Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

CYB5R3 overexpression exhibits sexual dimorphism: Mitochondrial and metabolic adaptations in transgenic female mice during calorie restriction.

There is a pressing need to develop new strategies for enhancing health in the elderly and preventing the rise in age-related diseases. Calorie restriction without malnutrition (CR) stands among the different antiaging interventions. Lifelong CR leads to increased expression and activity of plasma membrane CYB5R3, and male mice overexpressing CYB5R3 exhibit some beneficial adaptations that are also seen with CR. However, the mechanisms involved in both interventions could be independent since key aspects of energy metabolism and tissue lipid profile do not coincide, and many of the changes induced by CR in mitochondrial abundance and dynamics in the liver and skeletal muscle could be counteracted by CYB5R3 overexpression. In this study, we sought to elucidate the impact of CR on key markers of metabolic status, mitochondrial function, and pro-oxidant/antioxidant balance in transgenic (TG) female mice overexpressing CYB5R3 compared to their WT littermates. In females fed ad libitum, CYB5R3 overexpression decreased fat mass, led to a preferred utilization of fatty acids as an energy source, upregulated key antioxidant enzymes, and boosted respiration both in skeletal muscle and liver mitochondria, supporting that CYB5R3 overexpression is phenotypic closer to CR in females than in males. Whereas some markers of mitochondrial biogenesis and dynamics were found decreased in TG females on CR, as also found for the levels of Estrogen Receptor α, mitochondrial abundance and activity were maintained both in skeletal muscle and in liver. Our results reveal overlapping metabolic adaptations resulting from the overexpression of CYB5R3 and CR in females, but a specific crosstalk occurs when both interventions are combined, differing from the adaptations observed in TG males.

Physical, Thermal, and Optical Properties of Mn2+ and Nd3+ Containing Barium Phosphate Glasses.

This work reports on various properties and analysis of optical interactions in phosphate glasses containing red-emitting Mn2+ and near-infrared (NIR)-emitting Nd3+ ions, which are of interest for energy applications and solar spectral converters. The glasses were made by melting with 50P2O5-(48 - x)BaO-2MnO-xNd2O3 (x = 0, 0.5, 1.0, and 2.0 mol %) nominal compositions and characterized by X-ray diffraction, density and related physical properties, differential scanning calorimetry, dilatometry, UV-vis-NIR optical absorption, and photoluminescence spectroscopy with decay kinetics analysis. The glasses were X-ray amorphous, wherein the physical and thermal properties of the Mn2+/Nd3+-codoped glasses were largely impacted by Nd2O3 contents. The optical absorption spectra supported the occurrence of Mn2+ ions and the lack of Mn3+ in the codoped glasses, while the absorption due to Nd3+ ions increased steadily with Nd2O3 contents. Analyzing the glass absorption edges via Tauc and Urbach plots was further pursued for a comparison. The photoluminescence evaluation showed a consistent suppression of the emission from Mn2+ ions with increasing Nd3+ concentration, while the decay kinetics revealed shorter lifetimes in connection with increased Mn2+ → Nd3+ transfer efficiencies. Excitation of Mn2+ at 410 nm, however, led to the Nd3+ NIR emission being most intense for 1.0 mol % Nd2O3, despite the 4F3/2 emission decay analysis showing lifetime shortening throughout. Considering the compromise between red and NIR emissions, the Mn-containing glass doped with 0.5 mol % Nd2O3 is put in perspective with the concept of solar spectral conversion.

Heme utilization by the enterococci.

Heme consists of a tetrapyrrole ring ligating an iron ion and has important roles in biological systems. While well-known as the oxygen-binding molecule within hemoglobin of mammals, heme is also cofactor for several enzymes and a major iron source for bacteria within the host. The enterococci are a diverse group of Gram-positive bacteria that exist primarily within the gastrointestinal tract of animals. However, some species within this genus can transform into formidable opportunistic pathogens, largely owing to their extraordinary adaptability to hostile environments. Although enterococci cannot synthesize heme nor depend on heme to grow, several species within the genus encode proteins that utilize heme as a cofactor, which appears to increase their fitness and ability to thrive in challenging environments. This includes more efficient energy generation via aerobic respiration and protection from reactive oxygen species. Here, we review the significance of heme to enterococci, primarily the major human pathogen Enterococcus faecalis, use bioinformatics to assess the prevalence of hemoproteins throughout the genus, and highlight recent studies that underscore the central role of the heme-E. faecalis relationship in host-pathogen dynamics and interspecies bacterial interactions.

Enhancing Post-Mastectomy Care: Telehealth's Impact on Breast Reconstruction Accessibility for Breast Cancer Patients.

OBJECTIVE: To examine how the recent sharp rise in telemedicine has impacted trends in accessibility of breast reconstruction (BR). PATIENTS AND METHODS: A retrospective study reviewed patients who underwent a total mastectomy at our institution from 1 August 2016 to 31 January 2022. By comparing cohorts before and during the widespread implementation of telemedicine, we assessed telehealth's impact on healthcare accessibility, measured by distance from patients' residences to our institution. RESULTS: A total of 359 patients were included in this study. Of those, 176 received total mastectomy prior to the availability of telemedicine, and 183 in the subsequent period. There were similar baseline characteristics among patients undergoing mastectomy, including distance from place of residence to hospital (p = 0.67). The same proportion elected to receive BR between groups (p = 0.22). Those declining BR traveled similar distances as those electing the procedure, both before the era of widespread telemedicine adoption (40.3 and 35.6 miles, p = 0.56) and during the height of telemedicine use (22.3 and 61.3 miles, p = 0.26). When tracking follow-up care, significantly more patients during the pandemic pursued at least one follow-up visit with their original surgical team, indicative of the increased utilization of telehealth services. CONCLUSIONS: While the rate of BR remained unchanged during the pandemic, our findings reveal significant shifts in healthcare utilization, highly attributed to the surge in telehealth adoption. This suggests a transformative impact on breast cancer care, emphasizing the need for continued exploration of telemedicine's role in enhancing accessibility and patient follow-up in the post-pandemic era.

Genome Characterization and Phylogenetic Analysis of Scale Drop Disease Virus Isolated from Asian Seabass (Lates calcarifer).

Scale drop disease virus (SDDV), a double-stranded DNA virus in the family Iridoviridae, has been reported widely in southeast Asian countries as a causative agent of scale drop syndrome (SDS) in Asian seabass. SDS has resulted in high mortality and significant economic losses to the aquaculture industry. This study demonstrated the use of metagenomic methods to investigate bacterial and viral communities present in infected fish tissues and recover a complete genome of the causative agent named SDDV TH7_2019. Characterization of the TH7_2019 genome revealed a genome size of 131 kb with 134 putative ORFs encoding viral proteins potentially associated with host apoptosis manipulation. A comparative genome analysis showed a high degree of amino acid identity across SDDV strains, with variations in number of repeat sequences and mutations within core genes. Phylogenetic analyses indicate a close relationship among SDDV genomes. This research enhances our understanding of the genetic diversity and evolutionary relationship of SDDV, contributing valuable insights for further development of effective control strategies of SDDV.

The Fluorescent Cell Line SW620-GFP Is a Valuable Model to Monitor Magnetic Hyperthermia.

In this work, the cell line SW620-GFP has been used in a complete magnetic hyperthermia assay, from the preparation of the ferrofluid with folate-coated iron oxide nanoparticles to in vivo experiments. The physical and chemical characterization of the nanoparticles evidenced their superparamagnetic behaviour, an average diameter of 12 ± 4 nm, a 2 nm coat thickness, and a high-power loss density. The main innovation of the work is the exclusive capability of viable SW620-GFP cells to emit fluorescence, enabling fast analysis of both, cell viability in vitro with an epifluorescence microscope and tumour size and shape in vivo in a non-invasive manner using the iBox technology. Moreover, with this imaging technique, it was possible to demonstrate the successful tumour size reduction in mice applying magnetic hyperthermia three times a week over 3 weeks.

Contrasting Disease Progression, Microglia Reactivity, Tolerance, and Resistance to Toxoplasma gondii Infection in Two Mouse Strains.

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with the previously documented outcomes in BALB/c mice using an identical ocular route and parasite burden (2 × 105 tachyzoites), with saline as the control. Contrary to expectations, the Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while the survivors exhibited no apparent signs of infection. Comparative analysis revealed the T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while the infected Swiss albino mice showed enhanced avoidance responses. There was an important increase in microglial cells in the dentate gyrus molecular layer of the infected Swiss albino mice compared to the BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses identified three microglial morphological clusters, differentially affected by T. gondii infection across strains. The BALB/c mice exhibited increased microglial branching and complexity, while the Swiss albino mice showed reduced shrunken microglial arbors, diminishing their morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory regulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and resistance. Understanding these elements is critical in devising control measures for toxoplasmosis.

Retinal Vascular and Structural Changes in the Murine Alzheimer's APPNL-F/NL-F Model from 6 to 20 Months.

Alzheimer's disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities.

Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis. Emerging studies emphasize cellular senescence as a key mechanism implicated in the pathobiology of age-related diseases, including pulmonary fibrosis. Cellular senescence, marked by antagonistic pleiotropy, and the complex interplay with immunity, are pivotal in comprehending many aspects of lung fibrosis. Here, we review progress in novel concepts in cellular senescence, its association with the dysregulation of the immune response, and the evidence underlining its detrimental role in fibrosing ILDs.

Development of PLA-Waste Paper Biocomposites with High Cellulose Content.

In this study, the integration of paper industry waste with high cellulose content into biocomposites of polylactic acid (PLA), a widely used biobased polymer material, was investigated. The PLA/waste biocomposite samples (0-25 wt.%) were manufactured using the extrusion and injection moulding techniques. The mechanical test results showed improvements in terms of tensile properties and a decrease in impact strength as the percentage of residue increased. The melting temperature decreased, and the crystallinity increased in all biocomposites according to the Differential Scanning Calorimetry (DSC) analysis. Water absorption increased proportionally with the percentage of residue, attributed to the higher cellulose content in the biocomposites, determined by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) techniques. The scanning electron microscopy (SEM) fracture analysis demonstrated effective reinforcement-matrix cohesion, supporting the previously observed behaviour of the analysed materials. This work highlights the potential of using waste from the paper industry as reinforcement in PLA matrices, opening new perspectives for sustainable applications in the framework of the manufacture of composite materials.

Impact of Chlorella vulgaris Intake Levels on Performance Parameters and Blood Health Markers in Broiler Chickens.

This systematic review examines the effects of cumulative Chlorella vulgaris intake levels on broiler chickens, focusing on growth performance and systemic health markers. The review establishes a clear relationship between cumulative C. vulgaris intake and significant outcomes in poultry nutrition and health through a detailed analysis of various studies. The correlation analysis revealed that cumulative C. vulgaris intake levels ranging from 0.8 to 718 g/bird influenced growth rates and feed efficiency, following sigmoid models. Specifically, intakes of approximately 20 g/bird maximized final body weight (R2 = 0.616, p < 0.001), cumulative body weight gain (R2 = 0.627, p < 0.001) and daily weight gain (R2 = 0.639, p < 0.001). The feed conversion ratio also improved with increasing C. vulgaris intakes up to this level, although this was non-significant (R2 = 0.289, p = 0.117). In addition, similar cumulative C. vulgaris intake levels impacted plasma health markers in broilers, leading to reductions in triacylglycerols and cholesterol and improvements in immunoglobulin levels. These findings underscore the importance of carefully calibrated C. vulgaris supplementation strategies to optimise poultry growth and health without adverse effects. Future research should focus on refining C. vulgaris dosing guidelines and further exploring its long-term effects and mechanisms of action to enhance poultry health and production sustainability.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (ß = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

The road ahead to successful BBB opening and drug-delivery with focused ultrasound.

This review delves into the innovative technology of Blood-Brain Barrier (BBB) opening with low-intensity focused ultrasound in combination with microbubbles (LIFU-MB), a promising therapeutic modality aimed at enhancing drug delivery to the central nervous system (CNS). The BBB's selective permeability, while crucial for neuroprotection, significantly hampers the efficacy of pharmacological treatments for CNS disorders. LIFU-MB emerges as a non-invasive and localized method to transiently increase BBB permeability, facilitating the delivery of therapeutic molecules. Here, we review the procedural stages of LIFU-MB interventions, including planning and preparation, sonication, evaluation, and delivery, highlighting the technological diversity and methodological challenges encountered in current clinical applications. With an emphasis on safety and efficacy, we discuss the crucial aspects of ultrasound delivery, microbubble administration, acoustic feedback monitoring and assessment of BBB permeability. Finally, we explore the critical choices for effective BBB opening with LIFU-MB, focusing on selecting therapeutic agents, optimizing delivery methods, and timing for delivery. Overcoming existing barriers to integrate this technology into clinical practice could potentially revolutionize CNS drug delivery and treatment paradigms in the near future.

Zinc-Catalyzed Cyclization of Alkynyl Derivatives: Substrate Scope and Mechanistic Insights.

Novel alkyl zinc complexes supported by acetamidate/thioacetamidate heteroscorpionate ligands have been successfully synthesized and characterized. These complexes exhibited different coordination modes depending on the electronic and steric effects of the acetamidate/thioacetamidate moiety. Their catalytic activity has been tested toward the hydroelementation reactions of alkynyl alcohol/acid substrates, affording the corresponding enol ether/unsaturated lactone products under mild reaction conditions. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl substrate]. DFT calculations supported a reaction mechanism through the formation of the catalytically active species, an alkoxide-zinc intermediate, by a protonolysis reaction of the Zn-alkyl bond with the alcohol group of the substrate. Based on the experimental and theoretical results, a catalytic cycle has been proposed.

pH-Dependent Effects in Nanofluidic Memristors.

Multipore membranes with nanofluidic diodes show memristive and current rectifying effects that can be controlled by the nanostructure asymmetry and ionic solution characteristics in addition to the frequency and amplitude of the electrical driving signal. Here, we show that the electrical conduction phenomena, which are modulated by the interaction between the pore surface charges and the solution mobile ions, allow for a pH-dependent neuromorphic-like potentiation of the membrane conductance by voltage pulses. Also, we demonstrate that arrangements of memristors can be employed in the design of electrochemical circuits for implementing logic functions and information processing in iontronics.

Modeling the relative influence of socio-demographic variables on post-acute COVID-19 quality of life.

Background: Post-acute sequelae of SARS-CoV-2, referred to as "long COVID", are a globally pervasive threat. While their many clinical determinants are commonly considered, their plausible social correlates are often overlooked. Methods: Here, we use data from a multinational prospective cohort study to compare social and clinical predictors of differences in quality of life with long COVID. We further measure the extent to which clinical intermediates may explain relationships between social variables and quality of life with long COVID. Findings: Beyond age, neuropsychological and rheumatological comorbidities, educational attainment, employment status, and female sex were important predictors of long COVID-associated quality of life days (long COVID QALDs). Furthermore, most of their associations could not be attributed to key long COVID-predicting comorbidities. In Norway, 90% (95% CI: 77%, 100%) of the adjusted association between belonging to the top two quintiles of educational attainment and long COVID QALDs was not explained by these clinical intermediates. The same was true for 86% (73%, 100%) and 93% (80%,100%) of the adjusted association between full-time employment and long COVID QALDs in the United Kingdom (UK) and Russia. Additionally, 77% (46%,100%) and 73% (52%, 94%) of the adjusted associations between female sex and long COVID QALDs in Norway and the UK were unexplained by the clinical mediators. Interpretation: Our findings highlight that socio-economic proxies and sex are key predictors of long COVID QALDs and that other (non-clinical) mechanisms drive their observed relationships. Importantly, we outline a multi-method, adaptable causal approach for evaluating the isolated contributions of social disparities to experiences with long COVID. Funding: UK Foreign, Commonwealth and Development Office; Wellcome Trust; Bill & Melinda Gates Foundation; Oxford COVID-19 Research Response Funding; UK National Institute for Health and Care Research; UK Medical Research Council; Public Health England; Liverpool Experimental Cancer Medicine Centre; Research Council of Norway; Vivaldi Invest A/S; South Eastern Norway Health Authority.

Understanding Public Perceptions of Nipple and Scar Characteristics After Chest Wall Masculinization Surgery.

BACKGROUND: Surgical chest masculinization procedures, especially gender-affirming top surgery (GATS), are becoming increasingly prevalent in the USA. While a variety of surgical techniques have been established as both safe and effective, there is limited research examining ideal aesthetic nipple appearance and incision scar pattern. This study employs patient images to understand the public's perception on top surgery outcomes when adjusting for BMI ranges and Fitzpatrick skin types. METHODS: Images from RealSelf modified via Adobe Photoshop depicted various scar types and nipple-areolar complex (NAC) sizes/positions. A Qualtrics survey was distributed utilizing Amazon Mechanical Turk. Statistical analysis was performed through JMP Pro 17 for ordinal and categorical values, with a p value less than or equal to 0.05 statistically significant. RESULTS: A moderately sized and laterally placed NAC was preferred. A transverse scar that resembles the pectoral border between the level of the inframammary fold and pectoral insertion was deemed most masculine and aesthetic. Majority of results demonstrated that this is unaffected by Fitzpatrick skin types. Increased BMI images impacted public preferences, as a nipple placed farther from the transverse incision (p = 0.04) and a transverse scar position closer to the IMF was preferred in higher BMI patients. CONCLUSIONS: An understanding of the most popular NAC and scar choices, as well as how these factors may differ when considering a Fitzpatrick skin type or BMI categorization was attained. This validates the importance of patient-centered approach when employing surgical techniques in GATS. Future studies intend to obtain reports from actual patients considering GATS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable.