressure control data and the potential for residual confounding.

Hyperspectral drill-core scanning adds value to exploration campaigns by providing continuous, high-resolution mineralogical data over the length of entire boreholes. However, multivariate mineralogical data must be transformed into lithological domains such that it is compatible with interpolation techniques and be usable for geomodeling. Manual interpretation of multivariate drill-core data is a challenging, time-consuming and subjective task, and automated or semi-automated approaches are needed. However, naive machine-learning techniques that ignore the distinct spatial structure and multi-scale nature of geological systems tend to produce geologically unreasonable results. Automated geological logging and multi-scale hierarchical domaining of drill-cores has been previously addressed in several studies by means of scalograms from a wavelet transform and tessellation, albeit exploiting only univariate information. The methodology involves the extraction of the local first principal component at a neighborhood of each observation, and the segmentation of the resulting series of scores with a continuous wavelet transform for boundary detection. In this way, the correlation pattern between the variables is incorporated into the segmentation. The scalogram accurately locates the geological boundaries at depth and yields hierarchical geological domains with mineralogical composition characteristics. The performance of this approach is demonstrated on a synthetic as well as a real multivariate dataset. The real dataset consists of mineral abundances derived from drill-core hyperspectral imaging data acquired in Elvira, a shale-hosted volcanogenic massive sulfide deposit located in the Iberian Pyrite Belt, where 7000 m of drill-core were acquired along 80 boreholes. The extracted domains are sensible from a geological point of view and spatially coherent across the boreholes in cross-sections. The results at relevant scales were qualitatively validated by comparing against the lithological log. This method is fast, is appropriate for multivariate geological data along boreholes, and provides a choice of scales for hierarchical geological domains along boreholes with mineralogical composition characteristics that can be modeled in 3D. Our approach provides an automatic way to transform hyperspectral image-derived mineral maps into vertically coherent geological units that are appropriate inputs for 3D geological modeling workflows. Moreover, the method improves the boundary detection and geological domaining by making use of multivariate information.