Comprehensive Review of Aflatoxin and Ochratoxin A Dynamics: Emergence, Toxicological Impact, and Advanced Control Strategies.

Filamentous fungi exhibit remarkable adaptability to diverse substrates and can synthesize a plethora of secondary metabolites. These metabolites, produced in response to environmental stimuli, not only confer selective advantages but also encompass potentially deleterious mycotoxins. Mycotoxins, exemplified by those originating from Alternaria, Aspergillus, Penicillium, and Fusarium species, represent challenging hazards to both human and animal health, thus warranting stringent regulatory control. Despite regulatory frameworks, mycotoxin contamination remains a pressing global challenge, particularly within cereal-based matrices and their derived by-products, integral components of animal diets. Strategies aimed at mitigating mycotoxin contamination encompass multifaceted approaches, including biological control modalities, detoxification procedures, and innovative interventions like essential oils. However, hurdles persist, underscoring the imperative for innovative interventions. This review elucidated the prevalence, health ramifications, regulatory paradigms, and evolving preventive strategies about two prominent mycotoxins, aflatoxins and ochratoxin A. Furthermore, it explored the emergence of new fungal species, and biocontrol methods using lactic acid bacteria and essential mustard oil, emphasizing their efficacy in mitigating fungal spoilage and mycotoxin production. Through an integrative examination of these facets, this review endeavored to furnish a comprehensive understanding of the multifaceted challenges posed by mycotoxin contamination and the emergent strategies poised to ameliorate its impact on food and feed safety.

A life-history allele of large effect shortens developmental time in a wild insect population.

Developmental time is a key life-history trait with large effects on Darwinian fitness. In many insects, developmental time is currently under strong selection to minimize ecological mismatches in seasonal timing induced by climate change. The genetic basis of responses to such selection, however, is poorly understood. To address this problem, we set up a long-term evolve-and-resequence experiment in the beetle Tribolium castaneum and selected replicate, outbred populations for fast or slow embryonic development. The response to this selection was substantial and embryonic developmental timing of the selection lines started to diverge during dorsal closure. Pooled whole-genome resequencing, gene expression analysis and an RNAi screen pinpoint a 222 bp deletion containing binding sites for Broad and Tramtrack upstream of the ecdysone degrading enzyme Cyp18a1 as a main target of selection. Using CRISPR/Cas9 to reconstruct this allele in the homogenous genetic background of a laboratory strain, we unravel how this single deletion advances the embryonic ecdysone peak inducing dorsal closure and show that this allele accelerates larval development but causes a trade-off with fecundity. Our study uncovers a life-history allele of large effect and reveals the evolvability of developmental time in a natural insect population.

Cost-accuracy and patient experience assessment of blood pressure monitoring methods to diagnose hypertension: A comparative effectiveness study.

Objectives: Studies of the diagnosis of hypertension have emphasized long-term cost-effectiveness analysis, but the patient experience and costs of blood pressure monitoring methods at the diagnosis stage remain unclear. We studied four diagnostic methods: a new 1 h-automated office blood pressure (BP) monitoring, office BP measurement, home BP monitoring, and awake-ambulatory BP monitoring. Methods: We carried out a comparative effectiveness study of four methods of diagnosing hypertension in 500 participants with a clinical suspicion of hypertension from three primary healthcare (PHC) centers in Barcelona city (Spain). We evaluated the time required and the intrinsic and extrinsic costs of the four methods. The cost-accuracy ratio was calculated and differences between methods were assessed using ANOVA and Tukey's honestly significant difference (HSD) post-hoc test. Patient experience data were transformed using Rasch analysis and re-scaled from 0 to 10. Results: Office BP measurement was the most expensive method (€156.82, 95% CI: 156.18-157.46) and 1 h-automated BP measurement the cheapest (€85.91, 95% CI: 85.59-86.23). 1 h-automated BP measurement had the best cost-accuracy ratio (€ 1.19) and office BP measurement the worst (€ 2.34). Home BP monitoring (8.01, 95% CI: 7.70-8.22), and 1 h-automated BP measurement (7.99, 95% CI: 7.80-8.18) had the greatest patient approval: 66.94% of participants would recommend 1 h-automated BP measurement as the first or second option. Conclusion: The relationship between the cost-accuracy ratio and the patient experience suggests physicians could use the new 1 h-automated BP measurement as the first option and awake-ambulatory BP monitoring in complicated cases and cease diagnosing hypertension using office BP measurement.

S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit.

During DNA replication, the newly created sister chromatids are held together until their separation at anaphase. The cohesin complex is in charge of creating and maintaining sister chromatid cohesion (SCC) in all eukaryotes. In Saccharomyces cerevisiae cells, cohesin is composed of two elongated proteins, Smc1 and Smc3, bridged by the kleisin Mcd1/Scc1. The latter also acts as a scaffold for three additional proteins, Scc3/Irr1, Wpl1/Rad61, and Pds5. Although the HEAT-repeat protein Pds5 is essential for cohesion, its precise function is still debated. Deletion of the ELG1 gene, encoding a PCNA unloader, can partially suppress the temperature-sensitive pds5-1 allele, but not a complete deletion of PDS5. We carried out a genetic screen for high-copy-number suppressors and another for spontaneously arising mutants, allowing the survival of a pds5Δ elg1Δ strain. Our results show that cells remain viable in the absence of Pds5 provided that there is both an elevation in the level of Mcd1 (which can be due to mutations in the CLN2 gene, encoding a G1 cyclin), and an increase in the level of SUMO-modified PCNA on chromatin (caused by lack of PCNA unloading in elg1Δ mutants). The elevated SUMO-PCNA levels increase the recruitment of the Srs2 helicase, which evicts Rad51 molecules from the moving fork, creating single-stranded DNA (ssDNA) regions that serve as sites for increased cohesin loading and SCC establishment. Thus, our results delineate a double role for Pds5 in protecting the cohesin ring and interacting with the DNA replication machinery. IMPORTANCE Sister chromatid cohesion is vital for faithful chromosome segregation, chromosome folding into loops, and gene expression. A multisubunit protein complex known as cohesin holds the sister chromatids from S phase until the anaphase stage. In this study, we explore the function of the essential cohesin subunit Pds5 in the regulation of sister chromatid cohesion. We performed two independent genetic screens to bypass the function of the Pds5 protein. We observe that Pds5 protein is a cohesin stabilizer, and elevating the levels of Mcd1 protein along with SUMO-PCNA accumulation on chromatin can compensate for the loss of the PDS5 gene. In addition, Pds5 plays a role in coordinating the DNA replication and sister chromatid cohesion establishment. This work elucidates the function of cohesin subunit Pds5, the G1 cyclin Cln2, and replication factors PCNA, Elg1, and Srs2 in the proper regulation of sister chromatid cohesion.

Risk of Severe Coronavirus Disease 2019 Infection in Kidney Transplant Recipients.

BACKGROUND: Despite all efforts, the incidence of severe coronavirus disease 2019 (COVID-19) infection has been high in renal transplant recipients, as in other groups (eg, older adults, patients with comorbidities or immunosuppression). The detection of any possible predictor of gravity could improve the early approach in these patients. PATIENTS AND METHODS: We registered data from renal transplant recipients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection in our area for a year (March 2020 to March 2021). We collected demographics, comorbidity, body mass index, lymphocyte count, and vitamin D levels before the diagnosis. We performed statistical analysis using SPSS Statistics version 20 (IBM Corp, Armonk, NY, United States). RESULTS: Of 63 patients, 57.1% required hospital admission and 14.3% required intensive care. The incidence of acute renal failure was 28.6%; 34.9% developed hyperinflammatory syndrome; 67% had lymphopenia, which was severe in 13.1%; and 11 patients died. There was significant correlation between lymphocyte count before and during the infection. For hospitalization, we found differences in age, pulmonary disease, and renal function. Related factors for admission to an intensive care unit were obesity, severe lymphopenia, altered renal function, and low level of vitamin D. Predictors for mortality were age, renal function, and minimum lymphocyte count. CONCLUSION: In kidney transplant recipients with COVID-19 infection, renal function determines hospitalization, and body mass index determines admission to an intensive care unit. Previous vitamin D levels are also significantly lower in patients requiring intensive care. The analysis of lymphocyte count previous to infection is correlated with the minimum level during the disease, which is a predictor of mortality, and could be a prognosis factor.

Connecting the dots: Bridging virtual to in-person physical assessment.

When restrictions imposed by COVID-19 prevented prelicensure nursing students from practicing skills in the simulation center, the faculty designed a plan to bridge the gap from virtual to in-person skill performance for physical assessments. The faculty anticipated an inadequacy of head-to-toe assessment skills related to the lack of face-to-face clinical. Therefore, the faculty used the Plan-Do-Study-Act model (Agency for Healthcare Research and Quality, 2020) for quality improvement to address the skill performance issue. The plan used colored adhesive "garage sale" dots to identify anatomical landmarks to help students with correct stethoscope placement during their first in-person simulation after a virtual semester. Pre- and post-tests were administered to assess confidence in assessment skills. Using this method on standardized patients in simulation, nursing students reported increased confidence in stethoscope placement. Students of all healthcare disciplines could benefit from the economical dotting process to learn correct stethoscope placement.

Evolution of flower allometry and pigmentation in Mammillaria haageana (Cactaceae).

BACKGROUND: A puzzle in evolution is the understanding of how the environment might drive subtle phenotypic variation, and whether this variation is adaptive. Under the neutral evolutionary theory, subtle phenotypes are almost neutral with little adaptive value. To test this idea, we studied the infraspecific variation in flower shape and color in Mammillaria haageana, a species with a wide geographical distribution and phenotypic variation, which populations are often recognized as infraspecific taxa. RESULTS: We collected samples from wild populations, kept them in the greenhouse for at least one reproductive year, and collected newly formed flowers. Our first objective was to characterize tepal natural variation in M. haageana through geometric morphometric and multivariate pigmentation analyses. We used landmark-based morphometrics to quantify the trends of shape variation and tepal color-patterns in 20 M. haageana accessions, belonging to five subspecies, plus 8 M. albilanata accessions for comparison as the sister species. We obtained eight geometric morphometric traits for tepal shape and color-patterns. We found broad variation in these traits between accessions belonging to the same subspecies, without taxonomic congruence with those infraspecific units. Also the phenetic cluster analysis showed different grouping patterns among accessions. When we correlated these phenotypes to the environment, we also found that solar radiation might explain the variation in tepal shape and color, suggesting that subtle variation in flower phenotypes might be adaptive. Finally we present anatomical sections in M. haageana subsp. san-angelensis to propose some of the underlying tepal structural features that may give rise to tepal variation. CONCLUSIONS: Our geometric morphometric approach of flower shape and color allowed us to identify the main trends of variation in each accession and putative subspecies, but also allowed us to correlate these variation to the environment, and propose anatomical mechanisms underlying this diversity of flower phenotypes.

Mutagenic mechanisms of cancer-associated DNA polymerase ϵ alleles.

A single amino acid residue change in the exonuclease domain of human DNA polymerase ϵ, P286R, is associated with the development of colorectal cancers, and has been shown to impart a mutator phenotype. The corresponding Pol ϵ allele in the yeast Saccharomyces cerevisiae (pol2-P301R), was found to drive greater mutagenesis than an entirely exonuclease-deficient Pol ϵ (pol2-4), an unexpected phenotype of ultra-mutagenesis. By studying the impact on mutation frequency, type, replication-strand bias, and sequence context, we show that ultra-mutagenesis is commonly observed in yeast cells carrying a range of cancer-associated Pol ϵ exonuclease domain alleles. Similarities between mutations generated by these alleles and those generated in pol2-4 cells indicate a shared mechanism of mutagenesis that yields a mutation pattern similar to cancer Signature 14. Comparison of POL2 ultra-mutator with pol2-M644G, a mutant in the polymerase domain decreasing Pol ϵ fidelity, revealed unexpected analogies in the sequence context and strand bias of mutations. Analysis of mutational patterns unique to exonuclease domain mutant cells suggests that backtracking of the polymerase, when the mismatched primer end cannot be accommodated in the proofreading domain, results in the observed insertions and T>A mutations in specific sequence contexts.

Vacunación sublingual con bacterias inactivadas en pacientes nefrológicos con infección urinaria recurrente: experiencia en un centro de España / Sublingual vaccination with inactivated bacteria in recurrent urinary tract infection of nephrologic patients: experience in a center in Spain

Resumen Introducción: las infecciones del tracto urinario (ITU) son frecuentes en pacientes con enfermedad renal crónica (ERC). Una opción de tratamiento cuando estas infecciones son recurrentes es la vacunación bacteriana sublingual. Objetivo: determinar la respuesta a la vacunación bacteriana sublingual en pacientes nefrológicos con ITU recurrente. Materiales y métodos: estudio cuasi experimental en el que se evaluó la evolución en 15 meses de los pacientes con ITU recurrente que asistieron a consulta externa de nefrología. Tras recibir tratamiento antibiótico según antibiograma para cada ITU, los participantes tomaron un ciclo de la vacuna sublingual bacteriana Uromune® durante tres meses. Se recogieron datos sociodemográficos y sobre factores de riesgo asociados, análisis de sangre y orina, episodios de ITU en los seis meses previos y posteriores, microorganismos causantes, tratamiento antibiótico concomitante, respuesta al tratamiento y resolución de la ITU. Resultados: se incluyeron 26 pacientes (80,8 % mujeres) con una media de edad de 61,9±18,4 años, de los cuales el 46,2 % tenía diabetes y el 47,7 %, afectación de la función renal. La media de ITU fue 3,62±1,77 (rango: 1 -7) antes de la vacuna y de 1,69±1,77 (rango: 0-5) después. Se recogieron 184 urocultivos: 74,9 % positivos, 16,9 % negativos y 8,2 % contaminados. Las bacterias más frecuentes fueron Escherichia coli (55,4 %), Enterococcus faecalis (6 %) y Enterobacter cloacae (2,7 %). El 50 % de los participan- tes presentó síndrome miccional, que se asoció inversamente con la edad (p<0,05). El 26,9 % no volvió a tener ITU y el 73,1 % tuvo menos episodios. Los pacientes con ERC avanzada (estadios IV-V) respondieron peor a la vacuna (92,9 % vs 50 %, p=0,025). Conclusiones: la vacunación bacteriana sublingual es una buena opción de tratamiento para la ITU recurrente de pacientes con ERC, siendo más eficaz en los que presentan mejor función renal.

Abstract Introduction: Urinary tract infections (UTIs) are common in patients with chronic kidney disease. A treatment option in recurrent UTI is sublingual bacterial vaccination. The objective of this study was to determine the response to vaccination in nephrologic patients with recurrent UTI. Method: Quasi-experimental study before-after (15 months) in patients with recurrent UTI from the outpatient nephrology consultation. After receiving antibiotic treatment for each UTI, patients took one cycle of the sublingual bacterial vaccine Uromune? for three months. Sociodemographic data, associated risk factors, analysis, UTI in the previous and subsequent six months, microorganisms, concomitant antibiotic treatment, response to treatment and resolution of UTI were collected. Results: Twenty-six patients (80.8% female) of 61.9 ±18.4 years, 46.2% with diabetes and 47.7% with impaired renal function were included. The episodes of UTI were 3.62 ±1.77 (1-7) before and 1.69 ± 1.77 (0-5) after vaccination. In total, 184 urine cultures were collected: 74.9% positive, 16.9% negative and 8.2% contaminated. The most frequent bacteria were Escherichia coli (55.4%), Enterococcus faecalis (6%) and Enterobacter cloacae (2.7%). Fifty percent had voiding syndrome, which was inversely associated with age (p < 0.05); 26.9% did not have a UTI again and 73.1% had fewer episodes. Patients with advanced chronic disease (stages 4-5) reponded worse to the vaccine (92.9% vs 50%, p =0.025). Conclusions: Sublingual bacterial vaccination is a good treatment option in recurrent UTI of nephrologic patients, being more effective in those with better renal function.

Telomeres and stress in yeast cells: When genes and environment interact.

Telomeres are structures composed of simple DNA repeats and specific proteins that protect the eukaryotic chromosomal ends from degradation, and facilitate the replication of the genome. They are central to the maintenance of the genome integrity, and play important roles in the development of cancer and in the process of aging in humans. The yeast Saccharomyces cerevisiae has greatly contributed to our understanding of basic telomere biology. Our laboratory has carried out systematic screen for mutants that affect telomere length, and identified ∼500 genes that, when mutated, affect telomere length. Remarkably, all ∼500 TLM (Telomere Length Maintenance) genes participate in a very tight homeostatic process, and it is enough to mutate one of them to change the steady-state telomere length. Despite this complex network of balances, it is also possible to change telomere length in yeast by applying several types of external stresses. We summarize our insights about the molecular mechanisms by which genes and environment interact to affect telomere length.

Perceptual salience of derivational suffixes in visual word recognition.

This study analyzes the role of derivational suffixes in visual word recognition, tracking the eye movements of 31 participants in a sentence-reading task in Spanish. Perceptual salience of suffixes was operationalized as the proportion of letters represented by the suffixes with respect to the full words, that is, we relate the number of letters comprising the suffixes to the number of letters in the words in which they appear. The results reveal a significant role in first fixation duration of both word frequency - the more frequent the word, the shorter the fixations, and perceptual salience - the more salient the suffix, the longer the fixations. Moreover, in gaze duration, our results show a main effect of word length - the longer the word, the longer the fixations; word frequency; and significant interactions between word frequency and perceptual salience of suffixes on the one hand - the effect of word frequency is only significant when perceptual salience of suffixes is high, and between word frequency and word length on the other hand - the frequency effect decreases as word length increases. Overall results are interpreted in the light of the dual route models by which full-form and morphological processing interactively cooperate in visual word recognition.

Estudio de las infecciones del tracto urinario por Streptococcus gallolyticus subespecie pasteurianus / A study of urinary tract infections by Streptococcus gallolyticus ssp. pasteurianus

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Primer caso de sepsis por Ignatzschineria en España asociada a miasis. Descripción de un caso y revisión de la literatura / First case of sepsis by Ignatzschineria in Spain associated with myiasis. Description of a case and review of the literatura

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Dynamics of gold nanoparticle clusters observed with liquid-phase electron microscopy.

The dynamics of processes of nanoparticles such as diffusion, attraction and repulsion, and self-assembly of structures of nanoparticles at the solid-liquid interfaces differ significantly from those occurring for bulk conditions and their fundamental physical rules are still unknown. Here, we used liquid phase scanning transmission electron microscopy (LP-STEM) to study several aspects of nanoparticle dynamics of colloidal chitosan coated gold nanoparticle (TCHIT-AuNP) clusters in a liquid layer enclosed between two SiN membranes. We found that upon beam irradiation using an electron flux of 0.9 e-/sÅ2, the AuNPs assembled in clusters that shifted and rotated with time. The newly formed clusters could join and form larger clusters via a mechanism of oriented attachment. By increasing the electron flux to 6.2 e-/sÅ2, we observed the fragmentation of some of the clusters and TCHIT-AuNPs were exchanged between clusters. At the highest electron flux studied 25 e-/sÅ2, we observed AuNPs moving at a very slow speed compared to Brownian motion in liquid even though they were not directly attached or pinned to the liquid-enclosing membrane. Experiments using branched polyethylenimine (BPEI) coated AuNPs were carried out for comparison.

Thrombotic microangiopathy and accelerated hypertension after treatment with interferon beta / Microangiopatía trombótica e hipertensión acelerada tras tratamiento con interferón beta

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The Main Role of Srs2 in DNA Repair Depends on Its Helicase Activity, Rather than on Its Interactions with PCNA or Rad51.

Homologous recombination (HR) is a mechanism that repairs a variety of DNA lesions. Under certain circumstances, however, HR can generate intermediates that can interfere with other cellular processes such as DNA transcription or replication. Cells have therefore developed pathways that abolish undesirable HR intermediates. The Saccharomyces cerevisiae yeast Srs2 helicase has a major role in one of these pathways. Srs2 also works during DNA replication and interacts with the clamp PCNA. The relative importance of Srs2's helicase activity, Rad51 removal function, and PCNA interaction in genome stability remains unclear. We created a new SRS2 allele [srs2(1-850)] that lacks the whole C terminus, containing the interaction site for Rad51 and PCNA and interactions with many other proteins. Thus, the new allele encodes an Srs2 protein bearing only the activity of the DNA helicase. We find that the interactions of Srs2 with Rad51 and PCNA are dispensable for the main role of Srs2 in the repair of DNA damage in vegetative cells and for proper completion of meiosis. On the other hand, it has been shown that in cells impaired for the DNA damage tolerance (DDT) pathways, Srs2 generates toxic intermediates that lead to DNA damage sensitivity; we show that this negative Srs2 activity requires the C terminus of Srs2. Dissection of the genetic interactions of the srs2(1-850) allele suggest a role for Srs2's helicase activity in sister chromatid cohesion. Our results also indicate that Srs2's function becomes more central in diploid cells.IMPORTANCE Homologous recombination (HR) is a key mechanism that repairs damaged DNA. However, this process has to be tightly regulated; failure to regulate it can lead to genome instability. The Srs2 helicase is considered a regulator of HR; it was shown to be able to evict the recombinase Rad51 from DNA. Cells lacking Srs2 exhibit sensitivity to DNA-damaging agents, and in some cases, they display defects in DNA replication. The relative roles of the helicase and Rad51 removal activities of Srs2 in genome stability remain unclear. To address this question, we created a new Srs2 mutant which has only the DNA helicase domain. Our study shows that only the DNA helicase domain is needed to deal with DNA damage and assist in DNA replication during vegetative growth and in meiosis. Thus, our findings shift the view on the role of Srs2 in the maintenance of genome integrity.

Statistical Validation for Clinical Measures: Repeatability and Agreement of Kinect™-Based Software.

BACKGROUND: The rehabilitation process is a fundamental stage for recovery of people's capabilities. However, the evaluation of the process is performed by physiatrists and medical doctors, mostly based on their observations, that is, a subjective appreciation of the patient's evolution. This paper proposes a tracking platform of the movement made by an individual's upper limb using Kinect sensor(s) to be applied for the patient during the rehabilitation process. The main contribution is the development of quantifying software and the statistical validation of its performance, repeatability, and clinical use in the rehabilitation process. METHODS: The software determines joint angles and upper limb trajectories for the construction of a specific rehabilitation protocol and quantifies the treatment evolution. In turn, the information is presented via a graphical interface that allows the recording, storage, and report of the patient's data. For clinical purposes, the software information is statistically validated with three different methodologies, comparing the measures with a goniometer in terms of agreement and repeatability. RESULTS: The agreement of joint angles measured with the proposed software and goniometer is evaluated with Bland-Altman plots; all measurements fell well within the limits of agreement, meaning interchangeability of both techniques. Additionally, the results of Bland-Altman analysis of repeatability show 95% confidence. Finally, the physiotherapists' qualitative assessment shows encouraging results for the clinical use. CONCLUSION: The main conclusion is that the software is capable of offering a clinical history of the patient and is useful for quantification of the rehabilitation success. The simplicity, low cost, and visualization possibilities enhance the use of the software Kinect for rehabilitation and other applications, and the expert's opinion endorses the choice of our approach for clinical practice. Comparison of the new measurement technique with established goniometric methods determines that the proposed software agrees sufficiently to be used interchangeably.