Assessing the performance of commercial serological tests for SARS-CoV-2 diagnosis.

Objectives: The emergence of SARS-CoV-2 has triggered a global pandemic with profound implications for public health. Rapid changes in the pandemic landscape and limitations in in vitro diagnostics led to the introduction of numerous diagnostic devices with variable performance. In this study, we evaluated three commercial serological assays in Brazil for detecting anti-SARS-CoV-2 antibodies. Methods: We collected 90 serum samples from SARS-CoV-2-negative blood donors and 352 from SARS-CoV-2-positive, unvaccinated patients, categorized by symptom onset. Subsequently, we assessed the diagnostic performance of three commercial enzyme immunoassays: GOLD ELISA (enzyme-linked immunosorbent assay) COVID-19 Ig (immunoglobulin) G + IgM, Anti-SARS-CoV-2 NCP IgM ELISA, and Anti-SARS-CoV-2 NCP IgG ELISA. Results: Our findings revealed that the GOLD ELISA COVID-19 IgG + IgM exhibited the highest sensitivity (57.7%) and diagnostic odds ratio, surpassing the manufacturer's reported sensitivity in most analyzed time frames while maintaining exceptional specificity (98.9%). Conversely, the Anti-SARS-CoV-2 NCP IgG ELISA demonstrated lower sensitivity but aligned with independent evaluations, boasting a specificity of 100%. However, the Anti-SARS-CoV-2 NCP IgM ELISA exhibited lower sensitivity than claimed, particularly in samples collected shortly after positive reverse transcription polymerase chain reaction results. Performance improved 15-21 days after symptom onset and beyond 22 days, but in the first week, both Anti-SARS-CoV-2 NCP IgM ELISA and Anti-SARS-CoV-2 NCP IgG ELISA struggled to differentiate positive and negative samples. Conclusions: Our study emphasizes the need for standardized validation protocols to address discrepancies between manufacturer-claimed and actual performance. These insights provide essential information for health care practitioners and policymakers regarding the diagnostic capabilities of these assays in various clinical scenarios.

Optimizing Corn Crop Protection: The First Sampling Plan for Controlling Dalbulus maidis (Hemiptera: Cicadellidae).

Corn (Zea mays) is the most widely planted crop in the world. Dalbulus maidis (Hemiptera: Cicadellidae) is currently a primary corn pest. The starting point for the development of pest control decision-making systems is the determination of a conventional sampling plan. Therefore, this study aimed to determine a practical conventional sampling plan for D. maidis in corn crops. Insect density was evaluated in 28 commercial fields. Subsequently, D. maidis densities were sampled from fields ranging from 1 to 100 ha. Insect density conformed to a negative binomial distribution in 89.29% of the fields. The insect densities determined using the sampling plan had a low error rate (up to 15%). Sampling time and costs ranged from 2.06 to 39.45 min/ha and 0.09 to 1.81 USD/ha for fields of 1-100 ha, respectively. These results provide the first precise and representative conventional sampling plan for scouting D. maidis adults grown in corn fields. Therefore, the conventional sampling plan for D. maidis determined in this study is practical and can be incorporated into integrated pest management programs for corn crops owing to its representativeness, precision, speed, and low cost.

Marine coastal chemistry related to inland inputs in San Jorge gulf and the adjacent north coast.

Coastal regions are sectors where human activities impact the marine ecosystem, and if necessary control measures are not taken, they can generate negative consequences for health and ecosystem services. Within the framework of the Pampa Azul initiative and under the One Health paradigm, the interconnection between the terrestrial and marine environments of the San Jorge Gulf and the adjacent north coast has been studied. In November, 2022, a campaign was carried out aboard the R/V "Mar Argentino" at thirty-four stations near the coast. There, for the first time, simultaneously with in-situ measurements of physical variables, macronutrients (NO3-, PO4-3, Si(OH)4 and NH4+), particulate silica (BSi and LSi), trace metals in the particulate material (Cd, Cu, Cr, Fe and Pb) and the phytoplankton community were analyzed. The results showed a high nutrient dynamic, with a significant influence of natural stratification and anthropogenic condition due to the discharge of effluents off the cities of Comodoro Rivadavia and Caleta Olivia. Under natural conditions, NO3- and Si(OH)4 limited the surface primary production by 47 % and 41 %, respectively. Additionally, due to the anthropogenic contribution, NH4+ concentration reached 3 µM, increasing the proliferation of nanophytoplankton, among other consequences. As a result of nutrient dynamics, the uptake of Si(OH)4, the growth rate of diatoms and their production of BSi were decoupled. Furthermore, a significant correlation between LSi and Fe in particulate matter was evidenced, opening new lines of research that relate dust storms to primary productivity in this marine environment. The measured concentrations of trace metals do not appear to be a biological risk; however, contamination by Cd (37.6 µg g- 1 d.w.) and Cu (214.97 µg g- 1 d.w.) off Camarones poses a significant concern that must be addressed in the immediate future.

Shelf life effects on the bond strength and microhardness of self-adhesive resin cements.

Background: Among the main advantages of self-adhesive resin cements comprise good aesthetics, strong restoration-tooth bond and biocompatibility. However, some disadvantages, such as high viscosity level, color limitation and short shelf life should be mentioned. Thus, the aim of the current study was to assess bond strength between fiberglass post and root dentin in teeth subjected to self-adhesive resin cements with expired shelf life and hardness. Material and Methods: Sixty (60) single-rooted human teeth were sectioned and divided into 2 groups of different cements: U200 3M and MaxCem Elite Kerr. Each group was divided into 3 subgroups, based on self-adhesive resin cements' shelf life, namely: Within the use-time recommended by the manufacturer or no expiration date; 6 months after opening the aluminum blister; 12 months after opening the aluminum blister. Bond strength was measured through push-out test conducted in universal testing machine; fracture pattern was analyzed, and microhardness was investigated through Knoop test, based on hardness readings. Data were subjected to Shapiro-Wilk normality test; nonparametric test was applied to hardness data, whereas parametric test was applied to bond strength data. Hardness data were subjected to Kruskal-Wallis test, whereas bond strength data were subjected to analysis of variance, which was followed by Tukey test; both tests were conducted at 5% significance level (α = 0.05). Results: There was no statistically significant difference in knoop hardness values recorded for the material / time / root thirds combination (p=0.483). There was no statistically significant difference in bond strength values recorded for the Material / Time / Thirds combination (p=0.237). Conclusions: It was possible concluding that shelf life did not influence material's hardness and bond strength. Key words:Dental cements, Resin Cements, Shelf Life of Products.

A Nasal Vaccine Candidate, Containing Three Antigenic Regions from SARS-CoV-2, to Induce a Broader Response.

A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli. The N fragment belongs to the C-terminal domain whereas the S2 fragment spans the fibre structure in the post-fusion conformation of the spike protein. The resultant protein, named S2NDH, was able to form spherical particles of 10 nm, which forms aggregates upon mixture with the CpG ODN-39M. Both preparations were recognized by positive COVID-19 human sera. The S2NDH + ODN-39M formulation administered by the intranasal route resulted highly immunogenic in Balb/c mice. It induced cross-reactive anti-N humoral immunity in both sera and bronchoalveolar fluids, under a Th1 pattern. The cell-mediated immunity (CMI) was also broad, with positive response even against the N protein of SARS-CoV-1. However, neither neutralizing antibodies (NAb) nor CMI against the S2 region were obtained. As alternative, the RBD protein was included in the formulation as inducer of NAb. Upon evaluation in mice by the intranasal route, a clear adjuvant effect was detected for the S2NDH + ODN-39M preparation over RBD. High levels of NAb were induced against SARS-CoV-2 and SARS-CoV-1. The bivalent formulation S2NDH + ODN-39M + RBD, administered by the intranasal route, constitutes an attractive proposal as booster vaccine of sarbecovirus scope.

In vitro antimicrobial, antibiofilm photodynamic activity, and molecular dynamic simulations of tetra-cationic porphyrinmembrane interactions against foodborne microorganisms.

This manuscript presents a new report on the in vitro antimicrobial photo-inactivation of foodborne microorganisms (Salmonella spp. and Listeria monocytogenes) using tetra-cationic porphyrins. Isomeric tetra-cationic porphyrins (3MeTPyP, 4MeTPyP, 3PtTPyP, and 4PtTPyP) were tested, and antimicrobial activity assays were performed at specific photosensitizer concentrations under dark and white-light LED irradiation conditions. Among the tested bacterial strains, 4MeTPyP exhibited the highest efficiency, inhibiting bacterial growth within just 60 min at low concentrations (17.5 µM). The minimal inhibitory concentration of 4MeTPyP increased when reactive oxygen species scavengers were present, indicating the significant involvement of singlet oxygen species in the photooxidation mechanism. Furthermore, the checkerboard assay testing the association of 4MeTPyP showed an indifferent effect. Atomic force microscopy analyses and dynamic simulations were conducted to enhance our understanding of the interaction between this porphyrin and the strain's membrane.

Perspectives of healthcare professionals on training for quantitative G6PD testing during implementation of tafenoquine in Brazil (QualiTRuST Study).

Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.

Simplified and Detailed Evaluation of the Uncertainty of the Measurement of Microbiological Contamination of Pharmaceutical Products.

BACKGROUND: The control of the microbial contamination of pharmaceutical products, PP, is crucial to ensure their safety and efficacy. The validity of the monitoring of such contamination depends on the uncertainty of this quantification. Highly uncertain quantifications due to the variability of determinations or the magnitude of systematic effects affecting microbial growth or other analytical operations make analysis unfit for the intended use. The quantification of the measurement uncertainty expressing the combined effects of all random and systematic effects affecting the analysis allows the sound decision about quantification adequacy for their intended use. The complexity of the quantification of microbial analysis uncertainty led to the development of simplified ways of performing this evaluation. OBJECTIVE: This work assesses the adequacy of the simplified quantification of the uncertainty of the determination of the microbial contamination of PP by log transforming microbial count and dilution factor of the test sample whose uncertainty is combined in a log scale using the uncertainty propagation law. METHODS: This assessment is performed by a parallel novel bottom-up and accurate evaluation of microbial analysis uncertainty involving the Monte Carlo Method simulation of the Poisson log-normal distribution of counts and of the normally distributed measured volumes involved in the analysis. Systematic effects are assessed and corrected on results to compensate for their impact on the determinations. Poisson regression is used to predict precision affecting determinations on unknown test samples. RESULTS AND CONCLUSION: This work concludes that triplicate determinations are required to produce results with adequately low uncertainty and that simplified uncertainty quantification underevaluate or overevaluate the uncertainty from determinations based on low or high colonies numbers, respectively. Therefore, detailed uncertainty evaluations are advised for determinations between 50% and 200% of PP's maximum admissible contamination value.

The impact of social cohesion and risk communication on excess mortality due to COVID-19 in 213 countries: a retrospective analysis.

BACKGROUND: Tools for assessing a country's capacity in the face of public health emergencies must be reviewed, as they were not predictive of the COVID-19 pandemic. Social cohesion and risk communication, which are related to trust in government and trust in others, may have influenced adherence to government measures and mortality rates due to COVID-19. OBJECTIVE: To analyse the association between indicators of social cohesion and risk communication and COVID-19 outcomes in 213 countries. RESULTS: Social cohesion and risk communication, in their dimensions (public trust in politicians, trust in others, social safety nets, and equal distribution of resources index), were associated with lower excess mortality due to COVID-19. The number of COVID-19-related disorder events and government transparency were associated with higher excess mortality due to COVID-19. The lower the percentage of unemployed people, the higher the excess mortality due to COVID-19. Most of the social cohesion and risk communication variables were associated with better vaccination indicators, except for social capital and engaged society, which had no statistically significant association. The greater the gender equality, the better the vaccination indicators, such as the number of people who received all doses. CONCLUSION: Public trust in politicians, trust in others, equal distribution of resources and government that cares about the most vulnerable, starting with the implementation of programs, such as cash transfers and combating food insecurity, were factors that reduced the excess mortality due to COVID-19. Countries, especially those with limited resources and marked by social, economic, and health inequalities, must invest in strengthening social cohesion and risk communication, which are robust strategies to better cope with future pandemics.

Harmonização orofacial: evolução normativa e conflitos legais no reconhecimento da especialidade / Orofacial harmonization: normative evolution and legal conflicts for the recognition of the specialty

A Harmonização Orofacial (HOF) é especialidade odontológica reconhecida pelo Conselho Federal de Odontologia (CFO) e, no reconhecimento dessa especialidade, discussões internas e externas à classe odontológica surgiram. O presente artigo tem como objetivo levantar reflexões acerca do processo judicial n° 1003948-83.2019.4.01.3400 julgado pelo Tribunal Regional Federal (Seção Judiciária do Distrito Federal - 8ª Vara Federal) referente a HOF enquanto especialidade odontológica. Inicialmente, são discutidos os documentos que norteiam o ensino dos cursos de graduação e pós-graduação em odontologia. Em seguida, faz-se uma reflexão sobre o processo de reconhecimento da HOF como especialidade odontológica. Por fim, discute-se acerca do citado processo judicial, os principais pontos elencados pelas partes envolvidas no processo e eventuais consequências do desfecho desse processo para a classe odontológica. O reconhecimento da HOF enquanto especialidade odontológica não seguiu os trâmites que outras especialidades odontológicas seguiram e gerou debates educacionais e formativos sob uma perspectiva ética e legal. Ademais, tal reconhecimento fomentou debates relacionados ao conflito dos procedimentos dessa especialidade odontológica com procedimentos de especialidades médicas. Tais conflitos chegaram ao Poder Judiciário, que interveio em favor da Odontologia, contudo, isso não impede que o cirurgião-dentista seja responsabilizado profissionalmente pela realização de procedimentos que fogem ao escopo da odontologia

Orofacial Harmonization (HOF) is dental specialty recognized by the Federal Council of Dentistry (CFO) and, in recognition of this specialty, internal and external discussions of the dental class have arisen. This article aims to raise reflections on judicial process number 1003948-83.2019.4.01.3400 judged by the Federal Regional Court (Judicial Section of the Federal District - 8th Federal Court) referring to HOF as a dental specialty. Initially, the documents that guide the teaching of undergraduate and graduate courses in dentistry are discussed. Then, a reflection is made on the recognition process of HOF as a dental specialty. Finally, it discusses the judicial process number 1003948-83.2019.4.01.3400, the main points listed by the parties involved in the process, and the possible consequences of the outcome of this process for the dental class. The recognition of HOF as a dental specialty did not follow the procedures that other dental specialties followed and generated educational and training debates from an ethical and legal perspective. Furthermore, such recognition has fostered debates related to the conflict between procedures in this dental specialty and procedures in medical specialties. Such conflicts reached the Judiciary, which intervened in favor of Dentistry, however, this does not prevent the dental surgeon from being held professionally responsible for carrying out procedures that fall outside the scope of dentistry

Phylogenetic inferences based on distinct molecular markers reveals a novel Babesia (Babesia pantanalensis nov. sp.) and a Hepatozoon americanum-related genotype in crab-eating foxes (Cerdocyon thous).

Piroplasmids and Hepatozoon spp. Are apicomplexan protozoa that may cause disease in several canid species. The present study aimed to expand the knowledge on the diversity of piroplasmids and Hepatozoon in crab-eating foxes (Cerdocyon thous; n = 12) sampled in the Pantanal of Mato Grosso do Sul State, central-western Brazil. PCR assays based on the 18S rRNA were used as screening. Three (25%) and 11 (91.7%) were positive for piroplasmids and Hepatozoon spp., respectively. Co-infection was found in three C. thous. Phylogenetic analyses based on the near-complete 18S rRNA, cox-1 and hsp70 genes evidenced the occurrence of a novel of Babesia spp. (namely Babesia pantanalensis nov. sp.) closely related to Rangelia vitalii and Babesia sp. 'Coco'. This finding was supported by the genetic divergence analysis which showed (i) high divergence, ranging from 4.17 to 5.62% for 18 S rRNA, 6.16% for hps70 and 4.91-9.25% for cox-1 and (ii) the genotype network (which displayed sequences separated from the previously described Piroplasmida species by median vectors and several mutational events). Also, phylogenetic analysis based on the 18S rRNA gene of Hepatozoon spp. positioned the sequences obtained herein in a clade phylogenetically related to Hepatozoon sp. 'Curupira 2', Hepatozoon sp. detected in domestic and wild canids from Uruguay and Hepatozoon americanum. The present study described Babesia pantanalensis nov sp. and Hepatozoon closely related to H. americanum in crab-eating foxes from Brazil. Moreover, the coinfection by piroplasmids and Hepatozoon sp. for the first time in crab-eating foxes strongly suggesting that this wild canid species potentially acts as a bio-accumulate of hemoprotozoan in wild environment.

Injectable PEG Hydrogels with Tissue-Like Viscoelasticity Formed through Reversible Alendronate-Calcium Phosphate Crosslinking for Cell-Material Interactions.

Synthetic hydrogels provide controllable 3D environments, which can be used to study fundamental biological phenomena. The growing body of evidence that cell behavior depends upon hydrogel stress relaxation creates a high demand for hydrogels with tissue-like viscoelastic properties. Here, a unique platform of synthetic polyethylene glycol (PEG) hydrogels in which star-shaped PEG molecules are conjugated with alendronate and/or RGD peptides, attaining modifiable degradability as well as flexible cell adhesion, is created. Novel reversible ionic interactions between alendronate and calcium phosphate nanoparticles, leading to versatile viscoelastic properties with varying initial elastic modulus and stress relaxation time, are identified. This new crosslinking mechanism provides shear-thinning properties resulting in differential cellular responses between cancer cells and stem cells. The novel hydrogel system is an improved design to the other ionic crosslink platforms and opens new avenues for the development of pathologically relevant cancer models, as well as minimally invasive approaches for cell delivery for potential regenerative therapies.

First Record of the Genus Trochiliphagus Carriker 1960 (Amblycera: Ricinidae) Infesting a Hummingbird from Brazil.

Four genera and at least fifty species of chewing lice have been recorded infesting hummingbirds (Trochilidae). Here, we record for the first time, the genus Trochiliphagus in Brazil, as well as, a new host record for Trochiliphagus mellivorus Carriker, the fork-tailed woodnymph, Thalurania furcata.

Risk of spread of the Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera: Liviidae) in Ghana.

The impact of invasive species on biodiversity, food security and economy is increasingly noticeable in various regions of the globe as a consequence of climate change. Yet, there is limited research on how climate change affects the distribution of the invasive Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera:Liviidae) in Ghana. Using maxnet package to fit the Maxent model in R software, we answered the following questions; (i) what are the main drivers for D. citri distribution, (ii) what are the D. citri-specific habitat requirements and (iii) how well do the risk maps fit with what we know to be correctly based on the available evidence?. We found that temperature seasonality (Bio04), mean temperature of warmest quarter (Bio10), precipitation of driest quarter (Bio17), moderate resolution imaging spectroradiometer land cover and precipitation seasonality (Bio15), were the most important drivers of D. citri distribution. The results follow the known distribution records of the pest with potential expansion of habitat suitability in the future. Because many invasive species, including D. citri, can adapt to the changing climates, our findings can serve as a guide for surveillance, tracking and prevention of D. citri spread in Ghana.

Comprehensive analysis of clinical images contributions for melanoma classification using convolutional neural networks.

BACKGROUND: Timely diagnosis plays a critical role in determining melanoma prognosis, prompting the development of deep learning models to aid clinicians. Questions persist regarding the efficacy of clinical images alone or in conjunction with dermoscopy images for model training. This study aims to compare the classification performance for melanoma of three types of CNN models: those trained on clinical images, dermoscopy images, and a combination of paired clinical and dermoscopy images from the same lesion. MATERIALS AND METHODS: We divided 914 image pairs into training, validation, and test sets. Models were built using pre-trained Inception-ResNetV2 convolutional layers for feature extraction, followed by binary classification. Training comprised 20 models per CNN type using sets of random hyperparameters. Best models were chosen based on validation AUC-ROC. RESULTS: Significant AUC-ROC differences were found between clinical versus dermoscopy models (0.661 vs. 0.869, p < 0.001) and clinical versus clinical + dermoscopy models (0.661 vs. 0.822, p = 0.001). Significant sensitivity differences were found between clinical and dermoscopy models (0.513 vs. 0.799, p = 0.01), dermoscopy versus clinical + dermoscopy models (0.799 vs. 1.000, p = 0.02), and clinical versus clinical + dermoscopy models (0.513 vs. 1.000, p < 0.001). Significant specificity differences were found between dermoscopy versus clinical + dermoscopy models (0.800 vs. 0.288, p < 0.001) and clinical versus clinical + dermoscopy models (0.650 vs. 0.288, p < 0.001). CONCLUSION: CNN models trained on dermoscopy images outperformed those relying solely on clinical images under our study conditions. The potential advantages of incorporating paired clinical and dermoscopy images for CNN-based melanoma classification appear less clear based on our findings.

Evaluation of data collection bias of third molar stages of mineralisation for age estimation in the living.

Age assessment of the living is a fundamental procedure in the process of human identification, in order to guarantee fair treatment of individuals, which has ethical, civil, legal, and medical repercussions. The careful selection of the appropriate methods requires evaluation of several parameters: accuracy, precision of the method, as well as its reproducibility. The approach proposed by Mincer et al. adapted from Demirjian et al. exploring third molar mineralisation, is one of the most frequently considered for age estimation of the living. Thus, this work aims to assess potential bias in the data collection when applying the classification stages for dental mineralisation adapted by Mincer et al. A total of 102 orthopantomographs, of clinical origin, belonging to individuals aged between 12 and 25 years ([Formula: see text] = 20.12 years, SD = 3.49 years; 65 females, 37 males, all of Portuguese nationality) were included and a retrospective analysis performed by five observers with different levels of experience (high, average, and basic). The performance and agreement between five observers were evaluated using Weighted Cohen's Kappa and the Intraclass Correlation Coefficient. To access the influence of impaction on third molar classification, variables were tested using ordinal logistic regression Generalised Linear Model. It was observed that there were variations in the number of teeth identified among the observers, but the agreement levels ranged from moderate to substantial (0.4-0.8). Upon closer examination of the results, it was observed that although there were discernible differences between highly experienced observers and those with less experience, the gap was not as significant as initially hypothesised, and a greater disparity between the classifications of the upper (0.24-0.49) and lower third molars (>0.55) was observed. When bone superimposition is present, the classification process is not significantly influenced; however, variation in teeth angulation affects the assessment. The results suggest that with an efficient preparation, the level of experience as a factor can be overcome. Mincer and colleague's classification system can be replicated with ease and consistency, even though the classification of upper and lower third molars presents distinct challenges.

The role of metabolic syndrome as a mediator in the relationship between CCL11 levels and the presence of a mood episode with mixed features in young adults with bipolar disorder.

Mixed features presentation in bipolar disorder (BD) represents the most severe form of the disease. BD may lead to cognitive and functional deterioration, a process known as neuroprogression, which appears to be exacerbated by increased serum levels of CCL11, a neuroprogression-related cytokine. Metabolic syndrome (MetS) is highly prevalent in BD, and it is known that the presence of MetS may increase inflammation, which may contribute to increased CCL11 levels, and consequently impact on the severity of the disorder. What is not known is whether the MetS mediates the association between CCL11 levels and the presence of mood episodes with mixed features in BD. Therefore, the aim of this study was to investigate the mediating effect of MetS on the relationship between CCL11 levels and the presence of mood episodes with mixed features in BD, in a population-based study. This is a cross-sectional study that included 184 young adults, 92 with BD and 92 populational controls, matched by sex and age. BD diagnosis was assessed using the Mini International Neuropsychiatric Interview - PLUS. Mood episodes with mixed features was defined according to DSM-IV and DSM-5 criteria. MetS was defined according to the National Cholesterol Education Program (NCEP/ATP III). Substance use was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). CCL11 serum levels were analyzed using the multiplex analysis method Luminex 200™ system. The mediation model was tested using the MedMod module of the JAMOVI 2.4.8 software. Mediation analysis indicated a trend towards significance of MetS mediating the association between CCL11 and the presence of a mood episode with mixed features in BD (p = 0.065). Individuals with BD presenting with a mood episode with mixed features and MetS may have accelerated neuroprogression due to the influence of MetS on CCL11 levels, therefore, assessing for MetS occurrence in this population and implementing early interventions to prevent its development may be effective ways of delaying cognitive impairments related to this cytokine.

FRET Sensor-Modified Synthetic Hydrogels for Real-Time Monitoring of Cell-Derived Matrix Metalloproteinase Activity using Fluorescence Lifetime Imaging.

Matrix remodeling plays central roles in a range of physiological and pathological processes and is driven predominantly by the activity of matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) proteins. Our understanding of how MMPs regulate cell and tissue dynamics is often incomplete as in vivo approaches are lacking and many in vitro strategies cannot provide high-resolution, quantitative measures of enzyme activity in situ within tissue-like 3D microenvironments. Here, we incorporate a Förster resonance energy transfer (FRET) sensor of MMP activity into fully synthetic hydrogels that mimic many properties of the native ECM. We then use fluorescence lifetime imaging to provide a real-time, fluorophore concentration-independent quantification of MMP activity, establishing a highly accurate, readily adaptable platform for studying MMP dynamics in situ. MCF7 human breast cancer cells encapsulated within hydrogels highlight the detection of MMP activity both locally, at the sub-micron level, and within the bulk hydrogel. Our versatile platform may find use in a range of biological studies to explore questions in the dynamics of cancer metastasis, development, and tissue repair by providing high-resolution, quantitative and in situ readouts of local MMP activity within native tissue-like environments.