Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

A standardized clinical database for research in Chagas disease: The NHEPACHA network.

The NHEPACHA Iberoamerican Network, founded on the initiative of a group of researchers from Latin American countries and Spain, aims to establish a research framework for Chagas disease that encompasses diagnosis and treatment. For this purpose, the network has created a questionnaire to gather relevant data on epidemiological, clinical, diagnostic, and therapeutic aspects of the disease. This questionnaire was developed based on a consensus of expert members of the network, with the intention of collecting high-quality standardized data, which can be used interchangeably by the different research centers that make up the NHEPACHA network. Furthermore, the network intends to offer a clinical protocol that can be embraced by other researchers, facilitating comparability among published studies, as well as the development of therapeutic response and progression markers.

A guide for the generation of repositories of clinical samples for research on Chagas disease.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.

Iron homo- and heterobimetallic complexes supported by a symmetrical dinucleating ligand.

The selective synthesis of biomimetic Fe/Mn complexes able to mimic the geometry and catalytic activity of enzymes possessing this cofactor is still a challenge. Herein, we discuss the stepwise synthesis, characterization, and magnetic properties of a Fe(II)/Mn(II) species and related Fe(II)/Fe(II) complexes.

DNA methylation markers for oral cancer detection in non- and minimally invasive samples: a systematic review.

More than 50% of oral cancer (OC) patients are diagnosed with advanced-stage disease associated with poor prognosis and quality of life, supporting an urgent need to improve early OC detection. The identification of effective molecular markers by minimally invasive approaches has emerged as a promising strategy for OC screening. This systematic review summarizes and evaluates the performance of the DNA methylation markers identified in non- or minimally invasive samples for OC detection. PubMed's MEDLINE, Scopus, Embase, and Cochrane Library databases were systematically searched for studies that evaluated DNA methylation markers in non-invasive and/or minimally invasive samples (oral rinse/saliva, oral brush, and blood) from OC patients. Two investigators independently extracted data on study population characteristics, candidate methylation markers, testing samples, DNA methylation assay, and performance diagnostic outcomes. Methodological study quality was assessed with the Quality Assessment for Studies of Diagnostic Accuracy-2 tool. Thirty-one studies met the inclusion criteria for this systematic review. DNA methylation markers were evaluated in oral rinse/saliva (n = 17), oral brush (n = 9), and blood (n = 7) samples. Methylation-specific PCR (MSP) and quantitative-MSP were the most common DNA methylation assays. Regarding diagnostic performance values for salivary, oral brush, and blood DNA methylation markers, sensitivity and specificity ranged between 3.4-100% and 21-100%, 9-100% and 26.8-100%, 22-70% and 45.45-100%, respectively. Different gene methylation panels showed good diagnostic performance for OC detection. This systematic review discloses the promising value of testing DNA methylation markers in non-invasive (saliva or oral rinse) or minimally invasive (oral brush or blood) samples as a novel strategy for OC detection. However, further validation in large, multicenter, and prospective study cohorts must be carried out to confirm the clinical value of specific DNA methylation markers in this setting.

Emergent effects of synaptic connectivity on the dynamics of global and local slow waves in a large-scale thalamocortical network model of the human brain.

Slow-wave sleep (SWS), characterized by slow oscillations (SOs, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the mechanisms by which global and local SOs arise from micro-scale neuronal dynamics and network connectivity remain poorly understood. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and SWS, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. An increase in the overall synaptic strength led to synchronized global SO, while a decrease in synaptic connectivity produced only local slow-waves that would not propagate beyond local areas. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

Liquid Biopsies Based on Cell-Free DNA Integrity as a Biomarker for Cancer Diagnosis: A Meta-Analysis.

Liquid biopsies have been identified as a viable source of cancer biomarkers. We aim to evaluate the diagnostic accuracy of cell-free DNA integrity (cfDI) in liquid biopsies for cancer. A comprehensive literature search was conducted through PubMed, Embase, Web of Science, and Cochrane Library up to June 2024. Seventy-two study units from forty-six studies, comprising 4286 cancer patients, were identified and evaluated. The Quality Assessment for Studies of Diagnostic Accuracy-2 (QUADAS-2) was used to assess study quality. Meta-regression analysis was employed to investigate the underlying factors contributing to heterogeneity, alongside an evaluation of publication bias. The bivariate random-effect model was utilized to compute the primary diagnostic outcomes and their corresponding 95% confidence intervals (CIs). The pooled sensitivity, specificity, and positive and negative likelihood ratios of cfDI in cancer diagnosis were 0.70 and 0.77, 3.26 and 0.34, respectively. The overall area under the curve was 0.84, with a diagnostic odds ratio of 10.63. This meta-analysis suggested that the cfDI index has a promising potential as a non-invasive and accurate diagnostic tool for cancer. Study registration: The study was registered at PROSPERO (reference No. CRD42021276290).

What is Parental Monitoring?

Parental monitoring is a construct of longstanding interest in multiple fields-but what is it? This paper makes two contributions to the ongoing debate. First, we review how the published literature has defined and operationalized parental monitoring. We show that the monitoring construct has often been defined in an indirect and nonspecific fashion and measured using instruments that vary widely in conceptual content. The result has been a disjointed empirical literature that cannot accurately be described as the unified study of a single construct nor is achieving a cumulative scientific character. Second, we offer a new formulation of the monitoring construct intended to remedy this situation. We define parental monitoring as the set of all behaviors performed by caregivers with the goal of acquiring information about the youth's activities and life. We introduce a taxonomy identifying 5 distinct types of monitoring behaviors (Types 1-5), with each behavior varying along five dimensions (performer, target, frequency, context, style). We distinguish parental monitoring from 16 other parenting constructs it is often conflated with and position monitoring as one element within the broader parent-youth monitoring process: the continuous, dyadic interplay between caregivers and youth as they navigate caregivers attempts' to monitor youth. By offering an explicit and detailed conceptualization of monitoring, we aim to foster more rigorous and impactful research in this area.

Identification of bacteria in potential mutualism with toxic Alexandrium catenella in Chilean Patagonian fjords by in vitro and field monitoring.

The dinoflagellate Alexandrium catenella is a well-known paralytic shellfish toxin producer that forms harmful algal blooms, repeatedly causing damage to Chilean coastal waters. The causes and behavior of algal blooms are complex and vary across different regions. As bacterial interactions with algal species are increasingly recognized as a key factor driving algal blooms, the present study identifies several bacterial candidates potentially associated with Chilean Alexandrium catenella. This research narrowed down the selection of bacteria from the Chilean A. catenella culture using antibiotic treatment and 16S rRNA metabarcoding analysis. Subsequently, seawater from two Chilean coastal stations, Isla Julia and Isla San Pedro, was monitored for two years to detect Alexandrium species and the selected bacteria, utilizing 16S and 18S rRNA gene metabarcoding analyses. The results suggested a potential association between Alexandrium species and Spongiibacteraceae at both stations. The proposed candidate bacteria within the Spongiibacteraceae family, potentially engaging in mutualistic relationships with Alexandrium species, included the genus of BD1-7 clade, Spongiibbacter, and Zhongshania.

Estimating classification consistency of machine learning models for screening measures.

This article illustrates novel quantitative methods to estimate classification consistency in machine learning models used for screening measures. Screening measures are used in psychology and medicine to classify individuals into diagnostic classifications. In addition to achieving high accuracy, it is ideal for the screening process to have high classification consistency, which means that respondents would be classified into the same group every time if the assessment was repeated. Although machine learning models are increasingly being used to predict a screening classification based on individual item responses, methods to describe the classification consistency of machine learning models have not yet been developed. This article addresses this gap by describing methods to estimate classification inconsistency in machine learning models arising from two different sources: sampling error during model fitting and measurement error in the item responses. These methods use data resampling techniques such as the bootstrap and Monte Carlo sampling. These methods are illustrated using three empirical examples predicting a health condition/diagnosis from item responses. R code is provided to facilitate the implementation of the methods. This article highlights the importance of considering classification consistency alongside accuracy when studying screening measures and provides the tools and guidance necessary for applied researchers to obtain classification consistency indices in their machine learning research on diagnostic assessments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emergent effects of synaptic connectivity on the dynamics of global and local slow waves in a large-scale thalamocortical network model of the human brain.

Slow-wave sleep (SWS), characterized by slow oscillations (SO, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the understanding of how global and local SO emerges from micro-scale neuron dynamics and network connectivity remains unclear. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and slow-wave sleep, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. Increase of the overall synaptic strength led to synchronized global SO, while decrease of synaptic connectivity produced only local slow-waves that would not propagate beyond local area. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

Use of Residual Malt from an Artisanal Beer Brewing Process in the Biosynthesis of Silver Nanoparticles Mediated by Nucleating and Structure-Directing Agents.

Biosynthesized silver nanoparticles (AgNPs) are widely used in varied applications, which are morphology dependent. Consequently, a morphology-controlled synthesis is mandatory. Although there are several studies focused on the plant extract-based biosynthesis of metallic nanoparticles, the use of extracts obtained from agro-wastes is scant. Furthermore, information regarding morphology modification through the use of additional agents is even more scarce. Thus, in this study, AgNPs were synthesized using a malt extract (ME) obtained from an artisanal beer brewing process residue. Additionally, sodium chloride (NaCl), gum arabic (GA), and talc (T) were used in an attempt to modify the morphology of AgNPs. XRD, DLS, SEM, and TEM results demonstrate that stable AgNPs of different sizes and shapes were synthesized. FTIR, HPLC analysis, and the quantification of total proteins, free amino acids, reducing sugars, and total polyphenols before and after AgNPs synthesis showed that ME biomolecules allowed them to act as a source of reducing and stabilizing agents. Therefore, this study provides evidence that ME can be successfully used to biosynthesize AgNPs. Additionally, the antibacterial activity of AgNPs against Gram-negative and Gram-positive bacteria was evaluated. Results indicate that AgNPs show a higher antibacterial activity against Gram-positive bacteria.

Environmental evaluation of the Reloncaví estuary in southern Chile based on lipophilic shellfish toxins as related to harmful algal blooms.

The Reloncaví estuary in southern Chile is famous for its aquaculture. However, recurring harmful algal blooms have adversely affected mussel production. Therefore, regular monitoring of algal toxins is urgently needed to better understand the contamination status of the estuary. In this study, we quantified 15 types of lipophilic shellfish toxins in Metri Bay in the Reloncaví estuary on a biweekly basis for 4 years. We identified algal species using microscopy and metabarcoding analysis. We also measured water temperature, salinity, chlorophyll-a, and dissolved oxygen to determine the potential relationships of these parameters with algal toxin production. Our results revealed the presence of a trace amount of pectenotoxin and the causal phytoplankton Dinophysis, as well as yessotoxin and the causal phytoplankton Protoceratium. Statistical analysis indicated that fluctuations in water temperature affected the detection of these toxins. Additionally, metabarcoding analysis detected the highly toxic phytoplankton Alexandrium spp. in some samples. Although our results suggest that the level of lipophilic shellfish toxins in Metri Bay during the study period was insignificantly low using our current LC-MS method, the confirmed presence of highly toxic algae in Metri Bay raises concerns, given that favorable environmental conditions could cause blooms.

The Effects of Nebulized Lidocaine on the Laryngeal Adductor Reflex.

The laryngeal adductor reflex (LAR) is a brainstem reflex that closes the vocal fold and constitutes a new method for continuously monitoring the vagus and laryngeal nerves during different surgeries. Previous reports concluded that topical lidocaine in spray inhibited LAR responses. However, topical anesthesia in the upper airway may be necessary in awake intubation. We present six patients who underwent neck endocrine surgery due to an intrathoracic goiter that compromised the airway. Before awake intubation, a nebulization of lidocaine 5% was applied for at least 10 min. The intubation procedure was well tolerated, and bilateral LAR with suitable amplitudes for monitoring was obtained in all cases. In our series, the nebulization of lidocaine 5% did not affect the laryngeal adductor reflex. Laryngoscope, 134:4161-4164, 2024.

Latex vascular injection as method for enhanced neurosurgical training and skills.

Background: Tridimensional medical knowledge of human anatomy is a key step in the undergraduate and postgraduate medical education, especially in surgical fields. Training simulation before real surgical procedures is necessary to develop clinical competences and to minimize surgical complications. Methods: Latex injection of vascular system in brain and in head-neck segment is made after washing out of the vascular system and fixation of the specimen before and after latex injection. Results: Using this latex injection technique, the vascular system of 90% of brains and 80% of head-neck segments are well-perfused. Latex-injected vessels maintain real appearance compared to silicone, and more flexible vessels compared to resins. Besides, latex makes possible a better perfusion of small vessels. Conclusions: Latex vascular injection technique of the brain and head-neck segment is a simulation model for neurosurgical training based on real experiencing to improve surgical skills and surgical results.

Sources and profiles of toxins in shellfish from the south-central coast of Chile (36°â€’ 43° S).

The study of marine toxins in shellfish is of the utmost importance to ensure people's food safety. Marine toxins in shellfish and microalgae in the water column off the south-central coast of Chile (36°â€’43° S) were studied in a network of 64 stations over a 14-month period. The relative abundance of harmful species Alexandrium catenella, Alexandrium ostenfeldii, Protoceratium reticulatum, Dinophysis acuminata, Dinophysis acuta, Pseudo-nitzschia seriata group and P. delicatissima group was analyzed. The detection and quantification of lipophilic toxins and domoic acid (DA) in shellfish was determined by UHPLC-MS/MS, and for Paralytic Shellfish Toxins (PSTs) by HPLC-FD with post-column oxidation, while for a culture of A. ostenfeldii a Hylic-UHPLC-MS/MS was used. Results showed that DA, gonyautoxin (GTX)-2, GTX-3 and pectenotoxin (PTX)-2 were detected below the permitted limits, while Gymnodimine (GYM)-A and 13-desmethylespirolide C (SPX-1) were below the limit of quantitation. According to the distribution and abundance record of microalgae, DA would be associated to P. seriata and P. delicatissima-groups, PTX-2 to D. acuminata, and GTX-2, GTX-3, GYM-A, and SPX-1 to A. ostenfeldii. However, the toxin analysis of an A. ostenfeldii culture from the Biobío region only showed the presence of the paralytic toxins C2, GTX-2, GTX-3, GTX-5 and saxitoxin, therefore, the source of production of GYM and SPX is still undetermined.

Monoclonal gammopathy of renal significance: An atypical presentation of Waldenström's disease.

Waldenström's disease is a rare lymphoproliferative syndrome in the bone marrow and sometimes in lymphoid organs which secretes high amounts of monoclonal immunoglobulin M into serum. It can remain indolent for years and rarely affects the kidney, with intraglomerular rather than intratubular damage being predominant, in contrast to multiple myeloma. Different studies identified AL amyloidosis as the most frequent renal lesion, followed by cryoglobulinemic glomerulonephritis. Signs and symptoms may be unspecific, as well as renal manifestations, so collaboration between nephrologists, hematologists, and pathologists is crucial to establish the role of paraprotein in the development of renal damage. We present an atypical case of Waldenström's disease that had a minimal monoclonal peak and clinically debuted with nephritic and nephrotic syndromes. The diagnosis was cryoglobulinemic glomerulonephritis. Currently, there are numerous treatment options, without enough evidence yet to establish a standardised treatment.

Genetically divergent Francisella philomiragia associated with septic arthritis, Montevideo, Uruguay.

Here we report a case of septic arthritis associated with a genetically divergent Francisella philomiragia strain in a patient with chronic rheumatoid arthritis and Adult-onset Still's disease (AOSD) in Maldonado, Uruguay. In this study mass spectrometry together with whole-genome sequencing using Oxford Nanopore technology allowed for the correct identification of the etiologic agent.

Phosphorylation of pyruvate dehydrogenase inversely associates with neuronal activity.

For decades, the expression of immediate early genes (IEGs) such as FOS has been the most widely used molecular marker representing neuronal activation. However, to date, there is no equivalent surrogate available for the decrease of neuronal activity. Here, we developed an optogenetic-based biochemical screen in which population neural activities can be controlled by light with single action potential precision, followed by unbiased phosphoproteomic profiling. We identified that the phosphorylation of pyruvate dehydrogenase (pPDH) inversely correlated with the intensity of action potential firing in primary neurons. In in vivo mouse models, monoclonal antibody-based pPDH immunostaining detected activity decreases across the brain, which were induced by a wide range of factors including general anesthesia, chemogenetic inhibition, sensory experiences, and natural behaviors. Thus, as an inverse activity marker (IAM) in vivo, pPDH can be used together with IEGs or other cell-type markers to profile and identify bi-directional neural dynamics induced by experiences or behaviors.

Revealing subgroup-specific mechanisms of change via moderated mediation: A meditation intervention example.

OBJECTIVE: Effective psychosocial interventions exist for numerous mental health conditions. However, despite decades of research, limited progress has been made in clarifying the mechanisms that account for their beneficial effects. We know that many treatments work, but we know relatively little about why they work. Mechanisms of change may be obscured due to prior research collapsing across heterogeneous subgroups of patients with differing underlying mechanisms of response. Studies identifying baseline individual characteristics that predict differential response (i.e., moderation) may inform research on why (i.e., mediation) a particular subgroup has better outcomes to an intervention via tests of moderated mediation. METHOD: In a recent randomized controlled trial comparing a 4-week meditation app with a control condition in school system employees (N = 662), we previously developed a "Personalized Advantage Index" (PAI) using baseline characteristics, which identified a subgroup of individuals who derived relatively greater benefit from meditation training. Here, we tested whether the effect of mindfulness acquisition in mediating group differences in outcome was moderated by PAI scores. RESULTS: A significant index of moderated mediation (IMM = 1.22, 95% CI [0.30, 2.33]) revealed that the effect of mindfulness acquisition in mediating group differences in outcome was only significant among those individuals with PAI scores predicting relatively greater benefit from the meditation app. CONCLUSIONS: Subgroups of individuals may differ meaningfully in the mechanisms that mediate their response to an intervention. Considering subgroup-specific mediators may accelerate progress on clarifying mechanisms of change underlying psychosocial interventions and may help inform which specific interventions are most beneficial for whom. (PsycInfo Database Record (c) 2024 APA, all rights reserved).