Bipolar Camouflage: A Cerebellar Cognitive Affective Syndrome Case Report.

The cerebellar cognitive affective syndrome is a neuropsychiatric syndrome composed of affective (anxiety, depression, euphoria, and emotional lability) and cognitive symptoms (executive, attentional, and visuospatial deficits) that was described in the 1990s. We present the case of a 49-year-old woman with a history of an acute neurological episode at the age of 28, after which she reported a change in personality, brief and alternating periods of depression, hypomania, and mixed episodes, and cognitive impairment that had a major impact on her personal and occupational level of functioning. She was initially diagnosed with bipolar disorder, but a clinical, neuropsychological, and imaging re-evaluation prompted a diagnostic reconsideration in favor of a cerebellar cognitive affective syndrome. This enabled therapeutical and prognostic refinement. Here, we discuss the diagnostic challenges of this syndrome and the implications that an accurate diagnosis has for patients.

Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells.

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.

Advancing arteriovenous fistula needling: The role of physical exam and doppler ultrasound.

BACKGROUND: The success of haemodialysis (HD) critically depends on the effective use of arteriovenous fistulas (AVFs). The precise needling technique is vital to minimise complications and ensure functional vascular access. OBJECTIVE: This study assesses the effectiveness of a nursing consultation protocol, which integrates physical examination (PE) with Doppler Ultrasound (DUS), in preparing patients for the first AVF needling. DESIGN/PARTICIPANTS: A cross-sectional analysis at a Portuguese National Health Service Hospital engaged thirty new HD patients, four HD needling experienced nurses and one HD vascular access nurse. This study examines the accuracy of PE in assessing the matured AVF by the four nurses compared to a trained vascular access nurse encompassing systematic PE and DUS. MEASUREMENTS: The primary data incorporated AVF characteristics derived from PE (inspection, palpation, and auscultation) and DUS findings (vein depth, diameter, and blood flow). A secondary focus was evaluating the change in nurses' perceived needling complexity following the nursing consultation. RESULTS: The nursing consultation significantly enhanced the identification of crucial AVF features, such as accessory veins (p = 0.002), and improved the accuracy of AVF morphology assessments. This led to identifying longer needling tracks (p = 0.031) and a higher number of safe needling points (p = 0.016). Nurses reported a notable reduction in perceived complexity and potential adverse events following this method (p = 0.027). CONCLUSIONS: Integrating structured PE with DUS in a nursing consultation framework significantly improves the preparation for AVF needling. This approach enhances the efficiency and safety of AVF needling and boosts nurse confidence and patient care in HD settings.

Sofosbuvir Off-label Treatment of Yellow Fever Patients During an Outbreak in Brazil, 2018: A Cohort Study.

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.

Spectral characterization of a blue light-emitting micro-LED platform on skin-associated microbial chromophores.

The therapeutic application of blue light (380 - 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin, termed the skin microbiome. In conditions including acne vulgaris, blue light is thought to address this imbalance through the selective photoexcitation of microbial species expressing wavelength-specific chromophores, differentially affecting skin commensals and thus altering the relative species composition. However, the abundance and diversity of these chromophores across the skin microbiota remains poorly understood. Similarly, devices utilised for studies are often bulky and poorly characterised which if translated to therapy could result in reduced patient compliance. Here, we present a clinically viable micro-LED illumination platform with peak emission 450 nm (17 nm FWHM) and adjustable irradiance output to a maximum 0.55 ± 0.01 W/cm2, dependent upon the concentration of titanium dioxide nanoparticles applied to an accompanying flexible light extraction substrate. Utilising spectrometry approaches, we characterised the abundance of prospective blue light chromophores across skin commensal bacteria isolated from healthy volunteers. Of the strains surveyed 62.5% exhibited absorption peaks within the blue light spectrum, evidencing expression of carotenoid pigments (18.8%, 420-483 nm; Micrococcus luteus, Kocuria spp.), porphyrins (12.5%, 402-413 nm; Cutibacterium spp.) and potential flavins (31.2%, 420-425 nm; Staphylococcus and Dermacoccus spp.). We also present evidence of the capacity of these species to diminish irradiance output when combined with the micro-LED platform and in turn how exposure to low-dose blue light causes shifts in observed absorbance spectra peaks. Collectively these findings highlight a crucial deficit in understanding how microbial chromophores might shape response to blue light and in turn evidence of a micro-LED illumination platform with potential for clinical applications.

How can biomaterial-conjugated antimicrobial peptides fight bacteria and be protected from degradation?

The emergence of antibiotic-resistant bacteria is a serious threat to public health. Antimicrobial peptides (AMP) are a powerful alternative to antibiotics due to their low propensity to induce bacterial resistance. However, cytotoxicity and short half-lives have limited their clinical translation. To overcome these problems, AMP conjugation has gained relevance in the biomaterials field. Nevertheless, few studies describe the influence of conjugation on enzymatic protection, mechanism of action and antimicrobial efficacy. This review addresses this gap by providing a detailed comparison between conjugated and soluble AMP. Additionally, commonly employed chemical reactions and factors to consider when promoting AMP conjugation are reviewed. The overall results suggested that AMP conjugated onto biomaterials are specifically protected from degradation by trypsin and/or pepsin. However, sometimes, their antimicrobial efficacy was reduced. Due to limited conformational freedom in conjugated AMP, compared to their soluble forms, they appear to act initially by creating small protuberances on bacterial membranes that may lead to the alteration of membrane potential and/or formation of holes, triggering cell death. Overall, AMP conjugation onto biomaterials is a promising strategy to fight infection, particularly associated to the use of medical devices. Nonetheless, some details need to be addressed before conjugated AMP reach clinical practice. STATEMENT OF SIGNIFICANCE: Covalent conjugation of antimicrobial peptides (AMP) has been one of the most widely used strategies by bioengineers, in an attempt to not only protect AMP from proteolytic degradation, but also to prolong their residence time at the target tissue. However, an explanation for the mode of action of conjugated AMP is still lacking. This review extensively gathers works on AMP conjugation and puts forward a mechanism of action for AMP when conjugated onto biomaterials. The implications of AMP conjugation on antimicrobial activity, cytotoxicity and resistance to proteases are all discussed. A thorough review of commonly employed chemical reactions for this conjugation is also provided. Finally, details that need to be addressed for conjugated AMP to reach clinical practice are discussed.

Enhancing the epidemiological surveillance of SARS-CoV-2 using Sanger sequencing to identify circulating variants and recombinants.

Since the emergence of SARS-CoV-2 in December 2019, more than 12,000 mutations in the virus have been identified. These could cause changes in viral characteristics and directly impact global public health. The emergence of variants is a great concern due to the chance of increased transmissibility and infectivity. Sequencing for surveillance and monitoring circulating strains is extremely necessary as the early identification of new variants allows public health agencies to make faster and more effective decisions to contain the spread of the virus. In the present study, we identified circulating variants in samples collected in Belo Horizonte, Brazil, and detected a recombinant lineage using the Sanger method. The identification of lineages was done through gene amplification of SARS-CoV-2 by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). By using these specific fragments, we were able to differentiate one variant of interest and five circulating variants of concern. We were also able to detect recombinants. Randomly selected samples were sequenced by either Sanger or Next Generation Sequencing (NGS). Our findings validate the effectiveness of Sanger sequencing as a powerful tool for monitoring variants. It is easy to perform and allows the analysis of a larger number of samples in countries that cannot afford NGS.

Biotinylated Photocleavable Semiconductor Colloidal Quantum Dot Supraparticle Microlaser.

Luminescent supraparticles of colloidal semiconductor nanocrystals can act as microscopic lasers and are hugely attractive for biosensing, imaging, and drug delivery. However, biointerfacing these to increase functionality while retaining their main optical properties remains an unresolved challenge. Here, we propose and demonstrate red-emitting, silica-coated CdSxSe1-x/ZnS colloidal quantum dot supraparticles functionalized with a biotinylated photocleavable ligand. The success of each step of the synthesis is confirmed by scanning electron microscopy, energy dispersive X-ray and Fourier transform infrared spectroscopy, ζ-potential, and optical pumping measurements. The capture and release functionality of the supraparticle system is proven by binding to a neutravidin functionalized glass slide and subsequently cleaving off after UV-A irradiation. The biotinylated supraparticles still function as microlasers; e.g., a 9 µm diameter supraparticle has oscillating modes around 625 nm at a threshold of 58 mJ/cm2. This work is a first step toward using supraparticle lasers as enhanced labels for bionano applications.

Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol.

Introduction: SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses. Methods: To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. Results: The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). Discussion: Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.

Evaluation of humoral immune response after yellow fever infection: an observational study on patients from the 2017-2018 sylvatic outbreak in Brazil.

Between 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017-2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017-2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses.

One-Pot Microfluidics to Engineer Chitosan Nanoparticles Conjugated with Antimicrobial Peptides Using "Photoclick" Chemistry: Validation Using the Gastric Bacterium Helicobacter pylori.

Surface bioconjugation of antimicrobial peptides (AMP) onto nanoparticles (AMP-NP) is a complex, multistep, and time-consuming task. Herein, a microfluidic system for the one-pot production of AMP-NP was developed. Norbornene-modified chitosan was used for NP production (NorChit-NP), and thiolated-AMP was grafted on their surface via thiol-norbornene "photoclick" chemistry over exposure of two parallel UV LEDs. The MSI-78A was the AMP selected due to its high activity against a high priority (level 2) antibiotic-resistant gastric pathogen: Helicobacter pylori (H. pylori). AMP-NP (113 ± 43 nm; zeta potential 14.3 ± 7 mV) were stable in gastric settings without a cross-linker (up to 5 days in pH 1.2) and bactericidal against two highly pathogenic H. pylori strains (1011 NP/mL with 96 µg/mL MSI-78A). Eradication was faster for H. pylori 26695 (30 min) than for H. pylori J99 (24 h), which was explained by the lower minimum bactericidal concentration of soluble MSI-78A for H. pylori 26695 (32 µg/mL) than for H. pylori J99 (128 µg/mL). AMP-NP was bactericidal by inducing H. pylori cell membrane alterations, intracellular reorganization, generation of extracellular vesicles, and leakage of cytoplasmic contents (transmission electron microscopy). Moreover, NP were not cytotoxic against two gastric cell lines (AGS and MKN74, ATCC) at bactericidal concentrations. Overall, the designed microfluidic setup is a greener, simpler, and faster approach than the conventional methods to obtain AMP-NP. This technology can be further explored for the bioconjugation of other thiolated-compounds.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up.

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

Estimation of the main air pollutants from different biomasses under combustion atmospheres by artificial neural networks.

The production of biofuels to be used as bioenergy under combustion processes generates some gaseous emissions (CO, CO2, NOx, SOx, and other pollutants), affecting living organisms and requiring careful assessments. However, obtaining such information experimentally for data evaluation is costly and time-consuming and its in situ obtaining for regional biomasses (e.g., those from Northeast Brazil (NEB) is still a major challenge. This paper reports on the application of artificial neural networks (ANNs) for the prediction of the main air pollutants (CO, CO2, NO, and SO2) produced during the direct biomass combustion (N2/O2:80/20%) with the use of ultimate analysis (carbon, hydrogen, nitrogen, sulfur, and oxygen). 116 worldwide biomasses were used as input data, which is a relevant alternative to overcome the lack of experimental resources in NEB and obtain such information. Cross-validation was conducted with k-fold to optimize the ANNs and performance was analyzed with the use of statistical errors for accuracy assessments. The results showed an acceptable statistical performance for all architectures of ANNs, with 0.001-12.41% MAPE, 0.001-5.82 mg Nm-3 MAE, and 0.03-52.30 mg Nm-3 RMSE, highlighting the high precision of the emissions studied. On average, the differences between predicted and real values for CO, CO2, NO, and SO2 emissions from NEB biomasses were approximately 0.01%, 10-6%, 0.14%, and 0.05%, respectively. Pearson coefficient provided consistent results of concentration of the ultimate analysis in relation to the emissions studied and effectiveness of the test set in the developed models.

Preemptive use of ibuprofen and desensitizer decreases immediate tooth sensitivity after in-office bleaching: A triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: The authors evaluated the synergistic analgesic effect of preemptive administration of 400 mg of ibuprofen (IBU) and potassium fluoride 2% (KF2), both in isolation or combination, on the painful perception of tooth sensitivity after tooth bleaching. METHODS: Fifteen patients participated in this triple-blind, randomized, placebo-controlled clinical trial. The study used a crossover design for drug administration and a split-mouth design for desensitizer agent. Four paired groups were formed: IBU plus KF2 (IBU + KF2); IBU (IBU + placebo KF); KF2 (placebo IBU + KF2), and placebo (placebo IBU + placebo KF). The outcome measure was the perception of tooth sensitivity, assessed using a visual analog scale. Data were collected at 4 different times: immediately after tooth bleaching (baseline) and after 6, 30, and 54 hours. Statistical analysis was performed using the Friedman test and relative risk. RESULTS: IBU plus KF2 was found to be more effective in reducing tooth sensitivity immediately after bleaching (baseline) compared with the placebo group (P < .05). The risk of experiencing moderate or severe tooth sensitivity was approximately 4 times higher in the placebo group than in the IBU plus KF2 group (relative risk, 4.00; 95% CI, 1.01 to 15.81; P = .025). CONCLUSIONS: The combined use of 400 mg of IBU and KF2 appears to be beneficial in managing postbleaching tooth sensitivity. It provides a superior analgesic effect compared with placebo. PRACTICAL IMPLICATIONS: The preemptive administration of IBU plus KF2 reduces tooth sensitivity after tooth whitening when compared with placebo. This clinical trial was registered in the Brazilian Clinical Trials Registry Platform. The registration number is U1111-1249-8191.

Yellow fever virus infection in human hepatocyte cells triggers an imbalance in redox homeostasis with increased reactive oxygen species production, oxidative stress, and decreased antioxidant enzymes.

Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2'-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF.

Using spatiotemporal ratio analyses to quantitatively estimate water quality recovery of the Rio Doce.

The Fundão Dam breached on 5 November 2015 (the "Event"), resulting in the release of tailings, water, scoured sediment and/or soil, and other debris to downstream watercourses. Statistical analyses using historical and recent water quality measurements were conducted to assess the extent to which water quality in the Rio Doce was recovering to baseline conditions. A review of station- and/or parameter-specific water quality time series in the Rio Doce revealed two challenges: pre-Event data imbalance and seasonality. Due to the combined effects of these two factors, data gathered from Rio Doce water quality stations before the Event likely underestimated concentration ranges and limited the usefulness of common recovery assessment techniques such as times series and water quality standard exceedance analyses. These challenges were addressed by calculating quarterly and watershed-specific river-to-tributary ratios. R code was used to produce spatiotemporal time series for 44 investigated parameters that were measured both before and after the Event. The water quality recovery durations shown by the parameter- and/or region-specific river-to-tributary ratio time series indicated that (a) turbidity provides the most conservative measure for water quality recovery; (b) chemical parameters associated with the tailings, like manganese and iron recovered faster than turbidity; and (c) other investigated parameters unrelated to the tailings showed either no discernable impact or rapid recovery after the Event. The resulting parameter- and/or region-specific river-to-tributary ratio time series provided reliable and quantifiable estimates of water quality recovery durations. The water quality in the region furthest from Fundão Dam, in Espírito Santo, recovered one year after the Event, while water quality in the closest region to Fundão Dam, upstream of Risoleta Neves (Candonga) Dam, recovered 4.2 years after the Event. Integr Environ Assess Manag 2024;20:74-86. © 2023 Newfields Companies, LLC. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Single-cell profiling of MC1R-inhibited melanocytes.

The human red hair color (RHC) trait is caused by increased pheomelanin (red-yellow) and reduced eumelanin (black-brown) pigment in skin and hair due to diminished melanocortin 1 receptor (MC1R) function. In addition, individuals harboring the RHC trait are predisposed to melanoma development. While MC1R variants have been established as causative of RHC and are a well-defined risk factor for melanoma, it remains unclear mechanistically why decreased MC1R signaling alters pigmentation and increases melanoma susceptibility. Here, we use single-cell RNA sequencing (scRNA-seq) of melanocytes isolated from RHC mouse models to define a MC1R-inhibited Gene Signature (MiGS) comprising a large set of previously unidentified genes which may be implicated in melanogenesis and oncogenic transformation. We show that one of the candidate MiGS genes, TBX3, a well-known anti-senescence transcription factor implicated in melanoma progression, binds both E-box and T-box elements to regulate genes associated with melanogenesis and senescence bypass. Our results provide key insights into further mechanisms by which melanocytes with reduced MC1R signaling may regulate pigmentation and offer new candidates of study toward understanding how individuals with the RHC phenotype are predisposed to melanoma.

Neglect scoring modifications in the National Institutes of Health Stroke Scale improve right hemisphere stroke lesion volume prediction.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) does not equitably assess stroke severity in the two cerebral hemispheres. By attributing a maximum of two points for neglect and seven for language, it undervalues right hemisphere deficits. We aimed to investigate if NIHSS equally predicts right hemisphere lesion volumes in patients with and without neglect, and if a modification of the neglect scoring rules could increase its predictive capacity. METHODS: We analyzed a prospective cohort of acute right middle cerebral artery ischemic stroke patients. First, we calculated the correlation between NIHSS scores and lesion volume and analyzed the partial correlation of neglect. Then, we applied different modifications in the neglect scoring rules and investigated how they interfered with lesion volume predictive capacity. RESULTS: A total of 162 ischemic stroke patients were included, 108 with neglect and 54 without. The correlation between lesion volume and NIHSS was lower in patients with neglect (r = 0.540 vs. r = 0.219, p = 0.004) and neglect was a statistically significant covariate in the partial correlation analysis between NIHSS and lesion volume (p = 0.017). With the neglect score tripled and with the duplication or triplication of all neglect modalities, the correlation was significantly higher than with the standard NIHSS (p = 0.043, p = 0.005, p = 0.001, respectively). With these modifications, neglect was no longer a significant covariable in the partial correlation between lesion volume and NIHSS. CONCLUSION: A modification of NIHSS neglect scoring might improve the scale's capacity to predict lesion volume.

Waveguide-Integrated Colloidal Nanocrystal Supraparticle Lasers.

Supraparticle (SP) microlasers fabricated by the self-assembly of colloidal nanocrystals have great potential as coherent optical sources for integrated photonics. However, their deterministic placement for integration with other photonic elements remains an unsolved challenge. In this work, we demonstrate the manipulation and printing of individual SP microlasers, laying the foundation for their use in more complex photonic integrated circuits. We fabricate CdSxSe1-x/ZnS colloidal quantum dot (CQD) SPs with diameters from 4 to 20 µm and Q-factors of approximately 300 via an oil-in-water self-assembly process. Under a subnanosecond-pulse optical excitation at 532 nm, the laser threshold is reached at an average number of excitons per CQD of 2.6, with modes oscillating between 625 and 655 nm. Microtransfer printing is used to pick up individual CQD SPs from an initial substrate and move them to a different one without affecting their capability for lasing. As a proof of concept, a CQD SP is printed on the side of an SU-8 waveguide, and its modes are successfully coupled to the waveguide.