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The utility of borescope and ATP Biofluorescence for inspection of ophthalmic phaco handpiece lumen: a single-center observational study
The presence of residual debris in the phaco handpiece lumen is implicated in the onset of intraocular inflammation. While ATP bioluminescence testing is accepted for evaluating the cleanliness of surgical instruments, the borescope’s ability to facilitate a visual inspection of the internal integrity of phaco handpiece lumens remains underreported. This study aims to evaluate the efficacy of current cleaning protocols and explore the borescope’s utility in visually inspecting phaco handpieces. In this analysis, 41 phaco handpieces underwent borescope examination and ATP bioluminescence testing following thorough cleaning, with two inspections completed on each handpiece. Borescope inspections revealed that 56.10% of phaco handpieces harbored foreign materials or exhibited various forms of structural damage, such as corrosion, rust, green lint, and discoloration. However, ATP bioluminescence testing deemed the cleanliness of all handpieces satisfactory. This study demonstrates the value of a borescope in the visual inspection of phaco handpieces, revealing issues such as corrosion and rust that necessitated immediate flushing of the lumen with sterile distilled or deionized water. The detection of green lint led to the prohibition of placing textile fiber-containing sterile textile wipes on the operating table surface by sterile supply staff, enhancing patient safety measures. Future efforts will focus on addressing the challenges posed by corrosion and particulate formation during rinsing.
GluA2-containing AMPA receptors form a continuum of Ca2+-permeable channels
Associated factors for the utilization of institutional delivery services in Nepal: Findings from the Nepal Demographic Health Survey, 2022
Introduction Institutional delivery provides skilled obstetric health care, postnatal care, and essential medical timely intervention to enhance the health of mothers and children. In Nepal, the proportion of institutional deliveries has increased from 8 percent in 1996–79 percent in 2022, although it is not satisfactory. This study investigates disparities in the utilization of institutional delivery service across associated factors related to residential factors, socio-economic factors, health service-related factors, and bio-demographic factors. Methods We used secondary data from the Demographic and Health Survey (DHS) 2022 of Nepal. It involves a sample of 1977 eligible women aged 15–49 who had given birth within two-year preceding the survey. We considered institutional delivery as an outcome variable, while residential, socio-economic, bio-demographic, and health service-related factors as independent variables. Descriptive analysis and binary logistic regression analysis for crude and adjusted odds ratios (AOR) along with 95% confidence interval (CI) were utilized. Results Of the total 1977 women, 1569 (79.4%) opted for institutional delivery. Women belonging to the Muslim ethnic group had lower odds (AOR:0.500, 95% CI: 0.259–0.966, p < 0.050) compared to their reference group. Similarly, the likelihood of opting for institutional delivery was significantly lower among women who required more than 30 minutes time to reach a health facility (AOR:0.626, 95% CI: 0.491–0.800, p < 0.001) and those having 6 + parity (AOR:0.080, 95% CI: 0.032–0.205, p < 0.001) compared to their reference group. In the contrary, women from Terai region (AOR:2.428, 95% CI: 1.194–4.937, p < 0.050), Bagmati Province (AOR:2.327, 95% CI: 1.179–4.593, p < 0.050), secondary and higher education level (AOR:3.161, 95% CI: 2.141–4.668, p < 0.001), richest wealth group (AOR:13.451, 95% CI: 5.231–34.589, p < 0.001), and antenatal care (ANC) visits 4 and more times (AOR:5.084, 95% CI: 2.7963–9.242, p < 0.001), were noticed more likely to choose for institutional delivery compared to their reference group, respectively. Conclusion The result shows the ecological region, province, ethnic group, distance to reach health facility, parity, respondents’ education level, wealth index and ANC visits, and mother’s age in 5-year groups are the associated factors for the utilization of institutional delivery service in Nepal. It highlights the need for targeted interventions to enhance the utilization of institutional delivery services. Addressing socio-economic and geographical disparities, economic barriers, advancing education, promoting antenatal care visits, and ensuring nearer healthcare accessibility are crucial to achieving the equitable maternal and neonatal health care through institutional delivery in Nepal. It is concluded that more attention needs to be paid to areas where the severity persists by professionals and policymakers as well.
Identification of SIRT3 modulating compounds in deep-sea fungi metabolites: Insights from molecular docking and MD simulations
SIRT3, a crucial deacetylase that plays a key role in regulating mitochondrial acetylation, is tightly linked to metabolic processes and is essential for the maintenance of eukaryotic life. SIRT3 is a potential therapeutic target due to its key role in various diseases, including ageing, heart disease, cancer, and metabolic disorders. In this work, we aimed to identify potential SIRT3 inhibitors from the deep-sea fungal metabolites by employing molecular docking and ADMET analysis. Based on the binding affinities, ten compounds were selected whose docking scores were in the range of -9.693 to -8.327 kcal/mol. Further, four compounds Penipanoid C, Penicillactam, Quinolonimide, and Brevianamide R were selected based on the ADMET properties and subjected to Molecular dynamics simulations to assess the stability of these molecules with target. The stability analysis indicated that the selected compounds could act as lead compounds during in vitro assays to advance these drug candidates towards clinical drug development.
Retraction: Elucidating the monoamine oxidase B inhibitory effect of kaurene diterpenoids from Xylopia aethiopica: An in silico approach
Hypersensitivity pneumonitis associated with home mold exposure: A retrospective cohort analysis
Background Home mold exposure is a commonly overlooked cause of hypersensitivity pneumonitis. This is in part due to the limited literature supporting the association as well as the lack of exposure characterization available in reported cases. Notably, climate change, extreme weather patterns and frequent flooding continue to create conditions that promote home mold growth. As remediation has the potential to improve outcomes, clinicians need to remain vigilant in searching for and identifying potential mold exposure in suspected HP patients. The purpose of this study is to describe a large retrospective cohort of patients with home mold associated HP. Methods HP patients were identified retrospectively from our single center interstitial lung disease (ILD) database between 2011–2019. Patients with a moderate, high, or definite confidence diagnosis of HP were included. The presence of residential mold exposure was confirmed by medical chart review by a pulmonologist trained in exposure assessment. Results Home mold exposure was identified as the culprit antigen in 54 of 231 hypersensitivity pneumonitis patients. An invasive procedure (bronchoalveolar lavage, transbronchial biopsy, and/or surgical lung biopsy) was performed to confirm the diagnosis of HP in 85.7% of the cohort. Home mold was principally caused by chronic and/or recurring water intrusion. The most common locations of mold within the home included the bathroom, bedroom, and air conditioning unit. Transplant free survival was 97.7 months, which did not differ from the 50 HP patients in our cohort with HP associated with a mold exposure outside the home or patients in our cohort with HP associated with avian antigen exposure. Of the 41 patients who removed the exposure, 5 (12.2%) had a > 10% improvement in FVC, including 4 with fibrotic HP. Conclusion Our study is the largest to report an association between HP and home mold exposure and is the first report from the region of north Texas. As climate change continues to disrupt weather patterns causing storms and flooding in certain areas, clinicians should remain alert to the presence of mold and its potential contribution to development of HP.
An obesity paradox in preterm birth: A case control study
The March of Dimes Global action report indicated that preterm birth (PTB) rates are increasing in most countries. It is the most important cause of neonatal deaths and the second leading cause of death in children under age 5. Literature reporting the relationship between maternal pre-pregnancy body mass index (BMI) and PTB has previously yielded inconsistent conclusions. Our objective is to fill in the knowledge gap by evaluating the interaction of socio-economic status (SES) and BMI and its relationship to the rate of PTB. This is a case control study using the Natality Data of the National Vital Statistics System from the years 2020–2022. BMI was a significant factor in PTB for lower socioeconomic status (LSES) women. For every increase in BMI, there was a decrease in the probability of PTB (OR = 0.923, 95% CI 0.915–0.931, P < 0.001). Those who were LSES also had a curved relationship with PTB indicating that the as BMI increases, the odds of PTB decreases up until a BMI value, then the PTB rate increases. This relationship was not found in higher economic status women. Our study had two significant findings. We first found an obesity paradox in PTB for those mothers who are LSES. We also found that the relationship between BMI and PTB was not linear but curvilinear, bridging the gap in the conclusions of other studies. This study fills in the knowledge gap of BMI and PTB by adding the consideration of social class and by creating a polynomial BMI term.
Chronic stress drives depression by disrupting cellular housekeeping
Explaining subscription intention for video streaming platforms in China: Integrating the UTAUT2 model, perceived value theory, and S-O-R theory
Purpose This study examines the factors influencing the intention to subscribe to video streaming platforms in China through integrating the extended unified theory of acceptance and use of technology (UTAUT2), perceived value theory, and stimulus–organism–response (S-O-R) theory. Design/methodology/approach A quantitative study was conducted to test the hypothesized relationships among the constructs using partial least squares structural equation modeling (PLS-SEM). The sample included 506 viewers of video streaming platforms. Findings The results showed that performance expectancy, effort expectancy, social influence, and hedonic motivation had a positive relationship with subscription intention in video streaming platforms. Additionally, perceived value mediated these relationships. Also, habit was positively related to subscription intention. Finally, the attractiveness of alternatives moderated the relationship between perceived value and subscription intention of video streaming platforms in China. Originality/value This study introduces a moderated mediation mechanism to explain the intention to subscribe to video streaming platforms in China, utilizing the UTAUT2 model, perceived value theory, and S-O-R theory.
Regulated somatic hypermutation enhances antibody affinity maturation
Abstract Germinal centres are specialized microenvironments where B cells undergo affinity maturation. B cells expressing antibodies whose affinity is improved by somatic hypermutation are selected for expansion by limiting numbers of T follicular helper cells. Cell division is accompanied by mutation of the immunoglobulin genes, at what is believed to be a fixed rate of around 1 × 10 −3 per base pair per cell division 1 . As mutagenesis is random, the probability of acquiring deleterious mutations outweighs the probability of acquiring affinity-enhancing mutations. This effect might be heightened, and even become counterproductive, in B cells that express high-affinity antibodies and undergo the greatest number of cell divisions 2 . Here we experimentally examine a theoretical model that explains how affinity maturation could be optimized by varying the rate of somatic hypermutation such that cells that express higher-affinity antibodies divide more but mutate less per division. Data obtained from mice immunized with SARS-CoV-2 vaccines or a model antigen align with the theoretical model and show that cells producing high-affinity antibodies shorten the G0/G1 phases of the cell cycle and reduce their mutation rates. We propose that these mechanisms safeguard high-affinity B cell lineages and enhance the outcomes of antibody affinity maturation.
Post-stroke health-related quality of life following lower-extremity constraint-induced movement therapy - An observational survey study
Lower- extremity constraint-induced movement therapy (LE-CIMT) has proven effective in overcoming physical disabilities. Participating in the LE-CIMT requires some independent walking ability without aids that indicates a higher level of motor function than for the entire stroke population. However, only few studies evaluated health-related quality of life (HRQoL) after LE-CIMT. This study aimed to compare HRQoL of people who had participated in LE-CIMT post-stroke to the general population and evaluate whether descriptive characteristics and clinical result were associated with their HRQoL. An observational survey study with a questionnaire including the Swedish RAND-36 and Saltin–Grimby Physical Activity Level Scale was sent to 162 people. Reference data from the Mid-Health Survey in Sweden was used for norm-based comparisons of RAND-36. Respondents’ result from six-minute walk test post-LE-CIMT were used in the univariate analyse. The response rate was 65% (n = 106; 69 males and 37 females with a mean age of 62 ± 12 years). Ninety percent of the respondents could move around indoors and outdoors independently, despite this, 21% considered themselves physically inactive. The respondents had significantly reduced HRQoL compared to the general population in four of eight domains in the RAND-36: physical functioning (p = 0.001), role-functioning (physical; p < 0.001), general health (p = 0.010), and social functioning (p < 0.001). Regression analysis showed that longer walking distance significantly was associated with the RAND-36 physical functioning domain (β = 6.45, 95% confidence interval = 2.03–10.87, p = 0.005). People in the chronic phase post-stroke who had previously participated in LE- CIMT had reduced HRQoL compared to the general population regarding physical functioning, role-functioning physical, general health, and social functioning. A longer walking distance was associated with higher HRQoL in physical functioning domain, emphasising the importance of mobility training in post-stroke rehabilitation.
Network-based multi-class classifier to identify optimized gene networks for acute leukemia cell line classification
Unraveling the genetic regulatory networks that underlie diseases is essential for comprehending the intricate mechanisms of these conditions. While various computational strategies were developed, the approaches in the existing studies concerning network-based prediction and classification are based on the pre-estimated gene networks. However, the gene network that is pre-estimated fails to yield biologically meaningful explanations for classifying cell lines into particular clinical states. The reason for this limitation is the lack of inclusion of any information about the clinical status of cell lines during the process of network estimation. To achieve effective cell line classification and ensure the biological validity of the cell lines classification, we develop a computational strategy referred to as GRN-multiClassifier for network-based multi-class classification. The GRN-multiClassifier estimates gene network in a manner that simultaneously minimizes both the network estimation error and the negative log-likelihood function of multinomial logistic regression. That is, our strategy estimates optimized gene network to enable the multi-class classification of cell lines into specific clinical conditions. Monte Carlo simulations demonstrate the efficacy of the GRN-multiClassifier. We applied our strategy to network-based classification of acute leukemia cell lines into three distinct categories of acute leukemia. Our strategy shows outstanding performance in the classification of acute leukemia cell lines. The results for the acute leukemia marker identification are strongly supported by existing literature. The implications of our findings suggest that potential pathways involving the inhibition of ACTB and the molecular interactions between “HBA1&HBB,” “HBB&HBA1,” “IGKV1-5&IGHV4-31,” “IGHV4-31&IGKV1-5,” “HLA-DRA&CD74” and “ACTB&ACTB” could offer significant insights into the underlying mechanism of acute leukemia.
Extraction, analysis, and antifungal activity study of algae antibiotic active substances in plateau lakes
This study was carried out to assess the inhibitory activity of algae in plateau lakes against plant pathogenic fungi, and further conduct preliminary research and analysis on their antifungal active ingredients, in order to provide a certain basis for the development and utilization of algal secondary metabolite as anti-plant pathogenic fungal agents. Different solvent extraction methods using water, ethyl acetate, ethanol, and methanol were conducted to extract polyphenol metabolites from Ulothrix, Chlorella vulgaris, and Microcystis pseudofilamentosa Crow. The composition of the extracts was analyzed based on the UPLC-MS/MS detection platform, and the antifungal activity was determined. The results showed that the content of polyphenol metabolites extracted from Ulothrix using methanol was the highest, followed by ethyl acetate and ethanol. The water extraction method resulted in the highest loss of polyphenolic metabolites. Three species of Fusarium oxysporum were used as indicator fungus to determine the antifungal activities of algae extracts. The three types of algae extracts showed good antimicrobial effects on F. oxysporum. The polyphenol metabolites extracted from Ulothrix using methanol demonstrated the strongest antifungal activity, with up to 20 mm in diameter of inhibition zone. The metabolite with the weakest antifungal activity was M. pseudofilamentosa Crow, with an 8-mm diameter of inhibition zone. Based on the UPLC-MS/MS detection, 242 polyphenol metabolites were initially identified in the methanol extracts of the three algae, including 160 phenolic acids, 32 flavonoids, 17 flavonols, 7 dihydroflavones, 2 dihydroflavonols, 2 chalcones, 2 flavanols, 5 flavonoids, 5 lignans, and 10 coumarins. Principal component analysis, fold change analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to conduct differential metabolite screening and related metabolic pathway enrichment. The methanol extract samples of the three algae were mainly classified into two categories. Ten important differential metabolites and 15 important metabolic pathways were obtained. In addition, the methanol extracts of Ulothrix contained the largest variety of phenolic acid compounds, with a total of 75 phenolic acid compounds detected, which was followed by C. vulgaris, with 44 phenolic acid compounds detected, and M. pseudofilamentosa Crow, with 37 phenolic acid compounds. Compared with phenolic acid compounds, the quantitative differences of other polyphenols were smaller. Based on these results and those from the antifungal experimental analysis, phenolic acids in algae polyphenol metabolites are the main antifungal active ingredients.
The effect of mindfulness-based Tai Chi Chuan on mobile phone addiction among male college students is associated with executive functions
Objective Mindfulness-based Tai Chi Chuan (MTCC) have been shown to contribute to improvements in cognitive and executive functions. Changes in inhibition, an aspect of executive function, have been closely linked to mobile phone addiction. However, the relationship between these elements remains unclear. This study aims to investigate the effects of an 8-week MTCC intervention on executive function, mindfulness levels, and mobile phone addiction in male college students. Additionally, the study explores the role of executive function in improving mobile phone addiction through MTCC interventions. Methods Sixty-six male college students were selected as research subjects and randomly divided into a control group (33) and an experimental group (33). The control group maintained their normal physical activity levels without any additional intervention. In contrast, the experimental group underwent 8 weeks of MTCC training. Mindfulness levels were assessed using the Mindful Attention Awareness Scale (MAAS), while mobile phone addiction was evaluated by the Mobile Phone Addiction Index (MPAI). The Flanker task, 1-back task, and More-Odd Shifting task were employed to evaluate inhibition, updating, and shifting aspects of executive function, respectively. Results (1) The 8-week MTCC intervention significantly improved mobile phone addiction among male college students, with the intervention group showing a lower post-intervention MPAI score (46.09 ± 18.11) compared to the control group (56.55 ± 16.02), yielding a mean difference of −10.46 (95% CI: −18.92 to −1.99, p = 0.016). Mindfulness levels also improved significantly (p = 0.046), as did specific sub-functions of executive function: inhibition correct rate (p < 0.001), inhibition response (p = 0.001), and shifting correct rate (p = 0.001). No significant effects were observed for updating correct rate (p = 0.527) or updating response (p = 0.303). (2) Mobile phone addiction indices were significantly correlated with changes in inhibition response (r = 0.756, p = 0.000 < 0.01), updating response (r = 0.035, p = 0.045 < 0.05), and shifting response (r = 0.397, p = 0.022 < 0.05). (3) Mindfulness levels and inhibition levels were significantly correlated (r = 0.394, p = 0.023 < 0.05). (4) Changes in inhibition within executive functions partially mediated the improvement of mobile phone addiction, with the direct effect (0.716) and mediating effect (0.483) accounting for 59.72% and 40.28% of the total effect (1.199), respectively. Conclusion MTCC exercises significantly increase cognitive functions, leading to increased inhibition and attentiveness, and may be helpful in the prevention of addictions, including cell phone addictions.
Association between obstructive sleep apnea risk and atherosclerosis: A nationwide cross-sectional study in the Korean population
Objectives Obstructive sleep apnea (OSA) increases the risk of all-cause and cardiovascular mortality. This study aimed to investigate the association between OSA and atherogenic risk in the Koreans. Methods Data from 8,158 participants (mean age, 57.9 ± 11.7; male/female, 1:1.4) obtained from the Korea National Health and Nutrition Examination Survey between 2019 and 2021. OSA risk was screened using the STOP-BANG score, and atherogenic risk was measured using the atherogenic index of plasma (AIP). Logistic regression was used to evaluate the association between the STOP-BANG scores and high AIP and subgroups according to the presence of diabetes. Results The proportions of individuals with atherogenic risk (AIP > 0.24) were 13.7%, 27.6%, and 34.7% in the low-, intermediate-, and high-OSA risk groups (p < 0.001). After adjustment, individuals with intermediate and high OSA risk had 1.35 (95% confidence interval [CI], 1.16–1.58; p < 0.001) and 1.32 (95% CI, 1.08–1.61; p = 0.006) times higher odds of having atherogenic risk than those with low OSA risk. Among patients without diabetes, high OSA risk was not an independent factor affecting atherogenic risk (hazard ratio [HR], 1.17; 95% CI, 0.93–1.47). However, among patients with diabetes, compared with those with low OSA risk, those with intermediate (HR, 1.51; 95% CI, 1.05–2.19) and high OSA risk (HR, 1.58; 95% CI, 1.02–2.46) had significantly increased atherogenic risk. Conclusion OSA is linked to increased atherogenic risk in the Koreans, especially in individuals with diabetes, thus highlighting the importance of routine OSA screening to manage and reduce cardiovascular risks.
mTOR inhibition impacts the flagellin-augmented inflammatory and antimicrobial response of human airway epithelial cells to Pseudomonas aeruginosa
Objective The airway epithelium provides a first line of defense against pathogens by release of antimicrobial factors and neutrophil-attracting chemokines. Pseudomonas (P.) aeruginosa, a Gram-negative bacterium that expresses flagellin as an important virulence factor, is a common cause of injurious airway inflammation. The aim of our study was to determine the contribution of flagellin to the inflammatory, antimicrobial, and metabolic responses of the airway epithelium to P. aeruginosa. Furthermore, as we previously showed that targeting mTOR limited the glycolytic and inflammatory response induced by flagellin, we assessed the effect of rapamycin on human bronchial epithelial (HBE) cells stimulated with flagellated and non-flagellated P. aeruginosa. Methods Primary pseudostratified HBE cells, cultured on an air-liquid-interface, were treated on the basolateral side with medium, vehicle or rapamycin, exposed on the apical side with flagellated or flagellin-deficient P. aeruginosa, and analyzed for their inflammatory, antimicrobial, and glycolytic responses. Results Flagellin augmented the P. aeruginosa-induced expression of antimicrobial factors and secretion of chemokines by HBE cells but did not further increase the glycolytic response. Treatment of HBE cells with rapamycin inhibited mTOR activation in general and flagellin-augmented mTOR activation in particular, but did not affect the glycolytic response. Rapamycin, however, diminished the flagellin-augmented inflammatory and antimicrobial response induced by Pseudomonas. Conclusions These results demonstrate that flagellin is a significant factor that augments the inflammatory and antimicrobial response of human airway epithelial cells upon exposure to P. aeruginosa and suggest that mTOR inhibition by rapamycin in the airway epithelium diminishes these exaggerated responses.
Two different and robustly modeled DNA binding modes of Competence Protein ComP - systematic modeling with AlphaFold 3, RoseTTAFold2NA, Chai-1 and re-docking in HADDOCK
The competence protein ComP is a Type IV minor pilin and the extracellular DNA binding protein involved in natural transformation in the human pathogens Neisseria gonorrhoeae , Neisseria meningitidis, Eikenella corrodens and related Neisseriaceae bacteria. Details of the DNA binding mode of ComP is enigmatic, and the 3D structure of the DNA:: protein complex remains unresolved. Here we characterize the ComP orthologs in a set of Neisseriaceae family members, model their common structural domains and their interaction with different preferred 12 base pair long DNA binding motifs, DNA Uptake Sequences (DUS) and scrambled versions of these. Through systematic in silico modeling using AlphaFold 3, RoseTTAFold2NA, and Chai-1 and model comparisons, we bring a new understanding of the interactions between DNA and ComP. We report six distinct binding modes of which two, here named Epsilon and Gamma, were robustly modeled across platforms and different ComPs. The characteristics and robustness of the predicted models and DNA binding modes from each tool are assessed and discussed. This work expands the knowledge on the ComP:: DUS interaction and guides further wet- and dry-lab systematic and experimental characterization of these complexes through which molecular and clinical interventions may be developed.
Huge reproducibility project fails to validate dozens of biomedical studies
Transient silencing of hypermutation preserves B cell affinity during clonal bursting
Abstract In the course of antibody affinity maturation, germinal centre (GC) B cells mutate their immunoglobulin heavy- and light-chain genes in a process known as somatic hypermutation (SHM)1–4. Panels of mutant B cells with different binding affinities for antigens are then selected in a Darwinian manner, which leads to a progressive increase in affinity among the population5. As with any Darwinian process, rare gain-of-fitness mutations must be identified and common loss-of-fitness mutations avoided6. Progressive acquisition of mutations therefore poses a risk during large proliferative bursts7, when GC B cells undergo several cell cycles in the absence of affinity-based selection8–13. Using a combination of in vivo mouse experiments and mathematical modelling, here we show that GCs achieve this balance by strongly suppressing SHM during clonal-burst-type expansion, so that a large fraction of the progeny generated by these bursts does not deviate from their ancestral genotype. Intravital imaging and image-based cell sorting of a mouse strain carrying a reporter of cyclin-dependent kinase 2 (CDK2) activity showed that B cells that are actively undergoing proliferative bursts lack the transient CDK2low ‘G0-like’ phase of the cell cycle in which SHM takes place. We propose a model in which inertially cycling B cells mostly delay SHM until the G0-like phase that follows their final round of division in the GC dark zone, thus maintaining affinity as they clonally expand in the absence of selection.