BioMed Research International最新文献

Aims: Prediction of future deterioration in emergency department patients with infection is difficult, and existing prognostic tools are inaccurate. We evaluated the feasibility of deployment of a clinical decision support tool, Sepsis Advisor, which utilizes heart rate variability and laboratory values to predict future deterioration in emergency department patients with treated infection.

Methods: This study was an observational, prospective, Pilot Phase 1 feasibility implementation study involving two sites within a single academic health sciences centre. Then, 71 patients were enrolled, all with suspected/treated infection and systemic inflammatory response. Patients underwent 30 min of electrocardiograph recording. The generated predictive model and Sepsis Advisor report were shown to physicians observationally, > 48 h after clinical encounter, while assessing perceived usability, value, barriers and drivers with using the tool through interviews with nurses and physicians.

Results: Of the 71 patients enrolled, 65 (92%) had adequate duration of heart rate variability measurements to generate a predictive model (average recording: 25 ± 7 min); 100% had clinical data entry. Creatinine, lactate, and INR were drawn 97%, 56%, and 28% of the time and were incorporated into predictive models. Physician and nurse reported drivers for use included potential to facilitate communication, improve care, and ease of integration. Barriers included the need to understand and interpret results from the tool, time constraints, changing routines, and gaining buy-in. User-centered feedback informed four improved versions of the tool.

Conclusions: Observational deployment of a heart rate variability-based clinical decision support tool within the emergency department is feasible and perceived to have the potential to improve care.

The seminal Michaelis-Menten theorization for biological catalysis was based on "transition state" (TS), involving the formation of a topologically complementary substrate (S) and enzyme (E) complex (ES) at the "active site" of the latter. Rudolph Marcus put forth the theory of outer sphere electron transfer (ET) in a "donor-acceptor" TS complex, which was seen as a foundational framework for understanding ET reactions in chemical systems. Although these two theories are quite robust, the active site treatment of Michaelis-Menten may not be relevant in promiscuous/nonspecific xenobiotic-metabolizing redox enzymes, and Marcus theory's applicability to biological ET (BET) systems can be limited in interfacial protein-protein interactions. Herein, the "mathematical" necessity to venture beyond the "active site constraints" of interpreting redox enzyme kinetics and BETs is established first with fresh data. Also, (i) the classical explanation vouching for active site binding and protein-protein complexation-based BET in xenobiotic metabolism (mediated at the endoplasmic reticulum membranes of hepatocytes) and oxidative phosphorylation (multiprotein machinery at mitochondrial cristae) is demonstrated to be untenable, and (ii) tangible/viable murburn models were proposed in lieu. Therefore, toward the imperative goal of arriving at quantitative expressions correlating the parameters/variables involved, the foundational considerations of murburn ET and murzyme catalysis in simple heme systems are presented, with some assumptions/constraints. While some derivations are from ab initio considerations, others are heuristic/empirical, often needing experimental fitting. The linear time-course profiles of ET (substrate depletion) and the biphasic substrate-dependent (product formation) are well fit with the newly derived expressions. A mechanistic comparison of the murburn model vis-à-vis the longstanding P450cam explanation for drug/xenobiotic metabolism is also provided.

Single nucleotide polymorphisms (SNPs) play a crucial role in regulating vitamin D, parathyroid hormone (PTH), and calcitonin concentrations, which are involved in bone health. Some reports suggested that fractal analysis is useful in the morphometric analysis of the mandible trabecular bone in panoramic radiographs. Therefore, we investigated if SNPs in genes that influence vitamin D, calcitonin, and PTH levels are involved in condylar bone quality during the active growing phase of the mandible. Fractal dimension was obtained from the condyle region of interest (ROI) using panoramic radiographs and used to measure the complexity and the microarchitecture of the bone. Fractal dimension using the box-counting algorithm was then calculated. In order to avoid information bias, a script to automate the commands in the software ImageJ was generated to ensure consistency and minimize the potential for human error during the data analysis process. SNPs in vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), vitamin D binding protein (VDBP), SEC23 homolog A (SEC23A), calcitonin receptor (CALCR), and parathyroid hormone (PTH) were analyzed. DNA extracted from saliva was used for genotyping analysis of VDR (rs7975232, rs2228570, and rs1544410), CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs4588), SEC23A (rs8018720), CALCR (rs1801197), and PTH (rs6256, rs307247, and rs694). A statistical analysis was performed with an alpha error tolerance of 5%. A total of 100 children were included; 50 (50%) were boys and the age ranged from 5 to 14 years old. Fractal dimensions were compared among genotypes. The GT (mean = 1.20 and standard error = 0.03, p = 0.024) and TT genotypes (mean = 1.16 and standard error = 0.06, p = 0.047) in the gene VDBP (rs4588) presented lower fractal dimension. The GG genotype in SEC23A (rs8018720) (mean = 1.34 and standard error = 0.03, p = 0.011) and the TC genotype in PTH (rs694) showed an increased fractal dimension (mean = 1.29 and standard error = 0.03, p = 0.020). In conclusion, SNPs in VDBP, SEC23A, and PTH encoding genes are associated with mandibular condylar trabecular bone structure in children.

Toxoplasmosis is asymptomatic in infected individuals; however, infections acquired during pregnancy pose a significant risk of the development of congenital parasitosis, leading to poor pregnancy outcomes and various degrees of chorioretinitis later in life. This study was therefore designed to determine the seroprevalence of Toxoplasma gondii and its associated factors among pregnant women admitted for delivery in selected hospitals in Dar es Salaam. A hospital-based analytical cross-sectional study was conducted among 191 pregnant women who were admitted for delivery in the selected hospitals in Dar es Salaam, Tanzania. A pretested, Kiswahili-translated semistructured questionnaire was used to collect demographic characteristics of the respondents, as well as their risk profile and awareness on T. gondii. Collected blood samples were screened for T. gondii IgG and IgM using the FaStep TORCH IgG/IgM rapid test device as per the manufacturer's instructions. Data analysis was done using STATA Version 14 (StataCorp, Texas, United States); figures were plotted using Microsoft Excel [2024] (Microsoft Corporation, Redmond, Washington, United States). Crude and adjusted OR were estimated by bivariable and multivariable logistic regression analysis with respective 95% CIs, respectively. A p value less than or equal to 0.05 was considered statistically significant. The seroprevalence of T. gondii among study participants was found to be 20.94%. Multivariable logistic regression for factors associated with T. gondii serostatus was modeled. After controlling for other factors, consumption of rodents for food (A O R = 10.52, 95% C I = 1.13-97.79, p = 0.039) and consumption of game meat (A O R = 3.84, 95% C I = 1.56-9.46, p = 0.003) were the best predictors of T. gondii seropositivity. Consumption of untreated water for drinking among study participants was found to be very high, although it was not associated with T. gondii seropositivity. This calls for the need for implementation of public health education with a particular emphasis on proper cooking of game meat and rodents before consumption and proper treatment of drinking water.

Background: Pelvic organ prolapse (POP) is a common pelvic floor disorder in middle-aged and elderly women. Its pathophysiology is complex, involving weakened pelvic floor muscles and connective tissues. There is a need to explore its underlying pathogenesis and develop effective treatments.

Methods: We integrated single-cell sequencing (scRNA-seq) data analysis with Mendelian randomization (MR) analysis. scRNA-seq data of vaginal mucosal tissue were obtained from individuals with and without pelvic organ prolapse (POP); we then performed dimensionality reduction and cell subset identification. MR was conducted using GWAS summary statistics and eQTL data, following STROBE-MR guidelines. We also performed protein-protein interaction analysis, functional enrichment analysis, drug prediction, and molecular docking.

Results: We identified RBP7 as a POP risk factor and SCGB3A1 as a protective factor. RBP7 high expression increased POP risk (IVW, OR 1.262, 95% CI 1.093-1.459, p = 0.002), whereas SCGB3A1 high expression decreased it (IVW, OR 0.907, 95% CI 0.844-0.975, p = 0.008). We found associated key genes and their biological processes and signaling pathways. We also predicted potential drugs and their binding affinities.

Conclusion: The study highlights the significance of fibroblast gene expression changes in collagen metabolism for POP. It identified risk and protective genes and explored potential drugs. Future research should verify SCGB3A1 functions in fibroblasts, conduct preclinical drug trials, and clarify POP molecular mechanisms.

[This corrects the article DOI: 10.1155/2021/2899043.].

[This corrects the article DOI: 10.1155/2013/719858.].

The marine environment is a significant origin of bioactive substances like carotenoids. Marine carotenoids are secondary metabolites with mechanism-anchored benefits across redox, immune, and metabolic pathways, comprising antioxidant, anti-inflammatory, antidiabetic, anticancer, and antimicrobial activities. These bioactive compounds have garnered significant interest from the pharmaceutical, nutraceutical, and cosmetic industries, driving the exploration for novel natural reservoirs of carotenoids. However, most of the research has focused on carotenoids found in fruits, vegetables, and other higher plant components. Despite increasing interest, there are few publications on carotenoids found in marine sources such as seaweed, microalgae, and marine animals. This review summarizes chemistry, biosynthesis, extraction methods, bioavailability, and the bioactivities reported for major marine carotenoids (e.g., α- and β-carotene, lycopene, fucoxanthin, astaxanthin, zeaxanthin, canthaxanthin, spirilloxanthin, halocynthiaxanthin, neoxanthin, and peridinin).

There have been some concerns about the potential adverse consequences of proton pump inhibitors (PPIs) on bone health, specifically with respect to bone mineral density (BMD). The objective of the present investigation was to evaluate the impact of PPIs on BMD in the lumbar spine, femoral neck, and total hip regions. On the basis of PRISMA, a systematic review and meta-analysis were performed. PubMed, Scopus, Cochrane Library, and Google Scholar were used to find eligible observational studies published between January 2010 and January 2025. The ROBINS-I tool was employed to evaluate potential for bias, and studies with critical bias were excluded. To synthesize the data, random-effects models were utilized, and the I ² statistic was used to evaluate heterogeneity. The sensitivity analyses and publication bias were also performed. A systematic review and quantitative synthesis used 20 and seven records, respectively, of 170 records screened. The comprehensive pooled analysis revealed that the decrease in BMD with the use of PPIs was modest yet statistically significant (SMD -0.15, 95% CI -0.21 to 0.09) alongside a substantial degree of heterogeneity (I ² = 93.6%). Subgroup analysis demonstrated that there were significant decreases at the femoral neck (SMD -0.27, 95% CI -0.46 to -0.09), but not at the lumbar spine or the total hip. The funnel plot analysis indicated a certain level of asymmetry, and the sensitivity analysis indicated that the results were mostly robust; unless the study that excluded one outlier was used in the analysis, then the lumbar spine results would change. The use of PPIs is related to a significant but relatively small decrease in BMD, most obvious at the femoral neck, although findings across anatomical locations are heterogeneous. The results of this study support the cautious use of PPIs in all people at risk of osteoporosis and the need to conduct a high-quality prospective study to understand site-specific effects in the future.

To develop a telomere-related prognostic signature for esophageal carcinoma (ESCA), we integrated bioinformatics and machine learning approaches. Hub genes were identified from overlapping differentially expressed genes (DEGs). A prognostic model was constructed using LASSO and multivariate Cox regression, validated in independent GEO datasets, and further verified through cytological experiments. We also elucidated the mechanism by which MAPK12 promotes ESCA migration. The model robustly predicted survival of patients with ESCA, supported by both high-throughput data and experimental evidence. Our findings highlight MAPK12 as a promising biomarker and provide a theoretical basis for understanding ESCA pathogenesis and developing targeted therapies.