Improved pediatric ICU mortality prediction for respiratory diseases: machine learning and data subdivision insights.

The growing concern of pediatric mortality demands heightened preparedness in clinical settings, especially within intensive care units (ICUs). As respiratory-related admissions account for a substantial portion of pediatric illnesses, there is a pressing need to predict ICU mortality in these cases. This study based on data from 1188 patients, addresses this imperative using machine learning techniques and investigating different class balancing methods for pediatric ICU mortality prediction. This study employs the publicly accessible "Paediatric Intensive Care database" to train, validate, and test a machine learning model for predicting pediatric patient mortality. Features were ranked using three machine learning feature selection techniques, namely Random Forest, Extra Trees, and XGBoost, resulting in the selection of 16 critical features from a total of 105 features. Ten machine learning models and ensemble techniques are used to make accurate mortality predictions. To tackle the inherent class imbalance in the dataset, we applied a unique data partitioning technique to enhance the model's alignment with the data distribution. The CatBoost machine learning model achieved an area under the curve (AUC) of 72.22%, while the stacking ensemble model yielded an AUC of 60.59% for mortality prediction. The proposed subdivision technique, on the other hand, provides a significant improvement in performance metrics, with an AUC of 85.2% and an accuracy of 89.32%. These findings emphasize the potential of machine learning in enhancing pediatric mortality prediction and inform strategies for improved ICU readiness.

Impact of phthalate metabolites on vitamin D levels and subclinical inflammation: national health and nutrition examination survey, 2013-2018.

This study explores the association between phthalates and total vitamin D levels and the link between phthalates exposure and subclinical inflammation using monocyte percentage to high-density lipoprotein cholesterol ratio (MHR), utilizing three National Health and Nutrition Examination Survey (NHANES) survey cycles 2013-2018. This study is cross-sectional, utilizing one-time urine samples from randomly selected NHANES participants to assess phthalate metabolites. An inverse association between vitamin D and all Di(2-ethylhexyl) phthalate (DEHP) metabolites was found. The molar sum of DEHP metabolites was inversely associated with vitamin D (ß -2.329; 95% CI -3.937,-0.720). An inverse association was observed between monocarboxynonyl phthalate and vitamin D (ß -0.0278; 95% CI -0.0527,-0.00298). A similar relationship was found between monocarboxyoctyl phthalate and vitamin D (ß -0.0160; 95% CI -0.0242,-0.00775). There was no association between phthalate metabolites and MHR. Stratified analysis showed that the association between phthalate metabolites and MHR may vary according to vitamin D status.

Prevalence of asymptomatic hyperuricemia and its association with prediabetes, dyslipidemia and subclinical inflammation markers among young healthy adults in Qatar.

AIM: The aim of this study is to investigate the prevalence of asymptomatic hyperuricemia in Qatar and to examine its association with changes in markers of dyslipidemia, prediabetes and subclinical inflammation. METHODS: A cross-sectional study of young adult participants aged 18 - 40 years old devoid of comorbidities collected between 2012 and 2017. Exposure was defined as uric acid level, and outcomes were defined as levels of different blood markers. De-identified data were collected from Qatar Biobank. T-tests, correlation tests and multiple linear regression were all used to investigate the effects of hyperuricemia on blood markers. Statistical analyses were conducted using STATA 16. RESULTS: The prevalence of asymptomatic hyperuricemia is 21.2% among young adults in Qatar. Differences between hyperuricemic and normouricemic groups were observed using multiple linear regression analysis and found to be statistically and clinically significant after adjusting for age, gender, BMI, smoking and exercise. Significant associations were found between uric acid level and HDL-c p = 0.019 (correlation coefficient -0.07 (95% CI [-0.14, -0.01]); c-peptide p = 0.018 (correlation coefficient 0.38 (95% CI [0.06, 0.69]) and monocyte to HDL ratio (MHR) p = 0.026 (correlation coefficient 0.47 (95% CI [0.06, 0.89]). CONCLUSIONS: Asymptomatic hyperuricemia is prevalent among young adults and associated with markers of prediabetes, dyslipidemia, and subclinical inflammation.

Seroprevalence of camel brucellosis in Qatar.

Brucellosis is a significant zoonotic disease and one of the most common neglected diseases worldwide. It can infect a wide range of domestic and wild animal species. Infected animals are usually culled, causing substantial economic losses to animal owners and the country's economy in general. The disease is endemic among cattle, sheep, and goats in many countries around the Middle East and prevalent in most Gulf Cooperation Council countries, comprising a significant public health risk in the region. This study investigated the seroprevalence of brucellosis among camels in Qatar. Two hundred and forty-eight samples were collected from dromedary camels from 28 farms across the entire country. Each sample was tested for Brucella antibodies with both Rose Bengal and competitive enzyme-linked immunosorbent assay. Only samples that tested positive by both tests were considered seropositive for brucellosis. The overall prevalence was (20.6%, 95% CI, 15.7-26.1). The association between sex and seropositivity was slightly significant (Χ2 = 4.32, P = 0.04), with higher seroprevalence in females. Camels below breeding age (i.e., < 4 years old) showed decreased seropositivity (3.4%, 95% CI, 0.1-17.8), compared to (22.8%, 95% CI, 17.4-29.0) seropositivity in camels ≥ 4 years of age, with a significant association between age groups and seropositivity (P = 0.02). Our results indicate that the seroprevalence of brucellosis in Qatar's camels is alarming, mandating more efforts to control the disease. The findings of this study will aid in selecting better effective measures to control camel brucellosis in Qatar. Further studies need to be conducted on Brucella infection among camels to determine the predisposing risk factors and the steps that should be followed to control brucellosis.

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma.

The pathogenic profile of Pseudomonas aeruginosa is related to its ability to secrete a variety of virulence factors. Quorum sensing (QS) is a mechanism wherein small diffusible molecules, specifically acyl-homoserine lactones, are produced by P. aeruginosa to promote virulence. We show here that macrophage clearance of P. aeruginosa (PAO1) is enhanced by activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). Macrophages treated with a PPARγ agonist (pioglitazone) showed enhanced phagocytosis and bacterial killing of PAO1. It is known that PAO1 QS molecules are inactivated by PON-2. QS molecules are also known to inhibit activation of PPARγ by competitively binding PPARγ receptors. In accord with this observation, we found that infection of macrophages with PAO1 inhibited expression of PPARγ and PON-2. Mechanistically, we show that PPARγ induces macrophage paraoxonase 2 (PON-2), an enzyme that degrades QS molecules produced by P. aeruginosa Gene silencing studies confirmed that enhanced clearance of PAO1 in macrophages by PPARγ is PON-2 dependent. Further, we show that PPARγ agonists also enhance clearance of P. aeruginosa from lungs of mice infected with PAO1. Together, these data demonstrate that P. aeruginosa impairs the ability of host cells to mount an immune response by inhibiting PPARγ through secretion of QS molecules. These studies define a novel mechanism by which PPARγ contributes to the host immunoprotective effects during bacterial infection and suggest a role for PPARγ immunotherapy for P. aeruginosa infections.

Vitamin D deficiency is associated with anaemia among African Americans in a US cohort.

Vitamin D deficiency is highly prevalent in the US population and is associated with numerous diseases, including those characterised by inflammatory processes. We aimed to investigate the link between vitamin D status and anaemia, hypothesising that lower vitamin D status would be associated with increased odds of anaemia, particularly anaemia with inflammation. A secondary aim was to examine the effects of race in the association between vitamin D status and anaemia. We conducted a cross-sectional analysis in a cohort of generally healthy adults in Atlanta, GA (n 638). Logistic regression was used to evaluate the association between vitamin D status and anaemia. Serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/l (compared to 25(OH)D ≥ 50 nmol/l) was associated with anaemia in bivariate analysis (OR 2·64, 95% CI 1·43, 4·86). There was significant effect modification by race (P= 0·003), such that blacks with 25(OH)D < 50 nmol/l had increased odds of anaemia (OR 6·42, 95% CI 1·88, 21·99), v. blacks with 25(OH)D ≥ 50 nmol/l, controlling for potential confounders; this association was not apparent in whites. When categorised by subtype of anaemia, blacks with 25(OH)D < 50 nmol/l had significantly increased odds of anaemia with inflammation than blacks with serum 25(OH)D ≥ 50 nmol/l (OR 8·42, 95% CI 1·96, 36·23); there was no association with anaemia without inflammation. In conclusion, serum 25(OH)D < 50 nmol/l was significantly associated with anaemia, particularly anaemia with inflammation, among blacks in a generally healthy adult US cohort.

Hyperglycemia impedes lung bacterial clearance in a murine model of cystic fibrosis-related diabetes.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity associated with cystic fibrosis (CF), impacting more than half of patients over age 30. CFRD is clinically significant, portending accelerated decline in lung function, more frequent pulmonary exacerbations, and increased mortality. Despite the profound morbidity associated with CFRD, little is known about the underlying CFRD-related pulmonary pathology. Our aim was to develop a murine model of CFRD to explore the hypothesis that elevated glucose in CFRD is associated with reduced lung bacterial clearance. A diabetic phenotype was induced in gut-corrected CF transmembrane conductance regulator (CFTR) knockout mice (CFKO) and their CFTR-expressing wild-type littermates (WT) utilizing streptozotocin. Mice were subsequently challenged with an intratracheal inoculation of Pseudomonas aeruginosa (PAO1) (75 µl of 1-5 × 10(6) cfu/ml) for 18 h. Bronchoalveolar lavage fluid was collected for glucose concentration and cell counts. A portion of the lung was homogenized and cultured as a measure of the remaining viable PAO1 inoculum. Diabetic mice had increased airway glucose compared with nondiabetic mice. The ability to clear bacteria from the lung was significantly reduced in diabetic WT mice and control CFKO mice. Critically, bacterial clearance by diabetic CFKO mice was significantly more diminished compared with nondiabetic CFKO mice, despite an even more robust recruitment of neutrophils to the airways. This finding that CFRD mice boast an exaggerated, but less effective, inflammatory cell response to intratracheal PAO1 challenge presents a novel and useful murine model to help identify therapeutic strategies that promote bacterial clearance in CFRD.

Culture-free diagnostics of Pseudomonas aeruginosa infection by silver nanorod array based SERS from clinical sputum samples.

Pseudomonas aeruginosa can cause major infection in immunocompromised patients, and successful antibiotic treatment of the infection relies on accurate and rapid identification of the infectious agents. Here, we reported a culture-free diagnostic method based on the surface-enhanced Raman spectroscopy (SERS) of pyocyanin (PCN), a major biomarker of P. aeruginosa. This platform can detect PCN as low as 5 ppb or 2.38 × 10(-8) mol L(-1) in both aqueous solutions and spiked clinical sputum samples. It has also been used to dynamically monitor the excretion of PCN by P. aeruginosa during its growth. The presence of PCN has been detected by SERS in 15 clinical sputum samples, which indicates P. aeruginosa infection, with 95.6% sensitivity and 93.3% specificity. The system can advantageously process multiple specimens rapidly, overcomes the need for bacterial culture and diagnostic microbiology assays, and have widespread implications in the early detection of P. aeruginosa infection. FROM THE CLINICAL EDITOR: A surface enhanced Raman spectroscopy method optimized for the detection of P. aureginosa infections is presented in this paper. The presence of pyocyanin, a marker of this bacterium has been detected in 15 clinical sputum samples utilizing this method. A sensitivity of 95.6% and 93.3% specificity was reported, which suggests that the method may enable culture-free high throughput rapid detection of this infection.

Precision classification and quantitative analysis of bacteria biomarkers via surface-enhanced Raman spectroscopy and machine learning.

The SERS spectra of six bacterial biomarkers, 2,3-DHBA, 2,5-DHBA, Pyocyanin, lipoteichoic acid (LTA), Enterobactin, and ß-carotene, of various concentrations, were obtained from silver nanorod array substrates, and the spectral peaks and the corresponding vibrational modes were identified to classify different spectra. The spectral variations in three different concentration regions due to various reasons have imposed a challenge to use classic calibration curve methods to quantify the concentration of biomarkers. Depending on baseline removal strategy, i.e., local or global baseline removal, the calibration curve differed significantly. With the aid of convolutional neural network (CNN), a two-step process was established to classify and quantify biomarker solutions based on SERS spectra: using a specific CNN model, a remarkable differentiation and classification accuracy of 99.99 % for all six biomarkers regardless of the concentration can be achieved. After classification, six regression CNN models were established to predict the concentration of biomarkers, with coefficient of determination R2 > 0.97 and mean absolute error (MAE) < 0.27. The feature of important calculations indicates the high classification and quantification accuracies were due to the intrinsic spectral features in SERS spectra. This study showcases the synergistic potential of SERS and advanced machine learning algorithms and holds significant promise for bacterial infection diagnostics.

Vitamin D status affects proteomic profile of HDL-associated proteins and inflammatory mediators in dyslipidemia.

Vitamin D deficiency and dyslipidemia have substantial implications for human health globally. Vitamin D is essential for bone metabolism and immune modulation, and its insufficiency is linked to various chronic inflammatory conditions. Dyslipidemia, characterized by low levels of high-density lipoprotein (HDL) and elevated levels of low-density lipoprotein (LDL) and triglycerides, is also prevalent. Previous research has shown a connection between vitamin D deficiency and low HDL, but the precise mechanism by which vitamin D influences HDL production and its anti-inflammatory properties remains unclear. This study aimed to investigate the proteomic profiles of individuals with and without vitamin D deficiency and dyslipidemia, specifically focusing on the effects of vitamin D on HDL production, its anti-inflammatory potential, and the molecular pathways associated with vitamin D deficiency and dyslipidemia, particularly inflammation and cancer pathways. By analyzing the proteomic profiles of 274 participants from the Qatar Biobank database, we identified 1301 proteins. Our findings indicated a decrease in HDL-associated apolipoproteins (ApoM and ApoD) in individuals with both dyslipidemia and vitamin D deficiency. Conversely, participants with these conditions exhibited increased expression of acute-phase proteins (SAA1 and SOD1), which are associated with inflammation. Pathway enrichment analysis revealed heightened inflammatory activity in individuals with vitamin D deficiency and dyslipidemia, with notable enrichments in pathways such as MAPK, JAK-STAT, Ras signaling, cytokine-cytokine receptor interaction, AGE-RAGE, ErbB signaling, and cancer pathways. Overall, cases of vitamin D deficiency showed enrichment in inflammation pathways, while individuals with both vitamin D deficiency and dyslipidemia demonstrated enhanced activation of cancer and inflammation pathways.

Breastfeeding Duration Reduces the Risk of Childhood Leukemia and Modifies the Risk of Developing Functional Gastrointestinal Disorders.

Objective: The aim of this study was to test the hypothesis that the duration of breastfeeding in infancy reduces the risk of childhood leukemia or lymphoma, and modifies the risk of developing functional gastrointestinal disorders (FGIDs). Subjects and Methods: This case-control study involved the recruitment of children with lymphoid malignancy and functional gastrointestinal symptoms with healthy children as controls. Focused questionnaires were used to collect data on breastfeeding history and other key risk factors. Univariate and multivariate analyses were undertaken. Results: Of the 334 children with lymphoid malignancy, 65% were male. The control group included 334 age- and sex-matched participants. Most (n = 189; 56.6%) of the children with leukemia were <10 years of age. Differences between cases and controls included the duration of breastfeeding (p < 0.0001), mean birthweight (p < 0.001), maternal age (p < 0.001), paternal age (p < 0.001), birth order (p < 0.001), mean number of children (p < 0.001), BMI percentile (p = 0.042), and maternal smoking (p = 0.012). Breastfeeding duration of up to 6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for acute lymphoblastic leukemia (OR = 3.43, 95% confidence interval [CI] 2.37-4.98; p < 0.001), Hodgkin's lymphoma (OR = 1.58, 95% CI: 0.88-2.84, p = 0.120), Non-Hodgkin's lymphoma (OR = 2.14, 95% CI: 1.25-3.65, p = 0.005), and overall (OR = 1.95, 95% CI: 1.40-2.71, p < 0.001). Cases also differed from controls with regard to FGIDs, such as stomach ache (p < 0.001), dyspepsia (p < 0.001), early satiety (p = 0.017), bowel satisfaction (p < 0.001), bloating (p < 0.001), nausea (p = 0.005), vomiting (p = 0.039), constipation (p = 0.003), diarrhea (p = 0.010), gastrointestinal canal congestion (p =0.039), muscle aches pains (p = 0.008), fecal incontinence (p = 0.021), and indigestion (p = 0.003). A multivariate stepwise regression analysis revealed that maternal smoking (p < 0.001), formula feeding (p < 0.001), duration of breastfeeding (p < 0.001), birth order (p = 0.002), mother's age (p = 0.004) and the child's birthweight (p = 0.009) were predictors for leukemia. Further analysis showed that dyspepsia (p < 0.001), gastrointestinal tract canal congestion (p < 0.001), constipation (p = 0.009), diarrhea (p = 0.013), bowel satisfaction (p = 0.021), bloating (p = 0.022), duration of breastfeeding (p < 0.001), and stomach ache (p = 0.025) were significant predictors for developing FGID symptoms after adjusting for age, gender, and other confounding variables. Conclusion: This study confirmed that breastfeeding has some effect on reducing possible risk of childhood lymphoma and leukemia and FGID symptoms compared with healthy control children.

A Path towards Timely VAP Diagnosis: Proof-of-Concept Study on Pyocyanin Sensing with Cu-Mg Doped Graphene Oxide.

In response to the urgent requirement for rapid, precise, and cost-effective detection in intensive care units (ICUs) for ventilated patients, as well as the need to overcome the limitations of traditional detection methods, researchers have turned their attention towards advancing novel technologies. Among these, biosensors have emerged as a reliable platform for achieving accurate and early diagnoses. In this study, we explore the possibility of using Pyocyanin analysis for early detection of pathogens in ventilator-associated pneumonia (VAP) and lower respiratory tract infections in ventilated patients. To achieve this, we developed an electrochemical sensor utilizing a graphene oxide-copper oxide-doped MgO (GO - Cu - Mgo) (GCM) catalyst for Pyocyanin detection. Pyocyanin is a virulence factor in the phenazine group that is produced by Pseudomonas aeruginosa strains, leading to infections such as pneumonia, urinary tract infections, and cystic fibrosis. We additionally investigated the use of DNA aptamers for detecting Pyocyanin as a biomarker of Pseudomonas aeruginosa, a common causative agent of VAP. The results of this study indicated that electrochemical detection of Pyocyanin using a GCM catalyst shows promising potential for various applications, including clinical diagnostics and drug discovery.

Formulation of meningococcal capsular polysaccharide vaccine-loaded microparticles with robust innate immune recognition.

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis associated with a high mortality rate. Capsular polysaccharides (CPSs) are a major virulence factor and form the basis for serogroup designation and protective vaccines. The current polysaccharide meningococcal vaccines are available but are very expensive and require chemical conjugation. Here, we report a novel meningococcal vaccine formulation consisting of meningococcal CPS polymers encapsulated in albumin-based biodegradable microparticles that slowly release antigen and induce robust innate immune responses. Vaccines that elicit innate immunity are reported to have enhanced and protective adaptive immune responses. In this study, the meningococcal CPS-loaded microparticles, but not the empty microparticles, induced the release of IL-8, TNF-α and IL-1ß, enhanced phagocytic capacity and induced robust autophagy in macrophages. The novel meningococcal vaccine microparticles are robustly taken up by macrophages and elicit strong innate immune responses that enhance antigen presentation which is a prerequisite for inducing adaptive immunity.

ApoM binds endotoxin contributing to neutralization and clearance by High Density Lipoprotein.

Background: HDL possesses anti-inflammatory properties, however, the exact mechanism is not fully understood. Endotoxin is a potent inducers of TLR4 signaling, leading to inflammatory mediators' release. It has been estimated that TLR4 recognizes about 5% of circulating lipopolysaccharide whereas 95% is cleared by plasma lipoproteins, mainly HDL. ApoM is required for HDL biogenesis and 95% of plasma ApoM is found associated with HDL, both are significantly reduced during sepsis. Aim: The aim of this study is to investigate whether ApoM binds endotoxin and contributes to anti-inflammatory activity of HDL. Methods: Isothermal Titration Calorimetry (ITC) was used to determine the binding of ultrapure E. coli LPS to the recombinant ApoM protein. Purified human HDL and recombinant ApoM was used to investigate LPS neutralization using human and murine macrophages and computational simulation was performed. Result: ApoM shows high affinity for E. coli LPS, forming 1:1 complexes with Kd values below 1 µΜ, as revealed by ITC. The binding process is strongly exothermic and enthalpy-driven (ΔrH = -36.5 kJ/mol), implying the formation of an extensive network of interactions between ApoM and LPS in the bound state. Computational simulation also predicted high-affinity binding between ApoM and E. coli LPS and the best scoring models showed E. coli LPS docking near the calyx of ApoM without blocking the pocket. The biological significance of this interaction was further demonstrated in macrophages where purified HDL neutralized an E. coli LPS effect and significantly reduced TNFα release from human THP-1 cells. Conclusion: ApoM binds LPS to facilitate endotoxin neutralization and clearance by HDL.

Assessing the risk of cardiovascular diseases in relation to shisha smoking among adults in Qatar: An analytical cross-sectional study.

INTRODUCTION: Tobacco smoking is a preventable cause of disease and death worldwide. Shisha has become a popular method of smoking tobacco. In Qatar, the prevalence of smoking in 2019 was 25.2%, of which 20.9% was smoking shisha. Shisha smoking is thought to have a harmful effect on the cardiovascular system. The main objective of this study was to understand the relationship between shisha smoking and cardiovascular disease risks. METHODS: All data were obtained from the Qatar Biobank (QBB). The study population consisted of 1045 individuals, which included cases defined as participants who had a history of angina, heart attack and/or stroke and their matched healthy controls for age and gender. The measurement of both the exposure and the outcome was done through the survey provided by QBB. A conditional logistic regression model was used to assess the association between smoking and cardiovascular disease (CVD), and adjusted odds ratio (AOR) and 95% confidence intervals (CI) were calculated after adjusting for covariates. RESULTS: After adjusting for hypertension diagnosis, diabetes diagnosis, dyslipidemia diagnosis, abdominal obesity, and sedentary lifestyle, exclusive shisha smokers had 1.65 times higher odds of reporting cardiovascular disease diagnoses compared to non-smokers (95% CI: 0.71-1.91). Dual shisha and cigarette smokers also had 1.47 times higher odds of reporting cardiovascular disease diagnoses compared to non-smokers (95% CI: 0.88-2.45). CVD cases had a younger median age of initial shisha smoking compared to controls (20 years vs 25 years, p=0.003). CONCLUSIONS: Shisha smoking was associated with an increased risk of developing cardiovascular disease. However, this association did not reach the level of statistical significance within this study. A finding to consider that showed strong evidence is the younger age of initial shisha smoking in cases. Further studies are needed to demonstrate the true relationship between shisha smoking and cardiovascular disease.

Pathogenicity and virulence of monkeypox at the human-animal-ecology interface.

Monkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus, including ecology and evolution, possible drivers of transmission, clinical features and management, knowledge gaps, and research priorities to reduce the disease transmission. The origin, reservoir(s) and the sylvatic cycle of the virus in the natural ecosystem are yet to be confirmed. Humans acquire the infection through contact with infected animals, humans, and natural hosts. The major drivers of disease transmission include trapping, hunting, bushmeat consumption, animal trade, and travel to endemic countries. However, in the 2022 epidemic, the majority of the infected humans in non-endemic countries had a history of direct contact with clinical or asymptomatic persons through sexual activity. The prevention and control strategies should include deterring misinformation and stigma, promoting appropriate social and behavioural changes, including healthy life practices, instituting contact tracing and management, and using the smallpox vaccine for high-risk people. Additionally, longer-term preparedness should be emphasized using the One Health approach, such as systems strengthening, surveillance and detection of the virus across regions, early case detection, and integrating measures to mitigate the socio-economic effects of outbreaks.

Ultrasound-Based Image Analysis for Predicting Carotid Artery Stenosis Risk: A Comprehensive Review of the Problem, Techniques, Datasets, and Future Directions.

The carotid artery is a major blood vessel that supplies blood to the brain. Plaque buildup in the arteries can lead to cardiovascular diseases such as atherosclerosis, stroke, ruptured arteries, and even death. Both invasive and non-invasive methods are used to detect plaque buildup in the arteries, with ultrasound imaging being the first line of diagnosis. This paper presents a comprehensive review of the existing literature on ultrasound image analysis methods for detecting and characterizing plaque buildup in the carotid artery. The review includes an in-depth analysis of datasets; image segmentation techniques for the carotid artery plaque area, lumen area, and intima-media thickness (IMT); and plaque measurement, characterization, classification, and stenosis grading using deep learning and machine learning. Additionally, the paper provides an overview of the performance of these methods, including challenges in analysis, and future directions for research.

Cytotoxicity and Antibiofilm Activity of Silver-Polypropylene Nanocomposites.

The development of biocompatible nanomaterials that interface with human skin and tissue is critical for advancing prosthetics and other therapeutic medical needs. In this perspective, the development of nanoparticles with cytotoxicity and antibiofilm properties and biocompatibility characteristics are important. Metallic silver (Ag) exhibits good biocompatibility, but it is often challenging to integrate it into a nanocomposite without compromising its antibiofilm properties for optimal applications. In this study, new polymer nanocomposites (PNCs) with ultra-low filling content (0.0023-0.046 wt%) of Ag nanoplates were manufactured and tested. The cytotoxicity and antibiofilm activity of different composites with polypropylene (PP) matrix were examined. At first, PNCs surface were analyzed by means of AFM (atomic force microscopy) with phase contrast evaluation and FTIR (Fourier-transform infrared spectroscopy) to study the Ag nanoplates distribution. Subsequently, the cytotoxicity and growth properties of biofilms were assessed by MTT assay protocol and detection of nitric oxide radicals. Antibacterial and antibiofilm activities were measured against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (K. pneumoniae). The PNCs with silver exhibited antibiofilm activity although they did not inhibit regular planktonic bacterial growth. Moreover, the PNCs were not cytotoxic to mammalian cells and did not induce significant immune response. These features reveal the potential of the PNCs developed in this study for usage in fabrication of prosthetics and other smart structures for biomedical applications.

Gonococcal microparticle vaccine in dissolving microneedles induced immunity and enhanced bacterial clearance in infected mice.

There is an alarming rise in the number of gonorrhea cases worldwide. Neisseria gonorrhoeae, the bacteria that causes gonorrhea infection, has gradually developed antimicrobial resistance over the years. To date, there is no licensed vaccine for gonorrhea. This study investigates the in vivo immunogenicity of a whole-cell inactivated gonococci in a microparticle formulation (Gc-MP) along with adjuvant microparticles (Alhydrogel®- Alum MP and AddaVax™ MP) delivered transdermally using dissolving microneedles (MN). The proposed vaccine formulation (Gc-MP + Alum MP + AddaVax™ MP) was assessed for induction of humoral, cellular, and protective immune responses in vivo. Our results show the induction of significant gonococcal-specific serum IgG, IgG1, IgG2a, and vaginal mucosal IgA antibodies in mice immunized with Gc-MP + Alum MP + AddaVax™ MP and Gc-MP when compared to the control groups receiving blank MN or no treatment. The serum bactericidal assay revealed that the antibodies generated in mice after immunization with Gc-MP + Alum MP + AddaVax™ MP were bactericidal towards live Neisseria gonorrhoeae. Gc-MP + Alum MP + AddaVax™ MP and Gc-MP-immunized mice showed enhanced clearance rate of gonococcal bacterial infection post challenge. In contrast, the control groups did not begin to clear the infection until day 10. In addition, the mice which received Gc-MP + Alum MP + AddaVax™ MP showed enhanced expression of cellular immunity markers CD4 and CD8 on the surface of T cells in the spleen and lymph nodes. Taken together, the data shows that microneedle immunization with whole-cell inactivated gonococci MP in mice induced humoral, cellular, and protective immunity against gonococcal infection.

An Adjuvanted Inactivated SARS-CoV-2 Microparticulate Vaccine Delivered Using Microneedles Induces a Robust Immune Response in Vaccinated Mice.

SARS-CoV-2, the causal agent of COVID-19, is a contagious respiratory virus that frequently mutates, giving rise to variant strains and leading to reduced vaccine efficacy against the variants. Frequent vaccination against the emerging variants may be necessary; thus, an efficient vaccination system is needed. A microneedle (MN) vaccine delivery system is non-invasive, patient-friendly, and can be self-administered. Here, we tested the immune response produced by an adjuvanted inactivated SARS-CoV-2 microparticulate vaccine administered via the transdermal route using a dissolving MN. The inactivated SARS-CoV-2 vaccine antigen and adjuvants (Alhydrogel® and AddaVax™) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer matrices. The resulting MP were approximately 910 nm in size, with a high percentage yield and percent encapsulation efficiency of 90.4%. In vitro, the vaccine MP was non-cytotoxic and increased the immunostimulatory activity measured as nitric oxide release from dendritic cells. The adjuvant MP potentiated the immune response of the vaccine MP in vitro. In vivo, the adjuvanted SARS-CoV-2 MP vaccine induced high levels of IgM, IgG, IgA, IgG1, and IgG2a antibodies and CD4+ and CD8+ T-cell responses in immunized mice. In conclusion, the adjuvanted inactivated SARS-CoV-2 MP vaccine delivered using MN induced a robust immune response in vaccinated mice.