Nuclear factor-κB activation by transforming growth factor-ß1 drives tumour microenvironment-mediated drug resistance in neuroblastoma.

BACKGROUND: Intrinsic and extrinsic factors in the tumour microenvironment (TME) contribute to therapeutic resistance. Here we demonstrate that transforming growth factor (TGF)-ß1 produced in the TME increased drug resistance of neuroblastoma (NB) cells. METHODS: Human NB cell lines were tested in vitro for their sensitivity to Doxorubicin (DOX) and Etoposide (ETOP) in the presence of tumour-associated macrophages (TAM) and mesenchymal stromal cells/cancer-associated fibroblasts (MSC/CAF). These experiments were validated in xenotransplanted and primary tumour samples. RESULTS: Drug resistance was associated with an increased expression of efflux transporter and anti-apoptotic proteins. Upregulation was dependent on activation of nuclear factor (NF)-κB by TGF-ß-activated kinase (TAK1) and SMAD2. Resistance was reversed upon pharmacologic and genetic inhibitions of NF-κB, and TAK1/SMAD2. Interleukin-6, leukaemia inhibitory factor and oncostatin M were upregulated by this TGF-ß/TAK1/NF-κB/SMAD2 signalling pathway contributing to drug resistance via an autocrine loop activating STAT3. An analysis of xenotransplanted NB tumours revealed an increased presence of phospho (p)-NF-κB in tumours co-injected with MSC/CAF and TAM, and these tumours failed to respond to Etoposide but responded if treated with a TGF-ßR1/ALK5 inhibitor. Nuclear p-NF-κB was increased in patient-derived tumours rich in TME cells. CONCLUSIONS: The data provides a novel insight into a targetable mechanism of environment-mediated drug resistance.

Non-canonical Wnt pathway expression in the developing mouse and human retina.

The non-canonical Wnt pathway is an evolutionarily conserved pathway essential for tissue patterning and development across species and tissues. In mammals, this pathway plays a role in neuronal migration, dendritogenesis, axon growth, and synapse formation. However, its role in development and synaptogenesis of the human retina remains less established. In order to address this knowledge gap, we analyzed publicly available single-cell RNA sequencing (scRNAseq) datasets for mouse retina, human retina, and human retinal organoids over multiple developmental time points during outer retinal maturation. We identified ligands, receptors, and mediator genes with a putative role in retinal development, including those with novel or species-specific expression, and validated this expression using fluorescence in situ hybridization (FISH). By quantifying outer nuclear layer (ONL) versus inner nuclear layer (INL) expression, we provide evidence for the differential expression of certain non-canonical Wnt signaling components in the developing mouse and human retina during outer plexiform layer (OPL) development. Importantly, we identified distinct expression patterns of mouse and human FZD3 and WNT10A, as well as previously undescribed expression, such as for mouse Wnt2b in Chat+ starburst amacrine cells. Human retinal organoids largely recapitulated the human non-canonical Wnt pathway expression. Together, this work provides the basis for further study of non-canonical Wnt signaling in mouse and human retinal development and synaptogenesis.

Timing of previous heart failure hospitalization as a prognostic factor for emergency department heart failure patients.

To investigate whether the timing of a previous hospital admission for acute heart failure (AHF) is a prognostic factor for AHF patients revisiting the emergency department (ED) in the subsequent 12-month follow-up. All ED AHF patients enrolled in the previously described EAHFE registry were stratified by the presence or absence of an AHF hospitalization admission in the prior 12 months. The primary outcome was 12-month all-cause mortality post ED visit. Secondary end points were hospital admission, prolonged hospitalization (> 7 days), mortality during hospitalization and a 90-day post-discharge adverse composite event (ACE) rate, defined as ED revisits due to AHF, hospitalizations due to AHF, or all-cause mortality. Outcomes were adjusted for baseline and AHF episode characteristics.Of 5,757 patients included, the median age was 84 years (IQR 77-88); 57% were women, and 3,759 (65.3%) had an AHF hospitalization in the previous 12 months. The 12-month mortality was 37% (41.7% vs. 28.3% p < 0.001), hospital admission was 76.1% (78.8% vs. 71.1% p < 0.001) ACE was 60.2% (65.1% vs. 50.5% p < 0.001). In the adjusted analysis, patients with AHF hospitalization in the prior 12 months had a higher mortality (HR = 1.41; 95% CI 1.27-1.56), 90-day ACE rate (HR = 1.45: 95% CI 1.32-1.59), and more hospital admissions (OR = 1.32; 95% CI 1.16-1.51), with shorter times since the previous hospitalization being related to the outcomes analyzed. One-year mortality, adverse events at 90 days, and readmission rates are increased in ED AHF patients previously admitted within the last 12 months.

Developmental changes in brain activation during novel grammar learning in 8-25-year-olds.

While it is well established that grammar learning success varies with age, the cause of this developmental change is largely unknown. This study examined functional MRI activation across a broad developmental sample of 165 Dutch-speaking individuals (8-25 years) as they were implicitly learning a new grammatical system. This approach allowed us to assess the direct effects of age on grammar learning ability while exploring its neural correlates. In contrast to the alleged advantage of children language learners over adults, we found that adults outperformed children. Moreover, our behavioral data showed a sharp discontinuity in the relationship between age and grammar learning performance: there was a strong positive linear correlation between 8 and 15.4 years of age, after which age had no further effect. Neurally, our data indicate two important findings: (i) during grammar learning, adults and children activate similar brain regions, suggesting continuity in the neural networks that support initial grammar learning; and (ii) activation level is age-dependent, with children showing less activation than older participants. We suggest that these age-dependent processes may constrain developmental effects in grammar learning. The present study provides new insights into the neural basis of age-related differences in grammar learning in second language acquisition.

Effects of mixtures of herbicides on nutrient cycling and plant support considering current agriculture practices.

The use of mixtures of pesticides and consecutive pesticide applications challenge current regulations aimed at protecting ecosystem health due to unpredictable effects of complex and dynamic mixtures. In this study, we tested the ecotoxicological effects of mixtures of herbicides, applied following a real application scheme of soybean production on soil health in a mesocosm experiment. The experiment included two sequential applications; first, glyphosate + dicamba + clethodim, and 30 days later, flumioxazin + metolachlor. Commercial products were used at the recommended doses and at two other concentrations: half and double the recommended dose. Soybean plants were exposed to the herbicide-contaminated soil from the time of sowing to the beginning of pod formation. Half of the plants were harvested at the vegetative stage and the remaining plants at the reproductive stage to evaluate endpoints related to plant support and nutrient cycling. Plant biomass was significantly affected during the vegetative stage at the recommended and double the recommended dose, with the effects being mixture-dose dependent. Lower total and arbuscular colonization of mycorrhizas were also observed in double the recommended dose, and intermediate results were observed for the recommended dose. Nodule mass and phosphorous concentration in plants decreased with increasing herbicide doses. By the end of the experiment, nodule mass and total mycorrhizal colonization were low in the plants treated with double the recommended dose of herbicides. However, both endpoints reached similar values to the control at lower herbicide doses. Plant height and phenology were only lower at double the recommended dose during the experiment. The use of non-standard endpoints evidenced that important soil functions were transiently or permanently affected, while the realistic application scheme accounted for the impact of the management practice currently used. Pesticide risk assessment should therefore, incorporate both issues to effectively protect the ecosystems.

Genetic characterization of domestic pigs in the core zone of swine production of Argentina.

Argentina is a small player in the global pork market, contributing only 0.7% of the total production. With increasing global demand for meat, there is an opportunity for countries with an agricultural profile to grow their pork production. However, there is a need to understand the current state of the pork production sector in all aspects to inform decision-making. The aim of this study was to genetically characterize pig herds from different production strata in the primary region for pork production in the country. For this purpose, phylogenetic and genetic variability analyses were performed using the mitochondrial control region marker (n=95 pig samples). Moreover, genotyping of ryr1 and PRKAG3 genes (n=108 pig samples) were performed to evaluate the frequency of deleterious alleles for meat quality traits in the region. The results showed high levels of genetic variability in the pig herds (Hd= 0.840 ± 0.031 and π= 0.010 ± 0.001), with a creole sow and Iberian lineage standing out in the phylogeny. The genotyping of the ryr1 marker revealed the presence of the deleterious t allele in all analyzed strata. However, the RN-allele of the PRKAG3 gene was detected only in the two lower strata. This study represents the first analysis of the phylogenetic relationships among domestic pigs from Argentina and provides an initial assessment of genetic variability in the region. Additionally, the results present, for the first time, the frequency of deleterious alleles for pig production in the productive core area, demonstrating their prevalence.

Usage of immersive virtual reality as a relaxation method in an intensive care unit.

INTRODUCTION: The usage of immersive virtual reality (iVR) in the context of an intensive care unit (ICU) is scarce. Our objective was to assess the feasibility of the usage of iVR in critical patients with or without mechanical ventilation (MV) and to determine the anxiety degree before and after each session. METHODS: Analytical, descriptive, prospective, and cross-sectional research. Pilot test with 20 patients from a polyvalent ICU of a tertiary hospital. Adult patients were included, either connected or not to MV, watchful and calmed (RASS -1/+1) and without delirium (negative CAM-ICU). Oculus Go (Facebook Technologies, LLC) iVR glasses were the model used. The relaxation strategy consisted in the visualization of an experience of 15 min with scenes related to nature and fantasy, relaxing music with a plot. The sessions were individual, with the patient monitored in a fowler position or seated. The anxiety degree before and after each session was evaluated following a reduced version of the Spanish "Cuestionario de Ansiedad Estado-Rasgo (STAI-e)" and they were analysed using T samples coupled (statistical significance when p-value was <0.05). RESULTS: Incorporation of 20 patients with an average age of 63.9 years old (60% men). A total of 34 sessions of iVR were conducted. 32% patients mechanically ventilated, 32% high-flow oxygen therapy, 36% other breathing supports. 80% of the sessions were completed without serious side effects. A significant decrease in the anxiety degree was observed after each iVR session: first session mean change -2.68 (SD = 2.75), p = 0.000; second session mean change -1.86 (SD = 1.57), p = 0.021; third session mean change -1.67 (SD = 1.63), p = 0.054. CONCLUSION: The usage of iVR in the context of an ICU is feasible, even with patients mechanically ventilated. iVR reduces the anxiety degree in the critic patient, which suggests that "digital therapies" can be effective to improve the emotional state during their stay in the ICU.

Is unicentric familial papillary thyroid microcarcinoma different from multicentric?

BACKGROUND: Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS: Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION: Patients with FPTMC. STUDY GROUPS: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS: Cox regression analysis and survival analysis. RESULTS: Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS: Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.

Tick-borne pathogens in ticks from urban and suburban areas of north-western Spain: Importance of Ixodes frontalis harbouring zoonotic pathogens.

To identify the questing tick populations in urban and suburban areas from the city of Lugo (NW Spain), ticks were collected monthly by flagging. The presence of Borrelia spp., Rickettsia spp. and Anaplasma phagocytophilum also was determined by polymerase chain reaction (PCR) and sequence analysis. Overall, 342 questing ticks were collected; the tick abundance was higher in suburban (95.9%) than in urban areas (4.1%). Ixodes frontalis was the most abundant (86.5%); 88.5% were larvae, 11.1% nymphs and 0.3% adults. All development stages of I. ricinus (7.3%) and adults of Rhipicephalus sanguineus sensu lato (5.8%) and Dermacentor reticulatus (0.3%) were found. Rickettsia spp. (31.9%) was more prevalent than Borrelia spp. (2.7%); no ticks were positive to A. phagocytophilum. Six Rickettsia species were identified (R. slovaca, R. monacensis, R. massiliae, R. raoultii, R. sibirica subsp. mongolitimonae and R. aeschielmanii); Candidatus Rickettsia rioja and two novel Rickettsia species also were detected. In addition, Borrelia turdi (1.8%) and B. valaisiana (0.9%) were identified in Ixodes ticks. This is the first report of R. slovaca in R. sanguineus s.l. and of R. monacensis, R. raoultii, R. slovaca, R. sibirica subsp. mongolitimonae and Ca. R. rioja in I. frontalis. Since most of the pathogens detected are zoonotic, their presence in these areas may have implications for public health.

Consensus on complementary feeding from the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition: COCO 2023.

Complementary feeding (CF) is defined as the feeding of infants that complements breastfeeding, or alternatively, feeding with a breast milk substitute, and is a process that is more than simply a guide as to what and how to introduce foods. The information provided by healthcare professionals must be up-to-date and evidence-based. Most of the recommendations that appear in the different international guidelines and position papers are widely applicable, but some must be regionalized or adapted to fit the conditions and reality of each geographic zone. The Nutrition Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) summoned a group of experts from each of the society's member countries, to develop a consensus on CF, incorporating, whenever possible, local information adapted to the reality of the region. The aim of the present document is to show the results of that endeavor. Utilizing the Delphi method, a total of 34 statements on relevant aspects of CF were evaluated, discussed, and voted upon.

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury.

BACKGROUND AND AIMS: Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. APPROACH AND RESULTS: Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. CONCLUSIONS: We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-ß/IL-6 pathway in neuroblastoma.

Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF) and their precursor mesenchymal stromal cells (MSC) are often detected together in tumors, but how they cooperate is not well understood. Here, we show that TAM and CAF are the most abundant nonmalignant cells and are present together in untreated human neuroblastoma (NB) tumors that are also poorly infiltrated with T and natural killer (NK) cells. We then show that MSC and CAF-MSC harvested from NB tumors protected human monocytes (MN) from spontaneous apoptosis in an interleukin (IL)-6 dependent mechanism. The interactions of MN and MSC with NB cells resulted in a significant induction or increase in the expression of several pro-tumorigenic cytokines/chemokines (TGF-ß1, MCP-1, IL-6, IL-8, and IL-4) but not of anti-tumorigenic cytokines (TNF-α, IL-12) by MN or MSC, while also inducing cytokine expression in quiescent NB cells. We then identified a TGF-ß1/IL-6 pathway where TGF-ß1 stimulated the expression of IL-6 in NB cells and MSC, promoting TAM survival. Evidence for the contribution of TAM and MSC to the activation of this pathway was then provided in xenotransplanted NB tumors and patients with primary tumors by demonstrating a direct correlation between the presence of CAF and p-SMAD2 and p-STAT3. The data highlight a new mechanism of interaction between TAM and CAF supporting their pro-tumorigenic function in cancer.

Biological behavior of familial papillary thyroid microcarcinoma: Spanish multicenter study.

PURPOSE: Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain. METHODS: Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence). RESULTS: Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210-5.473; p = 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638-1000; p < 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405-333.333; p < 0.001). CONCLUSION: FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.

Study protocol: a comprehensive multi-method neuroimaging approach to disentangle developmental effects and individual differences in second language learning.

BACKGROUND: While it is well established that second language (L2) learning success changes with age and across individuals, the underlying neural mechanisms responsible for this developmental shift and these individual differences are largely unknown. We will study the behavioral and neural factors that subserve new grammar and word learning in a large cross-sectional developmental sample. This study falls under the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Dutch Research Council]) Language in Interaction consortium (website: https://www.languageininteraction.nl/ ). METHODS: We will sample 360 healthy individuals across a broad age range between 8 and 25 years. In this paper, we describe the study design and protocol, which involves multiple study visits covering a comprehensive behavioral battery and extensive magnetic resonance imaging (MRI) protocols. On the basis of these measures, we will create behavioral and neural fingerprints that capture age-based and individual variability in new language learning. The behavioral fingerprint will be based on first and second language proficiency, memory systems, and executive functioning. We will map the neural fingerprint for each participant using the following MRI modalities: T1-weighted, diffusion-weighted, resting-state functional MRI, and multiple functional-MRI paradigms. With respect to the functional MRI measures, half of the sample will learn grammatical features and half will learn words of a new language. Combining all individual fingerprints allows us to explore the neural maturation effects on grammar and word learning. DISCUSSION: This will be one of the largest neuroimaging studies to date that investigates the developmental shift in L2 learning covering preadolescence to adulthood. Our comprehensive approach of combining behavioral and neuroimaging data will contribute to the understanding of the mechanisms influencing this developmental shift and individual differences in new language learning. We aim to answer: (I) do these fingerprints differ according to age and can these explain the age-related differences observed in new language learning? And (II) which aspects of the behavioral and neural fingerprints explain individual differences (across and within ages) in grammar and word learning? The results of this study provide a unique opportunity to understand how the development of brain structure and function influence new language learning success.

An immature, dedifferentiated, and lineage-deconstrained cone precursor origin of N-Myc-initiated retinoblastoma.

Most retinoblastomas develop from maturing cone precursors in response to biallelic RB1 loss and are dependent on cone maturation-related signaling. Additionally, ∼2% lack RB1 mutations but have MYCN amplification (MYCNA), N-Myc protein overexpression, and more rapid and invasive growth, yet the MYCNA retinoblastoma cell of origin and basis for its responses to deregulated N-Myc are unknown. Here, using explanted cultured retinae, we show that ectopic N-Myc induces cell cycle entry in cells expressing markers of several retinal types yet induces continuous proliferation and tumorigenesis only in cone precursors. Unlike the response to RB1 loss, both immature cone arrestin-negative (ARR3-) and maturing ARR3+ cone precursors proliferate, and maturing cone precursors rapidly dedifferentiate, losing ARR3 as well as L/M-opsin expression. N-Myc-overexpressing retinal cells also lose cell lineage constraints, occasionally coexpressing the cone-specific RXRγ with the rod-specific NRL or amacrine-specific AP2α and widely coexpressing RXRγ with the progenitor and Müller cell-specific SOX9 and retinal ganglion cell-specific BRN3 and GAP43. Mechanistically, N-Myc induced Cyclin D2 and CDK4 overexpression, pRB phosphorylation, and SOX9-dependent proliferation without a retinoma-like stage that characterizes pRB-deficient retinoblastoma, despite continuous p16INK4A expression. Orthotopic xenografts of N-Myc-overexpressing retinal cells formed tumors with retinal cell marker expression similar to those in MYCN-transduced retinae and MYCNA retinoblastomas in patients. These findings demonstrate the MYCNA retinoblastoma origin from immature and lineage-deconstrained cone precursors, reveal their opportunistic use of an undifferentiated retinal progenitor cell feature, and illustrate that different cancer-initiating mutations cooperate with distinct developmental stage-specific cell signaling circuitries to drive retinoblastoma tumorigenesis.

Hair cortisol in polycystic ovary syndrome.

The aim of the study was to evaluate adrenal axis hyperactivation measuring hair cortisol levels, and its influence on the relationship among metabolic parameters, inflammation markers and androgens in adult women with PCOS. 44 women (18-34 years) with PCOS diagnosis and a control group of 49 healthy women (19-35 years) were included. In both gropus body mass index (BMI) was calculated and waist circumference (WC) was measured. Hair cortisol, total serum testosterone (TT), serum cortisol, 25 OH vitamin D (25OHD), insulin, high sensitivity C-reactive protein (hsCRP), triglycerides (TG), HDL cholesterol (HDL), glucose and leptin were measured. Bioavailable testosterone (bioT) was calculated. Hair cortisol concentration was higher and significantly different in PCOS patients compared to the control group (130 vs 63 pg/mg of hair, p < 0.001). Subsequently, patients with PCOS were divided into two groups according to hair cortisol levels: group 1 with normal hair cortisol concentration and group 2 with levels above the upper limit of the reference values (128 pg/mg of hair). In group 2, TT significantly correlated with 25OHD, hsCRP, TG/HDL index, BMI, WC, insulin and HOMA (p < 0.05); bioT correlated with hsCRP and leptin (p < 0.05). Finally, 25OHD was inversely correlated with leptin and with TG/HDL index (p < 0.05). High hair cortisol concentration in patients with PCOS confirmed hyperactivation of the HPA axis. The associations observed were only found in patients with PCOS with high hair cortisol levels (> 128 pg/mg of hair), showing a possible effect of HPA axis in these associations.

Simultaneous electrochemical immunosensing of relevant cytokines to diagnose and track cancer and autoimmune diseases.

This work reports the first dual magnetic beads (MBs) assisted immunoplatform for the simultaneous determination of BAFF (B cell activation factor) and APRIL (a proliferation-induced ligand), two cytokines related to immunity and tumour invasion, growth and metastasis. The electrochemical immunoplatform involves sandwich-type immunoassays implemented on magnetic microparticles functionalized with neutravidin (NA-MBs) or carboxylic groups (HOOC-MBs), and amperometric detection (Eapp =  - 0.20 V vs. Ag pseudo-reference electrode) at screen-printed dual carbon electrodes (SPdCE) using the H2O2/hydroquinone (HQ) system. The developed immunosensors provide improved sensitivity, with LOD values of 0.33 and 16.4 pg mL-1 for BAFF and APRIL, respectively, and much shorter assay time that those claimed for ELISA kits and allow their simultaneous determination. The dual immunosensor permits discrimination between healthy individuals and patients diagnosed with Systemic Lupus Erythematosus (SLE) or colorectal cancer (CRC) through the determination of both cytokines in 100-times diluted human sera with results in agreement with those provided by the individual ELISA methodologies.

The STRESS-NL database: A resource for human acute stress studies across the Netherlands.

Stress initiates a cascade of (neuro)biological, physiological, and behavioral changes, allowing us to respond to a challenging environment. The human response to acute stress can be studied in detail in controlled settings, usually in a laboratory environment. To this end, many studies employ acute stress paradigms to probe stress-related outcomes in healthy and patient populations. Though valuable, these studies in themselves often have relatively limited sample sizes. We established a data-sharing and collaborative interdisciplinary initiative, the STRESS-NL database, which combines (neuro)biological, physiological, and behavioral data across many acute stress studies in order to accelerate our understanding of the human acute stress response in health and disease (www.stressdatabase.eu). Researchers in the stress field from 12 Dutch research groups of 6 Dutch universities created a database to achieve an accurate inventory of (neuro)biological, physiological, and behavioral data from laboratory-based human studies that used acute stress tests. Currently, the STRESS-NL database consists of information on 5529 individual participants (2281 females and 3348 males, age range 6-99 years, mean age 27.7 ±â€¯16 years) stemming from 57 experiments described in 42 independent studies. Studies often did not use the same stress paradigm; outcomes were different and measured at different time points. All studies currently included in the database assessed cortisol levels before, during and after experimental stress, but cortisol measurement will not be a strict requirement for future study inclusion. Here, we report on the creation of the STRESS-NL database and infrastructure to illustrate the potential of accumulating and combining existing data to allow meta-analytical, proof-of-principle analyses. The STRESS-NL database creates a framework that enables human stress research to take new avenues in explorative and hypothesis-driven data analyses with high statistical power. Future steps could be to incorporate new studies beyond the borders of the Netherlands; or build similar databases for experimental stress studies in rodents. In our view, there are major scientific benefits in initiating and maintaining such international efforts.