Efficacy of oral anticoagulants in chronic kidney disease and hemodialysis patients with atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION: This meta-analysis seeks to evaluate the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in individuals with chronic kidney disease (CKD), end-stage renal disease (ESRD), and undergoing hemodialysis (HD) who also have atrial fibrillation (AF). EVIDENCE ACQUISITION: A comprehensive search of MEDLINE, clinicaltrials.gov, EMBASE, and Cochrane Database for relevant studies reporting the usefulness of OAC therapy for CKD, ESRD, and HD patients with AF was conducted from its inception until 1st May 2023. The studies that reported OR, RR, or HR for adult AF patients to investigate the efficacy of OAC in CKD, ESRD, and HD were included. Statistical analysis was completed using a generic inverse variance and random-effects model to calculate the combined HR and their corresponding 95% CIs for all outcomes. EVIDENCE SYNTHESIS: The meta-analysis included 33 studies with 178,956 patients. The analysis revealed that the DOACs, when compared to VKA, significantly lowered the risk of stroke or systemic embolism (HR: 0.81 [95% CI: 0.70, 0.93]; P=0.002; I2=62%), bleeding (HR: 0.77, [95% CI: 0.67, 0.89]; P=0.0003; I2=83%), and intracranial hemorrhage (HR: 0.56, [95% CI 0.47, 0.66]; P<0.00001; I2=0%). Similarly, the risks of cardiovascular death (HR: 0.88, [95% CI 0.78, 1.00]; P=0.05; I2=0%), all-cause mortality (HR: 0.88, [95% CI 0.70, 1.10]; P=0.25; I2=96%), and myocardial infarction (HR: 0.80, [95% CI 0.54, 1.17]; P= 0.25; I2= 0%) were lowered by DOAC, but the result was insignificant. No significant difference was seen in the risk of gastrointestinal bleeding between DOAC and VKA as well (HR: 0.95, [95% CI 0.75, 1.20]; P=0.65; I2=83%). CONCLUSIONS: Our meta-analysis confirms that DOACs are effective for managing AF in patients with kidney disease, with potential clinical implications for AF and CKD management. Further research should explore DOACs' reno-protective effects.

Addition of Mask to High-flow Nasal Oxygen: A Strategy to Improve Oxygenation in Hypoxemic Respiratory Failure Secondary to COVID-19.

PURPOSE: High-flow nasal cannula (HFNO) reduces the need for invasive mechanical ventilation in COVID-19 patients with hypoxemic-respiratory failure. During HFNO entrainment of room air dilutes the delivered fractional inspiratory oxygen (FiO2), thereby preventing improvement in oxygenation. The placement of a mask over HFNO to improve oxygenation has provided conflicting results. We aimed to determine and compare the effect of placing various mask types over HFNO on oxygen saturation (SPO2). MATERIALS AND METHODS: In this prospective physiological study 40 patients with COVID-19-associated hypoxemic respiratory failure on HFNO with O2 concentration <92% were included. The effect of placing different masks over HFNO on oxygenation, respiratory rate, heart rate, blood pressure, patient comfort, and partial pressure of carbon dioxide level (pCO2) was recorded after a prespecified time interval. RESULTS: We observed a significantly higher mean SPO2 and lower mean respiratory rate on using various study masks over HFNO compared to HFNO alone. On comparing various mask types, the use of N95 masks and nonrebreather (NRB) masks with O2 showed a significant increase in O2 concentration and reduction in respiratory rate compared to surgical mask (SM) and NRB without O2. The proportion of patients who achieved SPO2 of >92% was higher with the use of N95 masks (47.5%) or NRB with O2 (45%) over HFNO compared to SM (35%) and NRB without O2 (35%). No significant change was observed in heart rate, blood pressure, and CO2 level with the use of any mask over HFNO. CONCLUSION: This study demonstrates improvement in oxygenation and reduction in respiratory rate with the use of various masks over HFNO in patients of COVID-19-related hypoxemic-respiratory-failure. Significantly greater benefit was achieved with the use of N95 or NRB with O2 compared to SM or NRB without O2.

Utility of Serum Procalcitonin and Its Clearance in Predicting Outcomes in COVID-19 Patients.

Introduction Identification of coronavirus disease 2019 (COVID-19) patients at risk of worse clinical outcomes is crucial to improving patient care. Various biochemical markers have been used to predict outcomes in such patients. We aimed to evaluate the role of serum PCT (procalcitonin) and the utility of PCT clearance (PCTc) in predicting the outcome of patients with COVID-19 illness. Methods We prospectively included 39 patients with severe or critical COVID-19 illness with an age equal to more than 18 years. In addition to routine baseline investigations, serum PCT was measured at admission (PCT1) and day 5 of hospitalization (PCT2). PCTc was calculated using the formula [Formula: see text]. Results We observed that serum PCT at admission was significantly higher in non-survivors (median: 1.9 ng/ml IQR: 0.51-4.23) compared to survivors (median 0.35 (IQR: 0.1-1.2), p 0.002). On serial serum-PCT estimation, non-survivors had persistently elevated serum-PCT (median PCT1:1.9 ng/ml (IQR: 0.51-4.23) to median PCT2: 1.9ng/ml (IQR: 0.83-2.72), p 0.51) than survivors (median PCT1:0.35ng/ml (IQR: 0.1-1.19) to median PCT2: 0.15ng/ml (IQR: 0.05-0.29), p 0.01). However, no difference in serum PCTc was observed between the two groups (median: 35.3% (IQR: 12.5-84.9) in survivors vs. 71.7% (33.3-91.7) in non-survivors, p = 0.165). Conclusion Serum PCT is a potential biochemical marker that could predict outcomes in COVID-19 patients. Measurement of serial serum PCT and estimation of PCT clearance may serve as better predictors than a single value; however, well-designed studies are required to identify the definite role of serum PCT in COVID-19 patients of varying severity.

Performance of CBNAAT on Pleural Biopsies Obtained by Semirigid Thoracoscopy for Diagnosis of Unexplained Pleural Effusion: A Prospective Study from North India.

BACKGROUND: Exudative pleural effusions are commonly encountered in clinical practice, but in about one-fourth of cases, etiology remains elusive after initial evaluation. Medical thoracoscopy with semirigid thoracoscope is a minimally invasive procedure with high diagnostic yield for diagnosing pleural diseases, especially these undiagnosed exudative pleural effusions. In tubercular endemic areas, often, these effusions turn out to be tubercular, but the diagnosis of tubercular pleural effusion is quite challenging due to the paucibacillary nature of the disease. Although culture is the gold standard, it is time-consuming. Cartridge-based nucleic acid amplification test (CBNAAT) is a novel rapid diagnostic test for tuberculosis (TB) and has been recommended as the initial diagnostic test in patients suspected of having extrapulmonary TB (EPTB). MATERIALS AND METHODS: We conducted a prospective observational study of 50 patients with undiagnosed pleural effusion admitted to our tertiary care hospital. The primary aim of the study is to evaluate the diagnostic performance of CBNAAT on thoracoscopic guided pleural biopsy and compare it with conventional diagnostic techniques like histopathology and conventional culture. RESULTS: Of 50 undiagnosed pleural effusions, TB (50%) was the most common etiology. The overall diagnostic yield of semirigid thoracoscopy in this study was 74%. Our study showed that CBNAAT of pleural biopsies had a sensitivity of 36% only but a specificity of 100%. The sensitivity of CBNAAT was not far superior to the conventional culture. CONCLUSION: Tuberculosis (TB) is a common cause of undiagnosed pleural effusion in our set-up. CBNAAT testing of pleural biopsy, though, is a poor rule-out test for pleural TB, but it may aid in the early diagnosis of such patients.

An integrative proteomics approach identifies tyrosine kinase KIT as a therapeutic target for SPINK1-positive prostate cancer.

Elevated serine peptidase inhibitor, Kazal type 1 (SPINK1) levels in ∼10%-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis and identified tyrosine kinase KIT as highly enriched. Furthermore, high to moderate levels of KIT expression were detected in ∼85% of SPINK1-positive PCa specimens. We show KIT signaling orchestrates SPINK1-mediated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/ß-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling led to restoration of AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide distinct treatment modalities for advanced-stage SPINK1-positive patients.

A randomized, double-blind, dose-controlled study of the use of dexmedetomidine alone for procedural sedation of children and adolescents undergoing MRI scans.

BACKGROUND: Dexmedetomidine is a selective α2-adrenergic agonist originally approved for sedation of adults in the intensive care unit and subsequently approved for procedural sedation in adults undergoing medical procedures. Dexmedetomidine is widely used off-label for procedural sedation in children. AIMS: To evaluate efficacy and safety of monotherapy dexmedetomidine for magnetic resonance imaging procedural sedation of children ≥1month-<17years across three ascending doses. METHODS: Randomized, double-blind, dose-ranging study of procedural sedation recruited patients at USA and Japanese sites from February 2020 to November 2021. Patients were stratified into Cohort A (≥1month-<2years) or Cohort B (≥2-<17years). Cohort A loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.0 mcg/kg/1.0 mcg/kg/h, and 1.5 mcg/kg/1.5 mcg/kg/h. Cohort B loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.2 mcg/kg/1.0 mcg/kg/h, and 2.0 mcg/kg/1.5 mcg/kg/h. Primary endpoint was percentage of overall patients completing MRI without rescue propofol at the high versus low dose. Key secondary endpoint was percentage in each age cohort who did not require propofol at the high versus low dose. RESULTS: One hundred twenty-two patients received high- (n = 38), middle- (n = 42), or low-dose (n = 42) dexmedetomidine. A greater percentage completed MRI without propofol rescue, while receiving high- versus low-dose dexmedetomidine (24/38 [63.2%] vs. 6/42 [14.3%]) (odds ratio: 10.29, 95% confidence interval: 3.47-30.50, p < .001). Similar results were seen in both age cohorts. The most common adverse events were bradypnea, bradycardia, hypertension, and hypotension, and the majority were of mild-to-moderate severity. CONCLUSIONS: Dexmedetomidine was well tolerated. The high dose was associated with meaningfully greater efficacy compared with lower doses. Based on these results, the recommended starting dose for procedural sedation in children ≥1month-<2years is loading dose 1.5 mcg/kg/maintenance infusion 1.5 mcg/kg/h; children ≥2-<17years is loading dose 2.0 mcg/kg/maintenance infusion 1.5 mcg/kg/h.

Correction: Integrated silicon photonic MEMS.

[This corrects the article DOI: 10.1038/s41378-023-00498-z.].

Clinical outcomes of myocardial infarction with non-obstructive coronary arteries presenting with diabetic ketoacidosis: a propensity score-matched analysis.

INTRODUCTION AND OBJECTIVE: There is a paucity of data on patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and a decompensated diabetic state, diabetic ketoacidosis (DKA). Therefore, we aimed to investigate the outcomes of patients with MINOCA presenting with or without DKA. METHODS: We conducted this retrospective propensity score-matched analysis from January 1, 2015, to December 4, 2022. The patients with a principal admission diagnosis of ST-Elevation MI (STEMI) and discharge labeled as MINOCA (ICD-10-CM code 121.9) with DKA were analyzed. We performed a comparative analysis for MINOCA with and without DKA before and after propensity score matching for primary and secondary endpoints. RESULTS: Three thousand five hundred sixty-three patients were analyzed, and 1150 (32.27%) presented with DKA, while 2413 (67.72%) presented as non-DKA. The DKA cohort had over two-fold mortality (5.56% vs. 1.19%; p = 0.024), reinfarction (5.82% vs. 1.45%; p = 0.021), stroke (4.43% vs. 1.36%; p = 0.035), heart failure (6.89% vs. 2.11%; p = 0.033), and cardiogenic shock (6.43% vs. 1.78%; p = 0.025) in a propensity score-matched analysis. There was an increased graded risk of MINOCA with DM (RR (95% CI): 0.50 (0.36-0.86; p = 0.023), DKA (RR (95% CI): 0.46 (0.24-0.67; p = 0.001), and other cardiovascular (CV) risk factors. CONCLUSION: DKA complicates a portion of MINOCA and is associated with increased mortality and major adverse cardiovascular events (MACE).

Combination therapy of nitazoxanide with oseltamivir compared with oseltamivir in hospitalized patients with seasonal influenza.

Antiviral combinations have been proposed as treatment for influenza in order to increase the antiviral activity by action at different sites of action as well as obviate the emergence of drug resistance to the commonly used antiviral agents like oseltamivir. Nitazoxanide has been found to exhibit anti-influenza viral activity with clinical benefit in a previous study. We recruited 242 cases of SARI, among whon 67 were confirmed to have influenza viral infection. In a randomized blinded fashion, 34 patients received a combination of nitazoxanide and oseltamivir whereas 33 cases received oseltamivir alone. Clinical parameters were followed in both groups and the nasal swabs were re-tested on day 6 for influenza positivity and the cycle threshold (CT) values. No significant differences were observed in terms of time for resolution of fever, other symptoms, and SOFA scores. Nine patients succumbed during the course of the illness that included three in the oseltamivir group and six in the combination group. All but one of those who expired had an underlying co-morbid illness. Our preliminary data suggest that the addition of nitazoxanide does not improve outcomes in hospitalized patients with influenza. Larger studies are recommended for statistically robust conclusions.

MHD rotating flow over a stretching surface: The role of viscosity and aggregation of nanoparticles.

The magnetohydrodynamic (MHD) rotating flow that occurs across a stretching surface has numerous practical applications in a variety of domains. These fields include astronomy, engineering, the material sciences, and space exploration. The combined examination of magnetohydrodynamics rotating flow across a stretching surface, taking into consideration fluctuating viscosity and nanoparticle aggregation, has significant ramifications across several different domains. It is essential for both the growth of technology and the attainment of deeper insights into the complicated fluid dynamics to maintain research in this field. Given the aforementioned motivation, the principal aim of this study is to examine the effects of variable viscosity on the bidirectional rotating magnetohydrodynamic flow over a stretching surface. Aggregation effects on nanoparticles are used in the analysis. Titania (TiO2) is taken nanoparticle and ethylene glycol as base fluid. The nonlinear ordinary differential equations and the boundary conditions that correspond to them can be transformed into a dimensionless form by using a technique called similarity transformation. To get a numerical solution to the transformed equation, the Runge-Kutta 4th order (RK-4) method is utilized, and this is done in conjunction with the shooting method. The impact of various leading variables on dimensionless velocity, the coefficients of temperature, skin friction and local Nusselt number are graphically represented. Velocity profiles in both direction increases with increasing values of φ. The Nusselt number increases with increasing values of the radiation and temperature ratio parameters. When a 1 % volume fraction of nanoparticles is introduced, the Nusselt number exhibits a 0.174 % increase for the aggregation model compared to the regular fluid in the absence of radiation effects. When the aggregation model is used with a 1 % volume fraction of nanoparticles, the skin friction increases by 0.1153 % in the x direction and by 0.1165 % in the y direction compared to the regular fluid. Tables show the variation in Nusselt numbers, as well as a comparison of the effects of nanoparticle's aggregation model without and with radiation. Moreover, the numerical results obtained were compared with previously published data, demonstrating a satisfactory agreement. We firmly believe that this finding will have extensive implications for engineering and various industries.

Thermal analysis of micropolar hybrid nanofluid inspired by 3D stretchable surface in porous media.

Applications: the study of highly advanced hybrid nanofluids has aroused the interest of academics and engineers, particularly those working in the fields of chemical and applied thermal engineering. The improved properties of hybrid nanoliquids are superior to those of earlier classes of nanofluids (which are simply referred to as nanofluids). Therefore, it is essential to report on the process of analyzing nanofluids by passing them through elastic surfaces, as this is a typical practice in engineering and industrial applications. Purpose and methodology: the investigation of hybrid nanoliquids was the sole focus of this research, which was conducted using a stretched sheet. Using supporting correlations, an estimate was made of the improved thermal conductivity, density, heat capacitance, and viscosity. In addition, the distinctiveness of the model was increased by the incorporation of a variety of distinct physical limitations, such as thermal slip, radiation, micropolarity, uniform surface convection, and stretching effects. After that, a numerical analysis of the model was performed, and the physical results are presented. Core findings: the results of the model showed that it is possible to attain the desired momentum of hybrid nanofluids by keeping the fluidic system at a uniform suction, and that this momentum may be enhanced by increasing the force of the injecting fluid via a stretched sheet. Surface convection, thermal radiation, and high dissipative energy are all great physical instruments that can be used to acquire heat in hybrid nanofluids. This heat acquisition is significant from both an applied thermal engineering perspective and a chemical engineering perspective. The features of simple nano and common hybrid nanoliquids have been compared and the results indicate that hybrid nanofluids exhibit dominant behavior when measured against the percentage concentration of nanoparticles, which enables them to be used in large-scale practical applications.

Academic performance of children in relation to gender, parenting styles, and socioeconomic status: What attributes are important.

What are the effects of parenting styles on academic performance and how unequal are these effects on secondary school students from different gender and socioeconomic status families constitute the theme of this paper. A cross-sectional and purposive sampling technique was adopted to gather information from a sample of 448 students on a Likert scale. Chi-square, Kendall's Tau-c tests and hierarchical multiple regression analyses were used to determine the extent of the relationship among the variables. Chi-square and Kendall's Tau-c (Tc) test results established that the socioeconomic status of the respondent's family explained variation in children's academic performance due to parenting style; however, no significant difference was observed in the academic performance of students based on gender. Furthermore, hierarchal multiple regression analysis established that the family's socioeconomic status, authoritative parenting, permissive parenting, the interaction of socioeconomic status and authoritative parenting, and the interaction of socioeconomic status and permissive parenting were significant predictors (P<0.05) of students' academic performance. These predictor variables explained 59.3 percent variation in the academic performance of children (R2 = 0.593). Results of hierarchal multiple regression analysis in this study ranked ordered the most significant predictors of the academic performance of children in the following order. Family socioeconomic status alone was the strongest predictor (ß = 18.25), interaction of socioeconomic status and authoritative parenting was the second important predictor (ß = 14.18), authoritative parenting alone was third in importance (ß = 13.38), the interaction of socioeconomic status and permissive parenting stood at fourth place in importance (ß = 11.46), and permissive parenting was fifth (ß = 9.2) in influencing academic performance of children in the study area. Children who experienced authoritative parenting and were from higher socioeconomic status families perform better as compared to children who experienced authoritarian and permissive parenting and were from low socioeconomic status families.

Hepatic Artery Aneurysm/Pseudoaneurysm: An Unusual Cause of Upper Gastrointestinal (UGI) Bleeding and Biliary Obstruction Further Complicated by Glue Dislodgement Leading to Biliary Obstruction.

Hepatic artery aneurysms (HAA) and pseudoaneurysms are rare vascular abnormalities, that can lead to significant morbidity and mortality if left untreated. We present a case report of a 78-year-old lady with a hepatic artery aneurysm who initially presented with upper gastrointestinal bleeding (UGIB) and biliary obstruction and was treated by trans-arterial embolization. Recovery was complicated by glue embolisation leading to obstructive jaundice and biliary sepsis. This case highlights the importance of having a high index of suspicion for HAA and pseudoaneurysm when initial investigations including oesophago gastro duodenoscopy (OGD) are negative. Although rare, glue embolization should be considered in patients who present with obstructive jaundice and abdominal pain.

Flow and heat transfer of Al2O3 and γ-Al2O3 through a channel with non-parallel walls: a numerical study.

Nanofluids are referred to as nanometer suspensions in standard nanometer-sized fluid transfer. In this study, our focus was to examine the flow and transmission of heat through a non-parallel walled channel of nanofluids. For this purpose, we used the thermal transport in H2O composed of Al2O3 and γ-Al2O3 nanomaterials within the convergent/divergent channel for stretching/shrinking parameters. The flow was considered two-dimensional and unsteady. As a result, the flow of an unstable fluid, including various nanoparticles, was modeled within the convergent/divergent channel. A suitable similarity transformation was used to convert the complicated coupled system of differential equations into a non-dimensional form. For numerical solutions, the complicated system of equations was first transformed into a set of first-order differential equations using the shooting method. The Runge-Kutta (RK-4) method was then used to solve the reduced first-order equations. To comprehend the flow pattern and temperature and velocity profile deviations caused by dimensionless parameters, a graphical investigation was performed. Graphs were also used to investigate the variation in the velocity and temperature profiles for various emerging factors.

A novel framework for classification of two-class motor imagery EEG signals using logistic regression classification algorithm.

Robotics and artificial intelligence have played a significant role in developing assistive technologies for people with motor disabilities. Brain-Computer Interface (BCI) is a communication system that allows humans to communicate with their environment by detecting and quantifying control signals produced from different modalities and translating them into voluntary commands for actuating an external device. For that purpose, classification the brain signals with a very high accuracy and minimization of the errors is of profound importance to the researchers. So in this study, a novel framework has been proposed to classify the binary-class electroencephalogram (EEG) data. The proposed framework is tested on BCI Competition IV dataset 1 and BCI Competition III dataset 4a. Artifact removal from EEG data is done through preprocessing, followed by feature extraction for recognizing discriminative information in the recorded brain signals. Signal preprocessing involves the application of independent component analysis (ICA) on raw EEG data, accompanied by the employment of common spatial pattern (CSP) and log-variance for extracting useful features. Six different classification algorithms, namely support vector machine, linear discriminant analysis, k-nearest neighbor, naïve Bayes, decision trees, and logistic regression, have been compared to classify the EEG data accurately. The proposed framework achieved the best classification accuracies with logistic regression classifier for both datasets. Average classification accuracy of 90.42% has been attained on BCI Competition IV dataset 1 for seven different subjects, while for BCI Competition III dataset 4a, an average accuracy of 95.42% has been attained on five subjects. This indicates that the model can be used in real time BCI systems and provide extra-ordinary results for 2-class Motor Imagery (MI) signals classification applications and with some modifications this framework can also be made compatible for multi-class classification in the future.

Prognostic value of hematological parameters in older adult patients with acute coronary syndrome undergoing coronary intervention: a single centre prospective study.

BACKGROUND: Cardiovascular disease is a significant contributor to the disease burden in geriatric patients. Underlying systemic inflammation is thought to be the cause of age-related changes in the bone marrow and a major risk factor for atherosclerosis. The purpose of the study was to assess the accuracy of these hematological biomarkers in predicting 30-day mortality in older patients with acute coronary syndrome (ACS). METHODS: This was a prospective observational study of 601 older adult patients (age > 60 years) with ACS who underwent percutaneous coronary intervention over two years (2017-2019). The relationship between baseline hematological parameters and mortality was assessed during the 30-day follow-up. Logistic regression analysis and receiver operating characteristic curve analysis were done to evaluate for diagnostic accuracy of various hematological parameters. RESULTS: The mean age of presentation was 77 ± 17 years. The mean neutrophil-lymphocyte ratio (NLR) value was 5.07 ± 4.90 and the mean platelet-lymphocyte ratio (PLR) value was 108.65 ± 85.82. On univariate analysis, total leucocyte count [odds ratio (OR) = 0.85, P = 0.021], hematocrit (OR = 0.91, P = 0.018), NLR (OR = 1.10, P = 0.001) and PLR (OR = 1.05, P = 0.001) were associated with mortality. On receiver operating characteristic curve analysis, NLR predicted mortality with 68.1% and PLR with 65.7% accuracy. On multivariate analysis, NLR (OR = 1.096, 95% CI: 1.006-1.15, P = 0.035) was an independent predictor of 30-day mortality. CONCLUSIONS: For the risk classification of all elderly ACS patients, we highly advise using NLR rather than the total white blood cell count.

Spontaneous Confinement of mRNA Molecules at Biomolecular Condensate Boundaries.

Cellular biomolecular condensates, termed ribonucleoprotein (RNP) granules, are often enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules are not well understood. In this study, we performed single-molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SGs) and processing bodies (PBs), which are distinct in their molecular composition and function. We developed a photobleaching- and noise-corrected colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule's boundaries. We found that mRNAs are often localized at granule boundaries, an observation consistent with recently published data. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid-liquid interfaces, which is observed in various technological and biological processes. We also suggest that this confinement could be due to a combination of intermolecular interactions associated with, first, the screening of a portion of the RNP granule interface by the polymer and, second, electrostatic interactions due to a strong electric field induced by a Donnan potential generated across the thin interface.

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway.

OBJECTIVES: This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. METHODS: The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. RESULTS: LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1ß signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. CONCLUSION: LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

The Digital Hospital: A Scoping Review of How Technology Is Transforming Cardiopulmonary Care.

BACKGROUND: Innovative models of health care that involve advanced technology in the form of a digital hospital are emerging globally. Models include technology such as machine learning and smart wearables, that can be used to integrate patient data and improve continuity of care. This model may have benefits in situations where patient deterioration must be detected quickly so that a rapid response can occur such as cardiopulmonary settings. AIM: The purpose of this scoping review was to examine the evidence for a digital hospital model of care, in the context of cardiac and pulmonary settings. DESIGN: Scoping review. DATA SOURCES: Databases searched were using PsycInfo, Ovid MEDLINE, and CINAHL. Studies written in English and containing key terms related to digital hospital and cardiopulmonary care were included. The Joanna Briggs Institute methodology for systematic reviews was used to assess the risk of bias. RESULTS: Thirteen (13) studies fulfilled the inclusion criteria. For cardiac conditions, a deep-learning-based rapid response system warning system for predicting patient deterioration leading to cardiac arrest had up to 257% higher sensitivity than conventional methods. There was also a reduction in the number of patients who needed to be examined by a physician. Using continuous telemonitoring with a wireless real-time electrocardiogram compared with non-monitoring, there was improved initial resuscitation and 24-hour post-event survival for high-risk patients. However, there were no benefits for survival to discharge. For pulmonary conditions, a natural language processing algorithm reduced the time to asthma diagnosis, demonstrating high predictive values. Virtual inhaler education was found to be as effective as in-person education, and prescription error was reduced following the implementation of computer-based physician order entry electronic medical records and a clinical decision support tool. CONCLUSIONS: While we currently have only a brief glimpse at the impact of technology care delivery for cardiac and respiratory conditions, technology presents an opportunity to improve quality and safety in care, but only with the support of adequate infrastructure and processes. PROTOCOL REGISTRATION: Open Science Framework (OSF: DOI 10.17605/OSF.IO/PS6ZU).

Impact of variable thermal conductivity on flow of trihybrid nanofluid over a stretching surface.

The present article describes the impact of variable thermal conductivity on the flow of ternary hybrid nanofluid with cylindrical shape nanoparticles over a stretching surface. Three nanoparticles combine in base fluid polymer. The assumption made will be used to model an equations. Modeled equations are in the form of a system of partial differential equations are difficult to solve can be converted to system of an ordinary differential equations, through resemblance substitutions, and will be solved numerically. Numerical scheme of Runge-Kutta order four is coupled with the shooting method to solve the resulting equations. The graphs in the study illustrate how physical quantities, such as magnetic field, injection/suction, nanoparticles volume fraction, and variable thermal conductivity, affected the velocity, skin friction, temperature, and local Nusselt number. The velocity profiles deflate as the volume fraction rises. While the temperature rises with an increase in the volume fraction of nanoparticles for both injection and suction, the velocity profiles also decline as the injection and suction parameter increases. Furthermore, as the magnetic field increases, the temperature profile rises while the velocity profile falls. The temperature curves increase as thermal conductivity increases. Finally, as the magnetic field is strengthened, the Nusselt number and skin friction decrease. The combination of mathematical modeling, numerical solution techniques, and the analysis of physical quantities contributes to the advancement of knowledge in this ternary hybrid nanofluid.