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ABSTRACT Purpose: The epithelial-mesenchymal transition of human lens epithelial cells plays a role in posterior capsule opacification, a fibrotic process that leads to a common type of cataract. Hyaluronic acid has been implicated in this fibrosis. Studies have investigated the role of transforming growth factor (TGF)-β2 in epithelial-mesenchymal transition. However, the role of TGF-β2 in hyaluronic acid-mediated fibrosis of lens epithelial cell remains unknown. We here examined the role of TGF-β2 in the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells. Methods: Cultured human lens epithelial cells (HLEB3) were infected with CD44-siRNA by using the Lipofectamine 3000 transfection reagent. The CCK-8 kit was used to measure cell viability, and the scratch assay was used to determine cell migration. Cell oxidative stress was analyzed in a dichloro-dihydro-fluorescein diacetate assay and by using a flow cytometer. The TGF-β2 level in HLEB3 cells was examined through immunohistochemical staining. The TGF-β2 protein level was determined through western blotting. mRNA expression levels were determined through quantitative real-time polymerase chain reaction. Results: Treatment with hyaluronic acid (1.0 μM, 24 h) increased the epithelial-mesenchymal transition of HLEB3 cells. The increase in TGF-β2 levels corresponded to an increase in CD44 levels in the culture medium. However, blocking the CD44 function significantly reduced the TGF-β2-mediated epithelial-mesenchymal transition response of HLEB3 cells. Conclusions: Our study showed that both CD44 and TGF-β2 are critical contributors to the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells, and that TGF-β2 in epithelial-mesenchymal transition is regulated by CD44. These results suggest that CD44 could be used as a target for preventing hyaluronic acid-induced posterior capsule opacification. Our findings suggest that CD44/TGF-β2 is crucial for the hyaluronic acid-induced epithelial-mesenchymal transition of lens epithelial cells.
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OBJECTIVE: Qiliqiangxin Capsule (QL) was investigated for its possible role in cardiac hypertrophy in this study. METHODS: QL (0.5 mg/mL) was pre-treated in Neonatal Mouse Ventricular Cardiomyocytes (NMVCs) before induction of cardiomyocyte hypertrophy by Angiotensin II (Ang-II). Immunofluorescence staining for α-actinin was conducted to determine cell surface area. Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) of hypertrophy markers were examined. Ang-II infusion was given to stimulate cardiac hypertrophy in mice. The cardiac function of mice was detected by echocardiography, and the pathological status of myocardial tissue was observed. RESULTS: The surface of cardiomyocytes was enlarged by Ang-II, and ANP and BNP levels were increased. QL processing could save these changes. miR-382-5p was upregulated in Ang-II-treated NMVCs, and reducing miR-382-5p could further enhance the therapeutic effect of QL while elevating miR-382-5p weakened the protective effect of QL. QL could inhibit miR-382-5p expression to negatively regulate Activated Transcription Factor 3 (ATF3) expression. Enhancing ATF3 expression rescued miR-382-5p upregulation-mediated role in NMVCs. In addition, QL alleviated Ang-II-stimulated cardiac hypertrophy and cardiac dysfunction in mice. CONCLUSION: QL may alleviate cardiac hypertrophy and cardiac dysfunction via the miR-382-5p/ATF3 axis.
Subject(s)
Activating Transcription Factor 3 , Angiotensin II , Cardiomegaly , Drugs, Chinese Herbal , MicroRNAs , Myocytes, Cardiac , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , MicroRNAs/metabolism , Cardiomegaly/drug therapy , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Activating Transcription Factor 3/metabolism , Angiotensin II/pharmacology , Atrial Natriuretic Factor , Male , Natriuretic Peptide, Brain/metabolism , Mice , Mice, Inbred C57BL , Echocardiography , Up-Regulation/drug effects , Disease Models, AnimalABSTRACT
BACKGROUND: Supplementation with the Agave tequilana Weber blue variety fructans is a feasible treatment option for functional constipation (FC). However, its effects on colonic function have not yet been studied. This study assessed whole gut transit time (WGTT) and regional transit time using a wireless motility capsule (WMC) before and after supplementation with different fiber treatments in patients with FC. METHODS: A secondary analysis was performed on data collected from a randomized, double-blind clinical trial comparing agave fructans with psyllium plantago. WGTT, regional transit time, contractility, and pH were measured using WMC before and after fiber supplementation. Comparisons were performed using nonparametric tests. KEY RESULTS: Twenty patients with FC were evaluated, with a median age of 39 (25-54 years), and 18 (90%) were women. Five patients were included in each intervention group. There were no changes in WGTT or regional transit times between the groups (p > 0.05). Similarly, there were no differences in the changes experienced by regional or general contractility among the groups (p > 0.05). The cecal pH profile did not differ between the groups before and after fiber supplementation (p > 0.05). The percentages of clinical responses and consistency of bowel movements between the groups were similar. CONCLUSIONS & INFERENCES: FC presents a clinical response to a fiber challenge, regardless of the administered intervention. However, this response was not associated with improvement in contractility or regional transit time. We speculate that there are other mechanisms by which fiber consumption may improve FC.
Subject(s)
Agave , Constipation , Dietary Fiber , Fructans , Gastrointestinal Transit , Psyllium , Humans , Constipation/drug therapy , Constipation/physiopathology , Female , Gastrointestinal Transit/drug effects , Psyllium/therapeutic use , Male , Middle Aged , Adult , Hydrogen-Ion Concentration , Double-Blind Method , Dietary SupplementsABSTRACT
BACKGROUND: Video-capsule endoscopy (VCE) is an efficient tool that has proven to be highly useful in approaching several gastrointestinal diseases. VCE was implemented in Colombia in 2003, however current characterization of patients undergoing VCE in Colombia is limited, and mainly comes from two investigations conducted before the SARS-CoV-2 pandemic period. AIM: To describe the characteristics of patients undergoing VCEs and establish the main indications, findings, technical limitations, and other outstanding features. METHODS: A descriptive study was carried out using data from reports of VCE (PillCam SB3 system) use in a Gastroenterology Unit in Bogotá, Colombia between September 2019 and January 2023. Demographic and clinical variables such as indication for the VCE, gastric and small bowel transit times (GTT, SBTT), endoscopic preparation quality, and limitations were described [n (%), median (IQR)]. RESULTS: A total of 133 VCE reports were analyzed. Most were in men with a median age of 70 years. The majority had good preparation (96.2%), and there were technical limitations in 15.8% of cases. The main indications were unexplained anemia (91%) or occult bleeding (23.3%). The median GTT and SBTT were 14 and 30 minutes, respectively. The frequencies of bleeding stigma (3.79%) and active bleeding (9.09%) were low, and the most frequent abnormal findings were red spots (28.3%), erosions (17.6%), and vascular ectasias (12.5%). CONCLUSION: VCE showed high-level safety. The main indication was unexplained anemia. Active bleeding was the most frequent finding. Combined with artificial intelligence, VCE can improve diagnostic precision and targeted therapeutic interventions.
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This chapter describes methodological details for preparing specimens of Cryptococcus neoformans (although it can be applied to any species of the genus) and their subsequent analysis by scanning and transmission electron microscopy. Adaptations to conventional protocols for better preservation of the sample, as well as to avoid artifacts, are presented. The protocols may be used to examine both the surface ultrastructure and the interior of this pathogenic fungus in detail.
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Artifacts , Cryptococcus neoformans , Cryptococcus neoformans/ultrastructure , Microscopy, Electron, Transmission/methods , Microscopy, Electron, Scanning/methods , Specimen Handling/methodsABSTRACT
The importance of humoral immunity to fungal infections remains to be elucidated. In cryptococcosis, patients that fail to generate antibodies against antigens of the fungus Cryptococcus neoformans are more susceptible to the disease, demonstrating the importance of these molecules to the antifungal immune response. Historically, antibodies against C. neoformans have been applied in diagnosis, therapeutics, and as important research tools to elucidate fungal biology. Throughout the process of generating monoclonal antibodies (mAbs) from a single B-cell clone and targeting a single epitope, several immunization steps might be required for the detection of responsive antibodies to the antigen of interest in the serum. This complex mixture of antibodies comprises the polyclonal antibodies. To obtain mAbs, B-lymphocytes are harvested (from spleen or peripheral blood) and fused with tumor myeloma cells, to generate hybridomas that are individually cloned and specifically screened for mAb production. In this chapter, we describe all the necessary steps, from the immunization to polyclonal antibody harvesting, hybridoma generation, and mAb production and purification. Additionally, we discuss new cutting-edge approaches for generating interspecies mAbs, such as humanized mAbs, or for similar species in distinct host backgrounds.
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Antibodies, Fungal , Antibodies, Monoclonal , Cryptococcus neoformans , Hybridomas , Cryptococcus neoformans/immunology , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Animals , Humans , Hybridomas/immunology , Antibodies, Fungal/immunology , Antibodies, Fungal/isolation & purification , Mice , B-Lymphocytes/immunology , Cryptococcosis/immunology , Cryptococcosis/diagnosis , Antigens, Fungal/immunology , ImmunizationABSTRACT
Glucuronoxylomannan (GXM) is the principal capsular component in the Cryptococcus genus. This complex polysaccharide participates in numerous events related to the physiology and pathogenesis of Cryptococcus, which highlights the importance of establishing methods for its isolation and analysis. Conventional methods for GXM isolation have been extensively discussed in the literature. In this chapter, we describe two fast methods for obtaining extracellular fractions enriched with cryptococcal GXM.
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Cryptococcus , Polysaccharides , Polysaccharides/chemistry , Antigens, Fungal/immunology , Cryptococcus neoformans , Fungal Capsules/metabolism , Fungal Capsules/chemistry , HumansABSTRACT
Introduction: Deep cavernomas of eloquent areas, located in the region of the basal nuclei and thalamus, account for 9 to 36% of these encephalic vascular malformations. Internal capsule cavernomas are particularly challenging, as they are surrounded by important projection fibers and their manipulation can lead to permanent deficits. To demonstrate through surgical cases that cavernomas of the internal capsule can be approached by frontal craniotomy, via the superior frontal sulcus, in a curative manner and with low morbidity. Methods: We presented two cases of cavernomas of the internal capsule operated, whose treatment was microsurgical resection via frontal craniotomy and access to the lesion via the superior frontal sulcus, described step-by-step. To elucidate the rationale behind the decision, we used preoperative images with an emphasis on the patients' tractography and the importance of comparing these images with anatomical specimens dissected in the neuroanatomy and microsurgery laboratory. Results: The two cases of internal capsule cavernomas, one in the anterior limb and the other in the posterior limb, were treated surgically via the superior frontal sulcus. Discussion: Both patients showed radiological cure and clinical improvement in the post-operative segment. The patient consented to the procedure and to the publication of his/her image. Treatment of internal capsule cavernomas via the superior frontal sulcus has proven to be a safe and effective option.
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During periodontitis, the extracellular capsule of Porphyromonas gingivalis favors alveolar bone loss by inducing Th1 and Th17 patterns of lymphocyte response in the infected periodontium. Dendritic cells recognize bacterial antigens and present them to T lymphocytes, defining their activation and polarization. Thus, dendritic cells could be involved in the Th1 and Th17 response induced against the P. gingivalis capsule. Herein, monocyte-derived dendritic cells were obtained from healthy individuals and then stimulated with different encapsulated strains of P. gingivalis or two non-encapsulated isogenic mutants. Dendritic cell differentiation and maturation were analyzed by flow cytometry. The mRNA expression levels for distinct Th1-, Th17-, or T-regulatory-related cytokines and transcription factors, as well as TLR2 and TLR4, were assessed by qPCR. In addition, the production of IL-1ß, IL-6, IL-23, and TNF-α was analyzed by ELISA. The encapsulated strains and non-encapsulated mutants of P. gingivalis induced dendritic cell maturation to a similar extent; however, the pattern of dendritic cell response was different. In particular, the encapsulated strains of P. gingivalis induced higher expression of IRF4 and NOTCH2 and production of IL-1ß, IL-6, IL-23, and TNF-α compared with the non-encapsulated mutants, and thus, they showed an increased capacity to trigger Th1 and Th17-type responses in human dendritic cells.
Subject(s)
Cytokines , Dendritic Cells , Porphyromonas gingivalis , Th17 Cells , Toll-Like Receptor 2 , Toll-Like Receptor 4 , Porphyromonas gingivalis/immunology , Humans , Dendritic Cells/immunology , Dendritic Cells/metabolism , Dendritic Cells/microbiology , Th17 Cells/immunology , Th17 Cells/metabolism , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Cytokines/metabolism , Cell Differentiation , Th1 Cells/immunology , Interferon Regulatory Factors/metabolism , Interferon Regulatory Factors/genetics , Receptor, Notch2/genetics , Receptor, Notch2/metabolism , Cells, Cultured , Bacterial Capsules/immunology , Bacterial Capsules/metabolism , Bacteroidaceae Infections/immunology , Bacteroidaceae Infections/microbiology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
RESUMEN La enfermedad celiaca (EC) es un síndrome malabsortivo autoinmune que se presenta con intolerancia al gluten (gliadina). Los síntomas más frecuentes son diarrea, esteatorrea, pérdida de peso, debilidad, deficiencia de vitaminas y minerales. La probabilidad de desarrollar una EC complicada es relativamente baja, entre las principales manifestaciones de la misma tenemos esprue refractario, el linfoma de células T y la yeyunoileitis ulcerativa (YU) de los cuales pocos casos debutan con hemorragia digestiva. A continuación, presentamos el caso de un paciente de 51 años de edad que debutó con hemorragia digestiva debido a EC complicada, en donde se realizó video endoscopía digestiva alta (VEDA), videocolonoscopia (VCC), cápsula endoscópica (CE), enteroscopia y biopsia de yeyuno e íleon confirmando el diagnóstico de EC y yeyunoileitis ulcerativa.
ABSTRACT Celiac disease (CD) is an autoimmune malabsorption syndrome that presents with intolerance to gluten (gliadin), a protein found in wheat. The most common symptoms are diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiency. The probability of developing complicated CD is relatively low, among its main manifestations we have refractory sprue, T-cell lymphoma and ulcerative jejunitis (UY) of which a few cases develop gastrointestinal bleeding. Furthermore, we present the case of a 51-year-old patient who developed intestinal hemorrhage due to complicated CD, where upper digestive video endoscopy (VEDA), video colonoscopy (VCC), capsule endoscopy (CE) and biopsy of the jejunum and ileum were performed confirming the diagnosis of CD along with ulcerative jejunoileitis.
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Here, we conducted a comprehensive analysis of 356 Klebsiella pneumoniae species complex (KpSC) isolates that were classified as classical (cl), presumptive hypervirulent (p-hv) and hypermucoviscous-like (hmv-like). Overall, K. pneumoniae (82.3%), K. variicola (2.5%) and K. quasipneumoniae (2.5%) were identified. These isolates comprised 321 cl-KpSC, 7 p-hv-KpSC and 18 hmv-like-KpSC. A large proportion of cl-KpSC isolates were extended-spectrum-ß-lactamases (ESBLs)-producers (64.4%) and 3.4% of isolates were colistin-resistant carrying carbapenemase and ESBL genes. All p-hv-KpSC showed an antibiotic susceptible phenotype and hmv-like isolates were found to be ESBL-producers (8/18). Assays for capsule production and capsule-dependent virulence phenotypes and whole-genome sequencing (WGS) were performed in a subset of isolates. Capsule amount differed in all p-hv strains and hmv-like produced higher capsule amounts than cl strains; these variations had important implications in phagocytosis and virulence. Murine sepsis model showed that most cl strains were nonlethal and the hmv-like caused 100% mortality with 3 × 108 CFUs. Unexpectedly, 3/7 (42.9%) of p-hv strains required 108 CFUs to cause 100% mortality (atypical hypervirulent), and 4/7 (57.1%) strains were considered truly hypervirulent (hv). Genomic analyses confirmed the diverse population, including isolates belonging to hv clonal groups (CG) CG23, CG86, CG380 and CG25 (this corresponded to the ST3999 a novel hv clone) and MDR clones such as CG258 and CG147 (ST392) among others. We noted that the hmv-like and hv-ST3999 isolates showed a close phylogenetic relationship with cl-MDR K. pneumoniae. The information collected here is important to understand the evolution of clinically important phenotypes such as hypervirulent and ESBL-producing-hypermucoviscous-like amongst the KpSC in Mexican healthcare settings. Likewise, this study shows that mgrB inactivation is the main mechanism of colistin resistance in K. pneumoniae isolates from Mexico.
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Klebsiella Infections , Klebsiella pneumoniae , Animals , Mice , Klebsiella , Colistin , Phylogeny , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Phenotype , Microbial Sensitivity TestsABSTRACT
INTRODUCTION: Epilepsy is a disease characterized by an excessive discharge in neurons generally provoked without any external stimulus, known as convulsions. About 2 million people are diagnosed each year in the world. This process is carried out by a neurological doctor using an electroencephalogram (EEG), which is lengthy. METHOD: To optimize these processes and make them more efficient, we have resorted to innovative artificial intelligence methods essential in classifying EEG signals. For this, comparing traditional models, such as machine learning or deep learning, with cutting-edge models, in this case, using Capsule-Net architectures and Transformer Encoder, has a crucial role in finding the most accurate model and helping the doctor to have a faster diagnosis. RESULT: In this paper, a comparison was made between different models for binary and multiclass classification of the epileptic seizure detection database, achieving a binary accuracy of 99.92% with the Capsule-Net model and a multiclass accuracy with the Transformer Encoder model of 87.30%. CONCLUSION: Artificial intelligence is essential in diagnosing pathology. The comparison between models is helpful as it helps to discard those that are not efficient. State-of-the-art models overshadow conventional models, but data processing also plays an essential role in evaluating the higher accuracy of the models.
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Artificial Intelligence , Epilepsy , Humans , Epilepsy/diagnosis , Seizures/diagnosis , Algorithms , Machine Learning , ElectroencephalographyABSTRACT
INTRODUCTION: Hip instability following arthroscopy is a rare complication with a clinical spectrum ranging from gross dislocation (macro-instability) to micro-instability, characterized by pain and limitation for daily activities. Therefore, it should be considered as a potential differential diagnosis in patients experiencing persistent pain after hip arthroscopy. CASE PRESENTATION: A 41-year-old male presented with a history of anterior hip dislocation and macro-instability symptoms three years post-hip arthroscopy. Magnetic resonance imaging (MRI) revealed a disruption of the anterior hip capsule. The patient initiated physiotherapy and resumed activities, but ten months later, experienced another anterior dislocation. Pain and apprehension during external hip rotation were evident. Three-dimensional computed tomography (CT) indicated irregularities in the anterior and superior margin of the acetabulum, while MRI arthrogram showed a rupture of the anterior capsule and deficiency in the anterior hip ligaments. Open reconstruction of the anterior capsule was performed, resulting in favorable progression over the 5-year follow-up. DISCUSSION: This case highlights post-arthroscopy hip instability with a delayed presentation, possibly linked to chronic anterior capsule deficiency and inadequate acetabular coverage. Primary capsule repair after hip arthroscopy has proven effective in reducing the occurrence of instability symptoms and reoperations. CONCLUSIONS: Post-arthroscopic hip instability may manifest immediately after surgery or several years later. Open reconstruction of the anterior capsule emerges as a successful strategy for addressing this complication, demonstrating satisfactory outcomes in a 5-year follow-up.
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BACKGROUND AND AIM: The increasing incidence of Klebsiella pneumoniae infections, both in the community and in hospitals, is a huge health problem. This is due to the increasing resistance of the bacteria to antibiotics and biofilm formation, as well as the presence of a capsule. This study focuses on two main objectives: to survey the most common capsular types in local isolates for the first time in Anbar, Iraq, on molecular level and to distinguish between infectious pathogen strains using multilocus sequence typing (MLST) for more efficient epidemiological and surveillance analysis, in order to determine the source of these strains (invasive or purebred). METHODOLOGY: Multidrug-resistant (MDR) isolates adapted to genomic extraction and molecular screening of capsular type and MLST, and then to data processing by Pasteur Institut. RESULTS: For the first time, one isolate was registered as a new strain in the world with ST 6434; the other strains demonstrated as preregistered with ST16, ST218, and ST283. 33% of MDR isolates belonged to the capsular K2 type. CONCLUSION: The study's findings were not aligned with the global knowledge base about the distribution of capsular type in Asia. To prevent the spread of highly resistant strains, careful monitoring of virulence determinants is necessary in addition to the observation of antibiotic resistance.
Subject(s)
Interleukins , Klebsiella Infections , beta-Lactamases , Humans , beta-Lactamases/genetics , Multilocus Sequence Typing , Klebsiella pneumoniae , Iraq/epidemiology , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Virulence/genetics , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacologyABSTRACT
ABSTRACT Purpose: As superotemporal implantation of the Ahmed glaucoma valve is not always feasible in cases of refractory glaucoma, this study examined the characteristics and surgical outcomes of cases in which the valve was implanted in a nonsuperotemporal quadrant using a modified long scleral tunnel technique. Methods: This retrospective case-control study included 37 eyes with nonsuperotemporal quadrant--Ahmed glaucoma valve implantation in Group 1 and 69 eyes with superotemporal Ahmed glaucoma valve implantation in Group 2. The demographic characteristics of these groups, surgical outcomes, including complications, further surgical interventions, and surgical success rates were compared. Surgical success was defined as an intraocular pressure not exceeding 21 mmHg, accompanied by a minimum reduction of 20% in intraocular pressure from the baseline without any additional intraocular pressure-lowering procedures, and the absence of light perception loss or phthisis bulbi. Results: Group 1 had significantly higher numbers of eyes with secondary glaucoma and preoperative surgical procedures than Group 2 (p<0.05). Both groups had mean preoperative intraocular pressure values, and mean intraocular pressure values at the last visit of 34.2 and 27.9 months, 35.5 ± 1.5 and 35.8 ± 1.2 mmHg, and 14.5 ± 5 and 14.9 mmHg, respectively. Although both groups had 70.2% and 75.8% as their five-year cumulative probability of success, respectively, the rates of complications, revisional surgery, and additional surgical procedures did not differ significantly (p>0.05). Conclusion: The modified long scleral tunnel technique for Ahmed glaucoma valve implantation in nonsuperotemporal quadrants achieves intraocular pressure control and complication rates comparable to superotemporal implantation.
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This paper presents new perspectives on photonic technologies for capsule endoscopy. It first presents a review of conventional endoscopy (upper endoscopy and colonoscopy), followed by capsule endoscopy (CE), as well as their techniques, advantages, and drawbacks. The technologies for CEs presented in this paper include integration with the existing endoscopic systems that are commercially available. Such technologies include narrow-band imaging (NBI), photodynamic therapy (PDT), confocal laser endomicroscopy (CLE), optical coherence tomography (OCT), and spectroscopy in order to improve the performance of the gastrointestinal (GI) tract examination. In the context of NBI, two optical filters were designed and fabricated for integration into endoscopic capsules, allowing for the visualization of light centered at the 415 nm and 540 nm wavelengths. These optical filters are based on the principle of Fabry-Perot and were made of thin films of titanium dioxide (TiO2) and silicon dioxide (SiO2). Moreover, strategies and solutions for the adaptation of ECs for PDT are also discussed.
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Preventing the progressive deterioration of works of art over time is a topic of great interest to collectors and museums. With this aim, time capsules where environmental conditions remain unchanged are well known for preserving art. In this paper, a prototype of an IoT time capsule is presented with a focus on low cost in order to make it accessible to private collectors or small museums with tight budgets. Valencian 'sainetes' (small plays), which are considered materials of artistic interest, have been placed in a "time capsule", which is a manually made container with insulating materials for keeping small pieces for a long time. Environmental control has been performed with a low-cost microcontroller, sensors and actuators connected to a free online IoT platform. This platform recorded data and made decisions based on these data, sending cooling or heating orders to an environmental control system. The results obtained are very satisfactory and open interesting perspectives for future research. However, they also highlight some relevant technical and economic limitations that will have to be considered in the future.
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Fungal infections are a global public health challenge, especially among immunocompromised patients. Basidiomycetous yeasts, such as Rhodotorula mucilaginosa, have emerged as opportunistic pathogens, but have received less attention than Cryptococcus neoformans. This study aimed to characterize the polysaccharides of R. mucilaginosa and compare them with those of C. neoformans, analyzing their clinical implications. Comprehensive physicochemical, mechanical, and ultrastructural analyses of polysaccharides from both species were performed, revealing correlations with virulence and pathogenicity. R. mucilaginosa cells are surrounded by a capsule smaller than that produced by C. neoformans, but with similar polysaccharides. Those polysaccharides are also secreted by R. mucilaginosa. Cross-reactivity with R. mucilaginosa was observed in a diagnostic C. neoformans antigen test, using both in vitro and in vivo samples, highlighting the need for more reliable tests. Some R. mucilaginosa strains exhibited virulence comparable to that of C. neoformans in an invertebrate experimental model (Tenebrio molitor). This study contributes to a deeper understanding of yeast pathogenicity and virulence, highlighting the need for more accurate diagnostic tests to improve the differential diagnosis of infections caused by basidiomycetous yeasts.
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Cryptococcus neoformans is an encapsulated yeast that can cause cryptococcosis and cryptococcal meningitis, which conventional treatment involves antifungal drugs such as polyenes, flucytosine, azoles, and their combinations. However, the high cost, toxicity, and increase in fungi resistance to antifungal agents stimulate the search for therapeutic strategies such as drug repurposing and combination therapy. This study evaluated the activity of the antihypertensive verapamil (VEH) alone and combined with amphotericin B (AmB) against C. neoformans. VEH exhibited antifungal activity against C. neoformans with minimum inhibitory concentration and minimum fungicidal concentration of 118 µg per mL. The combination of VEH and AmB exhibited synergism, reducing at least eightfold both drugs' concentrations. Moreover, the combination decreased the size and glucuronoxylomannnan content of C. neoformans capsule. However, no difference was observed in ergosterol levels of C. neoformans after treatment with VEH and AmB in combination. Altogether, VEH in combination with AmB exhibits potential as a candidate as for the development of anti-cryptococcal drug.
Subject(s)
Cryptococcosis , Cryptococcus neoformans , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Cryptococcosis/drug therapy , Cryptococcosis/microbiology , Flucytosine/pharmacology , Flucytosine/therapeutic use , Microbial Sensitivity TestsABSTRACT
INTRODUCTION AND AIMS: Capsule endoscopy is part of the diagnostic approach to patients with suspected small bowel bleeding and data on its clinical impact are still limited in developing countries. The primary aim of the present study was to determine its impact on subsequent diagnostic and therapeutic decisions. MATERIAL AND METHODS: A retrospective study was conducted that included all the patients that underwent capsule endoscopy with the PillCam™ SB 3 Capsule system due to suspected small bowel bleeding treated at the Hospital Universitario Fundación Valle del Lili between January 2011 and December 2020. RESULTS: A total of 158 patients met the inclusion criteria. Mean patient age was 63 years (interquartile range [IQR], 52-74), 53.6% of the patients were women, and high blood pressure was the most frequent comorbidity (43.7%). The main indication was overt bleeding (58.2%). Of all the capsule endoscopies carried out, 63.9% showed lesions that were potentially responsible for bleeding. Medical or surgical treatment was indicated in 63.3% of the case total. Rebleeding at 6 months occurred in 15 patients and there were 2 deaths due to gastrointestinal bleeding at 6 months. CONCLUSIONS: Capsule endoscopy has a high impact on patients with suspected small bowel bleeding, with respect to clinical decision-making, as well as rebleeding, hospitalization, and mortality outcomes. The positivity rate of lesions potentially responsible for bleeding was similar to that reported in developed countries.