A systematic review of machine learning models for management, prediction and classification of ARDS.

AIM: Acute respiratory distress syndrome or ARDS is an acute, severe form of respiratory failure characterised by poor oxygenation and bilateral pulmonary infiltrates. Advancements in signal processing and machine learning have led to promising solutions for classification, event detection and predictive models in the management of ARDS. METHOD: In this review, we provide systematic description of different studies in the application of Machine Learning (ML) and artificial intelligence for management, prediction, and classification of ARDS. We searched the following databases: Google Scholar, PubMed, and EBSCO from 2009 to 2023. A total of 243 studies was screened, in which, 52 studies were included for review and analysis. We integrated knowledge of previous work providing the state of art and overview of explainable decision models in machine learning and have identified areas for future research. RESULTS: Gradient boosting is the most common and successful method utilised in 12 (23.1%) of the studies. Due to limitation of data size available, neural network and its variation is used by only 8 (15.4%) studies. Whilst all studies used cross validating technique or separated database for validation, only 1 study validated the model with clinician input. Explainability methods were presented in 15 (28.8%) of studies with the most common method is feature importance which used 14 times. CONCLUSION: For databases of 5000 or fewer samples, extreme gradient boosting has the highest probability of success. A large, multi-region, multi centre database is required to reduce bias and take advantage of neural network method. A framework for validating with and explaining ML model to clinicians involved in the management of ARDS would be very helpful for development and deployment of the ML model.

Machine learning, advanced data analysis, and a role in pregnancy care? How can we help improve preeclampsia outcomes?

The value of machine learning capacity in maternal health, and in particular prediction of preeclampsia will only be realised when there are high quality clinical data provided, representative populations included, different health systems and models of care compared, and a culture of rapid use and application of real-time data and outcomes. This review has been undertaken to provide an overview of the language, and early results of machine learning in a pregnancy and preeclampsia context. Clinicians of all backgrounds are encouraged to learn the language of Machine Learning (ML) and Artificial intelligence (AI) to better understand their potential and utility to improve outcomes for women and their families. This review will outline some definitions and features of ML that will benefit clinician's knowledge in the preeclampsia discipline, and also outline some of the future possibilities for preeclampsia-focussed clinicians via understanding AI. It will further explore the criticality of defining the risk, and outcome being determined.

Swietemicrolides A-D, mexicanolide-type limonoids from the bark of Swietenia macrophylla with in vitro cytotoxic and α-glucosidase inhibitory activities.

Four new mexicanolide-type limonoids, swietemicrolides A-D (1-4), together with three known compounds (5-7) were isolated from an ethyl acetate extract of the bark of Swietenia microphylla. 1 and 2 had 1,8-hemiacetal systems whilst 3 and 4 shared hexacyclic skeletons consisting of three fused five-membered rings. The structures of the isolated compounds were determined using spectroscopic methods. The five limonoids (1-5) were tested in vitro for their cytotoxic effects against two human cancer cell lines (KB carcinoma and A549 lung cancer cells) and α-glucosidase inhibitory activity. None of them showed significant cytotoxic activity, however, swietemicrolide C (3) exhibited strong effect towards α-glucosidase. Moreover, a possible biosynthetic pathway for compounds 1-4 was proposed to support a comprehensive understanding of the configurations of the new limonoids.

Simultaneous versus sequential fractional CO2 laser and subcision combination for management of post-acne atrophic scars: A split-face comparative study.

BACKGROUND: A combination of fractional CO2 laser and subcision is usually employed for the treatment of post-acne atrophic scars. However, the efficacy and safety of both simultaneous and sequential combination therapies should be explored. AIMS: To compare the efficacy and safety of simultaneous and sequential fractional CO2 laser and subcision combination therapies for post-acne atrophic scars. PATIENTS AND METHODS: This single-blind, split-face clinical trial included 34 patients with post-acne atrophic scars at our institution. Each patient underwent three sessions of subcision combined with fractional CO2 laser, with a 1-month interval between each session. The left side of the face was treated with simultaneous combination therapy, whereas the right side was treated with sequential combination therapy. Treatment efficacy was assessed at 4, 8, and 12 weeks; and 3 and 6 months after the last session. RESULTS: Simultaneous and sequential treatments demonstrated comparable efficacy. Regarding the adverse events, the side of the face undergoing simultaneous treatment experienced longer swelling duration, higher pain levels during laser treatment, and shorter downtime. CONCLUSIONS: Despite the longer swelling time and higher pain levels during laser treatment in the simultaneous treatment side, the effectiveness and satisfaction level of the CO2 fractional laser and subcision for treatment of the acne scars were comparable between the two combinations, with a shorter downtime for the simultaneous than for the sequential combination therapy.

Virtual Remote Pathology Education in Support of Virtual Remote Gynecologic-Oncology Training: The Open Pathology Education Network Pilot Proof of Concept Experience.

CONTEXT.­: The subspecialty workforce in pathology globally is inadequate for the demands of many modern therapies. The Open Pathology Education Network (OPEN) was formed to augment the global pathology workforce. The International Gynecologic Cancer Society (IGCS) virtual gynecologic-oncology (gyn-onc) fellowship training identified needs for higher-level pathology support. OBJECTIVE.­: To report on an OPEN-IGCS pilot project to support gyn-onc and pathology education efforts in a developing country. DESIGN.­: Curriculum with learning objectives and content from open sources was assembled. Mentoring sessions included bidirectional case sharing. Trainees received sequential curricula assignments and had options for communication outside mentoring sessions. Pretest and posttest digital slide assessments were included. Mentors attended the gynecology tumor board, allowing for the assessment of quality and accuracy of pathology diagnosis for cases discussed. RESULTS.­: Learners completing the pretest and posttest showed substantial improvement, with 2 practicing pathologists improving their diagnostic scores from 60% to an average of 95%. A third trainee-level participant also improved, but to a lesser degree. Qualitative assessments included increased confidence in presentation and an increased ability to anticipate questions, raise issues of expanded differential diagnoses, and articulate appropriate workup. Observations of clinicians who participated also noted increased confidence in participating pathologists. Secondary value included establishing an expanded network of support in other subspecialties for participants. Pathologic issues at the tumor board decreased, from more than 50% in the first 3 months of study to 0% in the last 3 months of study. The curriculum was embedded into a self-paced learning portal at courses.open-pathology.org. CONCLUSIONS.­: The OPEN-IGCS collaboration model shows the potential to provide subspecialty pathology training remotely.

Screening for Hypertension in Adults of a Northern Delta Province in Vietnam.

BACKGROUND: The proportion of people with hypertension is increasing, and those affected are relatively younger. Worldwide, it is estimated that people with high blood pressure are more than 1.5 billion people. In Vietnam, from 2002 to 2008, according to a national survey on hypertension and its risk factors within the prevention and control of cardiovascular disease program, the prevalence of hypertension was 25.1%. This is alarming because high blood pressure can cause serious complications, including death. OBJECTIVE: The study aimed to explore the blood pressure characteristics and hypertension prevalence in adults in a northern delta province of Vietnam, and describe some risk factors in hypertensive subjects screened through the program. METHODS: This was a cross-sectional study collecting data from people aged 18 years or older in 10 cantons and the city of Nam Dinh from July 15th to July 31st, 2020. Using semi-automatic OMRON sphygmomanometers, sitting blood pressure was measured three times according to standardized methods specified by the Ministry of Health and two National Vascular Societies. RESULTS: Blood pressure screening of 183,632 adults included 84,438 males, which accounted for 45.98%, with an average age of 60.36 ± 13.18 years. The estimated prevalence of hypertension was 27.20% (95% CI: 27.00% - 27.41%). The older the age, the higher the rate of hypertension in both sexes; the prevalence of hypertension over 65 years was 45.36%. Hypertension grade 1 accounted for 17.14%, followed by hypertension at grade 2 at 6.69%, and grade 3 at 1.15%; notably, the percentage of prehypertension accounted for 49.64%. The percentage of treated hypertension in Nam Dinh province was 56.85%, but the percentage of uncontrolled hypertension was 85.63%. CONCLUSION: The prevalence of hypertension in Nam Dinh province was relatively high (27.20%), although the number of treated patients was also high (56.85%); moreover, the proportion of uncontrolled hypertension remained extremely high (85.63%). Local campaigns and suitable interventions are required to detect hypertension in the early stages and increase awareness for treatment in the population.

Emergence of multidrug-resistant Staphylococcus haemolyticus in neonatal intensive care unit in Southern France, a genomic study.

An emergence of multidrug-resistant (MDR) Staphylococcus haemolyticus has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case-control analysis was conducted on 96 neonates, to identify risk factors associated with S. haemolyticus infection, focusing on clinical outcomes. Forty-eight MDR S. haemolyticus strains, isolated from neonates between October 2019 and July 2022, were investigated using routine in vitro procedures and whole-genome sequencing. Additionally, five S. haemolyticus isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal S. haemolyticus was significantly associated with low birth weight, lower gestational age, and central catheter use (p < 0.001). Sepsis was the most frequent clinical manifestation in this series (20/46, 43.5%) and was associated with five deaths. Based on whole-genome analysis, three S. haemolyticus genotypes were predicted: ST1 (6/53, 11%), ST25 (3/53, 5.7%), and ST29 (44/53, 83%), which included the subcluster II-A, predominantly emerging in the neonatal department. All strains were profiled in silico to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with in vitro antibiotic susceptibility tests. Moreover, in silico prediction of biofilm formation and virulence-encoding genes supported the association of ST29 with severe clinical outcomes, while the persistence in the NICU could be explained by the presence of antiseptic and heavy metal resistance-encoding genes. The clonality of S. haemolyticus ST29 subcluster II-A isolates confirms healthcare transmission causing severe infections. Based on these results, reinforced hygiene measures are necessary to eradicate the nosocomial transmission of MDR strains.

Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

Photodynamic treatment increases the lifespan and oxidative stress resistance of Caenorhabditis elegans.

Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 µM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.

Descemet Stripping Endothelial Keratoplasty in Patients With a Custom Foldable Silicone Artificial Iris: Safety and Efficacy Outcomes.

PURPOSE: To assess outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with custom artificial iris (CAI) implantation. METHODS: This is a retrospective, interventional, consecutive, surgical case series of patients who underwent DSEK after CAI implantation between 2010 and 2021 at 2 referral centers. Primary safety measures were loss of corrected distance visual acuity (CDVA), increase in intraocular pressure (IOP), development or progression of glaucoma, and intraoperative and postoperative complications. Efficacy measures were graft survival at year 1 and improvement in cosmesis at postoperative month 3. In general, measures were compared between baseline and postoperative year 1 while any complication was reported for the full follow-up period. RESULTS: Thirty-nine eyes of 39 patients were identified. 64.1% of eyes had acquired aniridia from trauma. The mean follow-up interval was 27.7 months (range 12.2-117.4). Median CDVA improved from logMAR 1.0 to 0.7 at year 1 (P = 0.0047). At the final follow-up, permanent loss of CDVA occurred in 25.6% of eyes, of which 90% was due to glaucoma. The most common postoperative complication was IOP elevation (66.7% of eyes). Graft survival at postoperative year 1 was 82.0% (95% confidence interval, 66.3-91.4). Secondary graft failure occurred in 28.2% of eyes at a mean duration of 39.7 months (SD 27.9 months) after DSEK. Cosmesis improved among 87.2% of eyes at postoperative month 3. CONCLUSIONS: DSEK is an effective procedure for addressing corneal edema in eyes with a CAI, but a majority develop elevated IOP and graft survival is shorter than in eyes without a CAI.

Regulatory T and B cells in pediatric Henoch-Schönlein purpura: friends or foes?

BACKGROUND AND OBJECTIVES: Henoch-Schönlein purpura (HSP) is the most common immunoglobulin A-mediated systemic vasculitis in childhood. We studied immune dysregulation in HSP by analyzing regulatory T (Treg), T helper 3 (Th3), and regulatory B cell (Breg) subpopulations that might intervene in immune activation, IgA production, and HSP clinical manifestations. METHODS: This prospective study included 3 groups of children: 30 HSP on acute phase, 30 HSP on remission, and 40 healthy controls (HCs) matched on age. Treg, Breg, and Th3 were analyzed by flow cytometry. Serum immunoglobulin and cytokine levels were quantified by ELISA and Luminex. RESULTS: Treg frequencies were higher in acute HSP than in remitting HSP and HCs (6.53% [4.24; 9.21] vs. 4.33% [3.6; 5.66], p = 0.002, and vs. 4.45% [3.01; 6.6], p = 0.003, respectively). Activated Th3 cells (FoxP3 + Th3 cells) tend to be more abundant in HSP than in HCs (78.43% [50.62; 80.84] vs. 43.30% [40.20; 49.32], p = 0.135). Serum IgA, IL-17, and latency-associated peptide (a marker of the anti-inflammatory cytokine TGF-beta production) were significantly and inflammatory cytokines TNF-alpha, IL-1-beta, and IL-6 were non-significantly higher in HSP than HCs. Bregs were identical between the groups, but, in patients with renal impairment, Breg percentage was lower compared to those without. Treg removal in PBMC culture resulted in an increase in IgA production in HSP proving a negative regulatory role of Tregs on IgA production. CONCLUSIONS: In pediatric HSP, immune activation persists in spite of an increase in Th3 and Tregs. Th3 could be involved in IgA hyperproduction, inefficiently downregulated by Tregs. Lack of Bregs appears linked to renal impairment.

Quantifying heterogeneity in an animal model of acute respiratory distress syndrome, a comparison of inspired sinewave technique to computed tomography.

The inspired sinewave technique (IST) is a non-invasive method to measure lung heterogeneity indices (including both uneven ventilation and perfusion or heterogeneity), which reveal multiple conditions of the lung and lung injury. To evaluate the reproducibility and predicted clinical outcomes of IST heterogeneity values, a comparison with a quantitative lung computed tomography (CT) scan is performed. Six anaesthetised pigs were studied after surfactant depletion by saline-lavage. Paired measurements of lung heterogeneity were then taken with both the IST and CT. Lung heterogeneity measured by the IST was calculated by (a) the ratio of tracer gas outputs measured at oscillation periods of 180 s and 60 s, and (b) by the standard deviation of the modelled log-normal distribution of ventilations and perfusions in the simulation lung. In the CT images, lungs were manually segmented and divided into different regions according to voxel density. A quantitative CT method to calculate the heterogeneity (the Cressoni method) was applied. The IST and CT show good Pearson correlation coefficients in lung heterogeneity measurements (ventilation: 0.71, and perfusion, 0.60, p < 0.001). Within individual animals, the coefficients of determination average ventilation (R2 = 0.53) and perfusion (R2 = 0.68) heterogeneity. Strong concordance rates of 98% in ventilation and 89% when the heterogeneity changes were reported in pairs measured by CT scanning and IST methods. This quantitative method to identify heterogeneity has the potential to replicate CT lung heterogeneity, and to aid individualised care in ARDS.

Low Percentage of Perforin-Expressing NK Cells during Severe SARS-CoV-2 Infection: Consumption Rather than Primary Deficiency.

Genetic defects in the ability to deliver effective perforin have been reported in patients with hemophagocytic lymphohistiocytosis. We tested the hypothesis that a primary perforin deficiency might also be causal in severe SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to intensive care units or non-intensive care units and age- and sex-matched healthy controls. Compared with healthy controls, the percentage of perforin-expressing CD3-CD56+ NK cells quantified by flow cytometry was low in COVID-19 patients (69.9 ± 17.7 versus 78.6 ± 14.6%, p = 0.026). There was no correlation between the proportions of perforin-positive NK cells and T8 lymphocytes. Moreover, the frequency of NK cells producing perforin was neither linked to disease severity nor predictive of death. Although IL-6 is known to downregulate perforin production in NK cells, we did not find any link between perforin expression and IL-6 plasma level. However, we unveiled a negative correlation between the degranulation marker CD107a and perforin expression in NK cells (r = -0.488, p = 10-4). PRF1 gene expression and the frequency of NK cells harboring perforin were normal in patients 1 y after acute SARS-CoV-2 infection. A primary perforin defect does not seem to be a driver of COVID-19 because NK perforin expression is 1) linked neither to T8 perforin expression nor to disease severity, 2) inversely correlated with NK degranulation, and 3) normalized at distance from acute infection. Thus, the cause of low frequency of perforin-positive NK cells appears, rather, to be consumption.

A hospital-based asynchronous ENT telehealth service for children with otitis media: Cost-minimisation and improved access.

AIM: The purpose of this study is to explore the effectiveness of a hospital-based asynchronous ear, nose, and throat (ENT) telehealth service (the Ear Portal) in reducing cost and improving access for children with otitis media. METHODS: Participants were recruited to the Ear Portal from a tertiary hospital ENT waiting list. Ear and hearing assessments were conducted during appointments by the Ear Portal research assistant, and data was stored for an asynchronous review by the Ear Portal multidisciplinary team. A cost-minimisation analysis was conducted for the Ear Portal and the standard care pathways. Waiting times to provide care for both pathways were calculated for children with semi-urgent (i.e. Category 2) and non-urgent (i.e. Category 3) referrals. RESULTS: The running cost for the Ear Portal was $67.70 for initial appointments and $37.34 for follow-up appointments. Conversely, the running cost for the standard care pathway was $154.65 for initial appointments and $86.10 for follow-up appointments. A total of 223 appointments were required to offset the initial Ear Portal investment of $19,384.00. The median waiting time for the Ear Portal from initial contact to care plan delivery was <30 days, whereas the median waiting times for children in the standard care pathway were 291 days (interquartile range (IQR) = 117) for Category 2 and 371 days (IQR = 311) for Category 3 referrals. CONCLUSION: Under the current circumstances, the Ear Portal service can reduce costs for the health care system by reducing marginal costs per patient in addition to providing ENT specialist care within the clinically recommended timeframes.

Primary sarcoma of the liver: A nationwide analysis of a rare mesenchymal tumor.

BACKGROUND AND OBJECTIVES: Primary liver sarcomas are rare malignancies. Prognostic factors associated with long-term survival remain poorly understood. The objective of this study is to determine factors associated with long-term survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with visceral sarcoma arising from the liver. Demographic factors, tumor characteristics, resection status, and survival were evaluated. Multivariate Cox regression analysis was performed to determine predictors of survival. RESULTS: A total of 743 patients with primary hepatic sarcoma were identified. The median tumor size was 10 cm. Only 30% (n = 221) of patients in the cohort underwent surgery. The 5-year overall survival rates were 47.9% for localized disease, 29.5% for regional disease, and 16.5% for distant disease, p < 0.001. Among patients who underwent surgical resection, patients with embryonal sarcoma had better 5-year survival compared with angiosarcoma and other histologic subtypes. On multivariate analysis, surgery was associated with improved survival, while older age, higher stage, and angiosarcoma histology were the strongest independent predictors of poor survival. CONCLUSIONS: Surgery remains the mainstay of treatment for this rare malignancy but is performed in less than one-third of patients. Angiosarcoma histology is associated with worse overall survival, while surgical resection remains the strongest predictor of improved overall survival.

Topical Tacrolimus Compared With Oral Tacrolimus for Postoperative Immunosuppression in Primary Keratolimbal Allograft.

PURPOSE: The aim of this study was to compare outcomes between topical tacrolimus and oral tacrolimus as the primary calcineurin inhibitor for postoperative immunosuppression after primary keratolimbal allograft (KLAL) transplantation for limbal stem cell deficiency (LSCD). METHODS: We performed a retrospective, comparative cohort study at a single tertiary referral center (University of MN) of all patients who underwent primary KLAL between 2014 and 2021. Eyes were grouped into those which received topical tacrolimus as the only calcineurin inhibitor (topical group) and eyes in which patients received oral tacrolimus with or without topical tacrolimus (oral group). Clinical and donor tissue data were obtained and compared between the 2 groups. RESULTS: In total, 27 eyes of 22 patients (median age 42 years, range 20-79 years) were included, of which 18 eyes were in the oral group and 9 eyes were in the topical group. The mean follow-up time was 33.2 ± 22.6 months. The most frequent etiology of LSCD was alkaline burn (33.3%). At 36 months, graft failure occurred in 6 eyes in the oral group (33.3%) and 2 eyes in the topical group (22.1%) ( P = 0.57). The failure rate in the oral group was 9.1 per 1000 person-months versus 8.4 per 1000 person-months in the topical group ( P = 0.96). The median improvement in BCVA was logMAR -0.975 and logMAR -0.45 for the oral and topical group, respectively ( P = 0.50). CONCLUSIONS: With careful patient selection, topical tacrolimus may be a viable alternative to oral tacrolimus in KLAL.

Macrophage IL-1ß-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic arthritis.

Objective: IL-1ß is a leaderless cytokine with poorly known secretory mechanisms that is barely detectable in serum of patients, including those with an IL-1ß-mediated disease such as systemic juvenile idiopathic arthritis (sJIA). Leukocyte microvesicles (MVs) may be a mechanism of IL-1ß secretion. The first objective of our study was to characterize IL-1ß-positive MVs obtained from macrophage cell culture supernatants and to investigate their biological functions in vitro and in vivo. The second objective was to detect circulating IL-1ß-positive MVs in JIA patients. Methods: MVs were purified by serial centrifugations from PBMCs, or THP-1 differentiated into macrophages, then stimulated with LPS ± ATP. MV content was analyzed for the presence of IL-1ß, NLRP3 inflammasome, caspase-1, P2X7 receptor, and tissue factor (TF) using ELISA, Western blot, or flow cytometry. MV biological properties were studied in vitro by measuring VCAM-1, ICAM-1, and E-selectin expression after HUVEC co-culture and factor-Xa generation test was realized. In vivo, MVs' ability to recruit leukocytes in a murine model of peritonitis was evaluated. Plasmatic IL-1ß-positive MVs were studied ex vivo in 10 active JIA patients using flow cytometry. Results: THP-1-derived macrophages stimulated with LPS and ATP released MVs, which contained NLRP3, caspase-1, and the 33-kDa precursor and 17-kDa mature forms of IL-1ß and bioactive TF. IL-1ß-positive MVs expressed P2X7 receptor and released soluble IL-1ß in response to ATP stimulation in vitro. In mice, MVs induced a leukocyte peritoneal infiltrate, which was reduced by treatment with the IL-1 receptor antagonist. Finally, IL-1ß-positive MVs were detectable in plasma from 10 active JIA patients. Conclusion: MVs shed from activated macrophages contain IL-1ß, NLRP3 inflammasome components, and TF, and constitute thrombo-inflammatory vectors that can be detected in the plasma from active JIA patients.

A new apotirucallane-type protolimonoid from the leaves of Paramignya trimera.

This study presents a phytochemical analysis of the leaves of Paramignya trimera, revealing the isolation of a new apotirucallane-type protolimonoid, identified as 25-O-methyl-1,2-dihydroprotoxylocarpin D (1), along with two known compounds (2 and 3). The known compounds were identified as (20S,21R,23R)-21,23-epoxy-7α,24,25-trihydroxy-21-O-methyl-3-oxoapotirucalla-14-ene (2) and 7α,24,25-trihydroxy-3-oxoapotirucalla-14-en-21,23-olide (3). The three apotirucallane-type protolimonoids (1-3) did not exhibit cytotoxicity against MCF-7 cells at a concentration of 100 µM. Interestingly, when MCF-7 cells were treated with compound 1 at various concentrations, a notable stimulatory response was observed, leading to a significant increase in cell viability, up to 127%.

Comorbidity Burden and Treatment Patterns of Psoriasis in Vietnam: Real-World Data from the EXPAND Study.

INTRODUCTION: Psoriasis is a multi-faceted, immune-mediated inflammatory disease associated with a wide range of comorbidities. Real-world data on treatment patterns, comorbidities, and economic burden in patients with psoriasis are needed for comprehensive patient care in Vietnam. METHODS: A retrospective chart review study was conducted using secondary data extracted from patients' medical records of two hospitals in Vietnam, with the aim of identifying adult patients with a confirmed diagnosis of psoriasis. The index date was defined as the date of first diagnosis between 1 January 2020 and 31 October 2021. Sociodemographic factors, disease characteristics, comorbidities, medication usage, drug survival, and medication costs were analyzed. RESULTS: A total of 661 patients were identified (mean ± standard deviation [SD] age 43.5 ± 14.8 years). The most prevalent comorbidity was dyslipidemia (49.6% of patients), followed by hypertension (23.4%), and psoriatic arthritis (10.4%). In total, 44% of patients received biologic therapies. Overall, 66.7% and 54.3% of patients receiving biologic and non-biologic therapies, respectively, had ≥ 1 comorbidity. Only 23.2% of patients with psoriasis-related comorbidities stopped therapy with biologics. Biologics had a longer retention time (17.0 months) than non-biologics (6.0 months) in patients with comorbidities. Patients with comorbidities had significantly higher total annual healthcare costs than those without comorbidities (in US dollars: USD901 vs. USD304; p < 0.001), mainly due to the relatively higher costs associated with the use of biologics. CONCLUSION: Patients with psoriasis in Vietnam experience a high disease and economic burden due to comorbidities. Evidence from this real-world study supports the need for routine monitoring of and an appropriate treatment course for psoriasis-related comorbidities.

Efficient symptomatic treatment and viral load reduction for children with influenza virus infection by nasal-spraying Bacillus spore probiotics.

Influenza virus is a main cause of acute respiratory tract infections (ARTIs) in children. This is the first double-blind, randomized, and controlled clinical trial examining the efficacy of nasal-spraying probiotic LiveSpo Navax, which contains 5 billion of Bacillus subtilis and B. clausii spores in 5 mL, in supporting treatment of influenza viral infection in pediatric patients. We found that the nasal-spraying Bacillus spores significantly shortened the recovery period and overall treatment by 2 days and increased treatment effectiveness by 58% in resolving all ARTIs' symptoms. At day 2, the concentrations of influenza virus and co-infected bacteria were reduced by 417 and 1152 folds. Additionally, the levels of pro-inflammatory cytokines IL-8, TNF-α, and IL-6 in nasopharyngeal samples were reduced by 1.1, 3.7, and 53.9 folds, respectively. Compared to the standard control group, treatment regimen with LiveSpo Navax demonstrated significantly greater effectiveness, resulting in 26-fold reduction in viral load, 65-fold reduction in bacterial concentration, and 1.1-9.5-fold decrease in cytokine levels. Overall, nasal-spraying Bacillus spores can support the symptomatic treatment of influenza virus-induced ARTIs quickly, efficiently and could be used as a cost-effective supportive treatment for respiratory viral infection in general.Clinical trial registration no: NCT05378022 on 17/05/2022.