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Background: Expanding and providing access to early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through testing community-based strategies among socially vulnerable communities (SVC) are critical to reducing health disparities. The Epidemiological Intelligence Community Network (EpI-Net) community-based intervention sought to increase coronavirus 2019 (COVID-19) testing uptake and prevention practices among SVC in Puerto Rico (PR). We evaluated EpI-Net's community leaders' capacity-building component by assessing pre-post COVID-19 public health workshops' tests' score changes and satisfaction among trained community leaders. Methods: A total of 24 community leaders from SVC in PR have completed four community workshops. Pre- and post-assessments were completed as part of the health promotors training program to evaluate participants' tests score changes and satisfaction outcomes. Results: Preliminary results showed: (1) high intervention retention levels of community leaders (85.7% acceptance rate); (2) change in post-test scores for community engagement strategies (p = 0.012); (3) change in post-test educational scores in COVID-19 prevention practices (p = 0.014); and (4) a change in scores in public health emergency management strategies (p < 0.001). Conclusions: The overall workshop satisfaction was 99.6%. Community leaders have shown the importance of community capacity building as a key component for intervention feasibility and impact. Trial registration: Our study was retrospectively registered under the ClinicalTrial.gov ID NCT04910542. [ABSTRACT FROM AUTHOR]

Background: Engineered stone silicosis is an emerging disease in many countries worldwide produced by the inhalation of respirable dust of engineered stone. This silicosis has a high incidence among young workers, with a short latency period and greater aggressiveness than silicosis caused by natural materials. Although the silica content is very high and this is the key factor, it has been postulated that other constituents in engineered stones can influence the aggressiveness of the disease. Different samples of engineered stone countertops (fabricated by workers during the years prior to their diagnoses), as well as seven lung samples from exposed patients, were analyzed by multiple techniques. Results: The different countertops were composed of SiO2 in percentages between 87.9 and 99.6%, with variable relationships of quartz and cristobalite depending on the sample. The most abundant metals were Al, Na, Fe, Ca and Ti. The most frequent volatile organic compounds were styrene, toluene and m-xylene, and among the polycyclic aromatic hydrocarbons, phenanthrene and naphthalene were detected in all samples. Patients were all males, between 26 and 46 years-old (average age: 36) at the moment of the diagnosis. They were exposed to the engineered stone an average time of 14 years. At diagnosis, only one patient had progressive massive fibrosis. After a follow-up period of 8 ± 3 years, four patients presented progressive massive fibrosis. Samples obtained from lung biopsies most frequently showed well or ill-defined nodules, composed of histiocytic cells and fibroblasts without central hyalinization. All tissue samples showed high proportion of Si and Al at the center of the nodules, becoming sparser at the periphery. Al to Si content ratios turned out to be higher than 1 in two of the studied cases. Correlation between Si and Al was very high (r = 0.93). Conclusion: Some of the volatile organic compounds, polycyclic aromatic hydrocarbons and metals detected in the studied countertop samples have been described as causative of lung inflammation and respiratory disease. Among inorganic constituents, aluminum has been a relevant component within the silicotic nodule, reaching atomic concentrations even higher than silicon in some cases. Such concentrations, both for silicon and aluminum showed a decreasing tendency from the center of the nodule towards its frontier. [ABSTRACT FROM AUTHOR]

Background: HIV incidence can be estimated with cross-sectional studies using clinical, serological, and molecular data. Worldwide, HIV incidence data in only men who have sex with men (MSM) are scarce and principally focus on those with healthcare or under treatment. However, better estimates can be obtained through studies with national representativeness. The objective was to estimate the prevalence, incidence, and factors associated with acquiring HIV in a national sample of MSM who attend meeting places, considering geographical regions.Methods: A nationally representative survey of MSM attending meeting places was performed in Mexico. Participants answered a questionnaire, and a dried blood spot (DBS) was collected. Samples were classified as recent infections using an algorithm with HIV status, antiretroviral therapy, and the result of BED-EIA assay. Parameters were analysed considering regions and demographic and sexual behaviour characteristics.Results: The national HIV prevalence was 17.4% with regional differences; the highest prevalence (20.7%) was found in Mexico City, and the lowest prevalence was found in the West region (11.5%). The incidence was 9.4 per 100 p/y, with regional values from 6.2 to 13.2 for the Northeast and the Centre regions, respectively. Age, age at sexual debut, low wealth index, and rewarded sex were associated with HIV prevalence. Centre region, use of private clinics as health services, and having sex exclusively with men were associated with recent HIV infections.Conclusions: The incidence and prevalence showed regional differences, suggesting a difference in the dynamics of HIV transmission; some regions have a greater case accumulation, and others have a greater rate of new infections. Understanding this dynamic will allow developing health programs focused on HIV prevention or treating people already living with HIV. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). Methods: Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. Results: Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils. Conclusions: Neuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH. [ABSTRACT FROM AUTHOR]

Background: Non-integrating episomal vectors have become an important tool for induced pluripotent stem cell reprogramming. The episomal vectors carrying the "Yamanaka reprogramming factors" (Oct4, Klf, Sox2, and L-Myc + Lin28) are critical tools for non-integrating reprogramming of cells to a pluripotent state. However, the reprogramming process remains highly stochastic, and is hampered by an inability to easily identify clones that carry the episomal vectors. Methods: We modified the original set of vectors to express spectrally separable fluorescent proteins to allow for enrichment of transfected cells. The vectors were then tested against the standard original vectors for reprogramming efficiency and for the ability to enrich for stoichiometric ratios of factors. Results: The reengineered vectors allow for cell sorting based on reprogramming factor expression. We show that these vectors can assist in tracking episomal expression in individual cells and can select the reprogramming factor dosage. Conclusions: Together, these modified vectors are a useful tool for understanding the reprogramming process and improving induced pluripotent stem cell isolation efficiency. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia. Methods: Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6 mL/kg, PEEP = 5cmH2O, and FiO2 = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls. Results: In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2. 0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0. 025; 12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8-1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01). Conclusion: In this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation. [ABSTRACT FROM AUTHOR]

Background: The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if and how this occurs in human endothelial cells remains unclear. Methods: We used a new directed differentiation protocol to create human induced pluripotent stem cell (hiPSC)-derived endothelial cells (iECs) from patients with fibrodysplasia ossificans progressiva (FOP), a congenital disease of heterotopic ossification caused by an activating R206H mutation in the Activin A type I receptor (ACVR1). This strategy allowed the direct assay of the cell-autonomous effects of ACVR1 R206H in the endogenous locus without the use of transgenic expression. These cells were challenged with BMP or Activin A ligand, and tested for their ability to activate osteogenesis, extracellular matrix production, and differential downstream signaling in the BMP/Activin A pathways. Results: We found that FOP iECs could form in conditions with low or absent BMP4. These conditions are not normally permissive in control cells. FOP iECs cultured in mineralization media showed increased alkaline phosphatase staining, suggesting formation of immature osteoblasts, but failed to show mature osteoblastic features. However, FOP iECs expressed more fibroblastic genes and Collagen 1/2 compared to control iECs, suggesting a mechanism for the tissue fibrosis seen in early heterotopic lesions. Finally, FOP iECs showed increased SMAD1/5/8 signaling upon BMP4 stimulation. Contrary to FOP hiPSCs, FOP iECs did not show a significant increase in SMAD1/5/8 phosphorylation upon Activin A stimulation, suggesting that the ACVR1 R206H mutation has a cell type-specific effect. In addition, we found that the expression of ACVR1 and type II receptors were different in hiPSCs and iECs, which could explain the cell typespecific SMAD signaling. Conclusions: Our results suggest that the ACVR1 R206H mutation may not directly increase the formation of mature chondrogenic or osteogenic cells by FOP iECs. Our results also show that BMP can induce endothelial cell dysfunction, increase expression of fibrogenic matrix proteins, and cause differential downstream signaling of the ACVR1 R206H mutation. This iPSC model provides new insight into how human endothelial cells may contribute to the pathogenesis of heterotopic ossification. [ABSTRACT FROM AUTHOR]

Background: Silicosis is an occupational disease for which no effective treatment is currently known. Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has shown to be safe in lung diseases. However, so far, no studies have analyzed whether bronchoscopic instillation of autologous BMDMCs is a safe route of administration in patients with silicosis. Methods: We conducted a prospective, non-randomized, single-center longitudinal study in five patients. Inclusion criteria were age 18-50 years, chronic and accelerated silicosis, forced expiratory volume in 1 s <60 % and >40 %, forced vital capacity ≥60 % and arterial oxygen saturation >90 %. The exclusion criteria were smoking, active tuberculosis, neoplasms, autoimmune disorders, heart, liver or renal diseases, or inability to undergo bronchoscopy. BMDMCs were administered through bronchoscopy (2 x 107 cells) into both lungs. Physical examination, laboratory evaluations, quality of life questionnaires, computed tomography of the chest, lung function tests, and perfusion scans were performed before the start of treatment and up to 360 days after BMDMC therapy. Additionally, whole-body and planar scans were evaluated 2 and 24 h after instillation. Results: No adverse events were observed during and after BMDMC administration. Lung function, quality of life and radiologic features remained stable throughout follow-up. Furthermore, an early increase of perfusion in the base of both lungs was observed and sustained after BMDMC administration. Conclusion: Administration of BMDMCs through bronchoscopy appears to be feasible and safe in accelerated and chronic silicosis. This pilot study provides a basis for prospective randomized trials to assess the efficacy of this treatment approach. Clinical trials.gov identifier: NCT01239862 Date of Registration: November 10, 2010 [ABSTRACT FROM AUTHOR]

Introduction: Malaria is the most relevant parasitic disease worldwide, and still accounts for 1 million deaths each year. Since current antimalarial drugs are unable to prevent death in severe cases, new therapeutic strategies have been developed. Mesenchymal stromal cells (MSC) confer host resistance against malaria; however, thus far, no study has evaluated the therapeutic effects of MSC therapy on brain and distal organ damage in experimental cerebral malaria. Methods: Forty C57BL/6 mice were injected intraperitoneally with 5 × 106 Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received saline or bone marrow (BM)-derived MSC (1×105) intravenously and were housed individually in metabolic cages. After 4 days, lung and kidney morphofunction; cerebrum, spleen, and liver histology; and markers associated with inflammation, fibrogenesis, and epithelial and endothelial cell damage in lung tissue were analyzed. Results: In P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia and mortality; 2) increased phagocytic neutrophil content in brain, even though BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with an increased number of Kupffer cells; 5) decreased kidney damage, without effecting significant changes in serum creatinine levels or urinary flow; and 6) reduced neutrophil infiltration, interstitial edema, number of myofibroblasts within interstitial tissue, and collagen deposition in lungs, resulting in decreased lung static elastance. These morphological and functional changes were not associated with changes in levels of tumor necrosis factor-a, keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or interferon-, which remained increased and similar to those of P. berghei animals treated with saline. BM-MSCs increased hepatocyte growth factor but decreased VEGF in the P. berghei group. Conclusions: BM-MSC treatment increased survival and reduced parasitemia and malaria pigment accumulation in spleen, liver, kidney, and lung, but not in brain. The two main organs associated with worse prognosis in malaria, lung and kidney, sustained less histological damage after BM-MSC therapy, with a more pronounced improvement in lung function. [ABSTRACT FROM AUTHOR]

We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the effects of intravenous and intratracheal administration of salbutamol on lung morphology and function, expression of ion channels, aquaporin, and markers of inflammation, apoptosis, and alveolar epithelial/endothelial cell damage in experimental pulmonary (p) and extrapulmonary (exp) mild acute respiratory distress syndrome (ARDS). Methods: In this prospective randomized controlled experimental study, 56 male Wistar rats were randomly assigned to mild ARDS induced by either intratracheal (n = 28, ARDSp) or intraperitoneal (n = 28, ARDSexp) administration of E. coli lipopolysaccharide. Four animals with no lung injury served as controls (NI). After 24 hours, animals were anesthetized, mechanically ventilated in pressure-controlled mode with low tidal volume (6 mL/kg), and randomly assigned to receive salbutamol (SALB) or saline 0.9% (CTRL), intravenously (i.v., 10 μg/kg/h) or intratracheally (bolus, 25 μg). Salbutamol doses were targeted at an increase of ≈ 20% in heart rate. Hemodynamics, lung mechanics, and arterial blood gases were measured before and after (at 30 and 60 min) salbutamol administration. At the end of the experiment, lungs were extracted for analysis of lung histology and molecular biology analysis. Values are expressed as mean ± standard deviation, and fold changes relative to NI, CTRL vs. SALB. Results: The gene expression of ion channels and aquaporin was increased in mild ARDSp, but not ARDSexp. In ARDSp, intravenous salbutamol resulted in higher gene expression of alveolar epithelial sodium channel (0.20 ± 0.07 vs. 0.68 ± 0.24, p < 0.001), aquaporin-1 (0.44 ± 0.09 vs. 0.96 ± 0.12, p < 0.001) aquaporin-3 (0.31 ± 0.12 vs. 0.93 ± 0.20, p < 0.001), and Na-K-ATPase-α (0.39 ± 0.08 vs. 0.92 ± 0.12, p < 0.001), whereas intratracheal salbutamol increased the gene expression of aquaporin-1 (0.46 ± 0.11 vs. 0.92 ± 0.06, p < 0.001) and Na-K-ATPase-α (0.32 ± 0.07 vs. 0.58 ± 0.15, p < 0.001). In ARDSexp, the gene expression of ion channels and aquaporin was not influenced by salbutamol. Morphological and functional variables and edema formation were not affected by salbutamol in any of the ARDS groups, regardless of the route of administration. Conclusion: Salbutamol administration increased the expression of alveolar epithelial ion channels and aquaporin in mild ARDSp, but not ARDSexp, with no effects on lung morphology and function or edema formation. These results may contribute to explain the negative effects of β2-agonists on clinical outcome in ARDS. [ABSTRACT FROM AUTHOR]

Background: The collagen-rich tumor stroma plays a crucial role in biliary tract cancer (BTC). Collagen biomarkers of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4G), type VIII collagen (PRO-C8), type XI collagen (PRO-C11), type XVII collagen (PRO-C17) and type VIII collagen (TUM) may be used as potential non-invasive biomarkers. Methods: We measured the seven biomarkers of collagen turnover in sera of 72 patients with BTC at baseline and after first and second chemotherapy cycle (CTX). Markers were also assessed in sera of 50 healthy controls and compared to levels of patients at baseline. The diagnostic and prognostic value of the markers was evaluated for overall survival (OS) and progression-free survival (PFS). Results: Patients had a median age of 65 years (IQR 57–70), while healthy controls were younger, with a median age of 46 years (IQR 38–54). The majority of patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma. Except C4G, all collagen turnover markers were significantly (p < 0.001) increased in serum from patients with BTC compared to healthy controls. PRO-C3 was the best marker to discriminate between patients with BTC and controls, reaching an area under a receiver operating characteristic (AUROC) of 0.98 (95% CI 0.95; 0.99) with a sensitivity (92%) and specificity (94%) balanced cutoff of 77.3 ng/ml. Patients with high levels (cohort separated by median split) of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73) followed by C3M (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36) and CA 19–9 (HR 2.52, 95% CI 1.37; 4.64) as reference biomarker had a shorter OS. Notably, only the novel marker PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). Associations with survival outcomes remained significant after adjusting for relevant risk factors (CA 19–9 and CEA at baseline, age, presence of metastases, weight, height and gender). Conclusion: The collagen turnover markers PRO-C8, C3M, PRO-C3 and the established biomarker CA 19–9 were prognostic for OS in patients with BTC while only PRO-C8 was also predictive for PFS. PRO-C3 showed the best diagnostic performance to discriminate between patients with BTC and controls. Trial registration: Trial registration number and date of registration NCT00661830 (NCT number) 15 April 2008 Trial registry The complete registry can found under: https://clinicaltrials.gov/study/NCT00661830?tab=table#administrative-information (last accessed 01/2025) Principal investigator and study sponsor Markus Moehler, MD Johannes Gutenberg University Mainz [ABSTRACT FROM AUTHOR]

Bullfrogs (Aquarana catesbeiana) are increasingly cultivated for their high nutritional value and adaptability to intensive aquaculture systems. However, ensuring optimal intestinal health and growth performance remains a challenge due to poor water quality and high stocking densities. This study evaluated the effects of varying dietary concentrations of citral, a natural compound from lemongrass essential oil, on the intestinal health, microbiota, antioxidant capacity, and growth performance of juvenile bullfrogs. A total of 200 juvenile bullfrogs (initial weight 6.85 ± 0.71 g) were randomly assigned into six groups, each receiving diets supplemented with citral at 0, 1, 2, 4, 8, and 16 mL/kg feed for 8 weeks. Citral supplementation significantly improved intestinal morphology, with goblet cell numbers, mucosal thickness, and villus-to-crypt ratios peaking at 2–4 mL/kg (P < 0.05). Optimal doses of 2–4 mL/kg also enhanced digestive enzyme activities, with α-amylase, lipase, and pepsin activities showing significant increases compared to the control group (P < 0.05). Antioxidant markers, including total antioxidant capacity (T-AOC) and glutathione (GSH), were highest at 2 mL/kg, while higher citral concentrations reduced superoxide dismutase (SOD) and catalase (CAT) activities, indicating potential oxidative stress at 8–16 mL/kg (P < 0.05). Citral also modulated the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Cetobacterium at 1–2 mL/kg (P < 0.05). However, microbial diversity decreased significantly at concentrations above 4 mL/kg. Growth performance analysis revealed that 4 mL/kg citral supplementation significantly improved weight gain rate (WGR), specific growth rate (SGR), carcass weight (CW), and feed efficiency (FE), while survival rates declined at 16 mL/kg (P < 0.05). A linear regression model determined the optimal dietary citral concentration to be 3.216–3.942 mL/kg. This study concludes that dietary citral at 2–4 mL/kg optimally enhances growth performance, intestinal health, and antioxidant capacity in juvenile bullfrogs, while higher concentrations may disrupt gut health and oxidative balance. These findings provide valuable insights into the use of natural compounds like citral for sustainable aquaculture practices. [ABSTRACT FROM AUTHOR]

Objective: To analyze the temporal and territorial relationship between health system financing fragmentation and maternal mortality in the last two decades in Mexico. Methods: We conducted an ecological-longitudinal study of the maternal mortality ratio (MMR) in the 32 states of Mexico during the period 2000–2022. Annual MMRs were estimated at the national and state levels according to health insurance. We compared the distribution of individual attributes and place of residence between deceased women with and without social security to identify overrepresented demographic profiles. Finally, we mapped state disparities in MMR by health insurance for the last four political administrations. Findings: MMR in Mexico decreased from 59.3 maternal deaths per hundred thousand live births in 2000 to 47.3 in 2018. However, from 2019 onwards, MMR increased from 48.7 in 2019 to 72.4 in 2022. Seven out of ten maternal deaths occurred in the population without social security from 2000 to 2018, then decreasing to six out of ten from 2020. Maternal deaths in the population without social security were more frequent among younger women, with less schooling, unmarried, and residing in rural areas, with higher Indigenous presence and greater social marginalization. From 2019 onwards, the MMR was higher in the population with social security. Conclusion: The results of this study confirm the close relationship between maternal mortality and social inequalities, and suggest that affiliation with social security has ceased to be a differentiating factor in recent years. Understanding the evolution of maternal mortality between the population with and without social security in Mexico allows us to quantify the gap in maternal deaths attributed to inequalities in access to maternal health services, which can contribute to the design of policies that mitigate these gaps. [ABSTRACT FROM AUTHOR]

Background: Dengue virus (DENV) infection, a mosquito-borne disease, presents a significant public health challenge globally, with diverse clinical manifestations. Although oral dengue manifestations are uncommon, they can serve as crucial diagnostic indicators and impact patient management in dental practice. This scoping review aims to map the evidence on the oral manifestations associated with DENV infection and their clinical implications for dental practice. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and was registered on PROSPERO (CRD42022337572). A comprehensive search was conducted across six electronic databases (MEDLINE, Web of Science, Scopus, Embase, Cochrane Library, and LILACS/BBO) up to June 2024. Eligible studies included case reports, case-control, cohort, and cross-sectional studies reporting oral manifestations in patients with DENV infection. Results: A total of 41 studies were included, comprising 17 case reports, 15 retrospective cohort studies, 4 prospective cohort studies, and 5 cross-sectional studies. Gingival bleeding, oral ulceration, bilateral inflammatory increase in the parotid glands, and lingual hematoma were the most frequently reported oral manifestations. Less common manifestations included Ludwig's angina, osteonecrosis of the jaw, and angular cheilitis. These findings suggest a broad spectrum of oral symptoms that could aid in the early identification and management of dengue patients. Conclusions: This review highlights the importance of recognizing oral manifestations in dengue patients, which can facilitate early diagnosis and intervention, particularly in dengue-endemic regions. Dental professionals play a crucial role in identifying these symptoms and improving patient outcomes. Further research is needed to explore the pathophysiological mechanisms underlying these manifestations and to develop standardized protocols for clinical assessment and management. Clinical relevance: This paper highlights the role of dental professionals in early dengue diagnosis, emphasizing oral manifestations like gingival bleeding. It promotes interdisciplinary care, improving patient outcomes and management in dengue-endemic regions. [ABSTRACT FROM AUTHOR]

Background and aims: Previous studies have confirmed that alcohol can increase the sensitivity of the pancreas to stressors and exacerbate the severity of pancreatitis when excessive alcohol intake is combined with other causes. In the current work, this study attempted to explore how does alcohol regulate cerulein-induced acute pancreatitis, especially before inflammation occurs. Methods: Proteomics was performed to analyze the differentially expressed proteins in pancreatic tissues from a rat model of pancreatitis. The metabolite levels in the pancreatic tissue, serum of rats and serum of persons with a history of alcohol consumption were detected by LC‒MS/MS. In the present study the impact of etomoxir (a carnitine palmitoyl-transferase 1A-specific inhibitor) treatment on AR42J cells treated with alcohol and the effect of etomoxir injection on the inflammatory response in an alcohol + cerulein-induced AAP rat model was evaluated. Results: When treated with the same amount of cerulein, the rats that ingested alcohol presented with more severe pancreatitis. The proteomics results revealed that the fatty acid degradation pathway was closely related to the development of alcoholic acute pancreatitis, and CPT1A exhibited the greatest increase (approximately twofold increase). The products (acylcarnitines) of CPT1A were changed in the serum of persons with a history of alcohol consumption. Etomoxir treatment mitigates the influence of alcohol stimulation on the aberrant expression of proteins associated with oxidative stress, increased ROS production, mitochondrial ultrastructural alterations and mitochondrial dysfunction in AR42J cells. Etomoxir injection reduced the inflammatory response in the AAP rat model. Conclusion: Alcohol upregulates CPT1A protein expression in pancreatic tissue, resulting in abnormal lipid metabolism. The products of lipid metabolism, ROS, contribute to mitochondrial ultrastructural alterations and mitochondrial dysfunction. These changes act as sentinel events that regulate acute pancreatitis. [ABSTRACT FROM AUTHOR]

Recent studies support the influence of paternal lifestyle and diet before conception on the health of the offspring via epigenetic inheritance through sperm DNA methylation, histone modification, and small non-coding RNA (sncRNA) expression and regulation. Smoking may induce DNA hypermethylation in genes related to anti-oxidation and insulin resistance. Paternal diet and obesity are associated with greater risks of metabolic dysfunction in offspring via epigenetic alterations in the sperm. Metabolic changes, such as high blood glucose levels and increased body weight, are commonly observed in the offspring of fathers subjected to chronic stress, in addition to an enhanced risk of depressive-like behaviour and increased sensitivity to stress in both the F0 and F1 generations. DNA methylation is correlated with alterations in sperm quality and the ability to fertilise oocytes, possibly via a differentially regulated MAKP81IP3 signalling pathway. Paternal exposure to toxic endocrine-disrupting chemicals (EDCs) is also linked to the transgenerational transmission of increased predisposition to disease, infertility, testicular disorders, obesity, and polycystic ovarian syndrome (PCOS) in females through epigenetic changes during gametogenesis. As the success of assisted reproductive technology (ART) is also affected by paternal diet, BMI, and alcohol consumption, its outcomes could be improved by modifying factors that are dependent on male lifestyle choices and environmental factors. This review discusses the importance of epigenetic signatures in sperm—including DNA methylation, histone retention, and sncRNA—for sperm functionality, early embryo development, and offspring health. We also discuss the mechanisms by which paternal lifestyle and environmental factors (obesity, smoking, EDCs, and stress) may impact the sperm epigenome. [ABSTRACT FROM AUTHOR]

Background: Ethnic and racial discrimination in maternal health care has been overlooked in academic literature and yet it is critical for achieving universal health coverage (UHC). There is a lack of empirical evidence on its impact on the effective coverage of maternal health interventions (ECMH) for Indigenous women in Mexico. Documenting progress in reducing maternal health inequities, particularly given the disproportionate impact of the Covid-19 pandemic on ethnic minorities, is essential to improving equity in health systems. Methods: We conducted a population-based, pooled cross-sectional, and retrospective analysis for 2009–2023, using data from the last three waves (2014, 2018, and 2023) of a nationally representative demographic survey (ENADID). Our study included n = 72,873 (N = 23,245,468) Mexican women aged 12–54 with recent live births. We defined ECMH as adequate antenatal care (ANC), skilled and/or institutional delivery care, timely postpartum care, and complication-free postpartum/puerperium. After describing sociodemographic characteristics and maternal health coverage by Indigenous status, we estimated a pooled fixed-effects multivariable regression model to adjust ECMH for relevant covariates. We used the Blinder-Oaxaca decomposition for nonlinear regression models to quantify inequities in ECMH due to ethnic-racial discrimination, defined as differences in outcomes attributable to differential treatment. Findings: Indigenous women had lower education, labor market participation, and socioeconomic position, higher parity, and more rural, poorer state residence than non-Indigenous women. They faced significant health coverage loss due to the dismantling of Seguro Popular, a public health insurance mechanism in place until the end of 2019, right before the start of the Covid pandemic. Adjusted ECMH was 25.3% for non-Indigenous women and 18.3% for Indigenous women, peaking at 28.8% and 21.2% in 2013–2018, declining to 25.7% and 18.7% pre-Covid (January 2019 to March 2020), and further declining to 24.0% and 17.4% during Covid, with an increase to 26.6% for non-Indigenous women post-Covid, while remaining similar for Indigenous women. Decomposition analyses revealed that during the analyzed period, 30.8% of the gap in ECMH was due to individual characteristics, 51.7% to ethnic-racial discrimination, and 17.5% to their interaction. From 2009 to 2012, 42.2% of the gap stemmed from observable differences, while 40.4% was due to discrimination. In the pre-Covid-19 phase, less than 1% was from observable characteristics, with 75.3% attributed to discrimination, which remained in the post-Covid-19 stage (78.7%). Conclusions: Despite modest health policy successes, the ethnic gap in ECMH remains unchanged, indicating insufficient action against inequity-producing structures. Ethnic and racial discrimination persists, exacerbated during the pandemic and coinciding with the government's cancellation of targeted social programs and public health insurance focused on the poorest populations, including Indigenous peoples. Thus, prioritizing maternal and child health underscores the need for comprehensive policies, including specific anti-racist interventions. Addressing these inequities requires the recognition of both observable and unobservable factors driven by discriminatory ideologies and the implementation of targeted measures to confront the complex interactions driving discrimination in maternal health care services for Indigenous women. [ABSTRACT FROM AUTHOR]

The concept of femoroacetabular impingement syndrome (FAIS) has received much attention over the past 20 years. Currently, it is believed that FAIS can lead to intra-articular pathologies such as labral tears and articular cartilage lesions, resulting in clinical symptoms and subsequent poor clinical outcomes. FAIS-related articular cartilage lesions are common but unique, and their natural course always leads to early osteoarthritis of the hip. However, despite these cartilage lesions having gradually gained considerable attention, limited consensus has been reached on key aspects, such as diagnosis, mechanisms, classification, and management strategies, which limits clinical and research advances. Hence, an intensive comprehensive overview based on the existing evidence is necessary. The purpose of this review was to introduce the general consensus, controversial issues, and recent advances in FAIS-related articular cartilage lesions. [ABSTRACT FROM AUTHOR]

Background: Hazard and risk assessment of nanomaterials (NMs) face challenges due to, among others, the numerous existing nanoforms, discordant data and conflicting results found in the literature, and specific challenges in the application of strategies such as grouping and read-across, emphasizing the need for New Approach Methodologies (NAMs) to support Next Generation Risk Assessment (NGRA). Here these challenges are addressed in a study that couples physico-chemical characterization with in vitro investigations and in silico similarity analyses for nine nanoforms, having different chemical composition, sizes, aggregation states and shapes. For cytotoxicity assessment, three methods (Alamar Blue, Colony Forming Efficiency, and Electric Cell-Substrate Impedance Sensing) are applied in a cross-validation approach to support NAMs implementation into NGRA. Results: The results highlight the role of physico-chemical properties in eliciting biological responses. Uptake studies reveal distinct cellular morphological changes. The cytotoxicity assessment shows varying responses among NMs, consistent among the three methods used, while only one nanoform gave a positive response in the genotoxicity assessment performed by comet assay. Conclusions: The study highlights the potential of in silico models to effectively identify biologically active nanoforms based on their physico-chemical properties, reinforcing previous knowledge on the relevance of certain properties, such as aspect ratio. The potential of implementing in vitro methods into NGRA is underlined, cross-validating three cytotoxicity assessment methods, and showcasing their strength in terms of sensitivity and suitability for the testing of NMs. Created with BioRender.com (publication license obtained) [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the direct associations among perceived doctor-patient relationship, authentic leadership, organizational climate, and job burnout, as well as the indirect pathways through job satisfaction, with the aim of offering potential preventive strategies at the organizational level. Methods: A total of 399 physicians from six tertiary hospitals in Anhui Province were enrolled by purposive sampling method. Structural equation modeling was performed to examine the proposed model. Results: The average score of the participants' job burnout was 35.22 (SD: 12.14), and the burnout rate was found to be 55.7%. Perceived doctor-patient relationship, organizational climate directly influenced job burnout. Perceived doctor-patient relationship, authentic leadership and organizational climate also indirectly influenced burnout through job satisfaction. Conclusions: The present study underscores the significant influence of the perceived doctor-patient relationship, authentic leadership and organizational climate in mitigating burnout, and further reveals that job satisfaction serves to alleviate burnout. It is crucial to emphasize the importance of both internal and external psychosocial and organizational environmental factors. Additionally, the study highlights the pivotal role of job satisfaction in influencing physician burnout. [ABSTRACT FROM AUTHOR]

Object: Aim to investigate the multi-omic characteristics of the bone marrow supernatant of relapsed acute myeloid leukemia (AML) and search for proteins and metabolites associated with relapse. Methods: A total of 40 bone marrow supernatant from 7 patients with relapsed AML and 33 patients with non-relapsed AML were collected for proteomics and metabonomics analysis. Unsupervised clustering was used to discover the characteristics of proteins and metabolites. The prognostic significances of proteins were assessed concerning the relapse status(including death) and relapse-free survival. Result: Totally 996 proteins and 4,831 metabolites were identified in bone marrow supernatant, and two of 7 clusters were revealed through unsupervised clustering and were associated with ASXL1, TP53, and RUNX1 mutations, which were listed as high-risk factors in the 2022 edition of the WHO classification of tumors of the hematopoietic and lymphoid tissues. Among the identified proteins and metabolites, 57 proteins and 190 metabolites were found to be closely related to relapse. Conclusion: This study has revealed a significant correlation between protein expression in the bone marrow microenvironment of AML and three high-risk mutations: ASXL1, TP53, and RUNX1. Based on this finding, we further identified 227 differential proteins closely associated with these three mutations, as well as 57 proteins directly related to disease recurrence. Additionally, lipid metabolism plays a crucial role in the occurrence and development of AML within its bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a degenerative joint disease that leads to a substantial decline in the well-being of older individuals. Chondrocyte senescence and the resultant damage to cartilage tissue, induced by elevated levels of reactive oxygen species within the joint cavity, are significant causative factors in OA development. Cerium oxide nanoparticles (CeONPs) present a promising avenue for therapeutic investigation due to their exceptional antioxidant properties. However, the limited effectiveness of drugs in the joint cavity is often attributed to their rapid clearance by synovial fluid. Methods: Polyethylene glycol-packed CeONPs (PEG-CeONPs) were synthesized and subsequently modified with the cartilage-targeting peptide WYRGRLGK (WY-PEG-CeO). The antioxidant free radical activity and the mimetic enzyme activity of PEG-CeONPs and WY-PEG-CeO were detected. The impact of WY-PEG-CeO on chondrocytes oxidative stress, cellular senescence, and extracellular matrix degradation was assessed using in vitro assays. The cartilage targeting and protective effects were explored in animal models. Results: WY-PEG-CeO demonstrated significant efficacy in inhibiting oxidative stress, cellular senescence, and extracellular matrix degradation in OA chondrocytes. The underlying mechanism involves the inhibition of the PI3K/AKT and MAPK signaling pathways. Animal models further revealed that WY-PEG-CeO exhibited a prolonged residence time and enhanced penetration efficiency in cartilage tissue, leading to the attenuation of pathological changes in OA. Conclusions: These findings suggest that WY-PEG-CeO exerts therapeutic effects in OA by inhibiting oxidative stress and suppressing the over-activation of PI3K/AKT and MAPK signaling pathways. This investigation served as a fundamental step towards the advancement of CeONPs-based interventions, providing potential strategies for the treatment of OA. [ABSTRACT FROM AUTHOR]

Background: Despite adequate treatment, a subgroup of patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, have persistent gastrointestinal symptoms that are not always related to mucosal damage. Recently, two autoantibodies, anti-CdtB and anti-vinculin, were validated as post-infectious IBS (PI-IBS) markers, however there is limited evidence of its diagnostic role in IBD population. Methods: Patients with more than 3 bowel movements/day and indication of colonoscopy were enrolled. Samples were collected at the time of colonoscopy for assessment of serum levels of anti-CdtB and anti-vinculin antibodies. Results: A total of 160 subjects were included in 4 groups: active IBD (n = 44); quiescent IBD and chronic diarrhea IBD-IBS (n = 25); predominant-diarrhea IBS (n = 45) and controls (n = 46). The mean value of the optical density for anti-CdtB was 1.2 ± 0.65 in group 1, 1.27 ± 0.64 in group 2, 1.49 ± 0.47 in the group 3 and 1.6 ± 0.68 in group 4, p = 0.012. For anti-vinculin, optical densities were: 1.34 ± 0.78 in group 1, 1.46 ± 0.92 in group 2, 1.31 ± 0.79 in group 3 and 1.41 ± 0.86 for controls (p = 0.875). Using a cut-off of 1.56 for anti-CdtB, the positivity between groups was n = 10 (22.7%) in group 1, n = 9 (34.6%) in group 2, 19 (43.2%) in group 3, 21 (45.7%) in group 4 (p = 0.106). The positivity of anti-vinculin using a cut-off of 1.6 was n = 18 (40.9%) in group 1, n = 11 (42.3%), n = 15 (34.1%), n = 22 (47.8%) (p = 0.622). Conclusions: Our findings show that anti-CdtB and anti-vinculin could not identify IBD-IBS patients or discriminate IBS-D from healthy controls. [ABSTRACT FROM AUTHOR]

Believing conspiracy narratives is frequently assumed to be a major cause of vaccine hesitancy, i.e., the tendency to forgo vaccination despite its availability. In this scoping review, we synthesise and critically evaluate studies that assess i) the occurrence of vaccine-related conspiracy narratives on the internet, ii) the prevalence of belief in vaccine-related conspiracy narratives, iii) the relationship between belief in conspiracy narratives and vaccination intention or vaccination uptake, and iv) interventions that reduce the impact of conspiracy narratives on vaccination intention. In July 2022, we conducted a literature search using three databases: PubMed, PsychInfo, and Web of Science. Following the PRISMA approach, of the 500 initially identified articles, 205 were eligible and analysed. The majority of identified studies were conducted in Europe and North America, were published in 2021 and 2022, and investigated conspiracy narratives around the COVID-19 vaccination. The prevalence of belief in various vaccine-related conspiracy narratives varied greatly across studies, from 2 to 77%. We identified seven experimental studies investigating the effect of exposure to conspiracy narratives on vaccination intentions, of which six indicated a small negative effect. These findings are complemented by the evidence from over 100 correlative studies showing a significant negative relationship between conspiracy beliefs and vaccination intention or uptake. Additionally, the review identified interventions (e.g., social norm feedback, fact-checking labels, or prebunking) that decreased beliefs in vaccine-related conspiracy narratives and, in some cases, also increased vaccination intentions. Yet, these interventions had only small effects. In summary, the review revealed that vaccine-related conspiracy narratives have spread to varying degrees and can influence vaccination decisions. Causal relationships between conspiracy beliefs and vaccination intentions remain underexplored. Further, the review identified a need for more research on interventions that can reduce the impact of conspiracy narratives. [ABSTRACT FROM AUTHOR]

Background: This study aims to develop and validate an integrated predictive model combining CT radiomics and clinical parameters for early assessment of acute pancreatitis severity. Methods: A retrospective cohort of 246 patients with acute pancreatitis was analyzed, with a 70%-30% split for training and validation groups. CT image segmentation was performed using ITK-SNAP, followed by the extraction of radiomics features. The stability of the radiomics features was assessed through inter-observer Intraclass Correlation Coefficient analysis. Feature selection was carried out using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. A radiomics model was constructed through logistic regression to compute the radiomics score. Concurrently, univariate and multivariate logistic regression were employed to identify independent clinical risk factors for the clinical model. The radiomics score and clinical variables were integrated into a combined model, which was visualized with a nomogram. Model performance and net clinical benefit were evaluated through the area under the receiver operating characteristic curve (AUC), the DeLong test, and decision curve analysis. Results: A total of 913 radiomics features demonstrated satisfactory consistency. Eight features were selected for the radiomics model. Serum calcium, C-reactive protein, and white blood cell count were identified as independent clinical predictors. The AUC of the radiomics model was 0.871 (95% CI, 0.793–0.949) in the training cohort and 0.859 (95% CI, 0.751–0.967) in the validation cohort. The clinical model achieved AUCs of 0.833 (95% CI, 0.756–0.910) and 0.810 (95% CI, 0.692–0.929) for the training and validation cohorts, respectively. The combined model outperformed both the radiomics and clinical models, with an AUC of 0.905 (95% CI, 0.837–0.973) in the training cohort and 0.908 (95% CI, 0.824–0.992) in the validation cohort. The DeLong test confirmed superior predictive performance of the combined model over both the radiomics and clinical models in the training cohort, and over the clinical model in the validation cohort. Decision curve analysis further demonstrated that the combined model provided greater net clinical benefit than the radiomics or clinical models alone. Conclusion: The clinical-radiomics model offers a novel tool for the early prediction of acute pancreatitis severity, providing valuable support for clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder. Its cerebral form presents as a learning and behavioral disorder that, if untreated, leads to rapid neurological regression, disability, and death within 10 years of diagnosis. Therefore, the disease significantly impacts patients' quality of life, making quality of life assessment crucial for effective medical treatment and care. However, no disease-specific quality of life scale exists for ALD. Therefore, we conducted qualitative research to determine the experiences of patients and their families as a preliminary step toward developing one. Results: Four mothers of patients with cerebral ALD were interviewed. Based on classification using the qualitative content analysis method, the verbatim transcripts were grouped into four themes: support needs for patients, support needs for families, the impact of treatment, and challenges within support systems. Conclusions: Support for patients and family members is required after ALD is diagnosed. In addition to addressing symptoms, daily life support and caregiving burden should be considered. Furthermore, several challenges and opportunities exist for improving treatment and support systems. Therefore, combining appropriate supporters and support systems according to the progressive and hereditary characteristics of ALD is crucial. [ABSTRACT FROM AUTHOR]