Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 µL) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.

Immune cells and checkpoints in pancreatic adenocarcinoma: Association with clinical and pathological characteristics.

INTRODUCTION: Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics. METHODS: Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma. RESULTS: CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated. CONCLUSIONS: PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.

Human platelet lysate supports SH-SY5Y neuroblastoma cell proliferation and differentiation into a dopaminergic-like neuronal phenotype under xenogeneic-free culture conditions.

SH-SY5Y is a human neuroblastoma cell line that can be differentiated into several neuronal phenotypes, depending on culture conditions. For this reason, this cell line has been widely used as an in vitro model of neurodegenerative conditions, such as Parkinson's disease (PD). However, most studies published to date used fetal bovine serum (FBS) as culture medium supplement for SH-SY5Y cell differentiation. We report on the testing of human platelet lysate (hPL) as a culture medium supplement to support SH-SY5Y cell culture. Both standard hPL and a fibrinogen-depleted hPL (FD-hPL) formulation, which does not require the addition of anticoagulants to culture media, promoted an increase in SH-SY5Y cell proliferation in comparison to FBS, without compromising metabolic activity. SH-SY5Y cells cultured in hPL or FD-hPL also displayed a higher number of neurite extensions and stained positive for MAP2 and synaptophysin, in the absence of differentiation stimuli; reducing hPL or FD-hPL concentration to 1% v/v did not affect cell proliferation or metabolic activity. Furthermore, following treatment with retinoic acid (RA) and further stimulation with brain-derived neurotrophic factor (BDNF) and nerve growth factor beta (NGF-ß), the percentage of SH-SY5Y cells stained positive for dopaminergic neuronal differentiation markers (tyrosine hydroxylase [TH] and Dopamine Transporter [DAT]) was higher in hPL or FD-hPL than in FBS, and gene expression of dopaminergic markers TH, DAT, and DR2 was also detected. Overall, the data herein presented supports the use of hPL to differentiate SH-SY5Y cells into a neuronal phenotype with dopaminergic features, and the adoption of FD-hPL as a fully xenogeneic free alternative to FBS to support the use of SH-SY5Y cells as a neurodegeneration model.

A conceptual model for evaluating eco-efficiency of thermal spraying processes.

Thermal spraying (TS) is one of the main processes for obtaining surfaces with the desired protective properties in various industrial applications. TS is an energy-intensive treatment required to heat the application material and consumes different resources. To assess the environmental impact of TS, it becomes necessary to integrate an approach that jointly analyses and evaluates the economic and environmental variables influencing the system. The concept of eco-efficiency (EE) added to the TS process allows for assessing the environmental and economic condition through the survey and application of eco-indicators. The lack of an EE evaluation model for TS processes was identified based on literature searches. Thus, the overall objective of this work is to propose a conceptual model to evaluate the EE of TS treatment, selecting environmental and economic indicators considered more impactful in the process. The model developed consists of three main steps: (i) the input and output indicators (environmental and economic) are identified by applying the Analytic Hierarchy Process (AHP) method; (ii) the structure to be employed in the model is defined; and (iii) the Data Envelopment Analysis (DEA) model is applied to define the EE evaluation form. The proposed model consists of clear and easy-to-follow steps for evaluating the EE of spraying processes, filling the gap found in the literature. The use of DEA allowed the integration of the environmental and economic indicators obtained from the TS processes to generate important insights for evaluating EE. The results prove the model's effectiveness in identifying the EE results for each analysed unit of the TS process. The model has provided an evaluation consistent with the existing studies, and the EE scores were assessed according to twenty-one decision-making units (DMUs) allowing the identification of the most eco-efficient DMUs concerning TS processes.

Antimicrobial properties of hindered amine light stabilizers in polymer coating materials and their mechanism of action.

UV-stabilizers are a class of additives that provide extended polymer resistance to UV-degradation, but have also been suggested to have antimicrobial activity, potentially preventing the spread of pathogens, and inhibiting microbial-induced biodegradation. In this work, we incorporated different UV-stabilizers, a hindered amine light stabilizer (HALS), Tinuvin 770 DF and Tinuvin PA 123, or a hybrid HALS/UV-absorber, Tinuvin 5151, in polyurethane formulations to produce lacquer-films, and tested their antimicrobial activity against Staphylococcus aureus (methicillin-resistant and -sensitive strains), Escherichia coli and Candida albicans. Lacquer-films incorporated with Tinuvin 770 DF showed strong antimicrobial performance against bacteria and fungi, while maintaining cytocompatibility. The mechanism of action revealed a positive relationship between Tinuvin 770 DF concentration, microbial death, and reactive nitrogen species (RNS), suggesting that RNS produced during autoxidation of Tinuvin 770 DF is responsible for the antimicrobial properties of this UV-stabilizer. Conversely, lacquer-films incorporated with Tinuvin 5151 or Tinuvin PA 123 exhibited no antimicrobial properties. Collectively, these results highlight the commercial potential of Tinuvin 770 DF to prevent photo- and biodegradation of polymers, while also inhibiting the spread of potentially harmful pathogens. Furthermore, we provide a better understanding of the mechanism underlying the biocidal activity of HALS associated to autooxidation of the amine group.

Sex-dependent differences in macaque brain mitochondria.

Mitochondrial bioenergetics in females and males is different. However, whether mitochondria from male and female brains display differences in enzymes of oxidative phosphorylation remains unknown. Therefore, we characterized mitochondrial complexes from the brains of male and female macaques (Macaca mulatta). Cerebral tissue from male macaques exhibits elevated content and activity of mitochondrial complex I (NADH:ubiquinone oxidoreductase) and higher activity of complex II (succinate dehydrogenase) compared to females. No significant differences between sexes were found in the content of α-ketoglutarate dehydrogenase or in the activities of cytochrome c oxidase and F1Fo ATPase. Our results underscore the need for further investigations to elucidate sex-related mitochondrial differences in humans.

Agronomic performance and technological quality of sugarcane submitted to different poultry litter dosages.

Sugarcane is a central crop for sugar and ethanol production. Investing in sustainable practices can enhance productivity, technological quality, mitigate impacts, and contribute to a cleaner energy future. Among the factors that help increase the productivity of sugarcane, the physical, chemical and biological parameters of the soil are amongst the most important. The use of poultry litter has been an important alternative for soil improvement, as it acts as a soil conditioner. Therefore, this work aimed to verify the best doses of poultry litter for the vegetative, reproductive and technological components of sugarcane. The experiment was carried out at Usina Denusa Destilaria Nova União S/A in the municipality of Jandaia, GO. The experimental design used was a complete randomized block design with four replications: 5 × 4, totaling 20 experimental units. The evaluated factor consisted of four doses of poultry litter plus the control (0 (control), 2, 4, 6 and 8 t ha-1). In this study, were evaluated the number of tillers, lower stem diameter, average stem diameter, upper stem diameter, plant height, stem weight and productivity. The technological variables of total recoverable sugar, recoverable sugar, Brix, fiber, purity and percentage of oligosaccharides were also evaluated. It was observed, within the conditions of this experiment, that the insertion of poultry litter did not interfere significantly in most biometric, productive and technological variables of the sugarcane. But it can also be inferred that there was a statistical trend toward better results when the sugarcane was cultivated with 4 t ha-1 of poultry litter.

Long-term storage stability of PGL-I coated ELISA plates for anti-Mycobacterium leprae IgM detection.

The assessment of ELISA plates coated with phenolic glycolipid-I/PGL-I revealed excellent stability during eight years of storage at room temperature, promoting consistent IgM antibody detection in multibacillary leprosy patients. These stable, standardized plates can significantly contribute to efficient leprosy serology research and support its widespread distribution and use in endemic countries.

Right ventricle pierced by a traditional sharp hair straightener: a case report.

The case presents a traumatic ventricular perforation of a girl, accidentally felt on a sharp instrument. The uniqueness of the case presented is due to the very high infrequency of injuries with this type of sharp object. The 7-year-old girl was transported to the hospital after accidentally falling on a sharp instrument. The child had no signs of heart failure. On opening the chest, it was found that the metal object was lodged in the right ventricle. Quickly proceeded to remove the object and suture the entry hole. After a short hospitalization, the child was discharged completely cured.

Mycorrhizal fungi arbuscular in organic and conventional sugarcane systems.

Organic production systems are increasingly gaining market share; however, there are still few studies on their influence on the activity of soil microorganisms in sugarcane. Arbuscular mycorrhizal fungi are extremely sensitive to environmental changes, and their activity can be used as a parameter of comparison and quality between organic and conventional systems. The objective of this work was to evaluate mycorrhizal activity in different varieties of sugarcane under two production systems. This work was carried out in a commercial plantation of the Jalles Machado plant in the municipality of Goianésia in Goiás, Brazil. The values of spore density in the soil, mycorrhizal colonization rate in the roots and easily extractable glomalin were evaluated, and the associated fungal species were identified. There was no effect of sugarcane variety on the number of spores or the glomalin content in the soil. The conventional system presented significantly lower mycorrhizal colonization rates than did the organic system. The varieties cultivated under the conventional planting system showed a greater diversity of arbuscular mycorrhizal fungi, where 12 of the 13 different species of mycorrhizal fungi found in both cultivation systems occurred.

Production of antigens expressed in Nicotiana benthamiana plant and Escherichia coli for the SARS-CoV-2 IgG antibody detection by ELISA.

The recent COVID-19 pandemic disclosed a critical shortage of diagnostic kits worldwide, emphasizing the urgency of utilizing all resources available for the development and production of diagnostic tests. Different heterologous protein expression systems can be employed for antigen production. This study assessed novel SARS-CoV-2 proteins produced by a transient expression system in Nicotiana benthamiana utilizing an infectious clone vector based on pepper ringspot virus (PepRSV). These proteins included the truncated S1-N protein (spike protein N-terminus residues 12-316) and antigen N (nucleocapsid residues 37-402). Two other distinct SARS-CoV-2 antigens expressed in Escherichia coli were evaluated: QCoV9 chimeric antigen protein (spike protein residues 449-711 and nucleocapsid protein residues 160-406) and QCoV7 truncated antigen (nucleocapsid residues 37-402). ELISAs using the four antigens individually and the same panel of samples were performed for the detection of anti-SARS-CoV-2 IgG antibodies. Sensitivity was evaluated using 816 samples from 351 COVID-19 patients hospitalized between 5 and 65 days after symptoms onset; specificity was tested using 195 samples collected before 2018, from domiciliary contacts of leprosy patients. Our findings demonstrated consistent test sensitivity, ranging from 85 % to 88 % with specificity of 97.5 %, regardless of the SARS-CoV2 antigen and the expression system used for production. Our results highlight the potential of plant expression systems as useful alternative platforms to produce recombinant antigens and for the development of diagnostic tests, particularly in resource-constrained settings.

Older Adults' Continuance Intentions for Online Physical Exercise Classes.

During the COVID-19 pandemic, lockdowns and social distancing measures drove the shift from in-person to online physical exercise classes, leading individuals to explore these digital alternatives. Guided by the Expectation-Confirmation Model, this article examines older adults' intentions to continue using online physical exercise classes. Semi-structured interviews were conducted with 17 adults aged 65 and older who had participated in online physical exercise classes during the pandemic. Transcripts were subject to thematic analysis using the NVivo software program. The results indicate that older adults recognize the usefulness of online physical exercise classes because of their ability to enhance their health and well-being. Their initial expectations were surpassed, and they were generally satisfied with the experience. However, in-person classes remained preferred due to their enhanced benefits. They also felt that the adoption of online classes was involuntary; instead of an autonomous decision guided by their needs and preferences, this was a viable solution imposed by the lockdown. Therefore, their continuance intentions are limited to specific conditions, namely a new lockdown or other physical impediments. Still, considering the flexibility that online physical exercise classes offer, accommodating time and physical constraints, participants highlighted the advantages of a hybrid approach for those who may face challenges attending in-person classes. Based on the findings, this article proposes that ECM provides a relevant, yet insufficient, framework for explaining older adults' continuance intentions for online physical exercise classes, suggesting the inclusion of additional explaining factors: perceived usefulness of non-technological alternatives, necessary conditions, and self-determination.

Time-Dependent Risk for Recurrence in Survivors of Major Adverse Cardiovascular Events.

INTRODUCTION: The prevalence of the population with a history of an occlusive cardiovascular event has been increasing in recent years, which means that a large number of patients will have a higher risk of presenting a fatal recurrence. The aim is to determine variables associated with time-to-recurrent cardiovascular events and analyze how changes in low-density lipoprotein cholesterol (LDL-C) levels during follow-up may be associated with this time-to-event. MATERIALS AND METHODS: This is a prospective observational cohort study of 727 adults with a history of at least one occlusive cardiovascular event recruited at a referral hospital in northeastern Colombia. Data from a follow-up period of a maximum of 33 months (median 26 months) (one death) were used to define how clinical and sociodemographic variables impact the recurrence of major adverse cardiovascular events (MACE). Analyses were performed based on proportional hazard models and time-dependent hazard models. RESULTS: Upon enrollment, 215 (30%) of the participants reported experiencing their most recent cardiovascular event within the preceding year. After two years, the recurrence rate was 12.38% (90/727). The risk of recurrence before two years was 3.9% (95% CI 2.7-5.6). In the multiple models, the presence of severe depression gives a Hazard Ratio of 8.25 (95% CI 2.98-22.86) and LDL ≥120 md/dl Hazard Ratio of 2.12 (95% CI 1.2 -3.9). It was found that LDL >120 mg/dl maintained over time increases the chances of recurrence by 1.7% (Hazard Ratio: 1.017, 95% CI 0.008-0.025). CONCLUSIONS: The present study allows us to identify a profile of patients who should be treated promptly in an interdisciplinary manner to avoid recurrences of coronary events.

Assessment of the knowledge, attitudes, and practices toward human tuberculosis amongst rural communities in Chad.

Introduction: Tuberculosis (TB) is an infectious zoonotic disease caused by bacteria belonging to the Mycobacterium tuberculosis complex. In sub-Saharan African countries such as Chad, TB is endemic and causes a high burden on humans and animals through morbidity, mortality, and reduced productivity in livestock. To effectively prevent and control the disease, strong coordination between policymakers, health and veterinary services, civil society organizations, and communities is needed. It also requires an understanding of the knowledge the communities have regarding TB. However, such knowledge is under-investigated, especially in rural areas. How knowledge affects people's attitudes and practices is also unclear. The main objective of this study was to investigate the knowledge, attitudes, and practices (KAP) of Chadian rural communities to better involve them in TB surveillance programs. Methods: A survey was conducted in 2021 in five rural health centers. Face-to-face interviews were conducted with persons suspected of having TB, and data on KAP were recorded and analyzed. Results: In total, 139 participants were enrolled. Overall, the knowledge and attitude of the participants were found to be good to moderate, with 126 (90.6%) and 97 (69.7%) having good knowledge and attitude, respectively. However, their practices were found to be rather weak, with only 40 (28.7%) participants having good practices. Men were found to have good knowledge about the disease significantly more often than women. Poor attitude was significantly associated with a mobile lifestyle compared to settled lifestyles and with farmers (mainly engaged in agriculture) compared to breeders (livestock keepers). Poor health practices were associated more with men than women and with settled lifestyles compared to a mobile lifestyle. Good practices were found to be in line with good knowledge and good attitudes; however, in the analyses, the association was not significant [OR knowledge = 5.83 (95% C.I. 0.6842.83), p = 0.112; OR attitude = 2.09 (95% C.I. 0.875.04), p = 0.100]. Furthermore, attitude was not associated with knowledge [OR = 1.03 (95% C.I. 0.303.55), p = 0.964]. Discussion and conclusion: Our study highlights the need for targeted sensitization and awareness campaigns for communities with poor knowledge and attitudes regarding TB. These campaigns should also include practical training to increase the level of good practice rather than simply providing knowledge.

Systematic Review of Chemical Compounds with Immunomodulatory Action Isolated from African Medicinal Plants.

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.

Pre-Gestational Obesity and Gestational Weight Gain as Predictors of Childhood Obesity.

OBJECTIVE: To evaluate the associations of pre-gestational body mass index (BMI) and gestational weight gain (GWG) with the risks of overweight, obesity, and adiposity in the first seven years of life in the offspring of a cohort of pregnant women. METHODS: Analysis of 751 mothers and their children participating in the PROGRESS cohort. These women were recruited in Mexico City between 2007 and 2010. Pre-gestational BMI was classified as normal, overweight, and obesity according to the WHO. GWG was calculated as the difference between the last reported pre-pregnancy weight and the pre-gestational weight and categorized as inadequate, adequate, or excessive, according to US IOM recommendations. Children's anthropometry was evaluated at 4-5 and 6-7 years of age. Adiposity was classified into three groups: normal (BMI z-score and waist circumference), overweight (BMI z-score>1), and overweight plus abdominal obesity (OW+AO). A generalized structural equation model (GSEM) was constructed to account for the temporal relationship between variables and to assess direct and indirect effects. RESULTS: A total of 49.3% of the women had excessive (13.8 ± 4.2 kg) and 19.8% inadequate (3.15 ± 3.4 kg) GWG. Women with pre-gestational overweight or obesity were more likely to have excessive GWG (OR 1.9 [95% CI: 1.32, 2.74] and 3.50 [95% CI: 1.83, 6.69], respectively). In the GSEM, excessive GWG was directly associated with OW+AO at 4-5 years. At 6-7 years, pre-gestational obesity was associated with OW+AO. CONCLUSION: Pre-gestational obesity and excessive GWG were independent predictors of childhood obesity.

Genetic Diversity and Population Structure of the Invasive Oriental Fruit Fly, Bactrocera dorsalis (Diptera: Tephritidae) in Burkina Faso.

Bactrocera dorsalis Hendel is a highly invasive horticultural pest that is of major economic importance worldwide. In Burkina Faso, it is one of the main insect pests that affects the production and exportation of mangos. Understanding the biology and the genetic dynamics of this insect pest provides crucial information for the development of effective control measures. The aim of this study was to understand the distribution, diversity, and genetic structure of B. dorsalis in Burkina Faso. Male flies were collected transversally in Burkina Faso and analyzed by PCR using 10 microsatellite markers. The results showed an abundance of B. dorsalis varying from 87 to 2986 flies per trap per day at the different sampling sites. The genetic diversity was high at all sites, with an average Shannon's Information Index (I) of 0.72 per site. The gene flow was high between study populations and ranged from 10.62 to 27.53 migrants. Bayesian admixture analysis showed no evidence of structure, while Discriminant Analysis of Principal Components identified three weakly separated clusters in the population of B. dorsalis in Burkina Faso. The results of this study could be used to optimize the effectiveness of current control interventions and to guide the implementation of new, innovative, and sustainable strategies.

The discovery of novel noncoding RNAs in 50 bacterial genomes.

Structured noncoding RNAs (ncRNAs) contribute to many important cellular processes involving chemical catalysis, molecular recognition and gene regulation. Few ncRNA classes are broadly distributed among organisms from all three domains of life, but the list of rarer classes that exhibit surprisingly diverse functions is growing. We previously developed a computational pipeline that enables the near-comprehensive identification of structured ncRNAs expressed from individual bacterial genomes. The regions between protein coding genes are first sorted based on length and the fraction of guanosine and cytidine nucleotides. Long, GC-rich intergenic regions are then examined for sequence and structural similarity to other bacterial genomes. Herein, we describe the implementation of this pipeline on 50 bacterial genomes from varied phyla. More than 4700 candidate intergenic regions with the desired characteristics were identified, which yielded 44 novel riboswitch candidates and numerous other putative ncRNA motifs. Although experimental validation studies have yet to be conducted, this rate of riboswitch candidate discovery is consistent with predictions that many hundreds of novel riboswitch classes remain to be discovered among the bacterial species whose genomes have already been sequenced. Thus, many thousands of additional novel ncRNA classes likely remain to be discovered in the bacterial domain of life.

Isolation of acute myeloid leukemia blasts from blood using a microfluidic device.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and associated with poor prognosis. Unfortunately, most of the patients that achieve clinical complete remission after the treatment will ultimately relapse due to the persistence of minimal residual disease (MRD), that is not measurable using conventional technologies in the clinic. Microfluidics is a potential tool to improve the diagnosis by providing early detection of MRD. Herein, different designs of microfluidic devices were developed to promote lateral and vertical mixing of cells in microchannels to increase the contact area of the cells of interest with the inner surface of the device. Possible interactions between the cells and the surface were studied using fluid simulations. For the isolation of leukemic blasts, a positive selection strategy was used, targeting the cells of interest using a panel of specific biomarkers expressed in immature and aberrant blasts. Finally, once the optimisation was complete, the best conditions were used to process patient samples for downstream analysis and benchmarking, including phenotypic and genetic characterisation. The potential of these microfluidic devices to isolate and detect AML blasts may be exploited for the monitoring of AML patients at different stages of the disease.

Inflammation and Exosomes in Fabry Disease Pathogenesis.

Fabry Disease (FD) is one of the most prevalent lysosomal storage disorders, resulting from mutations in the GLA gene located on the X chromosome. This genetic mutation triggers glo-botriaosylceramide (Gb-3) buildup within lysosomes, ultimately impairing cellular functions. Given the role of lysosomes in immune cell physiology, FD has been suggested to have a profound impact on immunological responses. During the past years, research has been focusing on this topic, and pooled evidence strengthens the hypothesis that Gb-3 accumulation potentiates the production of pro-inflammatory mediators, revealing the existence of an acute inflammatory process in FD that possibly develops to a chronic state due to stimulus persistency. In parallel, extracellular vesicles (EVs) have gained attention due to their function as intercellular communicators. Considering EVs' capacity to convey cargo from parent to distant cells, they emerge as potential inflammatory intermediaries capable of transporting cytokines and other immunomodulatory molecules. In this review, we revisit the evidence underlying the association between FD and altered immune responses and explore the potential of EVs to function as inflammatory vehicles.