An Ultrathin Coating of Microcapsules Enhances the Function of Encapsulated Hepatocyte Spheroids.

Maintaining the differentiated phenotype and function of primary hepatocytes in vitro and in vivo represents a distinct challenge. Our paper describes microcapsules comprised of a bioactive polymer and overcoated with an ultrathin film as a means of maintaining the function of entrapped hepatocytes for at least two weeks. We previously demonstrated that heparin (Hep)-based microcapsules improved the function of entrapped primary hepatocytes by capturing and releasing cell-secreted inductive signals, including hepatocyte growth factor (HGF). Further enhancement of hepatic function could be gained by loading exogenous HGF into microcapsules. In this study, we demonstrate that an ultrathin coating of tannic acid (TA) further enhances endogenous HGF signaling for entrapped hepatocytes and increases by 2-fold the rate of uptake of exogenous HGF by Hep microcapsules. Hepatocytes in overcoated microcapsules exhibited better function and hepatic gene expression than in capsules without a TA coating. Our study showcases the potential application of ultrathin coatings to modulate the bioactivity of microcapsules and may enable the use of encapsulated hepatocytes for modeling drug toxicity or treating liver diseases.

Proteome-wide Characterization and Pathophysiology Correlation in Non-ischemic Cardiomyopathies.

BACKGROUND AND OBJECTIVES: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. METHODS: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. RESULTS: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. CONCLUSIONS: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

Early unloading and clinical outcomes in patients with fulminant myocarditis undergoing VA-ECMO: results of a multicenter retrospective study.

INTRODUCTION AND OBJECTIVES: Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides effective cardiocirculatory support in patients with fulminant myocarditis, the most effective timing of venting is uncertain. We aimed to investigate the benefit of early venting among patients who underwent VA-ECMO for fulminant myocarditis. METHODS: Among 841 patients with acute myocarditis from 7 hospitals in the Republic of Korea, 217 patients with fulminant myocarditis who underwent VA-ECMO were included in this analysis. The patients were categorized into 2 groups: an early unloading group that underwent venting within 24hours of ECMO insertion, and the no or delayed unloading group. The primary outcome was a composite of death, cardiac replacement, or cardiovascular rehospitalization. RESULTS: Among 217 patients, 56 underwent early venting, 54 underwent delayed venting, and 107 did not undergo venting. On spline curves in 110 patients who underwent venting, rapid deterioration was observed as the timing of venting was delayed. The incidence of the primary outcome was lower in the early venting group than in the no or delayed unloading group (37.5% vs 58.4%; HR, 0.491; 95%CI, 0.279-0.863; P=.014). Among patients not experiencing the primary outcome within 6 months, clinical outcomes were similar after 6 months (P=.375). CONCLUSIONS: Early left heart unloading within 24hours of ECMO insertion is associated with a lower risk of a composite of death, cardiac replacement therapy, and cardiovascular rehospitalization in patients with fulminant myocarditis undergoing VA-ECMO. Registered at ClinicalTrials.gov (NCT05933902).

Heart Transplantation in a Patient With Rheumatic Heart Disease and Severe Left Atrial Calcification.

A 62-year-old woman who had undergone mitral valve replacement 24 years ago was admitted to the hospital with congestive heart failure. She needed heart transplantation for stage D heart failure. Preoperative cardiac computed tomographic scans showed a severely calcified left atrium and a large right atrium. Given that the left atrium's calcification was too severe to suture, the calcified left atrial wall was broadly resected, and the resected left atrial wall was reconstructed with a bovine pericardial patch for anastomosis with the donor's left atrial wall. The operation was completed without heavy bleeding, and the patient was discharged from the hospital with no complications.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Effectiveness of a Smartphone App-Based Intervention With Bluetooth-Connected Monitoring Devices and a Feedback System in Heart Failure (SMART-HF Trial): Randomized Controlled Trial.

BACKGROUND: Current heart failure (HF) guidelines recommend a multidisciplinary approach, discharge education, and self-management for HF. However, the recommendations are challenging to implement in real-world clinical settings. OBJECTIVE: We developed a mobile health (mHealth) platform for HF self-care to evaluate whether a smartphone app-based intervention with Bluetooth-connected monitoring devices and a feedback system can help improve HF symptoms. METHODS: In this prospective, randomized, multicenter study, we enrolled patients 20 years of age and older, hospitalized for acute HF, and who could use a smartphone from 7 tertiary hospitals in South Korea. In the intervention group (n=39), the apps were automatically paired with Bluetooth-connected monitoring devices. The patients could enter information on vital signs, HF symptoms, diet, medications, and exercise regimen into the app daily and receive feedback or alerts on their input. In the control group (n=38), patients could only enter their blood pressure, heart rate, and weight using conventional, non-Bluetooth devices and could not receive any feedback or alerts from the app. The primary end point was the change in dyspnea symptom scores from baseline to 4 weeks, assessed using a questionnaire. RESULTS: At 4 weeks, the change in dyspnea symptom score from baseline was significantly greater in the intervention group than in the control group (mean -1.3, SD 2.1 vs mean -0.3, SD 2.3; P=.048). A significant reduction was found in body water composition from baseline to the final measurement in the intervention group (baseline level mean 7.4, SD 2.5 vs final level mean 6.6, SD 2.5; P=.003). App adherence, which was assessed based on log-in or the percentage of days when symptoms were first observed, was higher in the intervention group than in the control group. Composite end points, including death, rehospitalization, and urgent HF visits, were not significantly different between the 2 groups. CONCLUSIONS: The mobile-based health platform with Bluetooth-connected monitoring devices and a feedback system demonstrated improvement in dyspnea symptoms in patients with HF. This study provides evidence and rationale for implementing mobile app-based self-care strategies and feedback for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05668000; https://clinicaltrials.gov/study/NCT05668000.

Effect of the Presence of Emergency Departments With 300 or More Hospital Beds in Health Service Areas on 30-Day Mortality in Korea: A Nationwide Retrospective Cross-sectional Study.

BACKGROUND: Disparities in emergency care accessibility exist between health service areas (HSAs). There is limited evidence on whether the presence of an emergency department (ED) that exceeds a certain hospital bed capacity is associated with emergency patient outcomes at the regional level. The objective of this study was to evaluate the effect of HSAs with or without of regional or local emergency centers with 300 or more hospital beds (EC300 or nEC300, respectively) by comparing the 30-day mortality of patients with severe emergency diseases (SEDs) admitted to the hospital through the ED. METHODS: The study retrospectively evaluated data from the National Health Information Database (NHID) of the National Health Insurance Service (NHIS) Claims database and enrolled patients who were admitted from the ED for SEDs. SEDs were defined using ICD-10 (International Classification of Diseases 10th Revision) codes for 28 disease categories with high severity, and 56 HSAs were designated as published by the NHIS. We performed hierarchical logistic regression analysis using multilevel models with the generalized linear mixed model (GLIMMIX) procedure to evaluate whether EC300 was associated with the 30-day mortality of SED patients, adjusting for patient-level, prehospital-level, hospital-level, and HSA-level variables. RESULTS: In total, 662 478 patients were analyzed, of whom 54 839 (8.3%) died within 30 days after hospital discharge. Of the 56 HSAs, 46 (82.1%) were included in the EC300 group. After adjustment for patient-level, prehospital-level, hospital-level, and HSA-level variables, nEC300 was significantly associated with increased 30-day mortality in SED patients (adjusted odds ratio [AOR]: 1.33, 95% CI: 1.137-1.153). In addition, patients who visited EDs with fewer annual SED admissions were associated with higher 30-day mortality. CONCLUSION: nEC300 had a greater risk of 30-day mortality in patients treated with SEDs than EC300. The results indicate that not only the number of EDs in each HSA is important for ensuring adequate patient outcomes but also the presence of EDs with adequate receiving capacity.

Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Fabrication of silicon-based nickel nanoflower-encapsulated gelatin microspheres as an active antimicrobial carrier.

Local antibiotic application might mitigate the burgeoning problem of rapid emergence of antibiotic resistance in pathogenic microbes. To accomplish this, delivery systems must be engineered. Hydrogels have a wide range of physicochemical properties and can mimic the extracellular matrix, rendering them promising materials for local antibacterial agent application. Here, we synthesized antibacterial silicon (Si)-based nickel (Ni) nanoflowers (Si@Ni) and encapsulated them in gelatin methacryloyl (GelMA) using microfluidic and photo-crosslink technology, constructing uniform micro-sized hydrogel spheres (Si@Ni-GelMA). Si@Ni and Si@Ni-GelMA were characterized using X-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Injectable Si@Ni-GelMA exhibited excellent antibacterial activities owing to the antibiotic effect of Ni against Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus, while showing negligible cytotoxicity. Therefore, the Si@Ni-GelMA system can be used as drug carriers owing to their injectability, visible light-mediated crosslinking, degradation, biosafety, and superior antibacterial properties.

Temporal Trends, Risk Factors, and Clinical Outcomes of De Novo Lymphoproliferative Disorders After Heart Transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, previous studies of PTLD after HTx are limited to single-center analyses or extrapolated from all solid organ transplantations. OBJECTIVES: The authors analyzed the temporal trends, risk factors, and clinical outcome of de novo PTLD specifically after HTx. METHODS: Using multi-institutional, multinational data from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, the authors evaluated the real-world data of PTLD after HTx, transplanted between January 2000 and June 2015. Multivariable analysis was done to identify risk factors for PTLD development after HTx. RESULTS: Among 28,136 HTx recipients, 1,069 (3.8%) developed PTLD within 10 years of transplantation. PTLD showed a bimodal age pattern with peak incidence in patients of pediatric age and late adulthood at transplantation. The early transplant era (2000-2007 vs 2008-2015), male recipient, and EBV donor-positive-recipient-negative match were independent risk factors of PTLD development within 3 years of transplantation, whereas maintenance therapy with cyclosporine vs tacrolimus at initial discharge was associated with a lower incidence. PTLD development within 3 years of transplantation was significantly associated with mortality (HR: 2.42 [95% CI: 2.01-2.91]; P < 0.001). Survival after PTLD diagnosis was higher in the recent transplant era. CONCLUSIONS: PTLD is relatively rare, but potentially fatal, post-transplant malignancy. PTLD incidence and mortality after HTx have decreased in the recent era. Strategies to minimize the risk of PTLD, and ensure early diagnosis and effective treatment are likely to improve outcomes in HTx.

Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement vs Percutaneous Mitral Valvuloplasty.

BACKGROUND: This study aimed to compare the outcomes, according to percutaneous mitral valvuloplasty (PMV) vs mitral valve replacement (MVR), of severe mitral stenosis (MS) with the updated criteria (MVA ≤ 1.5 cm2). METHODS: From the Multicenter Mitral Stenosis With Rheumatic Etiology (MASTER) registry of 3140 patients, we included patients with severe MS who underwent PMV or MVR between January 2000 and December 2021 except for previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm2 < MVA ≤ 1.5 cm2 and MVA ≤ 1.0 cm2, respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo intervention. RESULTS: Among 442 patients (mean 56.5 ±11.9 years, women 77.1%), the MVR group (n = 260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n = 182). During a mean follow-up of 6.9 ± 5.2 years with inverse probability-weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (P = 0.010). In subgroup analysis of patients with MS-MS and VS-MS, primary outcomes did not differ. However, the MVR group in patients with VS-MS showed better secondary outcomes (P = 0.012). CONCLUSIONS: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, because of increased early redo intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.

Nanoprojectile Secondary Ion Mass Spectrometry Enables Multiplexed Analysis of Individual Hepatic Extracellular Vesicles.

Extracellular vesicles (EVs) are nanoscale lipid bilayer particles secreted by cells. EVs may carry markers of the tissue of origin and its disease state, which makes them incredibly promising for disease diagnosis and surveillance. While the armamentarium of EV analysis technologies is rapidly expanding, there remains a strong need for multiparametric analysis with single EV resolution. Nanoprojectile (NP) secondary ion mass spectrometry (NP-SIMS) relies on bombarding a substrate of interest with individual gold NPs resolved in time and space. Each projectile creates an impact crater of 10-20 nm in diameter while molecules emitted from each impact are mass analyzed and recorded as individual mass spectra. We demonstrate the utility of NP-SIMS for statistical analysis of single EVs derived from normal liver cells (hepatocytes) and liver cancer cells. EVs were captured on antibody (Ab)-functionalized gold substrate and then labeled with Abs carrying lanthanide (Ln) MS tags (Ab@Ln). These tags targeted four markers selected for identifying all EVs, and specific to hepatocytes or liver cancer. NP-SIMS was used to detect Ab@Ln-tags colocalized on the same EV and to construct scatter plots of surface marker expression for thousands of EVs with the capability of categorizing individual EVs. Additionally, NP-SIMS revealed information about the chemical nanoenvironment where targeted moieties colocalized. Our approach allowed analysis of population heterogeneity with single EV resolution and distinguishing between hepatocyte and liver cancer EVs based on surface marker expression. NP-SIMS holds considerable promise for multiplexed analysis of single EVs and may become a valuable tool for identifying and validating EV biomarkers of cancer and other diseases.

Nanoprojectile Secondary Ion Mass Spectrometry Enables Multiplexed Analysis of Individual Hepatic Extracellular Vesicles.

Extracellular vesicles (EVs) are nanoscale lipid bilayer particles secreted by cells. EVs may carry markers of the tissue of origin and its disease state which makes them incredibly promising for disease diagnosis and surveillance. While the armamentarium of EV analysis technologies is rapidly expanding, there remains a strong need for multiparametric analysis with single EV resolution. Nanoprojectile (NP) secondary ion mass spectrometry (NP-SIMS) relies on bombarding a substrate of interest with individual gold NPs resolved in time and space. Each projectile creates an impact crater of 10-20 nm in diameter while molecules emitted from each impact are mass analyzed and recorded as individual mass spectra. We demonstrate the utility of NP-SIMS for analysis of single EVs derived from normal liver cells (hepatocytes) and liver cancer cells. EVs were captured on antibody (Ab)-functionalized gold substrate then labeled with Abs carrying lanthanide (Ln) MS tags (Ab@Ln). These tags targeted four markers selected for identifying all EVs, and specific to hepatocytes or liver cancer. NP-SIMS was used to detect Ab@Ln-tags co-localized on the same EV and to construct scatter plots of surface marker expression for thousands of EVs with the capability of categorizing individual EVs. Additionally, NP-SIMS revealed information about the chemical nano-environment where targeted moieties co-localized. Our approach allowed analysis of population heterogeneity with single EV resolution and distinguishing between hepatocyte and liver cancer EVs based on surface marker expression. NP-SIMS holds considerable promise for multiplexed analysis of single EVs and may become a valuable tool for identifying and validating EV biomarkers of cancer and other diseases.

Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor.

The ability to maintain functional hepatocytes has important implications for bioartificial liver development, cell-based therapies, drug screening, and tissue engineering. Several approaches can be used to restore hepatocyte function in vitro, including coating a culture substrate with extracellular matrix (ECM), encapsulating cells within biomimetic gels (Collagen- or Matrigel-based), or co-cultivation with other cells. This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids. These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors. We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes. We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor (HGF) into microcapsules and inhibiting transforming growth factor (TGF)-ß1 signaling. Overall, bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering, regenerative medicine, and drug testing applications.

The ReInforcement of adherence via self-monitoring app orchestrating biosignals and medication of RivaroXaban in patients with atrial fibrillation and co-morbidities: a study protocol for a randomized controlled trial (RIVOX-AF).

Background: Because of the short half-life of non-vitamin K antagonist oral anticoagulants (NOACs), consistent drug adherence is crucial to maintain the effect of anticoagulants for stroke prevention in atrial fibrillation (AF). Considering the low adherence to NOACs in practice, we developed a mobile health platform that provides an alert for drug intake, visual confirmation of drug administration, and a list of medication intake history. This study aims to evaluate whether this smartphone app-based intervention will increase drug adherence compared with usual care in patients with AF requiring NOACs in a large population. Methods: This prospective, randomized, open-label, multicenter trial (RIVOX-AF study) will include a total of 1,042 patients (521 patients in the intervention group and 521 patients in the control group) from 13 tertiary hospitals in South Korea. Patients with AF aged ≥19 years with one or more comorbidities, including heart failure, myocardial infarction, stable angina, hypertension, or diabetes mellitus, will be included in this study. Participants will be randomly assigned to either the intervention group (MEDI-app) or the conventional treatment group in a 1:1 ratio using a web-based randomization service. The intervention group will use a smartphone app that includes an alarm for drug intake, visual confirmation of drug administration through a camera check, and presentation of a list of medication intake history. The primary endpoint is adherence to rivaroxaban by pill count measurements at 12 and 24 weeks. The key secondary endpoints are clinical composite endpoints, including systemic embolic events, stroke, major bleeding requiring transfusion or hospitalization, or death during the 24 weeks of follow-up. Discussion: This randomized controlled trial will investigate the feasibility and efficacy of smartphone apps and mobile health platforms in improving adherence to NOACs. Trial registration: The study design has been registered in ClinicalTrial.gov (NCT05557123).

Implications of the Mitral Leaflet Coaptation Pattern on Clinical Outcomes in Patients With Functional Mitral Regurgitation.

The classification of secondary mitral regurgitation (MR) is based on atrial functional MR (AFMR) or ventricular functional MR (VFMR) and volume changes, but the mitral leaflet coaptation angle also contributes to the MR mechanism. The clinical implications of the coaptation angle on cardiovascular (CV) outcomes have not been well evaluated. A total of 469 consecutive patients (265 AFMR vs 204 VFMR) with more than moderate MR were evaluated for the occurrence of heart failure, mitral valve operations, and CV death. The coaptation angle was assessed by measuring the internal angle between both leaflets at mid-systole using the apical 3-chamber view. A coaptation angle ≥130° was classified as leaflet flattening, and an angle <130° was classified as leaflet tethering. AFMR and VFMR were associated with higher frequencies of leaflet flattening and tethering, respectively. AFMR was more likely to be associated with older age, atrial fibrillation, and preserved ejection fraction, all of which were related to leaflet flattening. During a follow-up of 2.3 years, 83 patients had heart failure (17.7%), 21 patients underwent mitral valve operations (4.5%), and 34 patients died (7%). Compared with leaflet tethering, leaflet flattening was more significantly related to CV events, whereas CV event rates were less markedly different in A/VFMR. Irrespective of A/VFMR, leaflet flattening and atrial fibrillation were associated with a higher frequency of CV events. Adjusted analysis showed that leaflet flattening remained an independent predictor of CV events (hazard ratio 3.5, 95% confidence interval 1.11 to 4.88, p = 0.003), whereas A/VFMR did not. In conclusion, the leaflet coaptation angle in patients with functional MR could provide risk stratification superior to that of A/VFMR. Leaflet flattening appears to be associated with unfavorable clinical outcomes.

Construction of a bioactive copper-based metal organic framework-embedded dual-crosslinked alginate hydrogel for antimicrobial applications.

Metal-organic frameworks (MOFs) containing bioactive metals have the potential to exhibit antimicrobial activity by releasing metal ions or ligands through the cleavage of metal-ligand bonds. Recently, copper-based MOFs (Cu-MOFs) with sustained release capability, porosity, and structural flexibility have shown promising antimicrobial properties. However, for clinical use, the controlled release of Cu2+ over an extended time period is crucial to prevent toxicity. In this study, we developed an alginate-based antimicrobial scaffold and encapsulated MOFs within a dual-crosslinked alginate polymer network. We synthesized Cu-MOFs containing glutarate (Glu) and 4,4'-azopyridine (AZPY) (Cu(AZPY)-MOF) and encapsulated them in an alginate-based hydrogel through a combination of visible light-induced photo and calcium ion-induced chemical crosslinking processes. We confirmed Cu(AZPY)-MOF synthesis using scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, and thermogravimetric analysis. This antimicrobial hydrogel demonstrated excellent antibacterial and antifungal properties against two bacterial strains (MRSA and S. mutans, with >99.9 % antibacterial rate) and one fungal strain (C. albicans, with >78.7 % antifungal rate) as well as negligible cytotoxicity towards mouse embryonic fibroblasts, making it a promising candidate for various tissue engineering applications in biomedical fields.

Family Interviews Inform School-based Nursing for Children with Type 1 Diabetes and their Families.

The purpose of this study was to better understand the burden(s) associated with type 1 diabetes mellitus (T1DM) on school-aged youth and families and subsequently identify strategies school nurses can adopt to reduce the impact of this disease. Family interviews (n = 5 families, comprised of 15 individual participants) were conducted using a semi-structured interview guide to further explore family members' experiences with T1DM. Directed content analysis was employed for theme identification. Themes reflect individual and family struggles, the importance of teamwork within families, navigating barriers, and facing uncertainty. Select themes provided the impetus for the development of a school-based program directed toward youth and families with T1DM. Plans include developing educational content plus therapeutic conversations with a focus on communication, care coordination, cognition, problem-solving, and strength-building. An emphasis will be placed on participant-directed program content with peer support for youth with T1DM and family members.