Genomic investigations of unexplained acute hepatitis in children.

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

Author Correction: Photoredox catalysis using infrared light via triplet fusion upconversion.

In Fig. 1c of this Letter, the orange axis label of the graph should have read 'FDPP upconversion photoluminescence (AU)' instead of 'TTBP upconversion photoluminescence (AU)'. This has been corrected online.

Photoredox catalysis using infrared light via triplet fusion upconversion.

Recent advances in photoredox catalysis have made it possible to achieve various challenging synthetic transformations, polymerizations and surface modifications1-3. All of these reactions require ultraviolet- or visible-light stimuli; however, the use of visible-light irradiation has intrinsic challenges. For example, the penetration of visible light through most reaction media is very low, leading to problems in large-scale reactions. Moreover, reactants can compete with photocatalysts for the absorption of incident light, limiting the scope of the reactions. These problems can be overcome by the use of near-infrared light, which has a much higher penetration depth through various media, notably biological tissue4. Here we demonstrate various photoredox transformations under infrared radiation by utilizing the photophysical process of triplet fusion upconversion, a mechanism by which two low-energy photons are converted into a higher-energy photon. We show that this is a general strategy applicable to a wide range of photoredox reactions. We tune the upconversion components to adjust the output light, accessing both orange light and blue light from low-energy infrared light, by pairwise manipulation of the sensitizer and annihilator. We further demonstrate that the annihilator itself can be used as a photocatalyst, thus simplifying the reaction. This approach enables catalysis of high-energy transformations through several opaque barriers using low-energy infrared light.

Synthesis of polymeric nanoparticles by double emulsion and pH-driven: encapsulation of antibiotics and natural products for combating Escherichia coli infections.

The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.

Olive oil nanoemulsion containing curcumin: antimicrobial agent against multidrug-resistant bacteria.

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.

Brazilian Women in Paralympic Sports: Uncovering Historical Milestones in the Summer Paralympic Games.

The journey of Brazilian female Paralympians transcends mere statistical increases in women's participation. Behind the modest athlete growth lies the reality of women who are doubly marginalized by the intersection of gender and disability in an arena tailored for able-bodied men. Our study aimed to catalyze critical discourses surrounding the historical trajectory of Paralympic women's sports. Through a comprehensive documentary analysis based on the Brazilian Paralympic Committee's official documents from 1976 to 2021, we sought to shed light on this complex scenario. Numerically, Brazil's representation comprised 229 women who, predominantly, had physical impairments and engaged in individual sports. In addition to a sporting legacy deeply entrenched in physical rehabilitation with limited opportunities for team-based sports, we observed negative influences stemming from ableist and sexist narratives. A thorough investigation into Paralympic milestones revealed a multitude of social barriers and highlighted the significant impact of societal changes in reshaping athletic opportunities and challenging traditional stereotypes.

Cyclopropenimine-Mediated CO2 Activation for the Synthesis of Polyurethanes and Small-Molecule Carbonates and Carbamates.

Carbon dioxide (CO2) is an abundant C1 feedstock with tremendous potential to produce versatile building blocks in synthetic applications. Given the adverse impact of CO2 on the atmosphere, it is of paramount importance to devise strategies for upcycling it into useful materials, such as polymers and fine chemicals. To activate such stable molecule, superbases offer viable modes of binding to CO2. In this study, a superbase cyclopropenimine derivative was found to exhibit exceptional proficiency in activating CO2 and mediating its polymerization at ambient temperature and pressure for the synthesis of polyurethanes. The versatility of this reaction can be extended to monofunctional amines and alcohols, yielding a variety of functional carbonates and carbamates.

Anisotropic Multiexciton Quintet and Triplet Dynamics in Singlet Fission via Pulsed Electron Spin Resonance.

The quintet triplet-pair state may be generated upon singlet fission and is a critical intermediate that dictates the fate of excitons, which can be exploited for photovoltaics, information technologies, and biomedical imaging. In this report, we demonstrate that continuous-wave and pulsed electron spin resonance techniques such as phase-inverted echo-amplitude detected nutation (PEANUT), which have emerged as the primary tool for identifying the spin pathways in singlet fission, probe fundamentally different triplet-pair species. We directly observe that the generation rate of high-spin triplet pairs is dependent on the molecular orientation with respect to the static magnetic field. Moreover, we demonstrate that this observation can prevent incorrect analysis of continuous-wave electron spin resonance (cw-ESR) measurements and provide insight into the design of materials to target specific pathways that optimize exciton properties for specific applications.

Unraveling Triplet Formation Mechanisms in Acenothiophene Chromophores.

The evolution of molecular platforms for singlet fission (SF) chromophores has fueled the quest for new compounds capable of generating triplets quantitatively at fast time scales. As the exploration of molecular motifs for SF has diversified, a key challenge has emerged in identifying when the criteria for SF have been satisfied. Here, we show how covalently bound molecular dimers uniquely provide a set of characteristic optical markers that can be used to distinguish triplet pair formation from processes that generate an individual triplet. These markers are contained within (i) triplet charge-transfer excited state absorption features, (ii) kinetic signatures of triplet-triplet annihilation processes, and (iii) the modulation of triplet formation rates using bridging moieties between chromophores. Our assignments are verified by time-resolved electron paramagnetic resonance (EPR) measurements, which directly identify triplet pairs by their electron spin and polarization patterns. We apply these diagnostic criteria to dimers of acenothiophene derivatives in solution that were recently reported to undergo efficient intermolecular SF in condensed media. While the electronic structure of these heteroatom-containing chromophores can be broadly tuned, the effect of their enhanced spin-orbit coupling and low-energy nonbonding orbitals on their SF dynamics has not been fully determined. We find that SF is fast and efficient in tetracenothiophene but that anthradithiophene exhibits fast intersystem crossing due to modifications of the singlet and triplet excited state energies upon functionalization of the heterocycle. We conclude that it is not sufficient to assign SF based on comparisons of the triplet formation kinetics between monomer and multichromophore systems.

Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia.

Phosphomannomutase 2 (PMM2) deficiency causes Congenital Disorder of Glycosylation (PMM2-CDG), but does not have a recognised association with Inflammatory Bowel Disease (IBD). A distinct clinical syndrome of hyperinsulinism and autosomal recessive polycystic kidney disease (HIPKD) arises in the context of a specific variant in the PMM2 promotor, either in homozygosity, or compound heterozygous with a deleterious PMM2 variant. Here, we describe the development of IBD in three patients with PMM2-HIPKD, with onset of IBD at 0, 6, and 10 years of age. In each case, intestinal inflammation coincided with the unusual finding of gastric antral foveolar hyperplasia. IBD disease was of variable severity at onset but well controlled with conventional and first-line biologic treatment approaches. The organ-level pattern of disease manifestations in PMM2-HIPKD-IBD may reflect a loss of cis-acting regulatory control by hepatocyte nuclear factor 4 alpha (HNF4A). Analysis of published transcriptomic data suggests that IBD most likely arises due to an impact on epithelial cellular function. We identify a specific pattern of variation in PMM2 as a novel association of early-onset IBD with distinctive gastric pathology.

Antibiotic resistance profiles on pathogenic bacteria in the Brazilian environments.

The present study aimed to elaborate a review of multidrug-resistant (MDR) bacteria in soil, food, aquatic environments, cattle, poultry, and swine farms in Brazil. Initially, the literature database for published papers from 2012 to 2023 was Scientific Electronic Library Online (SciELO), U.S. National Library of Medicine (PubMed), and Google Scholar, through the descriptors: antimicrobial resistance, resistance profile, multidrug resistance, environmental bacteria, and pathogenic bacteria. The studies demonstrated the prevalence of pathogenic and resistant bacteria in environments that favor their rapid dissemination. Bacteria of medical importance, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Salmonella spp., Shigella spp., Vibrio spp., were present in samples from animal farms and foods, including cheese and milk, urban aquatic environments, hospital effluents, and shrimp farms. Studies suggested that important bacteria have been disseminated through different niches with easy contact with humans, animals, and food, demonstrating the danger of the emergence of increasingly difficult conditions for treating and controlling these infections. Thus, better understanding and characterizing the resistance profiles of bacteria in these regions, mainly referring to MDR bacteria, can help develop solutions to prevent the progression of this public health problem.

Body surface area is a predictor of maturity status in school children and adolescents.

BACKGROUND: Generally, Body surface area (BSA) changes significantly during growth and maturation. These increases portend a possible relationship between body size as determined by BSA with maturational status in children and adolescents. OBJECTIVE: To determine the relationship between maturity status (MS) obtained by non-invasive anthropometric methods and body surface area (BSA) in children and adolescents of both sexes in a regional population of Chile. Additionally, we sought to verify the type of linear or nonlinear relationship between MS and BSA in both sexes. METHODS: A descriptive (cross-sectional) study was designed in 950 children and adolescents of both sexes (539 males and 411 females). The age range ranged from 6.0 to 17.9 years. Anthropometric measurements were evaluated: body weight, standing height, sitting height. MS was assessed by means of two non-invasive anthropometric techniques. Both techniques predict peak years of growth velocity (APHV) through a regression equation for each sex. BSA (m2) was estimated by means of the Haycock equation. RESULTS: The R2 in the linear model is relatively lower (R2 = 0.80 to 0.89 in males and 0.74 to 0.66 in females) in relation to the nonlinear quadratic model (R2 = 0.81 in males and 0.76 to 0.69). The quadratic nonlinear quadratic model reflected an adequate fit (RMSE) for the data set, being in men (RMSE = 1.080 and 1.125), while in women (RMSE = 1.779 and 1.479). CONCLUSION: BSA is positively associated with MS determined by two non-invasive methods in Chilean children and adolescents: The nonlinear quadratic model was a better fit to the data distribution. The results suggest the use of BSA as a possible predictor of maturity status in Chilean youth.

Interplay between Magnetoresistance and Kondo Resonance in Radical Single-Molecule Junctions.

We report transport measurements on tunable single-molecule junctions of the organic perchlorotrityl radical molecule, contacted with gold electrodes at low temperature. The current-voltage characteristics of a subset of junctions shows zero-bias anomalies due to the Kondo effect and in addition elevated magnetoresistance (MR). Junctions without Kondo resonance reveal a much stronger MR. Furthermore, we show that the amplitude of the MR can be tuned by mechanically stretching the junction. On the basis of these findings, we attribute the high MR to an interference effect involving spin-dependent scattering at the metal-molecule interface and assign the Kondo effect to the unpaired spin located in the center of the molecule in asymmetric junctions.

Cross-Cultural Translation and Adaptation of the Perceived Recovery Status Scale to Brazilian Portuguese.

CONTEXT: One of the primary training variables, although often overlooked, is recovery level achieved before starting subsequent training sessions. To find a more practical measurement that is consonant with the daily training routine, the Perceived Recovery Status (PRS) scale is proposed. In this perspective, the present study aimed to translate and culturally adapt the PRS scale into Brazilian Portuguese. DESIGN: This was a clinical measurement. METHODS: The cross-cultural translation was performed according to guidelines. Linguistic validation consisted of 5 stages: forward translation, translation synthesis, back translation, analysis of inconsistencies, and cognitive debriefing. RESULTS: During forward translation, different interpretations were obtained from the 2 translators (versions V1 and V2). Supported by an expert committee, a combined version (V3) was obtained from V1 and V2. During back translation, different interpretations were obtained from the 2 translators (versions V4 and V5). Discrepancies, applicability, and cultural equivalence were documented and analyzed by the expert committee participating in the cross-cultural translation procedure. During the cognitive debriefing, a group of 5 Brazilian people from the general population were asked to participate in a cognitive debriefing to assess the comprehensibility of the translated items. CONCLUSIONS: The PRS was translated and culturally adapted to Brazilian Portuguese (PRS-Brasil).

Quantifying Exciton Transport in Singlet Fission Diblock Copolymers.

Singlet fission (SF) is a mechanism of exciton multiplication in organic chromophores, which has potential to drive highly efficient optoelectronic devices. Creating effective device architectures that operate by SF critically depends on electronic interactions across multiple length scales─from individual molecules to interchromophore interactions that facilitate multiexciton dephasing and exciton diffusion toward donor-acceptor interfaces. Therefore, it is imperative to understand the underpinnings of multiexciton transport and interfacial energy transfer in multichromophore systems. Interestingly, block copolymers (BCPs) can be designed to control multiscale interactions by tailoring the nature of the building blocks, yet SF dynamics are not well understood in these macromolecules. Here, we designed diblock copolymers comprising an inherent energy cleft at the interface between a block with pendent pentacene chromophores and an additional block with pendent tetracene chromophores. The singlet and triplet energy offset between the two blocks creates a driving force for exciton transport along the BCP chain in dilute solution. Using time-resolved optical spectroscopy, we have quantified the yields of key energy transfer steps, including both singlet and triplet energy transfer processes across the pentacene-tetracene interface. From this modular BCP architecture, we correlate the energy transfer time scales and relative yields with the length of each block. The ability to quantify these energy transfer processes provides valuable insights into exciton transport at critical length scales between bulk crystalline systems and small-molecule dimers─an area that has been underexplored.

Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts.

OBJECTIVE: Living donor liver transplantation (LDLT) using small grafts, especially left lobe grafts (H1234-MHV) (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved. METHODS: Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG (H1234-MHV) in a single Enterprise. The median graft-to-recipient weight ratio was 0.84%, with graft-to-recipient weight ratio <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right lobe graft (H5678) (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival. RESULTS: Graft survival rates at 1, 3, and 5 years were 94%, 90%, and 83%, respectively, with no differences between LLG (H1234-MHV) and RLG (H5678). Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed model for end-stage liver disease score and LLG (H1234-MHV) as independent risk factors for EAD and splenectomy as a protective factor (odds ratio: 0.09; P =0.03). For LLG (H1234-MHV)-LDLT, patients who underwent prereperfusion splenectomy tended to have better 1-year graft survival than those receiving postreperfusion splenectomy. CONCLUSIONS: LLG (H1234-MHV) are feasible in adult LDLT with excellent outcomes comparable to RLG (H5678). Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival.

Measuring effects of medication adherence on time-varying health outcomes using Bayesian dynamic linear models.

One of the most significant barriers to medication treatment is patients' non-adherence to a prescribed medication regimen. The extent of the impact of poor adherence on resulting health measures is often unknown, and typical analyses ignore the time-varying nature of adherence. This article develops a modeling framework for longitudinally recorded health measures modeled as a function of time-varying medication adherence. Our framework, which relies on normal Bayesian dynamic linear models (DLMs), accounts for time-varying covariates such as adherence and non-dynamic covariates such as baseline health characteristics. Standard inferential procedures for DLMs are inefficient when faced with infrequent and irregularly recorded response data. We develop an approach that relies on factoring the posterior density into a product of two terms: a marginal posterior density for the non-dynamic parameters, and a multivariate normal posterior density of the dynamic parameters conditional on the non-dynamic ones. This factorization leads to a two-stage process for inference in which the non-dynamic parameters can be inferred separately from the time-varying parameters. We demonstrate the application of this model to the time-varying effect of antihypertensive medication on blood pressure levels for a cohort of patients diagnosed with hypertension. Our model results are compared to ones in which adherence is incorporated through non-dynamic summaries.

Inferring medication adherence from time-varying health measures.

Medication adherence is a problem of widespread concern in clinical care. Poor adherence is a particular problem for patients with chronic diseases requiring long-term medication because poor adherence can result in less successful treatment outcomes and even preventable deaths. Existing methods to collect information about patient adherence are resource-intensive or do not successfully detect low-adherers with high accuracy. Acknowledging that health measures recorded at clinic visits are more reliably recorded than a patient's adherence, we have developed an approach to infer medication adherence rates based on longitudinally recorded health measures that are likely impacted by time-varying adherence behaviors. Our framework permits the inclusion of baseline health characteristics and socio-demographic data. We employ a modular inferential approach. First, we fit a two-component model on a training set of patients who have detailed adherence data obtained from electronic medication monitoring. One model component predicts adherence behaviors only from baseline health and socio-demographic information, and the other predicts longitudinal health measures given the adherence and baseline health measures. Posterior draws of relevant model parameters are simulated from this model using Markov chain Monte Carlo methods. Second, we develop an approach to infer medication adherence from the time-varying health measures using a sequential Monte Carlo algorithm applied to a new set of patients for whom no adherence data are available. We apply and evaluate the method on a cohort of hypertensive patients, using baseline health comorbidities, socio-demographic measures, and blood pressure measured over time to infer patients' adherence to antihypertensive medication.

Radio-cephalic fistula recovered with drainage to median basilic vein by straightening of the forearm cephalic vein: A case report.

The distal arteriovenous fistula (AVF) has less complications and better patency than the proximal fistula, when it works properly. The complications of outflow of the fistula are complex, and it is necessary to analyze all solutions to solve the problem. We introduce a novel approach to solve outflow problems of a radio-cephalic AVF by straightening of the forearm cephalic vein with drainage into the median basilic vein.

Socio-environmental disasters and their impacts: socioeconomic consequences of the oil spill in the northeast region of Brazil.

The 2019 oil spill was the biggest in Brazilian history. Oil was found along more than 3,000 km of the Brazilian coastline, mainly in the Northeast, in more than 1,000 localities. This article analyzes the disaster's damage using a sample of interviewers who were impacted - fishers, tourism and beach hawkers - distributed along 40 of the affected municipalities in the Northeast Region of Brazil. The socio-economic indicators obtained by the research show that the impacts were not homogeneous between the segments and cities researched. Localities specialized in tourism and with a workforce relatively more specialized in fishing were the most affected. Accordingly, the populations of fishers and beach hawkers suffered the most severe impacts in terms of income reduction and the sale of products. These agents report a negative impact of the disaster on their work activities of 73% (fishers) and 65% (beach vendors), while the lodging and food sectors reported losses in about 38% of the cases. The interviewees' health indicators demonstrated that the volunteers at the oil spill clean- up suffered damage due to the exposure experienced, evidencing the public health emergency dimension of the disaster.