Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD). Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature. Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics. Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems. Funding: No funding received.
Ecto-5'-nucleotidase (CD73) hydrolyses 5'AMP to adenosine and inorganic phosphate. Breast cancer cells (MDA-MB-231) express high CD73 levels, and this enzyme has been found to play a tumour-promoting role in breast cancer. However, no studies have sought to investigate whether CD73 has differential affinity or substrate preferences between noncancerous and cancerous breast cells. In the present study, we aimed to biochemically characterise ecto-5'-nucleotidase in breast cancer cell lines and assess whether its catalytic function and tumour progression are correlated in breast cancer cells. The results showed that compared to nontumoral breast MCF-10A cells, triple-negative breast cancer MDA-MB-231 cells had a higher ecto-5'-nucleotidase expression level and enzymatic activity. Although ecto-5'-nucleotidase activity in the MDA-MB-231 cell line showed no selectivity among monophosphorylated substrates, 5'AMP was preferred by the MCF-10A cell line. Compared to the MCF-10A cell line, the MDA-MB-231 cell line has better hydrolytic ability, lower substrate affinity, and high inhibitory potential after treatment with a specific CD73 inhibitor α,ßmethylene ADP (APCP). Therefore, we demonstrated that a specific inhibitor of the ecto-5-nucleotidase significantly reduced the migratory and invasive capacity of MDA-MB-231 cells, suggesting that ecto-5-nucleotidase activity might play an important role in metastatic progression.
Autophagy is a cellular degradation pathway mediated by highly conserved autophagy-related genes (Atgs). In our previous work, we showed that inhibiting autophagy under starvation conditions leads to significant physiological changes in the insect vector of Chagas disease Rhodnius prolixus; these changes include triacylglycerol (TAG) retention in the fat body, reduced survival and impaired locomotion and flight capabilities. Herein, because it is known that autophagy can be modulated in response to various stimuli, we further investigated the role of autophagy in the fed state, following blood feeding. Interestingly, the primary indicator for the presence of autophagosomes, the lipidated form of Atg8 (Atg8-II), displayed 20%-50% higher autophagic activation in the first 2 weeks after feeding compared to the third week when digestion was complete. Despite the elevated detection of autophagosomes, RNAi-mediated suppression of RpAtg6 and RpAtg8 did not cause substantial changes in TAG or protein levels in the fat body or the flight muscle during blood digestion. We also found that knockdown of RpAtg6 and RpAtg8 led to modest modulations in the gene expression of essential enzymes involved in lipid metabolism and did not significantly stimulate the expression of the chaperones BiP and PDI, which are the main effectors of the unfolded protein response. These findings indicate that impaired autophagy leads to slight disturbances in lipid metabolism and general cell proteostasis. However, the ability of insects to fly during forced flight until exhaustion was reduced by 60% after knockdown of RpAtg6 and RpAtg8. This change was accompanied by TAG and protein increases as well as decreased ATP levels in the fat body and flight muscle, indicating that autophagy during digestion, i.e., under fed conditions, is necessary to sustain high-performance activity.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease usually associated with severe weakness and death within 2-5 years. SOD1 mutations cause hereditary ALS in autosomal dominant and rarely in recessive pattern. We describe a new phenotype of slowly progressive fALS due to homozygous SOD1 mutations (c.358G > C, p.Val120Leu) in a Brazilian family. We reviewed the medical chart and interviewed the index patient and other relatives. A 41-year-old man developed weakness in his legs, leading to frequent falls, followed over the next few months with progressive arm fasciculations and muscle atrophy. The SOD1 enzymatic activity in erythrocytes was slightly decreased. A genetic test panel disclosed homozygous SOD1 mutations (c.358G > C, p.Val120Leu). His asymptomatic parents also carried one mutant allele and 2 brothers and a sister had died with ALS. We reported a new family with homozygous SOD1 mutation and slowly progressive ALS course. Further studies are necessary to confirm whether this mutation can also lead to disease in heterozygosis with incomplete penetrance.
In recent years, tubular nanostructures have been related to immense advances in various fields of science and technology. Considerable research efforts have been centred on the theoretical prediction and manufacturing of non-carbon nanotubes (NTs), which meet modern requirements for the development of novel devices and systems. In this context, diatomic inorganic nanotubes formed by atoms of elements from the 13th group of the periodic table (B, Al, Ga, In, Tl) and nitrogen (N) have received much research attention. In this study, the elastic properties of single-walled boron nitride, aluminium nitride, gallium nitride, indium nitride, and thallium nitride nanotubes were assessed numerically using the nanoscale continuum modelling approach (also called molecular structural mechanics). The elastic properties (rigidities, surface Young's and shear moduli, and Poisson's ratio) of nitride nanotubes are discussed with respect to the bond length of the corresponding diatomic hexagonal lattice. The results obtained contribute to a better understanding of the mechanical response of nitride compound-based nanotubes, covering a broad range, from the well-studied boron nitride NTs to the hypothetical thallium nitride NTs.
A reliable and greener alternative to the usual extraction methods is reported for the determination of pesticide residues in soybeans. This novel approach combines the classical QuEChERS extraction method with a DLLME (dispersive liquid-liquid microextraction) step, utilizing a deep eutectic solvent (DES) - camphor: hexanoic acid (1:1 molar ratio) - as the microextraction solvent. This DES has never been employed in pesticide analysis by gas chromatography-mass spectrometry of complex matrices like soybeans. A Plackett-Burman screening design was employed to optimize sample preparation variables of QuEChERS (amount of sodium chloride and magnesium sulfate, and amount of PSA and C18 sorbents) and DLLME (pH of medium, amount of sodium chloride, and volume of microextraction solvent). This design allowed for a systematic evaluation of the impact of each parameter on the method's performance. The optimized method was evaluated using a certified reference material and commercial samples of soybeans. The method exhibited high accuracy and precision for most of the analytes under study, demonstrating its applicability for pesticide residue analysis in soybeans. To assess the greenness and practicality of the developed method, the Analytical Greenness (AGREE) and Blue Applicability Grade Index (BAGI) metric systems were employed, respectively. Overall, the proposed QuEChERS-DLLME method using a DES solvent is a reliable and greener alternative to conventional extraction methods for the determination of pesticide residues in soybeans. Its high performance, coupled with its environmental friendliness, makes it a promising tool for food safety analysis.
Gas Chromatography-Mass Spectrometry , Glycine max , Liquid Phase Microextraction , Pesticide Residues , Pesticide Residues/analysis , Pesticide Residues/isolation & purification , Glycine max/chemistry , Gas Chromatography-Mass Spectrometry/methods , Liquid Phase Microextraction/methods , Deep Eutectic Solvents/chemistry , Limit of Detection , Reproducibility of Results
PURPOSE: Retrospective evaluation of bilateral same-day myringoplasty outcomes. METHODS: Patients who underwent bilateral same-day myringoplasty from 2005 to 2019. RESULTS: Thirty-eight patients underwent bilateral myringoplasty. Mean age was 44.5 years and 55.3% patients were male. Tragal perichondrium-cartilage composite graft was the most frequently used graft material (82.9%). Perforation closure was achieved in 78.9%. Postoperative Pure Tone Average and Air-Bone Gap decreased significantly (p < 0.05), except for the Air-Bone Gap of the right ear (p = 0.058). The complications were cholesteatoma (1.3%), otorrhea (6.6%) and tympanic membrane retraction (1.3%). CONCLUSIONS: Bilateral same-day myringoplasty is a feasible procedure in selected patients. Good anatomic and functional outcomes, as well as a low rate of complications, are achieved with this procedure, improving patient comfort and allowing for a reduction in operation time and costs.
Acrylamide is an amide formed in the Maillard reaction, with asparagine as the primary amino acid precursor. The intake of large amounts of acrylamide has induced genotoxic and carcinogenic effects in hormone-sensitive tissues of animals. The enzime asparaginase is one of the most effective methods for lowering the formation of acrylamide in foods such as potatoes. However, the reported sensory outcomes for coffee have been unsatisfactory so far. This study aimed to produce coffees with reduced levels of acrylamide by treating them with asparaginase while retaining their original sensory and bioactive profiles. Three raw samples of Coffea arabica, including two specialty coffees, and one of Coffea canephora were treated with 1000, 2000, and 3000 ASNU of the enzyme. Asparagine and bioactive compounds (chlorogenic acids-CGA, caffeine, and trigonelline) were quantified in raw and roasted beans by HPLC and LC-MS, while the determination of acrylamide and volatile organic compounds was performed in roasted beans by CG-MS. Soluble solids, titratable acidity, and pH were also determined. Professional cupping by Q-graders and consumer sensory tests were also conducted. Results were analyzed by ANOVA-Fisher, MFA, PCA and Cluster analyses, with significance levels set at p ≤ 0.05. Steam treatment alone decreased acrylamide content by 18.4%, on average, and 6.1% in medium roasted arabica and canefora coffees. Average reductions of 32.5-56.0% in acrylamide formation were observed in medium roasted arabica beans when 1000-3000 ASNU were applied. In the canefora sample, 59.4-60.7% reductions were observed. However, steam treatment primarily caused 17.1-26.7% reduction of total CGA and lactones in medium roasted arabica samples and 13.9-22.0% in canefora sample, while changes in trigonelline, caffeine, and other evaluated chemical parameters, including the volatile profiles were minimal. Increasing enzyme loads slightly elevated acidity. The only sensory changes observed by Q-graders and or consumers in treated samples were a modest increase in acidity when 3000 ASNU was used in the sample with lower acidity, loss of mild off-notes in control samples, and increased perception of sensory descriptors. The former was selected given the similarity in chemical outcomes among beans treated with 2000 and 3000 ASNU loads.
Acrylamide , Asparaginase , Asparagine , Coffea , Coffee , Taste , Acrylamide/analysis , Asparagine/analysis , Coffea/chemistry , Coffee/chemistry , Humans , Volatile Organic Compounds/analysis , Cooking/methods , Alkaloids/analysis , Chlorogenic Acid/analysis , Caffeine/analysis , Male , Food Handling/methods , Maillard Reaction , Hot Temperature , Chromatography, High Pressure Liquid , Seeds/chemistry , Female
Breakfast cereals play a crucial role in children's diets, providing essential nutrients that are vital for their growth and development. Children are known to be more susceptible than adults to the harmful effects of food contaminants, with mycotoxins being a common concern in cereals. This study specifically investigated aflatoxin B1 (AFB1), enniatin B (ENNB), and sterigmatocystin (STG), three well-characterized mycotoxins found in cereals. The research aimed to address existing knowledge gaps by comprehensively evaluating the bioaccessibility and intestinal absorption of these three mycotoxins, both individually and in combination, when consumed with breakfast cereals and milk. The in vitro gastrointestinal method revealed patterns in the bioaccessibility of AFB1, ENNB, and STG. Overall, bioaccessibility increased as the food progressed from the stomach to the intestinal compartment, with the exception of ENNB, whose behavior differed depending on the type of milk. The ranking of overall bioaccessibility in different matrices was as follows: digested cereal > cereal with semi-skimmed milk > cereal with lactose-free milk > cereal with soy beverage. Bioaccessibility percentages varied considerably, ranging from 3.1% to 86.2% for AFB1, 1.5% to 59.3% for STG, and 0.6% to 98.2% for ENNB. Overall, the inclusion of milk in the ingested mixture had a greater impact on bioaccessibility compared to consuming the mycotoxins as a single compound or in combination. During intestinal transport, ENNB and STG exhibited the highest absorption rates when ingested together. This study highlights the importance of investigating the combined ingestion and transport of these mycotoxins to comprehensively assess their absorption and potential toxicity in humans, considering their frequent co-occurrence and the possibility of simultaneous exposure.
Breakfast , Digestion , Edible Grain , Food Contamination , Intestinal Absorption , Mycotoxins , Edible Grain/chemistry , Mycotoxins/analysis , Humans , Food Contamination/analysis , Animals , Child , Milk/chemistry , Biological Availability
The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic ß-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic ß-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity.
Mycotoxins can inflict harmful effects on diverse organs, and mounting evidence indicates their potential involvement in human neurodegenerative diseases. Given the common occurrence of these toxins in food, there is an increasing demand for a comprehensive assessment of their combined toxicity to enhance our understanding of their potential hazards. This research investigates mycotoxin exposure from widely consumed cereal-based products, including enniatin B (ENNB), sterigmatocystin (STG), aflatoxin B1 (AFB1), cyclopiazonic acid (CPZ), citrinin (CIT), and ochratoxin A (OTA). Employing the median-effect equation based on Chou and Talalay's mass-action law, we assessed their cytotoxicity in human SH-SY5Y neuronal cells. Notably, ENNB displayed the highest neurotoxicity (IC50 = 3.72 µM), followed by OTA (9.10 µM) and STG (9.99 µM). The combination of OTA + STG exhibited the highest toxicity (IC50 = 3.77 µM), while CPZ + CIT showed the least detrimental effect. Approximately 70 % of tested binary combinations displayed synergistic or additive effects, except for ENNB + STG, ENNB + AFB1, and CPZ + CIT, which showed antagonistic interactions. Intriguingly, the senary combination displayed moderate antagonism at the lowest exposure and moderate synergism at higher doses. OTA exhibited predominantly synergistic interactions, comprising approximately 90 %, a noteworthy finding considering its prevalence in food. Conversely, ENNB interactions tended to be antagonistic. The most remarkable synergy occurred in the STG and CIT combination, enabling a 50-fold reduction in CIT dosage for an equivalent toxic effect. These findings highlight the biological relevance of robust synergistic interactions, emphasizing the need to assess human exposure hazards accurately, particularly considering frequent mycotoxin co-occurrence in environmental and food settings.
Mycotoxins , Neuroblastoma , Humans , Mycotoxins/toxicity , Aflatoxin B1 , Edible Grain
BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.
Axial Spondyloarthritis , HLA-B27 Antigen , Phenotype , Registries , Humans , HLA-B27 Antigen/blood , HLA-B27 Antigen/genetics , Male , Brazil/epidemiology , Female , Adult , Middle Aged , Prospective Studies , Sex Factors , Cohort Studies , Quality of Life , Spondylarthritis/ethnology , Age of Onset , Severity of Illness Index
The quantification of carotid plaque has been routinely used to predict cardiovascular risk in cardiovascular disease (CVD) and coronary artery disease (CAD). To determine how well carotid plaque features predict the likelihood of CAD and cardiovascular (CV) events using deep learning (DL) and compare against the machine learning (ML) paradigm. The participants in this study consisted of 459 individuals who had undergone coronary angiography, contrast-enhanced ultrasonography, and focused carotid B-mode ultrasound. Each patient was tracked for thirty days. The measurements on these patients consisted of maximum plaque height (MPH), total plaque area (TPA), carotid intima-media thickness (cIMT), and intraplaque neovascularization (IPN). CAD risk and CV event stratification were performed by applying eight types of DL-based models. Univariate and multivariate analysis was also conducted to predict the most significant risk predictors. The DL's model effectiveness was evaluated by the area-under-the-curve measurement while the CV event prediction was evaluated using the Cox proportional hazard model (CPHM) and compared against the DL-based concordance index (c-index). IPN showed a substantial ability to predict CV events (p < 0.0001). The best DL system improved by 21% (0.929 vs. 0.762) over the best ML system. DL-based CV event prediction showed a ~ 17% increase in DL-based c-index compared to the CPHM (0.86 vs. 0.73). CAD and CV incidents were linked to IPN and carotid imaging characteristics. For survival analysis and CAD prediction, the DL-based system performs superior to ML-based models.
This study investigates the individual and combined effects of the mycotoxins, Aflatoxin B1 (AFB1), Enniatin B (ENNB) and Sterigmatocystin (STG), on the cellular viability of gastric (NCI-N87), intestinal (Caco-2), hepatic (Hep-G2) and renal (Hek-293) cells, shedding light on synergistic or antagonistic effects using a constant ratio combination design proposed by Chou-Talalay. These toxins are prevalent in cereal-based foods, frequently consumed by children which raises concerns about their exposure to these mycotoxins. This population is particularly vulnerable to the effects of these toxins due to their underdeveloped organs and incompletely structured physiological processes. Results showed that ENB was the most toxic of the three mycotoxins across all cell lines, while STG and AFB1 showed lower toxicity. The combination of ENNB + STG was found to be the most potent in terms of binary mixtures. In regard to ternary combinations, Caco-2 cells are more sensitive to the tested mycotoxins, whereas NCI-N87 cells show lower levels of cell damage. Worrying dose reduction values (>10-fold) were found for ENNB in binary and ternary combinations at low exposure levels. These findings are significant for establishing initial reference values, which play a pivotal role in estimating reference doses that are subsequently incorporated into the broader risk assessment process.
Aflatoxin B1 , Depsipeptides , Sterigmatocystin , Humans , Sterigmatocystin/toxicity , Aflatoxin B1/toxicity , Depsipeptides/toxicity , Cell Survival/drug effects , Caco-2 Cells , Liver/drug effects , Kidney/drug effects , Intestines/drug effects , HEK293 Cells , Hep G2 Cells
BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, mainly affecting children, young adults, and the elderly. It is an aggressive cancer with a poor prognosis, exhibiting low survival rates even with standard treatment. Recently, circular RNA molecules capable of influencing gene expression through various functions, with their main role being acting as microRNA sponges and reducing their intracellular expression, have been identified. Recent studies have linked circular RNAs to osteosarcoma development and progression. Therefore, the present study aimed to investigate the alteration in circular RNA expression during osteosarcoma development and progression. METHODS: An integrative literature review was conducted from September 10th to November 12th, 2021, using the following databases: PubMed/MEDLINE, SCOPUS, Web of Science, OVID, and EMBASE. 129 full articles were included in the review. The obtained data were organized using a standardized data collection instrument, which included the following information: altered expression profile of circular RNAs, associated cancer hallmarks, clinical-pathological relationships of circular RNAs, and perspectives on the studied circular RNAs. RESULTS: A total of 94 distinct circular RNAs were identified, predominantly showing an increased expression pattern. Approximately 91% of the studies that aimed to identify the mechanisms of action of circular RNAs highlighted the function of circular RNAs as microRNA sponges. The most associated cancer hallmarks with the identified circular RNAs were proliferative signaling induction, invasion and metastasis, and resistance to cell death. The altered expression of these circular RNAs generally correlated with a worse prognosis for patients, as evidenced by clinical features such as shorter survival, advanced Enneking and/or TNM stage, higher incidence of metastasis, larger tumor size, and increased chemoresistance. CONSLUSION: These findings indicate the significance of circular RNA molecules in osteosarcoma carcinogenesis, suggesting their potential as new prognostic and/or diagnostic biomarkers, as well as alternative therapeutic targets in the fight against osteosarcoma.
Bone Neoplasms , Disease Progression , Osteosarcoma , RNA, Circular , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs , Osteosarcoma/genetics , Osteosarcoma/pathology , Osteosarcoma/metabolism , Osteosarcoma/mortality , Prognosis , RNA, Circular/genetics
Acanthamoeba castellanii, a free-living amoeba, can be pathogenic to humans causing a corneal infection named Acanthamoeba keratitis (AK). The mannose-binding protein (MBP) is well established as the major factor related to Acanthamoeba pathogenesis. However, additional factors that participate in the adhesion process and protect trophozoites from cytolytic effects caused by host immune responses remain unknown. Ectonucleotidases, including 3'-nucleotidase/nuclease (3'-NT/NU), a bifunctional enzyme that was recently reported in A. castellanii, are frequently related to the establishment of parasitic infections. We verified that trophozoites can hydrolyze 3'-AMP, and this activity is similar to that observed in other protists. The addition of 3'-AMP increases the adhesion of trophozoites to LLC-MK2 epithelial cells, and this stimulation is completely reversed by DTT, an inhibitor of ecto-3'-nucleotidase activity. Lesions in corneal cells caused by AK infection may elevate the extracellular level of 3'-AMP. We believe that ecto-3'-nucleotidase activity can modulate the host immune response, thus facilitating the establishment of parasitic infection. This activity results from the generation of extracellular adenosine, which can bind to purinergic receptors present in host immune cells. Positive feedback may occur in this cascade of events once the ecto-3'-nucleotidase activity of trophozoites is increased by the adhesion of trophozoites to LLC-MK2 cells.
Acanthamoeba castellanii , Adenosine , Cell Adhesion , Trophozoites , Acanthamoeba castellanii/enzymology , Adenosine/metabolism , Cell Line , Animals , Nucleotidases/metabolism , Epithelial Cells/parasitology
Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS2 was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm2, 30 min, 180 J/cm2) confirmed that MoS2 nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS2 (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit-ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS2 + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS2 hydrogels, indicating a combined effect of photothermal and chemotherapy.
INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.
Carotid Stenosis , Cost-Benefit Analysis , Mass Screening , Stroke , Humans , Carotid Stenosis/diagnosis , Mass Screening/methods , Stroke/prevention & control , Stroke/etiology , Practice Guidelines as Topic , Risk Factors , Cardiovascular Diseases/prevention & control , Myocardial Infarction/prevention & control , Myocardial Infarction/diagnosis , Asymptomatic Diseases , Life Style
BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g-1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Cooking , Diclofenac , Digestion , Food Contamination , Seafood , Diclofenac/metabolism , Diclofenac/chemistry , Animals , Food Contamination/analysis , Seafood/analysis , Fishes/metabolism , Bass/metabolism , Humans , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/chemistry , Smegmamorpha/metabolism , Models, Biological
Background: Intellectual disabilities refer to a permanent brain condition that interferes with a learner's ability to perform basic living tasks, academic tasks and social interactions. By observing the motor proficiency levels of these learners, one can determine the extent of a learner's possible physical motor proficiency barriers. Objective: To determine the motor proficiency levels of learners with moderate to severe intellectual disabilities using the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) Brief Form. Method: This quantitative descriptive study included 46 learners (17 girls and 29 boys) from a Mangaung school for learners with special needs between the ages of 15 and 17 years. Results: Indicated that 31 learners (67.4%) out of 46 learners identified with moderate to severe intellectual disabilities had a well-below average; 11 learners (23.9%) had a below average and only 4 learners (8.7%) had average motor proficiency levels. Conclusion: Alarmingly, this indicates that the majority of learners have severe motor difficulties that may reduce these learners' abilities to perform tasks using gross and fine motor skills. Reported motor proficiency levels can be used as a guide to direct future motor intervention programmes. Contribution: Timely interventions are central to improving learners' motor difficulties. This study focused on providing information regarding the motor proficiency levels of South African learners with ID that was not previously explored. This was an attempt to bridge the gap in knowledge pertaining to the use of standardised motor proficiency tests for South African learners with ID.
