COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

Targeting heme in sickle cell disease: new perspectives on priapism treatment.

Men with sickle cell disease (SCD) frequently experience priapism, defined as prolonged, painful erections occurring without sexual arousal or desire. This urological emergency can lead to penile fibrosis and permanent erectile dysfunction if not treated adequately. Due to its complex pathophysiology, there is currently no effective preventative treatment for this condition. Recent studies have highlighted the dysfunction of the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) pathway in erectile tissues as a critical mechanism in developing priapism in SCD. Additionally, further research indicates that intravascular hemolysis promotes increased smooth muscle relaxation in the corpus cavernosum and that excess heme may significantly contribute to priapism in SCD. Pharmacological treatments should ideally target the pathophysiological basis of the disease. Agents that reduce excess free heme in the plasma have emerged as potential therapeutic candidates. This review explores the molecular mechanisms underlying the excess of heme in SCD and its contribution to developing priapism. We discuss pharmacological approaches targeting the excess free heme in the plasma, highlighting it as a potential therapeutic target for future interventions in managing priapism.

Altered sleep and diurnal consequences in women with dysmenorrhea: study from the EPISONO database.

PURPOSE: Our study aimed to identify alterations in sleep, inflammatory mediators, fatigue and quality of life in women with dysmenorrhea and compare them to women without dysmenorrhea. METHODS: The sample comprised 328 women from a Brazilian cross-sectional sleep study, EPISONO (2007), who had undergone 1-night polysomnography (PSG) type I and completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were used to assess levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The 2 groups were distributed based on the presence or absence of dysmenorrhea symptoms. RESULTS: Sleep efficiency was significantly lower in the group of women with dysmenorrhea (82.5% ± 13.8) compared to the non-dysmenorrhea group (86.2% ± 10.9). Dysmenorrhea was associated with significantly higher scores of fatigue and worse scores in the physical quality of life. No statistical differences were detected in inflammatory markers between the 2 groups. DISCUSSION: Fatigue and physical quality of life were presented in women with dysmenorrhea, as was reduced sleep efficiency, although no alteration on inflammatory markers were observed. CONCLUSION: These findings show that dysmenorrhea can have a deleterious effect on women's sleep, with repercussions on daily routines and quality of life.

Sleep disturbances associated with DEAF1 pathogenic variants.

Neurodevelopmental disorders and sleep disturbances share genetic risk factors. DEAF1 genetic variants are associated with rare syndromes in which sleep disturbances are commonly reported, yet the specific sleep disorders in these patients, and the molecular mechanisms underlying this association, are unknown. We aimed to pinpoint specific biological processes that may be disrupted by pathogenic variants in this gene, comparing a list of DEAF1 regulatory target genes with a list of insomnia-associated genes, and using the intersect gene list as the input for pathway enrichment analysis. Thirty-nine DEAF1 regulatory targets were also identified as insomnia-associated genes, and the intersecting gene list was found to be strongly associated with immune processes, ubiquitin-mediated proteolysis pathways and regulation of the cell cycle. This preliminary study highlights pathways that may be disrupted by DEAF1 pathogenic mutations and might be putative factors underlying the manifestation of insomnia in patients harboring such variants.

Isospora pichororei n. sp. (Chromista: Apicomplexa: Eimeriidae) from rufous-capped spinetails Synallaxis ruficapilla Vieillot, 1819 (Passeriformes: Furnariidae: Synallaxiinae) in South America.

Spinetails are a suboscine passerines of the genus Synallaxis Vieillot, 1818 which have great interest for ornithology, given the wide diversity of 37 species that are distributed throughout the Neotropical region. Despite this wide diversity and distribution, Synallaxis spp. have never been recorded as hosts of coccidian parasites. In this context, the current study describes a new species of Isospora Schneider, 1881 from rufous-capped spinetails Synallaxis ruficapilla Vieillot, 1819 captured in the Itatiaia National Park, which is a federal conservation unit in Southeastern Brazil. The oocysts of Isospora pichororei Genovez-Oliveira & Berto n. sp. are subspheroidal to ovoidal, measuring on average 25 by 21 µm. Micropyle is present, but discrete. Oocyst residuum absent, but one or two polar granules are present. Sporocysts are ellipsoidal with slightly pointed posterior end, measuring on average 17 by 10 µm. Stieda and sub-Stieda bodies are present. Sporocyst residuum is clustered among the vermiform sporozoites, which have striations, refractile bodies and nucleus. This morphology was different from the other Isospora spp. recorded in the host family Furnariidae. Molecular identification was targeted by the amplification and sequencing of a locus of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. This sequence had the highest similarity of 99.5% with a sequence deposited for Isospora oliveirai Ortúzar-Ferreira & Berto, 2020, which is a coccidian species that parasitizes suboscine tityrids Schiffornis virescens (Lafresnaye, 1838), also in the Itatiaia National Park. Phylogenetic analysis grouped some species in subclades, including I. pichororei with I. oliveirai; however, it was inconclusive in an expectation of parasite-host coevolution. Finally, I. pichororei is established as new to science, being the first description from Synallaxinae and the third description from Furnariidae. Furthermore, this is the first Isospora sp. from the host family Furnariidae to have a molecular supplementation by sequencing a locus of the cox1 gene of the mitochondrial genome.

Coccidia of Guinea fowls: Validity of recorded Eimeria spp. (Apicomplexa: Eimeriidae) and first molecular identification of Eimeria grenieri Yvoré & Aycardi, 1967.

Guinea fowls, Numida meleagris (L., 1758), are galliform birds native to sub-Saharan Africa, but introduced in several countries around the world for domestic breeding and/or animal production. This species is considered more resistant to disease by Eimeria spp. than other domestic galliform birds. Here we review the Eimeria spp. known to infect species of Numididae and provide the first molecular identification of an Eimeria sp. from Guinea fowls. There are currently 3 named eimerians from Guinea fowls; Eimeria numidae Pellerdy, 1962; Eimeria grenieri Yvoré and Aycardi, 1967; and Eimeria gorakhpuri Bhatia & Pande, 1967. We reviewed each of these species descriptions and documented their taxonomic shortcomings. From that, we suggest that E. gorakhpuri is a junior synonym of E. numidae. In conclusion, we have morphologically redescribed in detail E. grenieri from N. meleagris from Rio de Janeiro and provided molecular supplementation through sequencing of three non-overlapping loci in cox1 and cox3 genes and fragments of small and large subunit mitochondrial rDNA.

Removal of acephate and methamidophos from water: Coagulation and adsorptive treatment approaches.

Pesticides has transformed the agricultural industry, primarily by enhancing productivity. However, the indiscriminate use of such compounds can adversely affect human health and disrupt ecosystem balance. Limited knowledge exists regarding the removal of these compounds from water, particularly for organophosphate pesticides when employing conventional treatment technologies. Therefore, this study aimed to assess the removal of acephate (ACE) and methamidophos (MET) - considered priority pesticides in Brazil - from waters with high and low turbidity during the clarification process carried out with aluminum sulfate (AS) and ferric chloride (FC), either alone or combined with powdered activated carbon (PAC) adsorption. All water samples were submitted to solid phase extraction (SPE C18 cartridges) prior to acephate and methamidophos analysis by HPLC MS/MS. The clarification process with either AS or FC coagulant did not efficiently remove acephate or methamidophos and maximum average removal (27 %) was observed with waters of high turbidity when using ferric chloride as coagulant. Addition of mineral PAC was also ineffective for removing both pesticides. However, the use of vegetable PAC (10 mg/L) resulted in better removal percentages, up to 80%, but only for methamidophos. The limited removal rates were attributed to the high hydrophilicity of acephate and methamidophos, along with their neutral charge at coagulation pH. These factors hinder the interaction of such organophosphorus pesticides with the flocs formed during coagulation as well as with PAC surface.

Exploring the potential of all-aqueous immiscible systems for preparing complex biomaterials and cellular constructs.

All-aqueous immiscible systems derived from liquid-liquid phase separation of incompatible hydrophilic agents such as polymers and salts have found increasing interest in the biomedical and tissue engineering fields in the last few years. The unique characteristics of aqueous interfaces, namely their low interfacial tension and elevated permeability, as well as the non-toxic environment and high water content of the immiscible phases, confer to these systems optimal qualities for the development of biomaterials such as hydrogels and soft membranes, as well as for the preparation of in vitro tissues derived from cellular assembly. Here, we overview the main properties of these systems and present a critical review of recent strategies that have been used for the development of biomaterials with increased levels of complexity using all-aqueous immiscible phases and interfaces, and their potential as cell-confining environments for micropatterning approaches and the bioengineering of cell-rich structures. Importantly, due to the relatively recent emergence of these areas, several key design considerations are presented, in order to guide researchers in the field. Finally, the main present challenges, future directions, and adaptability to develop advanced materials with increased biomimicry and new potential applications are briefly evaluated.

Subjective sleep assessment in individuals with SYNGAP1-associated syndrome.

STUDY OBJECTIVES: Sleep disturbances are common in neurodevelopmental disorders (NDDs), affecting patients and caregivers' quality of life. SYNGAP1-associated syndrome, a rare NDD, is marked by intellectual disability, developmental delay, epilepsy, and sleep issues. However, research on sleep quality in these individuals is limited. This study aimed to evaluate genetic variants, epilepsy, and sleep patterns in SYNGAP1-associated syndrome patients and their caregivers. METHODS: An online survey was applied to 11 caregivers of individuals diagnosed with SYNGAP1-associated syndrome. Specific clinical inquiries were included, addressing childbirth, previous surgeries, and medication use. Inquiries about epilepsy included type of epilepsy, type and frequency of seizures, anti-seizure medications, and complementary non-pharmacological treatments. Children's Sleep Habits Questionnaire (CSHQ) was applied to assess the patients' sleep profile. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of caregivers. RESULTS: Genetic analysis showed heterozygous mutations in SYNGAP1, often leading to loss of function. Epilepsy was present in 82% of participants, with 77.8% having drug-resistant seizures. Using the Children's Sleep Habits Questionnaire (CSHQ), 81.8% of patients exhibited poor sleep habits, including bedtime resistance, anxiety, night awakenings, parasomnias, and daytime sleepiness. Caregivers also reported poor sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). CONCLUSIONS: This study highlights the high prevalence of epilepsy and sleep problems in SYNGAP1-associated syndrome, impacting both patients and caregivers. Further research is crucial to understand the syndrome's effects on sleep disturbances, emphasizing the need for targeted interventions to improve sleep quality in individuals with rare genetic syndromes and their caregivers.

Bioadhesive Polymeric Films Containing Rhamnolipids, An Innovative Antimicrobial Topical Formulation.

Acne affects most of the world's population, causing an impact on the self-esteem of adolescents and young adults. One of the causes is the presence of the bacteria Cutibacterium acnes which are part of the natural microbiota of the skin. Topical treatments consist of anti-inflammatory and antibiotics, which could select resistant strains. Alternatives to the antibiotic are biocomposites that have antimicrobial activity like biosurfactants which are produced by bacteria. An innovative way of applying these compounds is bioadhesive polymeric films that adhere to the skin and release the active principle topically. Rhamnolipids have great potential to be used in the treatment of acne because they present antimicrobial activity against C. acnes in low and safe concentrations (MIC of 15.62 µg/mL, CBM of 31.25 µg/mL and CC50 of 181.93 µg/mL). Four films with different rhamnolipids concentrations (0.0; 0.1; 0.2; and 0.3%, w/w) were obtained as to visual appearance, mass variation, thickness, density, solubility, pH, water vapor transmission, mechanical properties (folding endurance, bioadhesion strength, tensile strength, elongation at break and Young's modulus), scanning electron microscopy and infrared. The results show that these formulations had a homogeneous appearance; elastic mechanical properties; pH similar to human skin and bioadhesive. The polymeric films containing rhamnolipids were effective against C. acnes, in the in vitro test, at the three concentrations tested, the film with the highest concentration (0.3%, w/w) being the most promising for presenting the highest antimicrobial activity. Thus, the polymeric film containing rhamnolipids has the potential to be used in the treatment of acne.

The diagnostic and prognostic role of miR-146b-5p in differentiated thyroid carcinomas.

Introduction: Samples classified as indeterminate correspond to 10-20% of cytologies obtained by fine needle biopsy of thyroid nodules, preventing an adequate distinction between benign and malignant lesions and leading to diagnostic thyroidectomies that often prove unnecessary, as most cases are benign. Furthermore, although the vast majority of patients with differentiated thyroid cancer (DTC) have such a good prognosis that active surveillance is permitted as an initial therapeutic option, relapses are not rare, and a non-negligible number of patients experience poor outcomes. MicroRNAs (miR) emerge as potential biomarkers capable of helping to define more precise management of patients in all these situations. Methods: Aiming to investigate the clinical utility of miR-146b-5p in the diagnostic of thyroid nodules and evaluating its prognostic potential in a realworld setting, we studied 89 thyroid nodule samples, correlating miR-146b-5p expression with clinical tools such as the 8th edition from the American Joint Committee on Cancer (AJCC/UICC) and the American Thyroid Association Guideline Stratification Systems for the rate of recurrence (RR). Results: miR-146b-5p expression levels distinguished benign from malignant thyroid FNA samples (p< 0.0001). For indeterminate nodules, overexpression of miR-146b-5p with a cut-off of 0.497 was able to diagnose malignancy with a 90% accuracy; specificity=87.5%; sensitivity=100%. An increased expression of miR-146b-5p was associated with greater RR (p=0.015). A cut-off of 2.21 identified cases with more vascular involvement (p=0.013) and a cut-off of 2.420 was associated with a more advanced TNM stage (p-value=0.047). Discussion: We demonstrated that miR-146b5p expression in FNA samples is able to differentiate benign from malignant indeterminate nodules and is associated with an increased risk of recurrence and mortality, suggesting that this single miRNA may be a useful diagnostic and prognostic marker in the personalized management of DTC patients.

Kinesin binding as a shared pathway underlying the genetic basis of male factor infertility and insomnia.

OBJECTIVE: To study whether male factor infertility and insomnia share genetic risk variants and identify any molecular, cellular, and biologic interactions between these traits. DESIGN: The in silico study was performed. Two lists of genetic variants were manually curated through a literature review, one of those associated with male factor infertility and the other with insomnia. Genes were assigned to these variants to compose male factor infertility-associated (454 genes) and insomnia-associated (921 genes) gene lists. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Enrichment of biologic pathways and protein-protein interaction analysis. RESULT(S): Twenty-eight genes were common to both lists, representing a greater overlap than would be expected by chance. In the 28 genes contained in the intersection list, there was a significant enrichment of pathways related to kinesin binding. A protein-protein interaction analysis using the intersection list as input retrieved 25 nodes and indicated that two of them were kinesin-related proteins (PLEKHM2 and KCL1). CONCLUSION(S): The shared male factor infertility and insomnia genes, and the biologic pathways highlighted in this study, suggest that further functional investigations into the interplay between fertility and sleep are warranted.

Juvenile language disorders and their interaction with dentistry: a bibliometric analysis.

Language disorders may interfere with social integration and affectpersonal development. Beca-use the balance of the stomatognathic system can interfere with language, it is important for speech therapy and dentistry to work together, providing multidisciplinar y Healthcare. AIM: To analyze the 100 most frequently cited articles on language disorders in children and adolescents and assess the interplay with dentistry by means of a bibliometric analysis. MATERIALS AND METHOD: A search of the 100 most frequently cited articles up to December 2021 on language disorders was performed in the Web of Science Core Collection database. Four researchers extracted the data on number of citations, title, authors, country, year of publication, journals, study design, prevalent clinical conditions, and area of expertise. The analyses were performed using VOSviewer and Excel. RESULTS: The total number of citations ranged from 251 to 1,431. Four articles were cited more than 1,000 times. Bishop DVM (10 articles; 3,653 citations) and Tomblin JD (10 articles; 4,261 citations) were the most frequently cited authors. The institutions with the largest number of publications were the University of Oxford/England (11%) and the University of Kansas/USA (8%). Observational study design was the most frequent (77%). Autism spectrum disorder (18%) and dyslexia (14%) were the most broadly investigated clinical conditions. Speech-language pathology (32%) was the area of expertise with the largest number of articles, and none of the top 100 studies showed interplay with dentistry. CONCLUSION: The 100 most widely cited articles on language disorders are mostly observational, mainly address autism spectrum disorder, and are in the field of speech-language pathology No study reported interplay with dentistry.

Os disturbios de linguagem podem interferir na integrando social e afetar o desenvolvimento dos individuos. O trabalho multidisciplinar entre fonoaudiologia e odontologia é muito importante para a promogdo da saúde. O equilibrio do sistema estomatognático interfere na linguagem. OBJETIVO: Analisar os100 artigos mais citados sobre distúrbios de linguagem em criannas e adolescentes e verificar a interando com a odontologia por meio de análise bibliométrica. MATERIAL E MÉTODO: Foi realizada uma busca pelos 100 artigos mais citados sobre distúrbios de linguagem na base de dados Web of Science Core Collection até dezembro de 2021. Quatro pesquisadores extrairam os dados referentes a número de citanoes, titulo, autores, país, ano de publicando, periódicos, desenho de estudo, condinoes clínicas prevalentes e área de especializando. As análises foram realizadas utilizando VOSviewer e Excel. RESULTADOS: O número total de citanoes variou de 251 a 1.431. Quatro artigos foram citados mais de 1.000 vezes. Bishop DVM (10 artigos; 3.653 citanoes) e Tomblin JD (10 artigos; 4.261 citanoes) foram os autores mais frequentemente citados. As instituinoes com maior número de publicanoes foram a Universidade de Oxford/Inglaterra (11%) e a Universidade de Kansas/EUA (8%). O desenho de estudo observacional foi o mais frequente (77%). O transtorno do espectro autista (18%) e a dislexia (14%) foram as condinoes clínicas mais amplamente investigadas. A Fonoaudiologia (32%) foi a área de atuando com maior número de artigos e nenhum estudo, entre os top100, mostrou interando com a Odontologia. CONCLUSÃO: Os 100 artigos mais citados sobre distúrbios de linguagem sdo em sua maioria observacionais, abordam principalmente transtornos do espectro do autismo e estdo na área de fonoaudiologia. Nenhum estudo apresentou interando com a odontologia.

Population Dynamics is a Cancer Driver.

Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as cell turnover rate (CTOR). Despite being in steady state, tissues have different population dynamics and leading to diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimize the contribution of ANSEL in cancer growth.

The multidrug resistance protein 4 is expressed and functionally active in isolated bladder from pig.

Multidrug resistance proteins type 4 (MRP4) and 5 (MRP5) play pivotal roles in the transport of cyclic nucleotides in various tissues. However, their specific functions within the lower urinary tract remain relatively unexplored. This study aimed to investigate the effect of pharmacological inhibition of MRPs on cyclic nucleotide signaling in isolated pig bladder. The relaxation responses of the bladder were assessed in the presence of the MRP inhibitor, MK571. The temporal changes in intra- and extracellular levels of cAMP and cGMP in stimulated tissues were determined by mass spectrometry. The gene (ABCC4) and protein (MRP4) expression were also determined. MK571 administration resulted in a modest relaxation effect of approximately 26% in carbachol-precontracted bladders. The relaxation induced by phosphodiesterase inhibitors such as cilostazol, tadalafil, and sildenafil was significantly potentiated in the presence of MK571. In contrast, no significant potentiation was observed in the relaxation induced by substances elevating cAMP levels or stimulators of soluble guanylate cyclase. Following forskolin stimulation, both intracellular and extracellular cAMP concentrations increased by approximately 15.8-fold and 12-fold, respectively. Similarly, stimulation with tadalafil + BAY 41-2272 resulted in roughly 8.2-fold and 3.4-fold increases in intracellular and extracellular cGMP concentrations, respectively. The presence of MK571 reduced only the extracellular levels of cGMP. This study reveals the presence and function of MRP4 transporters within the porcine bladder and paves the way for future research exploring the role of this transporter in both underactive and overactive bladder disorders.NEW & NOTEWORTHY This study investigates the impact of pharmacological inhibition of MRP4 and MRP5 transporters on cyclic nucleotide signaling in isolated pig bladders. MK571 administration led to modest relaxation, with enhanced effects observed in the presence of phosphodiesterase inhibitors. However, substances elevating cAMP levels remained unaffected. MK571 selectively reduced extracellular cGMP levels. These findings shed light on the role of MRP4 transporters in the porcine bladder, opening avenues for further research into bladder disorders.

Effects of microplastics on the kidneys: a narrative review.

Microplastics (MPs) and nanoplastics are small synthetic organic polymer particles (<5 mm and <1 µm, respectively) that originate directly from plastic compounds or result from the degradation of plastic. These particles are a global concern because they are widely distributed in water, air, food, and soil, and recent scientific evidence has linked MPs to negative biological effects. Although these particles are difficult to detect in humans, MPs have been identified in different biological fluids and tissues, such as the placenta, lung, intestines, liver, blood, urine, and kidneys. Human exposure to MPs can occur by ingestion, inhalation, or dermal contact, potentially causing metabolic alterations. Data from experimental and clinical studies have revealed that the ability of MPs to promote inflammation, oxidative stress, and organ dysfunction and negatively affect clinical outcomes is associated with their accumulation in body fluids and tissues. Although evidence of the putative action of MPs in the human kidney is still scarce, there is growing interest in studying MPs in this organ. In addition, chronic kidney disease requires investigation because this condition is potentially prone to MP accumulation. The purpose of the present article is (i) to review the general aspects of MP generation, available analytic methods for identification, and the main known biological toxic effects; and (ii) to describe and critically analyze key experimental and clinical studies that support a role of MPs in kidney disease.

Association Between Depressive Symptoms, Cognitive Status, and the Dual-Task Performance Index in Older Adults: A Cross-Sectional Study.

The Performance Index (P-Index) is a measure for evaluating mobility-related dual-task performance in older adults. The identification of specific clinicodemographic factors predictive of P-Index scores, however, remains unclear. This cross-sectional study analyzed data from 120 community-dwelling older adults (average age 71.3 ± 11.23 years) to explore clinicodemographic variables that influence P-Index scores during the instrumented timed up and go test. Unadjusted analyses suggested several factors, including age, gender, body mass index, Mini-Mental Status Examination scores, functional reach test performance, history of falls, ethnicity, Geriatric Depression Scale scores, alcohol consumption, and educational levels, as potential predictors of P-Index. However, adjusted multinomial multiple regression analysis revealed Geriatric Depression Scale and Mini-Mental Status Examination scores as the exclusive independent predictors of P-Index classifications, segmented into high, intermediate, or low (percentiles ≤ 25, 26-74, or ≥ 75, respectively). A significant association was observed between the manifestation of depressive symptoms, lower Mini-Mental Status Examination scores, and reduced cognitive-motor performance. The findings implicate depressive symptoms and low cognitive performance as substantial impediments to optimal dual-task mobility within this cohort. Further studies are warranted to examine the efficacy of cognitive stimulation and antidepressant therapy, in augmenting mobility-related dual-task performance among older adults.

Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.

Despite presenting a worse prognosis and being associated with highly aggressive tumors, triple-negative breast cancer (TNBC) is characterized by the higher frequency of tumor-infiltrating lymphocytes, which have been implicated in better overall survival and response to therapy. Though recent studies have reported the capacity of B lymphocytes to recognize overly-expressed normal proteins, and tumor-associated antigens, how tumor development potentially modifies B cell response is yet to be elucidated. Our findings reveal distinct effects of 4T1 and E0771 murine tumor development on B cells in secondary lymphoid organs. Notably, we observe a significant expansion of total B cells and plasma cells in the tumor-draining lymph nodes (tDLNs) as early as 7 days after tumor challenge in both murine models, whereas changes in the spleen are less pronounced. Surprisingly, within the tumor microenvironment (TME) of both models, we detect distinct B cell subpopulations, but tumor development does not appear to cause major alterations in their frequency over time. Furthermore, our investigation into B cell regulatory phenotypes highlights that the B10 Breg phenotype remains unaffected in the evaluated tissues. Most importantly, we identified an increase in CD19 + LAG-3 + cells in tDLNs of both murine models. Interestingly, although CD19 + LAG-3 + cells represent a minor subset of total B cells (< 3%) in all evaluated tissues, most of these cells exhibit elevated expression of IgD, suggesting that LAG-3 may serve as an activation marker for B cells. Corroborating with these findings, we detected distinct cell cycle and proliferation genes alongside LAG-3 analyzing scRNA-Seq data from a cohort of TNBC patients. More importantly, our study suggests that the presence of LAG-3 B cells in breast tumors could be associated with a good prognosis, as patients with higher levels of LAG-3 B cell transcripts had a longer progression-free interval (PFI). This novel insight could pave the way for targeted therapies that harness the unique properties of LAG-3 + B cells, potentially offering new avenues for improving patient outcomes in TNBC. Further research is warranted to unravel the mechanistic pathways of these cells and to validate their prognostic value in larger, diverse patient cohorts.

Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction?

Methylglyoxal (MGO) is a highly reactive α-dicarbonyl compound formed endogenously from 3-carbon glycolytic intermediates. Methylglyoxal accumulated in plasma and urine of hyperglycemic and diabetic individuals acts as a potent peptide glycation molecule, giving rise to advanced glycation end products (AGEs) like arginine-derived hydroimidazolone (MG-H1) and carboxyethyl-lysine (CEL). Methylglyoxal-derived AGEs exert their effects mostly via activation of RAGE, a cell surface receptor that initiates multiple intracellular signaling pathways, favoring a pro-oxidant environment through NADPH oxidase activation and generation of high levels of reactive oxygen species (ROS). Diabetic bladder dysfunction is a bothersome urological complication in patients with poorly controlled diabetes mellitus and may comprise overactive bladder, urge incontinence, poor emptying, dribbling, incomplete emptying of the bladder, and urinary retention. Preclinical models of type 1 and type 2 diabetes have further confirmed the relationship between diabetes and voiding dysfunction. Interestingly, healthy mice supplemented with MGO for prolonged periods exhibit in vivo and in vitro bladder dysfunction, which is accompanied by increased AGE formation and RAGE expression, as well as by ROS overproduction in bladder tissues. Drugs reported to scavenge MGO and to inactivate AGEs like metformin, polyphenols, and alagebrium (ALT-711) have shown favorable outcomes on bladder dysfunction in diabetic obese leptin-deficient and MGO-exposed mice. Therefore, MGO, AGEs, and RAGE levels may be critically involved in the pathogenesis of bladder dysfunction in diabetic individuals. However, there are no clinical trials designed to test drugs that selectively inhibit the MGO-AGEs-RAGE signaling, aiming to reduce the manifestations of diabetes-associated bladder dysfunction. This review summarizes the current literature on the role of MGO-AGEs-RAGE-ROS axis in diabetes-associated bladder dysfunction. Drugs that directly inactivate MGO and ameliorate bladder dysfunction are also reviewed here.

A LC-MS/MS method for the simultaneous determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma and its clinical application in patients with chronic kidney disease.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry method for the determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma samples. Strata-X 33 µm solid-phase extraction cartridges were used for the extraction of the catecholamines from human plasma samples. The catecholamines were separated in a 150 × 3 mm Shim-pack GIST C18-AQ column with 3 µm particle size, placed in an oven at 40°C and perfused with 82% mobile phase A (acetonitrile-H2O; 90:10, v/v) + 0.4% acetic acid and 18% mobile phase B (deionized H2O) + 0.2% formic acid at a flow rate of 340 µl/min in isocratic mode. The injected volume was 4 µl and the run lasted 4 min. The method was linear from 0.1 to 20 ng/ml and the lower limit of quantification was 0.1 ng/ml for all analytes. The method was applied to evaluate the plasma levels of catecholamines in plasma of patients with chronic kidney disease and allowed the detection for the first time of circulating levels of the novel catecholamines 6-bromodopamine and 6-cyanodopamine.