EEG functional connectivity as a Riemannian mediator: An application to malnutrition and cognition.

Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.

Frailty and Cancer Prognosis.

PURPOSE OF REVIEW: This review aims to summarize the current evidence regarding the prognostic role of frailty in older patients diagnosed with cancer and to explore the evidence regarding its prognostic implications in cancer survivors. RECENT FINDINGS: Frailty has been consistently associated with mortality/overall survival, postoperative complications, short- and long-term postoperative mortality, length of stay, among other adverse health-related outcomes in several oncological contexts. The possible association between frailty and treatment toxicity has been less explored, however most studies suggest frailty is a predictor of treatment induced toxicity. In addition, in cancer survivors, frailty is a risk factor for cardiovascular disease, incident type 2 diabetes mellitus, mortality, altered cognitive performance and increased symptom severity. Due to its usefulness in establishing prognosis and informing treatment decision making, it is expected that frailty screening and assessment will continue to gain popularity as part of the pretreatment evaluation of older patients with cancer.

Microbiota unbalance in relation to high-risk human papillomavirus cervical infection.

OBJECTIVES: To assess vaginal dysfunction using basic vaginal states and the presence of lactobacillary microbiota in patients with human papillomavirus (HPV) infection with no squamous intra-epithelial lesions (SIL), with low-grade squamous intra-epithelial lesions (L-SIL), and with high-grade squamous intra-epithelial lesions (H-SIL) or squamous cell carcinoma compared with a control group (HPV-negative); to establish the prevalence of bacterial vaginosis, candidiasis, and trichomoniasis in the different age groups; and to characterize the species of lactobacilli according to the type of lesion. METHODS: A cross-sectional study was carried out of patients who underwent clinical examination and collection of vaginal fornixes to study basic vaginal states and culture. Species identification of lactobacilli was performed by mass spectrometry. The results were analyzed using the χ2 and Fisher's tests; p<0.05 was considered significant. High-risk viral types were determined using a multiplex real-time polymerase chain reaction test. RESULTS: A total of 741 patients were analyzed and divided into three age groups: Group 1 aged 18-24 years (n=138), Group 2 aged 25-50 years (n=456), and Group 3 aged >50 years (n=147). All groups were further divided into an HPV-negative (control) group and an HPV-positive group without lesions, with L-SIL, or with H-SIL/squamous cell carcinoma. The prevalence of unbalanced basic vaginal states in patients with H-SIL/squamous cell carcinoma was 72.7% (p=0.03) in Group 1, 53.1% (p=0.05) in Group 2, and no cases of unbalance were detected in Group 3. The prevalence of bacterial vaginosis in women with H-SIL/squamous cell carcinoma in Group 1 was 54.5% and in Group 2 was 43.7%. Patients with H-SIL/squamous cell carcinoma had a prevalence of 21.4% of Lactobacillus crispatus, 42.9% of L. jensenii, and 14.3% of L. iners. CONCLUSIONS: A greater unbalance of vaginal microbiota was observed in patients with SIL, especially in those with H-SIL/squamous cell carcinoma. In this group, an increase in L. jensenii and L. iners compared with control was found. L. crispatus had a similar prevalence to the control group. It is important to characterize the lactobacilli species since the unbalance alters the vaginal microenvironment and acts as a co-factor in the persistence of HPV infection.

Polarizing white light interferometry for phase measurements using two simultaneous interferograms.

Our research introduces a design for a polarization phase-shifting white light interferometric system (PPS-WLIS) that operates in a transmissive mode for measuring the slope phase of transparent objects. It comprises a cyclic path interferometer (lateral shear interferometer) coupled with a multiplexing Michelson interferometer. The system uses polarization to produce two parallel interferograms with polarization modulated with relative shifts simultaneously. To determine the optical phase, we used a two-step algorithm for phase demodulation that does not necessitate precise phase shifts, making the system more straightforward to operate. As a result, we could observe variations in the object associated with optical phase changes. Furthermore, our method simplifies the phase-shift interferometry process by requiring only one capture, making it an effective way to examine objects at dynamic events. As an illustration, we demonstrated the temperature measurement generated by a section of a candle flame.

Effect of the Protein Corona Formation on Antibody Functionalized Liquid Lipid Nanocarriers.

The main aim of this study is to report basic knowledge on how a protein corona (PC) could affect or modify the way in which multifunctionalized nanoparticles interact with cells. With this purpose, we have firstly optimized the development of a target-specific nanocarrier by coupling a specific fluorescent antibody on the surface of functionalized lipid liquid nanocapsules (LLNCs). Thus, an anti-HER2-FITC antibody (αHER2) has been used, HER2 being a surface receptor that is overexpressed in several tumor cells. Subsequently, the in vitro formation of a PC has been developed using fetal bovine serum supplemented with human fibrinogen. Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Laser Doppler Electrophoresis (LDE), and Gel Chromatography techniques have been used to assure a complete physico-chemical characterization of the nano-complexes with (LLNCs-αHER2-PC) and without (LLNCs-αHER2) the surrounding PC. In addition, cellular assays were performed to study the cellular uptake and the specific cellular-nanocarrier interactions using the SKBR3 (high expression of HER2) breast cancer cell line and human dermal fibroblasts (HDFa) (healthy cell line without expression of HER2 receptors as control), showing that the SKBR3 cell line had a higher transport rate (50-fold) than HDFa at 60 min with LLNCs-αHER2. Moreover, the SKBR3 cell line incubated with LLNCs-αHER2-PC suffered a significant reduction (40%) in the uptake. These results suggest that the formation of a PC onto LLNCs does not prevent specific cell targeting, although it does have an important influence on cell uptake.

Valoration of the Synthetic Antioxidant Tris-(Diterbutyl-Phenol)-Phosphite (Irgafos P-168) from Industrial Wastewater and Application in Polypropylene Matrices to Minimize Its Thermal Degradation.

Industrial wastewater from petrochemical processes is an essential source of the synthetic phenolic phosphite antioxidant (Irgafos P-168), which negatively affects the environment. For the determination and analysis of Irgafos P-168, DSC, HPLC-MS, and FTIR methodologies were used. Solid phase extraction (SPE) proved to be the best technique for extracting Irgafos from wastewater. HPLC-MS and SPE determined the repeatability, reproducibility, and linearity of the method and the SPE of the standards and samples. The relative standard deviations, errors, and correlation coefficients for the repeatability and reproducibility of the calibration curves were less than 4.4% and 4.2% and greater than 0.99955, respectively. The analysis of variance (ANOVA), using the Fisher method with confidence in 95% of the data, did not reveal significant differences between the mentioned parameters. The removal of the antioxidant from the wastewater by SPE showed recovery percentages higher than 91.03%, and the chemical characterization of this antioxidant by FTIR spectroscopy, DSC, TGA, and MS showed it to be structurally the same as the Irgafos P-168 molecule. The recovered Irgafos was added to the polypropylene matrix, significantly improving its oxidation times. An OIT analysis, performed using DSC, showed that the recovered Irgafos-blended polypropylene (PP) demonstrated oxidative degradation at 8 min. With the addition of the Irgafos, the oxidation time was 13 min. This increases the polypropylene's useful life and minimizes the environmental impact of the wastewater.

Early protein energy malnutrition impacts life-long developmental trajectories of the sources of EEG rhythmic activity.

Protein Energy Malnutrition (PEM) has lifelong consequences on brain development and cognitive function. We studied the lifelong developmental trajectories of resting-state EEG source activity in 66 individuals with histories of Protein Energy Malnutrition (PEM) limited to the first year of life and in 83 matched classmate controls (CON) who are all participants of the 49 years longitudinal Barbados Nutrition Study (BNS). qEEGt source z-spectra measured deviation from normative values of EEG rhythmic activity sources at 5-11 years of age and 40 years later at 45-51 years of age. The PEM group showed qEEGt abnormalities in childhood, including a developmental delay in alpha rhythm maturation and an insufficient decrease in beta activity. These profiles may be correlated with accelerated cognitive decline.

Harmonized-Multinational qEEG norms (HarMNqEEG).

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

Motivations and concerns of patients considering participation in an implementation study of a hereditary cancer risk assessment program in diverse primary care settings.

PURPOSE: Understanding the motivations and concerns of patients from diverse populations regarding participation in implementation research provides the needed evidence about how to design and conduct studies for facilitating access to genetics services. Within a hereditary cancer screening study assessing a multifaceted intervention, we examined primary care patients' motivations and concerns about participation. METHODS: We surveyed and interviewed study participants after they enrolled, surveyed those who did not complete enrollment, and used descriptive qualitative and quantitative methods to identify motivations and concerns regarding participation. RESULTS: Survey respondents' most common motivations included a desire to learn about their future risk (81%), receiving information that may help family (58%), and a desire to advance research (34%). Interviews revealed 3 additional important factors: affordability of testing, convenience of participation, and clinical relationships supporting research decision-making. Survey data of those who declined enrollment showed that the reasons for declining included concerns about privacy (38%), burdens of the research (19%), and their fear of not being able to cope with the genetic information (19%). CONCLUSION: Understanding the facilitating factors and concerns that contribute to decisions about research may reveal ways to improve equity in access to care and research that could lead to greater uptake of genomic medicine across diverse primary care patient populations.

Factors Associated with Nonattendance to a Geriatric Clinic among Mexican Older Adults.

INTRODUCTION: Outpatient appointment nonattendance (NA) represents a public health problem, increasing the risk of unfavorable health-related outcomes. Although NA is significant among older adults, little is known regarding its correlates. This study aimed to identify the correlates (including several domains from the geriatric assessment) of single and repeated NA episodes in a geriatric medicine outpatient clinic, in general and in the context of specific comorbidities. METHODS: This is a cross-sectional study including data from 3,034 older adults aged ≥60 years with ≥1 scheduled appointments between January 1, 2016, and December 31, 2016. Appointment characteristics as well as sociodemographic, geographical, and environmental information were obtained. Univariate and multivariate multinomial regression analyses were carried out. RESULTS: The mean age was 81.8 years (SD 7.19). Over a third (37.4%) of participants missed one scheduled appointment, and 14.4% missed ≥2. Participants with a history of stroke (OR 1.336, p = 0.041) and those with a greater number of scheduled appointments during the study time frame (OR 1.182, p < 0.001) were more likely to miss one appointment, while those with Parkinson's disease (OR 0.346, p < 0.001), other pulmonary diseases (OR 0.686, p = 0.008), and better functioning for activities of daily living (ADL) (OR 0.883, p < 0.001) were less likely to do so. High socioeconomic level (OR 2.235, p < 0.001), not having a partner (OR 1.410, p = 0.006), a history of fractures (OR 1.492, p = 0.031), and a greater number of scheduled appointments (OR 1.668, p < 0.001) increased the risk of repeated NA, while osteoarthritis (OR 0.599, p = 0.001) and hypertension (OR 0.680, p = 0.002) decreased it. In specific comorbidity populations (hypertension, type 2 diabetes mellitus, and cancer), better ADL functioning protected from a single NA, while better mobility functioning protected from repeated NA in older patients with hypertension and cancer. DISCUSSION/CONCLUSION: Identifying geriatric factors linked to an increased probability of NA may allow one to anticipate its likelihood and lead to the design and implementation of preventive strategies and to an optimization of the use of available health resources. The impact of these factors on adherence to clinical visits requires further investigation.

Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews.

BACKGROUND: Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral - a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study. METHODS: Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard. We conducted semi-structured interviews with participants about barriers and facilitators to tool use and overall tool acceptability; interviews were recorded and professionally transcribed. Transcripts were coded based on a codebook developed using inductive techniques, and coded excerpts were reviewed to identify overarching themes related to barriers and facilitators to family history self-assessment and acceptability of the study tool. RESULTS: Interviewees endorsed the tool as easy to navigate and understand. However, they described barriers related to family history information, literacy and language, and certain tool functions. Participants offered concrete, easy-to-implement solutions to each barrier. Despite experience barriers to use of the tool, most participants indicated that electronic family history self-assessment was acceptable or preferable in comparison to clinician-collected family history. CONCLUSIONS: Even for participants who experienced barriers to tool use, family history self-assessment was considered an acceptable alternative to clinician-collected family history. Barriers experienced could be overcome with minor adaptations to the current family history tool. TRIAL REGISTRATION: This study is a sub-study of the Cancer Health Assessments Reaching Many (CHARM) trial, ClinicalTrials.gov, NCT03426878. Registered 8 February 2018.

Retrospective assessment of barriers and access to genetic services for hereditary cancer syndromes in an integrated health care delivery system.

BACKGROUND: A critical step in access to genetic testing for hereditary cancer syndromes is referral for genetic counseling to assess personal and family risk. Individuals meeting testing guidelines have the greatest need to be evaluated. However, referrals to genetics are underutilized in US patients with hereditary cancer syndromes, especially within traditionally underserved populations, including racial and ethnic minorities, low-income, and non-English speaking patients. METHODS: We studied existing processes for referral to genetic evaluation and testing for hereditary cancer risk to identify areas of potential improvement in delivering these services, especially for traditionally underserved patients. We conducted a retrospective review of 820 referrals to the Kaiser Permanente Northwest (KPNW) genetics department containing diagnosis codes for hereditary cancer risk. We classified referrals as high- or low-quality based on whether sufficient information was provided to determine if patients met national practice guidelines for testing. Through chart abstraction, we also assessed consistency with practice guidelines, whether the referral resulted in a visit to the genetics department for evaluation, and clinical characteristics of patients receiving genetic testing. RESULTS: Most referrals (n = 514, 63%) contained sufficient information to assess the appropriateness of referral; of those, 92% met practice guidelines for genetic testing. Half of referred patients (50%) were not offered genetic evaluation; only 31% received genetic testing. We identified several barriers to receiving genetic evaluation and testing, the biggest barrier being completion of a family history form sent to patients following the referral. Those with a referral consistent with testing guidelines, were more likely to receive genetic testing than those without (39% vs. 29%, respectively; p = 0.0058). Traditionally underserved patients were underrepresented in those receiving genetic evaluation and testing relative to the overall adult KPNW population. CONCLUSIONS: Process improvements are needed to increase access to genetic services to diagnose hereditary cancer syndromes prior to development of cancer.

Molecular Recognition of Surface Trans-Sialidases in Extracellular Vesicles of the Parasite Trypanosoma cruzi Using Atomic Force Microscopy (AFM).

Trans-sialidases (TS) are important constitutive macromolecules of the secretome present on the surface of Trypanosoma cruzi (T. cruzi) that play a central role as a virulence factor in Chagas disease. These enzymes have been related to infectivity, escape from immune surveillance and pathogenesis exhibited by this protozoan parasite. In this work, atomic force microscopy (AFM)-based single molecule-force spectroscopy is implemented as a suitable technique for the detection and location of functional TS on the surface of extracellular vesicles (EVs) released by tissue-culture cell-derived trypomastigotes (Ex-TcT). For that purpose, AFM cantilevers with functionalized tips bearing the anti-TS monoclonal antibody mAb 39 as a sense biomolecule are engineered using a covalent chemical ligation based on vinyl sulfonate click chemistry; a reliable, simple and efficient methodology for the molecular recognition of TS using the antibody-antigen interaction. Measurements of the breakdown forces between anti-TS mAb 39 antibodies and EVs performed to elucidate adhesion and forces involved in the recognition events demonstrate that EVs isolated from tissue-culture cell-derived trypomastigotes of T. cruzi are enriched in TS. Additionally, a mapping of the TS binding sites with submicrometer-scale resolution is provided. This work represents the first AFM-based molecular recognition study of Ex-TcT using an antibody-tethered AFM probe.

Hybrid Cements: Mechanical Properties, Microstructure and Radiological Behavior.

The use of more eco-efficient cements in concretes is one of the keys to ensuring construction industry sustainability. Such eco-efficient binders often contain large but variable proportions of industrial waste or by-products in their composition, many of which may be naturally occurring radioactive materials (NORMs). This study explored the application of a new gamma spectrometric method for measuring radionuclide activity in hybrid alkali-activated cements from solid 5 cm cubic specimens rather than powder samples. The research involved assessing the effect of significant variables such as the nature of the alkaline activator, reaction time and curing conditions to relate the microstructures identified to the radiological behavior observed. The findings showed that varying the inputs generated pastes with similar reaction products (C-S-H, C-A-S-H and (N,C)-A-S-H) but different microstructures. The new gamma spectrometric method for measuring radioactivity in solid 5 cm cubic specimens in alkaline pastes was found to be valid. The variables involved in hybrid cement activation were shown to have no impact on specimen radioactive content. The powder samples, however, emanated 222Rn (a descendent of 226Ra), possibly due to the deformation taking place in fly ash structure during alkaline activation. Further research would be required to explain that finding.

Prevalence of thyroid dysfunction in healthy adults according to the estimated iodine intake in 24-hour urine samples: The SALMEX cohort.

PURPOSE: The aim of this study was to evaluate the prevalence of thyroid dysfunction in a cohort of healthy individuals in Mexico City, as well as to investigate the potential associations of these results with their estimated iodine intake (EII) as reflected by their 24-hour urinary iodine excretion (24-h UIE). METHODS: From the SALMEX cohort, 683 adults provided an appropriate 24-h urine sample. Thyroid function tests and thyroid antibody concentrations were determined in the participants' sera. We analyzed discrepancies between the commonly used urinary parameters to determine the iodine intake status and the performance of thyroglobulin (Tg) as a biomarker of its status in the adult population. RESULTS: The prevalence of dysthyroidism was high, being similar to other studies. Subclinical hypothyroidism was detected in 5.0% of individuals, clinical hypothyroidism in 1.8% of individuals, and sub-clinical hyperthyroidism in 2.8% of individuals. The median EII was 285 µg/d (IQR 215.0-369.0); 94% of individuals had EII >150 µg/d recommended daily allowance (RDA) in adults. The urinary iodine concentration (UIC) and the UIE had relative biases in their averages of 34.4%. The Tg median was 7.21 ng/mL. The prevalence of increased Tg was 6.15%. There was no correlation between Tg and EII (r= 0.019, p= 0.606). CONCLUSIONS: Thyroid dysfunction was highly prevalent in this population. Our cohort revealed a slight discrepancy between dysthyroidism manifestations and iodine intake markers; the latter represent a population with adequate iodine intake. Further studies are necessary to clearly define the prevalence of thyroid dysfunction as well as the iodine nutritional status in Mexico.

Assessment of bacteriophage vB_Pd_PDCC-1 on bacterial dynamics during ontogenetic development of the longfin yellowtail (Seriola rivoliana).

The Seriola genus includes species of worldwide commercial importance due to its rapid growth and easy adaptability to confinement conditions. However, like other fish species, large mortalities occur during their early life stages, where the main problems are caused by opportunistic bacteria. Disease control strategies are thus urgently needed. The present study aimed to evaluate the efficacy of phage vB_Pd_PDCC-1 during the early development of longfin yellowtail (Seriola rivoliana), as well as its effect on microbial communities. This broad-host-range phage was added to the culture every 3 days starting from the egg-stage until 12 days after hatching (DAH) at a concentration of 1.41×1010 plaque-forming units (PFU) per mL and at a multiplicity of infection (MOI) of 1. The results showed positive effects (p<0.05) on egg hatching, survival, growth, and pigmentation area in treated larvae. Moreover, high-throughput sequencing analysis of 16S rRNA genes showed that phage administration did not produce significant changes (p>0.05) in the composition and structure of the associated microbiota. However, sequences affiliated to the Gammaproteobacteria class were displaced by those belonging to the Alphaproteobacteria class over time regardless of the treatment received. At the family level, there was a decrease in Rhodobacteraceae, Pseudoalteromonadaceae, and Flavobacteriaceae in both groups over time. To our best knowledge, this study represents the first attempt to evaluate the effect of a phage as a biological control agent during ontogenetic development of longfin yellowtail larvae. KEY POINTS: • Phages can be used against proliferation of Vibrio in fish cultures. • Seriola includes several important commercial fish species due to its rapid growth. • Phages do not cause significant changes in the associated microbiota.

Electroencephalographic and morphometric abnormalities in psychopath offenders.

The main goals of the present study were to replicate and extend current knowledge related to paralimbic dysfunctions associated with psychopathy. The research evaluated the quantitative electroencephalography, current density (CD) source and synchronization likelihood analysis during the rest condition and structural magnetic resonance imaging images to compare volumetric and cortical thickness, in inmates recruited from two prisons located in Havana City. The Psychopathy Checklist-Revised (PCL-R) was used as a quantitative measure of psychopathy. This study showed most beta energy and less alpha activity in male psychopath offenders. Low-resolution electromagnetic tomography signified an increase of beta activity in psychopath offender groups within paralimbic regions. The superior temporal gyrus volume was associated with the F1 factor while the fusiform, anterior cingulate and associative occipital areas were primarily associated with the F2 factor of PCL-R scale. Cortical thickness in the left dorsal anterior cingulate cortex and the temporal pole was negatively associated with PCL-R total score.

Recent Advances in ZnO-Based Carbon Monoxide Sensors: Role of Doping.

Monitoring and detecting carbon monoxide (CO) are critical because this gas is toxic and harmful to the ecosystem. In this respect, designing high-performance gas sensors for CO detection is necessary. Zinc oxide-based materials are promising for use as CO sensors, owing to their good sensing response, electrical performance, cost-effectiveness, long-term stability, low power consumption, ease of manufacturing, chemical stability, and non-toxicity. Nevertheless, further progress in gas sensing requires improving the selectivity and sensitivity, and lowering the operating temperature. Recently, different strategies have been implemented to improve the sensitivity and selectivity of ZnO to CO, highlighting the doping of ZnO. Many studies concluded that doped ZnO demonstrates better sensing properties than those of undoped ZnO in detecting CO. Therefore, in this review, we analyze and discuss, in detail, the recent advances in doped ZnO for CO sensing applications. First, experimental studies on ZnO doped with transition metals, boron group elements, and alkaline earth metals as CO sensors are comprehensively reviewed. We then focused on analyzing theoretical and combined experimental-theoretical studies. Finally, we present the conclusions and some perspectives for future investigations in the context of advancements in CO sensing using doped ZnO, which include room-temperature gas sensing.

Biophysical and Biochemical Comparison of Extracellular Vesicles Produced by Infective and Non-Infective Stages of Trypanosoma cruzi.

Extracellular vesicles (EVs) are small lipid vesicles released by either any prokaryotic or eukaryotic cell, or both, with a biological role in cell-to-cell communication. In this work, we characterize the proteomes and nanomechanical properties of EVs released by tissue-culture cell-derived trypomastigotes (mammalian infective stage; (TCT)) and epimastigotes (insect stage; (E)) of Trypanosoma cruzi, the etiologic agent of Chagas disease. EVs of each stage were isolated by differential centrifugation and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), electron microscopy and atomic force microscopy (AFM). Measurements of zeta-potential were also included. Results show marked differences in the surface molecular cargos of EVs between both stages, with a noteworthy expansion of all groups of trans-sialidase proteins in trypomastigote's EVs. In contrast, chromosomal locations of trans-sialidases of EVs of epimastigotes were dramatically reduced and restricted to subtelomeric regions, indicating a possible regulatable expression of these proteins between both stages of the parasite. Regarding mechanical properties, EVs of trypomastigotes showed higher adhesion compared to the EVs of epimastigotes. These findings demonstrate the remarkable surface remodeling throughout the life cycle of T. cruzi, which shapes the physicochemical composition of the extracellular vesicles and could have an impact in the ability of these vesicles to participate in cell communication in completely different niches of infection.

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia characterized by epistaxis, mucocutaneous telangiectases, and arteriovenous malformations (AVM) in the visceral organs. The diagnosis of HHT is based on clinical Curaçao criteria, which show limited sensitivity in children and young patients. Here, we carried out a liquid biopsy by which we isolated total RNA from plasma exosome samples. A cohort of 15 HHT type 1 patients, 15 HHT type 2 patients, and 10 healthy relatives were analyzed. Upon gene expression data processing and normalization, a statistical analysis was performed to explore similarities in microRNA expression patterns among samples and detect differentially expressed microRNAs between HHT samples and the control group. We found a disease-associated molecular fingerprint of 35 miRNAs over-represented in HHT vs. controls, with eight being specific for HHT1 and 11 for HHT2; we also found 30 under-represented, including nine distinct for HHT1 and nine for HHT2. The analysis of the receiver operating characteristic (ROC) curves showed that eight miRNAs had good (AUC > 75%) or excellent (AUC > 90%) diagnosis value for HHT and even for type HHT1 and HHT2. In addition, we identified the cellular origin of these miRNAs among the cell types involved in the vascular malformations. Interestingly, we found that only some of them were incorporated into exosomes, which suggests a key functional role of these exosomal miRNAs in the pathophysiology of HHT.