Crystal-Phase Engineering in Heterogeneous Catalysis.

The performance of a chemical reaction is critically dependent on the electronic and/or geometric structures of a material in heterogeneous catalysis. Over the past century, the Sabatier principle has already provided a conceptual framework for optimal catalyst design by adjusting the electronic structure of the catalytic material via a change in composition. Beyond composition, it is essential to recognize that the geometric atomic structures of a catalyst, encompassing terraces, edges, steps, kinks, and corners, have a substantial impact on the activity and selectivity of a chemical reaction. Crystal-phase engineering has the capacity to bring about substantial alterations in the electronic and geometric configurations of a catalyst, enabling control over coordination numbers, morphological features, and the arrangement of surface atoms. Modulating the crystallographic phase is therefore an important strategy for improving the stability, activity, and selectivity of catalytic materials. Nonetheless, a complete understanding of how the performance depends on the crystal phase of a catalyst remains elusive, primarily due to the absence of a molecular-level view of active sites across various crystal phases. In this review, we primarily focus on assessing the dependence of catalytic performance on crystal phases to elucidate the challenges and complexities inherent in heterogeneous catalysis, ultimately aiming for improved catalyst design.

FKBP3 aggravates the malignant phenotype of diffuse large B-cell lymphoma by PARK7-mediated activation of Wnt/ß-catenin signalling.

Diffuse large B-cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506-binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co-immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/ß-catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/ß-catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.

Carbon Dots with Spatially-Mediated-N/S-Co-Doping Enabling One-Year Stable Lubricant with Oil Leakage Detection Capability.

The dispersion stability of nano-lubricating additives is crucial for the shelf life of lubricant and its practical applications. Nitrogen-sulfur co-doped carbon dots (N,S@CDs) via a one-step hydrothermal method with nitropyrene and thiourea as raw materials are hereby presented. The N and S elements are selectively distributed throughout the entire carbon skeleton with a doping amount of 22.6 at%. The as-synthesized N,S@CDs exhibit excellent dispersion stability in PEG200 and maintain stability for over one year. The experiment results indicate that N,S@CDs significantly improve the anti-wear and friction reduction properties of PEG200, while the friction coefficient is reduced from 0.25 to 0.09 with 1.5 wt% N,S@CDs addition, and the wear volume, depth, and width are reduced by 68%, 52%, and 57%, respectively. The good lubrication performance is attributed to N,S@CDs excellent dispersion stability, enhanced filling and polishing effects, and complex tribochemical reactions caused by heteroatom doping to form a stable protective film on the worn surface. Furthermore, the as-prepared N,S@CDs exhibit intrinsic fluorescence intensity in PEG200 with the photoluminescence quantum yield (PLQY) of 12.5% and remain fluorescent stable during the long-term friction process, therefore the N,S@CDs have a potential application prospect in non-destructive detection of oil leakage via fluorescence labeling method.

Effect of the Telemedicine Enhanced Asthma Management Through the Emergency Department (TEAM-ED) Program on Asthma Morbidity: A Randomized Controlled Trial.

OBJECTIVE: To test the effectiveness of a telemedicine-based program in reducing asthma morbidity among children who present to the emergency department (ED) for asthma, by facilitating primary care follow-up and promoting delivery of guideline-based care. STUDY DESIGN: We included children (3-12 years of age) with persistent asthma who presented to the ED for asthma, who were then randomly assigned to Telemedicine Enhanced Asthma Management through the Emergency Department (TEAM-ED) or enhanced usual care. TEAM-ED included (1) school-based telemedicine follow-ups, completed by a primary care provider, (2) point-of-care prompting to promote guideline-based care, and 3) an opportunity for 2 additional telemedicine follow-ups. The primary outcome was the mean number of symptom-free days (SFDs) over 2 weeks at 3, 6, 9, and 12 months. RESULTS: We included 373 children from 2016 through 2021 (participation rate 68%; 54% Black, 32% Hispanic, 77% public insurance; mean age, 6.4 years). Demographic characteristics and asthma severity were similar between groups at baseline. Most (91%) TEAM-ED children had ≥1 telemedicine visit and 41% completed 3 visits. At 3 months, caregivers of children in TEAM-ED reported more follow-up visits (66% vs 48%; aOR, 2.07; 95% CI, 1.28-3.33), preventive asthma medication actions (90% vs 79%; aOR, 3.28; 95% CI, 1.56-6.89), and use of a preventive medication (82% vs 69%; aOR, 2.716; 95% CI, 1.45-5.08), compared with enhanced usual care. There was no difference between groups in medication adherence or asthma morbidity. When only prepandemic data were included, there was greater improvement in SFDs over time for children in TEAM-ED vs enhanced usual care. CONCLUSIONS: TEAM-ED significantly improved follow-up and preventive care after an ED visit for asthma. We also saw improved SFDs with prepandemic data. The lack of overall improvement in morbidity and adherence indicates the need for additional ongoing management support. TRIAL REGISTRATION: NCT02752165.

Targeting PDE4B (Phosphodiesterase-4 Subtype B) for Cardioprotection in Acute Myocardial Infarction via Neutrophils and Microcirculation.

BACKGROUND: Timely and complete restoration of blood flow is the most effective intervention for patients with acute myocardial infarction. However, the efficacy is limited by myocardial ischemia-reperfusion (MI/R) injury. PDE4 (phosphodiesterase-4) hydrolyzes intracellular cyclic adenosine monophosphate and it has 4 subtypes A-D. This study aimed to delineate the role of PDE4B (phosphodiesterase-4 subtype B) in MI/R injury. METHODS: Mice were subjected to 30-minute coronary artery ligation, followed by 24-hour reperfusion. Cardiac perfusion was assessed by laser Doppler flow. Vasomotor reactivities were determined in mouse and human coronary (micro-)arteries. RESULTS: Cardiac expression of PDE4B, but not other PDE4 subtypes, was increased in mice following reperfusion. PDE4B was detected primarily in endothelial and myeloid cells of mouse and human hearts. PDE4B deletion strikingly reduced infarct size and improved cardiac function 24-hour or 28-day after MI/R. PDE4B in bone marrow-derived cells promoted MI/R injury and vascular PDE4B further exaggerated this injury. Mechanistically, PDE4B mediated neutrophil-endothelial cell interaction and PKA (protein kinase A)-dependent expression of cell adhesion molecules, neutrophil cardiac infiltration, and release of proinflammatory cytokines. Meanwhile, PDE4B promoted coronary microcirculatory obstruction and vascular permeability in MI/R, without affecting flow restriction-induced thrombosis. PDE4B blockade increased flow-mediated vasodilatation and promoted endothelium-dependent dilatation of coronary arteries in a PKA- and nitric oxide-dependent manner. Furthermore, postischemia administration with piclamilast, a PDE4 pan-inhibitor, improved cardiac microcirculation, suppressed inflammation, and attenuated MI/R injury in mice. Incubation with sera from patients with acute myocardial infarction impaired acetylcholine-induced relaxations in human coronary microarteries, which was abolished by PDE4 inhibition. Similar protection against MI/R-related coronary injury was recapitulated in mice with PDE4B deletion or inhibition, but not with the pure vasodilator, sodium nitroprusside. CONCLUSIONS: PDE4B is critically involved in neutrophil inflammation and microvascular obstruction, leading to MI/R injury. Selective inhibition of PDE4B might protect cardiac function in patients with acute myocardial infarction designated for reperfusion therapy.

A Guanosine-Derived Antitumor Supramolecular Prodrug.

The prodrug strategy for its potential to enhance the pharmacokinetic and/or pharmacodynamic properties of drugs, especially chemotherapeutic agents, has been widely recognized as an important means to improve therapeutic efficiency. Irinotecan's active metabolite, 7-ethyl-10-hydroxycamptothecin (SN38), a borate derivative, was incorporated into a G-quadruplex hydrogel (GB-SN38) by the ingenious and simple approach. Drug release does not depend on carboxylesterase, thus bypassing the side effects caused by ineffective activation, but specifically responds to the ROS-overexpressed tumor microenvironment by oxidative hydrolysis of borate ester that reduces serious systemic toxicity from nonspecific biodistribution of SN38. Comprehensive spectroscopy was used to define the structural and physicochemical characteristics of the drug-loaded hydrogel. The GB-SN38 hydrogel's high level of biosafety and notable tumor-suppressive properties were proven in in vitro and in vivo tests.

Medication fill duration in pediatric hypertension: adherence, blood pressure control, and disparities.

BACKGROUND: Medication nonadherence is a barrier to hypertension control. The Centers for Disease Control and Prevention recommends prescribing 90-day fills for maintenance medications yet antihypertensives are often dispensed as 30-day fills. Our objectives were to examine how often patients receive 30-day supplies of medication despite prescriptions for longer duration and to examine the effect of medication fill duration on adherence and hypertension control. METHODS: We conducted a retrospective cohort study of pediatric patients with hypertension over a 3-year period. For each patient, days prescribed per fill were compared to days dispensed per fill using pharmacy reports and insurance claim data. Proportion of Days Covered (PDC) was calculated to estimate adherence. Hypertension control was determined by provider assessment of control and blood pressure measurement at the final visit. RESULTS: Final cohort included 449 patients. A total of 70% had at least one prescription for ≥ 90 days but only 37% had at least one dispense for ≥ 90 days. There was no difference in the likelihood of being prescribed a 90-day fill by insurance type (public vs. private); however, patients with public insurance were less likely to be dispensed a 90-day fill (OR = 0.068, p < 0.001). Patients who received 90-day fills had better adherence (median PDC 77.5% vs. 58.1%, p < 0.001) and were more likely to have hypertension control based on provider assessment. CONCLUSIONS: Longer fill duration is associated with improved adherence and hypertension control. Patients with public insurance are markedly less likely to be dispensed 90-day fills, a modifiable barrier to improving adherence.

PHPB ameliorates memory deficits and reduces oxidative injury in Alzheimer's disease mouse model by activating Nrf2 signaling pathway.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

Directional Electron Flow in a Selenoviologen-Based Tetracationic Cyclophane for Enhanced Visible-Light-Driven Hydrogen Evolution.

Directional electron flow in the photocatalyst enables efficient charge separation, which is essential for efficient photocatalysis of H2 production. Here, we report a novel class of tetracationic cyclophanes (7) incorporating bipyridine Pt(II) and selenoviologen. X-ray single-crystal structures reveal that 7 not only fixes the distances and spatial positions between its individual units but also exhibits a box-like rigid electron-deficient cavity. Moreover, host-guest recognition phenomena are observed between 7 and ferrocene, forming host-guest complexes with a 1:1 stoichiometry in MeCN. 7 exhibits good redox properties, narrow energy gaps, and strong absorption in the visible range (370-500 nm) due to containing two selenoviologen (SeV2+) units. Meanwhile, the femtosecond transient absorption (fs-TA) reveals that 7 has stabilized dicationic biradical, efficient charge separation, and facilitates directional electron flow to achieve efficient electron transfer due to the formation of rigid cyclophane and electronic architecture. Then, 7 is applied to visible-light-driven hydrogen evolution with high hydrogen production (132 µmol), generation rate (11 µmol/h), turnover number (221), and apparent quantum yield (1.7%), which provides a simplified and efficient photocatalytic strategy for solar energy conversion.

Bilateral Embedded Anchoring via Tailored Polymer Brush for Large-Area Air-processed Blue Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

Photoelectric characteristics of hydrogen-terminated polycrystalline diamond MESFETs.

In the field of diamond MESFETs, this work is what we believe to be the first to investigate the optoelectronic properties of hydrogen-terminated polycrystalline diamond MESFETs under visible and near-UV light irradiation. It is shown that the diamond MESFETs are well suited for weak light detection in the near-ultraviolet region around the wavelength of 368 nm, with a responsivity of 6.14 × 106 A/W and an external quantum efficiency of 2.1 × 107 when the incident light power at 368.7 nm is only 0.75 µW/cm2. For incident light at 275.1 nm, the device's sensitivity and EQE increase as the incident light power increases; at an incident light power of 175.32 µW/cm2 and a VGS of -1 V, the device's sensitivity is 2.9 × 105 A/W and the EQE is 1.3 × 106. For incident light in the wavelength range of 660 nm to 404 nm with an optical power of 70 µW/cm2, the device achieves an average responsivity of 1.21 × 105 A/W. This indicates that hydrogen-terminated polycrystalline diamond MESFETs are suitable for visible and near-UV light detection, especially for weak near-UV light detection. However, the transient response test of the device shows a long relaxation time of about 0.2 s, so it is not yet suitable for high-speed UV communication or detection.

A study of disparities in access to genetic care pre- and post-pandemic.

We aimed to explore the delivery of pediatric genetic care before and during the COVID-19 pandemic and assess if disparities in care existed or emerged. We retrospectively reviewed the electronic medical record for patients 18 years old or younger seen in the Division of Pediatric Genetics between September 2019-March 2020 and April-October 2020. Outcomes included time between referral and new visit, recommendation and completion of genetic testing and/or follow-up visit within 6 months, and telemedicine versus in-person format. Outcomes were compared pre- and post-COVID-19 emergence across ethnicity, race, age, health insurance, socioeconomic status (SES), and use of medical interpretation services. Three hundred thirteen total records were reviewed with comparable demographics between cohorts. Cohort 2 had shorter times between referral and new visit, greater telemedicine utilization, and a greater proportion of testing completed. Younger patients tended to have shorter times between referral and initial visit. In Cohort 1, those with Medicaid insurance or no coverage had longer referral-initial visit times. In Cohort 2, there were differences in testing recommendation based on age. For all outcomes, no disparities were observed across ethnicity, race, SES, or use of medical interpretation services. This study characterizes the impact of the pandemic on pediatric genetics care delivery at our center and may have wider implications.

Simulation-based Ultrasound Curriculum for Novice Clinicians to Assess Neonatal Endotracheal Tube Position.

Background: To evaluate the efficacy of a simulation-based mastery curriculum to train clinicians with limited-to-no sonography experience how to use ultrasound (US) to assess neonatal endotracheal tube (ETT) positioning. Methods: In a single-centered, prospective, educational study, 29 neonatology clinicians participated in a simulation-based mastery curriculum composed of a didactic lecture, followed by a one-on-one simulation session using a newly designed, three-dimensional (3D) printed US phantom model of the neonatal trachea and aorta. After mastery training, clinicians were evaluated with a performance checklist on their skills obtaining US images and assessing ETT positioning in the US phantom model. They also completed pre- and postcurriculum knowledge assessment tests and self-assessment surveys. The data were analyzed using Wilcoxon signed rank tests and repeated measures analysis of variance. Results: The mean checklist score improved significantly during three attempts (mean difference: 2.6552; 95% confidence interval [CI]: 2.2578-3.0525; P < 0.0001). The mean time to perform US decreased significantly from the first to third attempt (mean difference: -1.8276 min; 95% CI: -3.3391 to - 0.3161; P = 0.0196). In addition, there was a significant improvement in median knowledge assessment scores (50% vs. 80%; P < 0.0001) and survey ratings on knowledge and self-efficacy (P < 0.0001). Conclusion: Clinicians with limited-to-no sonography experience demonstrated improved knowledge and skill acquisition in using US to assess ETT positioning through simulation-based mastery training. The use of 3D modeling enhances simulation experiences and optimizes the quality of training during limited opportunities to achieve procedural competency in a controlled environment before further application into the clinical setting.

Subendocardial Involvement as an Underrecognized Cardiac MRI Phenotype in Myocarditis.

Background Subendocardial late gadolinium enhancement (LGE) detected with cardiac MRI in myocarditis represents a diagnostic dilemma, since it may resemble myocardial ischemia. Purpose To explore and compare the histopathologic characteristics and clinical features and outcomes in patients with myocarditis with and without subendocardial involvement at cardiac MRI. Materials and Methods This retrospective study evaluated 39 patients with myocarditis pathologically proven by means of either endomyocardial biopsy or explant pathologic findings between 2015 and 2020. Patients were divided into two groups according to cardiac MRI phenotype: 18 with subendocardial involvement (mean age ± standard deviation, 40 years ± 17; 10 women) and 21 with no subendocardial involvement (mean age, 35 years ± 11; six women). The median follow-up period was 784 days (interquartile range [IQR], 90-1123 days). The Student t test, Mann-Whitney U test, and univariable Cox regression were used for statistical analyses. Results In the 18 patients with subendocardial involvement, 12 (67%) had lymphocytic myocarditis and six (33%) had giant cell myocarditis. Patients with subendocardial involvement compared with those without subendocardial involvement had lower left ventricular ejection fraction (mean ± standard deviation, 27% ± 11 vs 41% ± 19; P = .004), larger LGE extent (median, 13% [IQR, 10%-22%] vs 5% [IQR, 2%-17%]; P < .001), higher rates of cardiac death or transplant (eight of 18 patients [44%] vs one of 21 patients [4.8%]; P = .006), higher probability of giant cell myocarditis (six of 18 [33%] vs one of 21 [4.8%]; P = .02), and more major adverse cardiovascular events (MACE) (15 of 18 [83%] vs seven of 21 [33%]; P = .002). In a subgroup of patients with comparable LGE extent (median, 15% vs 16%; P = .40) and left ventricular ejection fraction (median, 27% vs 31%; P = .26), the prognostic difference in terms of MACE remained (15 of 17 patients [88%] vs five of 10 [50%]; P = .02). Conclusion Subendocardial involvement detected with cardiac MRI in myocarditis indicated more severe clinical features, including a higher frequency of severe lymphocytic myocarditis or giant cell myocarditis and worse prognosis. © RSNA, 2021 See also the editorial by de Roos in this issue.

Identification of pathology-confirmed vulnerable atherosclerotic lesions by coronary computed tomography angiography using radiomics analysis.

OBJECTIVES: To explore whether radiomics-based machine learning (ML) models could outperform conventional diagnostic methods at identifying vulnerable lesions on coronary computed tomographic angiography (CCTA). METHODS: In this retrospective study, 36 heart transplant recipients with coronary heart disease (CAD) and end-stage heart failure were included. Pathological cross-section samples of 350 plaques were collected and coregistered to patients' preoperative CCTA images. A total of 1184 radiomic features were extracted from CCTA images. Through feature selection and stratified fivefold cross-validation, we derived eight radiomics-based ML models for lesion vulnerability prediction. An independent set of 196 plaques from another 8 CAD patients who underwent heart transplants was collected to validate radiomics-based ML models' diagnostic accuracy against conventional CCTA feature-based diagnosis (presence of at least 2 high-risk plaque features). The performance of the prediction models was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI). RESULTS: The training group used to develop radiomics-based ML models contained 200/350 (57.1%) vulnerable plaques and the external validation group was composed of 67.3% (132/196) vulnerable plaques. The radiomics-based ML model based on eight radiomic features showed excellent cross-validation diagnostic accuracy (AUC: 0.900 ± 0.033). In the validation group, diagnosis based on conventional CCTA features demonstrated moderate performance (AUC: 0.656 [95% CI: 0.593 -0.718]), while the radiomics-based ML model showed higher diagnostic ability (0.782 [95% CI: 0.710 -0.846]). CONCLUSIONS: Radiomics-based ML models showed better diagnostic ability than the conventional CCTA features at assessing coronary plaque vulnerability. KEY POINTS: • CCTA has great potential in the diagnosis of vulnerable coronary artery lesions. • Radiomics model built through CCTA could discriminate coronary vulnerable lesions in good diagnostic ability. • Radiomics model could improve the ability of vulnerability diagnosis against traditional CCTA method, sensitivity especially.

Changes in Glucose Breath Test in Cystic Fibrosis Patients Treated With 1 Month of Lumacaftor/Ivacaftor.

BACKGROUND: Alteration of the airway microbiota is a hallmark of cystic fibrosis (CF) pulmonary disease. Dysfunction of cystic fibrosis transmembrane regulator (CFTR) in the intestine also promotes changes in local microbiota such as small intestinal bacterial overgrowth (SIBO), which is common in CF. We evaluated whether therapy with the CFTR modulator combination lumacaftor/ivacaftor (luma/iva) has a beneficial impact on SIBO as measured by breath testing (BT). METHODS: A multicenter longitudinal study of CFTR-dependent disease profiling (NCT02477319) included a prospective evaluation for SIBO by BT. Tidal breath samples were collected after fasting and 15, 30, 45, 60, 90, and 120 minutes after ingestion of glucose, before and 1 month after subjects initiated luma + iva. RESULTS: Forty-two subjects enrolled in the sub-study (mean age = 23.3 years; 51% female; 9.5% Latinx); 38 completed a hydrogen BT at both time points, of which 73.7% had a positive BT before luma/iva (baseline) and 65.8% had a positive test after luma/iva ( P = 0.44); shifts from negative to positive were also seen. Use of azithromycin (63.1%) and inhaled antibiotics (60.5%) were not associated with positive BT. Acid-blocking medications were taken by 73% of those with a negative BT at baseline and by 35% with a positive baseline BT ( P = 0.04). CONCLUSION: We found a high rate of positive hydrogen breath tests in individuals with CF, confirming that SIBO is common. One month of luma/iva did not significantly change the proportion of those with positive breath hydrogen measurements.

Is cell regeneration and infiltration a double edged sword for porcine aortic valve deterioration? A large cohort of histopathological analysis.

BACKGROUND AND OBJECTIVE: Bioprostheses are the most common prostheses used for valve replacement in the Western medicine. The major flaw of bioprostheses is the occurrence of structural valve deterioration (SVD). This study aimed to assess the pathological features of porcine aortic valve (PAV)-SVD based on histomorphological and immunopathological characteristics of a large cohort of patients. METHODS: Histopathological data of 109 cases with resected PAV were collected. The type and amount of infiltrated cells were evaluated in the different types of bioprosthetic SVD by immunohistochemical staining. RESULTS: The most common cause of SVD was calcification, leaflet tear, and dehiscence (23.9%, 19.3%, and 18.3%, respectively). Immunohistochemical staining demonstrated that macrophages were infiltrated in the calcified, lacerated and dehiscence PAV, in which both M1 and M2 macrophages were existed in the calcified PAV. Importantly, the higher content of M1 macrophages and less content of M2 macrophages were found in the lacerated and dehiscence PAV, and MMP-1 expression was mainly found in the lacerated PAV. The endothelialization rate of leaflet dehiscence was higher than that of calcified and lacerated leaflets. A large number of CD31+/CD11b+ cells was aggregated in the spongy layer in the lacerated and dehiscence PAV. CONCLUSION: Cell regeneration and infiltration is a double edged sword for the PAV deterioration. Macrophage infiltration is involved in the different types of SVD, while only MMP-1 expression is involved in lacerated leaflets. The macrophage subtype of circulating angiogenic cells in dehiscence and tear PAV could be identified, which could reserve macrophages in the PAV-SVD.

Effect of the School-Based Asthma Care for Teens (SB-ACT) program on asthma morbidity: a 3-arm randomized controlled trial.

Urban adolescents with asthma often have inadequate preventive care. We tested the effectiveness of the School-Based Asthma Care for Teens (SB-ACT) program on asthma morbidity and preventive medication adherence.Methods:Subjects/Setting- 12-16yr olds with persistent asthma in Rochester, NY schools. Design- 3-group randomized trial (2014-2019). SB-ACT Intervention- Two core components: 1) Directly observed therapy (DOT) of preventive asthma medications, provided in school for at least 6-8 weeks for the teen to learn proper technique and experience the benefits of daily preventive therapy; 2) 4-6 weeks later, 3 sessions of motivational interviewing (MI) to discuss potential benefits from DOT and enhance motivation to take medication independently. We included 2 comparison groups: 1) DOT-only for 6-8wks, and 2) asthma education (AE) attention control. Masked follow-up assessments were conducted at 3, 5, and 7mos. Outcomes- Mean number of symptom-free days (SFDs)/2 weeks and medication adherence. Analyses- Modified intention-to-treat repeated measures analysis.Results: We enrolled 430 teens (56% Black, 32% Hispanic, 85% Medicaid). There were no group differences at baseline. We found no difference in SFDs at any follow-up timepoint. More teens in the SB-ACT and DOT-only groups reported having a preventive asthma medication at each follow-up (p<.001), and almost daily adherence at 3 and 5-months (p<.001, p=.003) compared to AE. By 7 months there were no significant differences between groups in adherence (p=.49).Conclusion: SB-ACT improved preventive medication availability and short-term adherence but did not impact asthma symptoms. Further work is needed to create developmentally appropriate and effective interventions for this group.

Bioprosthetic mitral valve stenosis secondary to hypereosinophilic syndrome.

Herein we present a case of hypereosinophilic syndrome (HES) with recurrent involvement of mitral valve. The patient developed mitral regurgitation secondary to HES. Surgical mitral valve replacement was performed successfully. The prosthetic valve dysfunction occurred 3 years later and echocardiography showed severe mitral valve stenosis. Extensive mural thrombi were discovered on both sides of the stenotic valve with eosinophilic infiltration. The patient underwent a repeated mechanical prosthesis replacement and recovered uneventfully.

The Effect of a Short Course of Tocolytic Indomethacin on Urinary Biomarkers in Premature Infants.

OBJECTIVE: The aim of this study was to determine the effects of a 2-day prenatal course of indomethacin on the premature kidney as reflected by serum creatinine and urinary biomarkers. STUDY DESIGN: Urine of infants ≤32 weeks was collected for the first 14 days and analyzed for cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, ß2 microglobulin, epidermal growth factor, uromodulin, and microalbumin. Bivariate analysis compared serum creatinine and biomarkers of exposed (INDO) and unexposed (CONT) subjects. RESULTS: Fifty-seven infants (35 CONT and 22 INDO) were studied. The cohorts were similar in gestational age, birthweight, race, gender, nephrotoxic medication exposure, and Apgar's scores. CONT had more dopamine exposure and included more pre-eclamptic mothers (p = 0.005). No difference in creatinine-based acute kidney injury or the log transformed mean, maximum, and minimum values of urinary biomarkers was detected. CONCLUSION: Our findings suggest that a short course of tocolytic indomethacin does not result in neonatal acute kidney injury. KEY POINTS: · A short prenatal course of indomethacin does not result in neonatal acute kidney injury (AKI).. · Urinary EGF might have a promising role as a more sensitive biomarker for early detection of AKI in premature infants..