A re-assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight.

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

The impact of norepinephrine dose reporting heterogeneity on mortality prediction in septic shock patients.

BACKGROUND: Norepinephrine (NE) is a cornerstone drug in the management of septic shock, with its dose being used clinically as a marker of disease severity and as mortality predictor. However, variations in NE dose reporting either as salt formulations or base molecule may lead to misinterpretation of mortality risks and hinder the process of care. METHODS: We conducted a retrospective analysis of the MIMIC-IV database to assess the impact of NE dose reporting heterogeneity on mortality prediction in a cohort of septic shock patients. NE doses were converted from the base molecule to equivalent salt doses, and their ability to predict 28-day mortality at common severity dose cut-offs was compared. RESULTS: 4086 eligible patients with septic shock were identified, with a median age of 68 [57-78] years, an admission SOFA score of 7 [6-10], and lactate at diagnosis of 3.2 [2.4-5.1] mmol/L. Median peak NE dose at day 1 was 0.24 [0.12-0.42] µg/kg/min, with a 28-day mortality of 39.3%. The NE dose showed significant heterogeneity in mortality prediction depending on which formulation was reported, with doses reported as bitartrate and tartrate presenting 65 (95% CI 79-43)% and 67 (95% CI 80-47)% lower ORs than base molecule, respectively. This divergence in prediction widened at increasing NE doses. When using a 1 µg/kg/min threshold, predicted mortality was 54 (95% CI 52-56)% and 83 (95% CI 80-87)% for tartrate formulation and base molecule, respectively. CONCLUSIONS: Heterogeneous reporting of NE doses significantly affects mortality prediction in septic shock. Standardizing NE dose reporting as base molecule could enhance risk stratification and improve processes of care. These findings underscore the importance of consistent NE dose reporting practices in critical care settings.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.

Where do ICU trainees really look? An eye-tracking analysis of gaze patterns during central venous catheter insertion.

BACKGROUND: There is limited knowledge about gaze patterns of intensive care unit (ICU) trainee doctors during the insertion of a central venous catheter (CVC). The primary objective of this study was to examine visual patterns exhibited by ICU trainee doctors during CVC insertion. Additionally, the study investigated whether differences in gaze patterns could be identified between more and less experienced trainee doctors. METHODS: In a real-life, prospective observational study conducted at the interdisciplinary ICU at the University Hospital Zurich, Switzerland, ICU trainee doctors underwent eye-tracking during CVC insertion in a real ICU patient. Using mixed-effects model analyses, the primary outcomes were dwell time, first fixation duration, revisits, fixation count, and average fixation time on different areas of interest (AOI). Secondary outcomes were above eye-tracking outcome measures stratified according to experience level of participants. RESULTS: Eighteen participants were included, of whom 10 were inexperienced and eight more experienced. Dwell time was highest for CVC preparation table (p = 0.02), jugular vein on ultrasound image (p < 0.001) and cervical puncture location (p < 0.001). Concerning experience, dwell time and revisits on jugular vein on ultrasound image (p = 0.02 and p = 0.04, respectively) and cervical puncture location (p = 0.004 and p = 0.01, respectively) were decreased in more experienced ICU trainees. CONCLUSIONS: Various AOIs have distinct significance for ICU trainee doctors during CVC insertion. Experienced participants exhibited different gaze behavior, requiring less attention for preparation and handling tasks, emphasizing the importance of hand-eye coordination.

Use of a gas-operated ventilator as a noninvasive bridging respiratory therapy in critically Ill COVID-19 patients in a middle-income country.

During the COVID-19 pandemic, there was a notable undersupply of respiratory support devices, especially in low- and middle-income countries. As a result, many hospitals turned to alternative respiratory therapies, including the use of gas-operated ventilators (GOV). The aim of this study was to describe the use of GOV as a noninvasive bridging respiratory therapy in critically ill COVID-19 patients and to compare clinical outcomes achieved with this device to conventional respiratory therapies. Retrospective cohort analysis of critically ill COVID-19 patients during the first local wave of the pandemic. The final analysis included 204 patients grouped according to the type of respiratory therapy received in the first 24 h, as follows: conventional oxygen therapy (COT), n = 28 (14%); GOV, n = 72 (35%); noninvasive ventilation (NIV), n = 49 (24%); invasive mechanical ventilation (IMV), n = 55 (27%). In 72, GOV served as noninvasive bridging respiratory therapy in 42 (58%) of these patients. In the other 30 patients (42%), 20 (28%) presented clinical improvement and were discharged; 10 (14%) died. In the COT and GOV groups, 68% and 39%, respectively, progressed to intubation (P ≤ 0.001). Clinical outcomes in the GOV and NIV groups were similar (no statistically significant differences). GOV was successfully used as a noninvasive bridging respiratory therapy in more than half of patients. Clinical outcomes in the GOV group were comparable to those of the NIV group. These findings support the use of GOV as an emergency, noninvasive bridging respiratory therapy in medical crises when alternative approaches to the standard of care may be justifiable.

Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci.

BACKGROUND: Vision depends on the interplay between photoreceptor cells of the neural retina and the underlying retinal pigment epithelium (RPE). Most genes involved in inherited retinal diseases display specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. RESULTS: To understand the role of differential chromatin architecture in establishing tissue-specific expression at inherited retinal disease loci, we mapped genome-wide chromatin interactions using in situ Hi-C and H3K4me3 HiChIP on neural retina and RPE/choroid from human adult donor eyes. We observed chromatin looping between active promoters and 32,425 and 8060 candidate CREs in the neural retina and RPE/choroid, respectively. A comparative 3D genome analysis between these two retinal tissues revealed that 56% of 290 known inherited retinal disease genes were marked by differential chromatin interactions. One of these was ABCA4, which is implicated in the most common autosomal recessive inherited retinal disease. We zoomed in on retina- and RPE-specific cis-regulatory interactions at the ABCA4 locus using high-resolution UMI-4C. Integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish revealed tissue-specific CREs interacting with ABCA4. CONCLUSIONS: Through comparative 3D genome mapping, based on genome-wide, promoter-centric, and locus-specific assays of human neural retina and RPE, we have shown that gene regulation at key inherited retinal disease loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes at retinal disease loci, but also delineate the search space for non-coding genomic variation underlying unsolved inherited retinal diseases.

Diabetes as risk factor to severity of dengue in naïve patients.

Background: Dengue cases can progress to severe ant life-threating forms particularly in subsequent heterologous infections. However, recent studies had explored additional risk factors, including underlying health conditions, even in individuals without prior exposure to dengue, notably, in patients with endothelial dysfunction and chronic inflammation. This study examines the link between diabetes and the development of severe dengue disease in dengue-naive patients during the 2019 dengue outbreak in São Jose do Rio Preto, Brazil. Methodology: We enrolled 529 laboratory-confirmed dengue cases, identified through DENV RT-PCR or NS1 antigen assays in a hospital cohort of acute febrile illness. Subsequently, we investigated the presence of anti-dengue and anti-Zika IgG antibodies. Samples testing positive for Zika were excluded from the analyses. Two groups were analyzed: naïve (DV-), and dengue history (DV+). Results: Initially, presence of diabetes and kidney disease, as well as being dengue-naive, were associated with a higher frequency of severe and potentially severe clinical outcomes. Multivariate analysis identified diabetes as a risk factor, while the presence of anti-dengue antibodies was considered protective. Analysis of dengue naïve samples, highlighted diabetes as an independent risk factor to severe forms of dengue disease. In DV+ patients, no condition was highlighted as a risk factor by univariate analysis or multivariate analysis. Conclusions: We investigated and confirmed diabetes as a risk factor for severe dengue disease in individuals without prior dengue or Zika exposure. Our conclusions raise significant concerns given diabetes' ever increasing global prevalence and its potential impact on patients with or previous dengue exposure.

Mapping the Landscape: Simulation Centers in Portugal.

INTRODUCTION: Simulation-based training has emerged as a vital component of healthcare education. This study aims to characterize Portuguese simulation centers concerning their geographic distribution and key features, providing stakeholders with valuable insights to inform strategic decisions. METHODS: A cross-sectional survey-based study was conducted over two years (2021-2023) to investigate the geographical dispersion and characteristics of simulation centers in Portugal. Descriptive statistics and thematic analysis were used to analyze data. RESULTS: Twenty-three Portuguese simulation centers were included. Major urban areas and coastal regions bring together 20 simulation centers (86.96%). A large percentage (71.93%) of centers were affiliated with academic institutions, while five centers (21.74%) were clinically affiliated. Emergency care, Anesthesiology and Intensive Medicine, Pediatrics, and Gynecology and Obstetrics were identified as the national key areas of intervention. DISCUSSION: Significant geographical disparity raises concerns about unequal access to professional training opportunities using simulation. Centers should be encouraged to incorporate developing technologies and innovative pedagogical methodologies and to expand their training repertoire into relatively uncharted territories. CONCLUSION: Several issues have been identified within the national simulation network. Stakeholders and policymakers should prioritize equitable access, bolster the prevalence of clinical affiliated centers, foster innovation, and facilitate strategic coordination.

Evaluation of Increasing Dietary Concentrations of a Multi-Enzyme Complex in Feedlot Lambs' Rations.

The objective of this study was to evaluate the effects of increasing levels of the M-E complex (xylanase, glucanase, cellulase, and invertase) Optimax E® on the performance of growing lambs, their digestibility, and their rumen microbiota, and to estimate NEm, NEg, and ruminal methane levels. Forty lambs (Katahdin x Dorset; 22.91 ± 4.16 kg) were randomly assigned to dietary concentrations of ME (0, 0.2, 0.4, and 0.8% DM) and fed individually for 77 days. Increasing M-E improved feed conversion (p < 0.05) as well as NEm and NEg (p < 0.05), which were associated with increased in vivo DM and NDF digestion (linear and quadratic p < 0.01). Few microbial families showed abundancy changes (Erysipelotrichaceae, Christensenellaceae, Lentisphaerae, and Clostridial Family XIII); however, the dominant phylum Bacteroidetes was linearly reduced, while Firmicutes increased (p < 0.01), resulting in a greater Firmicutes-to-Bacteroidetes ratio. Total Entodinium showed a quadratic response (p < 0.10), increasing its abundancy as the enzyme dose was augmented. The daily emission intensity of methane (per kg of DMI or AGD) was reduced linearly (p < 0.01). In conclusion, adding the M-E complex Optimax E® to growing lambs' diets improves their productive performance by acting synergistically with the rumen microbiota, modifying the Firmicutes-to-Bacteroidetes ratio toward more efficient fermentation, and shows the potential to reduce the intensity of greenhouse gas emissions from lambs.

Technical success, procedural safety, and efficacy of the Silk Vista Baby in the treatment of cerebral aneurysms over a mid-to-long-term follow-up.

Background: Long-term follow-up of cerebral aneurysms treated with the Silk Vista Baby (SVB) flow diverter is lacking. This study aimed to assess the technical success, procedural safety, and efficacy of the SVB (Balt, Montmorency, France) for the treatment of intracranial aneurysms in small cerebral vessels over a mid-to long-term follow-up. Methods: We retrospectively analyzed a prospectively maintained database of patients treated with the SVB between September 2018 and June 2021. Data regarding patient demographics, aneurysm characteristics, and technical procedures were also collected. Angiographic and clinical findings were recorded during the procedure and over a period of at least 12 months. Results: Angiographic and clinical follow-up data were available for 50 patients/50 aneurysms. The procedural complication rate was 8%. At 12 months, the final results showed a technical success rate of 100%, the re rupture rate was 0%, neuromorbidity and mortality rates of 4 and 0%, respectively, and an almost complete occlusion rate of 94%. Conclusion: Treatment of complex intracranial aneurysms with the SVB was safe and effective. Long-term results showed high rates of adequate and stable occlusions.

Carboxyhemoglobin predicts oxygenator performance and imminent oxygenator change in extracorporeal membrane oxygenation.

BACKGROUND: The continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid-base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change. RESULTS: Out of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO2 (estimate for log(COHb): - 2.176 [95% CI - 2.927, - 1.427], p < 0.0001) and with a shorter time to oxygenator change (estimate for log(COHb): - 67.895 [95% CI - 74.209, - 61.542] hours, p < 0.0001). COHb was predictive of oxygenator change within 6 h (estimate for log(COHb): 5.027 [95% CI 1.670, 15.126], p = 0.004). CONCLUSION: COHb correlates with oxygenator performance and can be predictive of imminent oxygenator change. Therefore, longitudinal measurements of COHb in clinical routine might be a cheap and more granular candidate for ECMO surveillance that should be further analyzed in a controlled prospective trial design.

Intermediate-Term Clinical Outcomes of High-Density Autologous Chondrocyte Implantation in Patients with Concomitant Anterior Cruciate Ligament Reconstruction and Focal Chondral Lesions.

OBJECTIVE: To investigate intermediate-term clinical results in patients with concomitant anterior cruciate ligament (ACL) reconstruction and chondral defect treated with high-density autologous chondrocyte implantation (HD-ACI) compared to patients without ACL tear but with a chondral lesion and HD-ACI treatment. DESIGN: Forty-eight patients with focal chondral lesions underwent HD-ACI (24 with ACL reconstruction after an ACL injury and 24 with an intact ACL). Follow-up assessments occurred at 6, 12, and 24 months. Patient-reported knee function and symptoms were assessed using the International Knee Documentation Committee (IKDC) questionnaire, pain was measured using the Visual Analog Scale (VAS), and adverse events were monitored. Physical activity was assessed using the Tegner Activity Level Scale, and cartilage healing was evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. RESULTS: No significant adverse events occurred during follow-up. Both groups showed significant improvements at 2 years compared to baseline (VAS: 8.0 ± 1.3 to 1.4 ± 2.0 [normal ACL]; 7.4 ± 2.3 to 2.1 ± 2.3 [ACL reconstruction]; IKDC: 39.2 ± 10.6 to 76.1 ± 22.0 [intact ACL]; 35.6 ± 12.1 to 74.6 ± 20.9 [ACL reconstruction]). Patients in both groups exceeded the minimal clinically important difference (MCID) for IKDC scores. The Tegner Activity Level Scale decreased immediately after surgery and increased after 2 years, with 70.6% (normal ACL) and 89.5% (ACL reconstruction) returning to their preinjury activity levels. No significant differences in the MOCART score were observed between the groups. CONCLUSIONS: ACL reconstruction does not appear to reduce the outcomes (at 2 years) of HD-ACI.

Effect of vertical stopcock position on start-up fluid delivery in syringe pumps used for microinfusions.

The purpose of this in vitro study was to evaluate the impact of the vertical level of the stopcock connecting the infusion line to the central venous catheter on start-up fluid delivery in microinfusions. Start-up fluid delivery was measured under standardized conditions with the syringe outlet and liquid flow sensors positioned at heart level (0 cm) and exposed to a simulated CVP of 10 mmHg at a set flow rate of 1 ml/h. Flow and intraluminal pressures were measured with the infusion line connected to the stopcock primarily placed at vertical levels of 0 cm, + 30 cm and - 30 cm or primarily placed at 0 cm and secondarily, after connecting the infusion line, displaced to + 30 cm and - 30 cm. Start-up fluid delivery 10 s after opening the stopcock placed at zero level and after opening the stopcock primarily connected at zero level and secondary displaced to vertical levels of + 30 cm and - 30 cm were similar (- 10.52 [- 13.85 to - 7.19] µL; - 8.84 [- 12.34 to - 5.33] µL and - 11.19 [- 13.71 to - 8.67] µL (p = 0.469)). Fluid delivered at 360 s related to 65% (zero level), 71% (+ 30 cm) and 67% (- 30 cm) of calculated infusion volume (p = 0.395). Start-up fluid delivery with the stopcock primarily placed at + 30 cm and - 30 cm resulted in large anterograde and retrograde fluid volumes of 34.39 [33.43 to 35.34] µL and - 24.90 [- 27.79 to - 22.01] µL at 10 s, respectively (p < 0.0001). Fluid delivered with the stopcock primarily placed at + 30 cm and - 30 cm resulted in 140% and 35% of calculated volume at 360 s, respectively (p < 0.0001). Syringe infusion pumps should ideally be connected to the stopcock positioned at heart level in order to minimize the amounts of anterograde and retrograde fluid volumes after opening of the stopcock.

A Polyherbal Mixture with Nutraceutical Properties for Ruminants: A Meta-Analysis and Review of BioCholine Powder.

BioCholine Powder is a polyherbal feed additive composed of Achyrantes aspera, Trachyspermum ammi, Azadirachta indica, and Citrullus colocynthis. The objective of this study was to analyze published results that support the hypothesis that the polyherbal product BioCholine Powder has rumen bypass choline metabolites through a meta-analysis and effect size analysis (ES). Using Scopus, Web of Science, ScienceDirect, PubMed, and university dissertation databases, a systematic search was conducted for experiments published in scientific documents that evaluated the effects of BioCholine supplementation on the variables of interest. The analyzed data were extracted from twenty-one publications (fifteen scientific articles, three abstracts, and three graduate dissertations available in institutional libraries). The studies included lamb growing-finishing, lactating ewes and goats, calves, and dairy cows. The effects of BioCholine were analyzed using random effects statistical models to compare the weighted mean difference (WMD) between BioCholine-supplemented ruminants and controls (no BioCholine). Heterogeneity was explored, and three subgroup analyses were performed for doses [(4 (or 5 g/d), 8 (10 g/d)], supplementation in gestating and lactating ewes (pre- and postpartum supplementation), and blood metabolites by species and physiological state (lactating goats, calves, lambs, ewes). Supplementation with BioCholine in sheep increased the average daily lamb gain (p < 0.05), final body weight (p < 0.01), and daily milk yield (p < 0.05) without effects on intake or feed conversion. Milk yield was improved in small ruminants with BioCholine prepartum supplementation (p < 0.10). BioCholine supplementation decreased blood urea (p < 0.01) and increased levels of the liver enzymes alanine transaminase (ALT; p < 0.10) and albumin (p < 0.001). BioCholine doses over 8 g/d increased blood glucose, albumin (p < 0.10), cholesterol, total protein, and globulin (p < 0.05). The ES values of BioCholine in retained energy over the control in growing lambs were +7.15% NEm (p < 0.10) and +9.25% NEg (p < 0.10). In conclusion, adding BioCholine Powder to domestic ruminants' diets improves productive performance, blood metabolite indicators of protein metabolism, and liver health, showing its nutraceutical properties where phosphatidylcholine prevails as an alternative that can meet the choline requirements in ruminants.

Mechanisms of copper and zinc bioremoval by microalgae and bacteria grown in nutrient rich wastewaters.

Swine farming produces large quantities of nutrient-rich wastewater, which often contains metals such as Cu and Zn, used as feed additives for pigs. These metals must be removed from the wastewater before discharge but their retention in the biomass can limit its subsequent utilization. Photobioreactors are a very promising alternative for swine wastewater treatment, as the consortium of microalgae and bacteria growing symbiotically in these reactors allows high nutrient and metal removal efficiency at moderate costs. This work studies the mechanisms of removal of Cu(II) and Zn(II) by the two types of microorganisms growing in these photobioreactors. A microalga commonly used in wastewater treatment (Scenedesmus almeriensis) and an activated sludge were kept in contact with synthetic wastewater containing 100 mg/L of Cu and Zn. After 72 h, Scenedesmus almeriensis removed 43% of Cu and 45% of Zn, while activated sludge removed 78% of Cu and 96% of Zn. Single and sequential extractions of the biomasses using different extracting reagents revealed that biosorption on protonable groups is the dominant removal mechanisms. Mild reagents solubilized 69% of Cu and 94% of Zn from the microalgae and 76% of Cu and 93% of Zn from the activated sludge. Low metal concentrations in the oxidizable and residual fractions evidenced minimal bioaccumulation inside the cells. FTIR and ESEM-EDX analysis confirmed biosorption by ion exchange and complexation as the main metal remediation mechanisms. The weak bonds of the biosorbed Cu and Zn ions are beneficial for the valorization of biomass and the obtaining of safe bioproducts.

Cryptic circulation of chikungunya virus in São Jose do Rio Preto, Brazil, 2015-2019.

BACKGROUND: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent. METHODOLOGY/PRINCIPAL FINDINGS: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR. CONCLUSIONS/SIGNIFICANCE: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention.