Percutaneous Retrieval of an Embolized Transcatheter Mitral Valve Repair Clip Causing ST-Segment Elevation Myocardial Infarction.

Mitral valve repair clip detachment and embolization is a rare phenomenon, with few reported cases. We describe a case of subacute transcatheter mitral valve repair clip embolization presenting as an inferior ST-segment elevation myocardial infarction, with subsequent successful percutaneous device retrieval. (Level of Difficulty: Intermediate.).

Volatile compounds analysis and biodegradation strategy of beany flavor in pea protein.

Pea protein has attracted the attention of consumers owing to its non-GMO, hypoallergenic, and high nutritional value, however, the beany flavor limits its applicability. Hence, GC-MS and GC-IMS were applied to assess the influence of Saccharomyces cerevisiae and Lactobacillus plantarum on the beany flavor of pea protein. Specifically, 51 and 65 volatiles were detected in pea proteins via GC-MS and GC-IMS, respectively. Odor activity value results showed that the components contributing to the beany flavor mainly included: 2-pentylfuran, (E, E)-2,4-decadienal, hexanal, nonanal, (E, E)-2,4-nonadienal, octanal, (E)-2-nonenal and (E)-2-octenal. S. cerevisiae and L. plantarum fermentation could remove 79.65% and 78.94% of the major beany flavor aldehydes from pea protein, respectively. Principal component analysis and hierarchical cluster analysis indicated that the unfermented and fermented pea protein samples can be distinguished by volatile compounds. These results provide a reference for the removal of beany off-flavors from pea proteins by fermentation.

UNOS policy change benefits high-priority patients without harming those at low priority.

The heart transplantation policy change (PC) has improved outcomes in high-acuity (Old 1A, New 1-3) patients, but the effect on low-priority (Old 1B/2, New 4-6) patients is unknown. We sought to determine if low-priority patient outcomes were compromised by benefits to high-priority patients by evaluating for interaction between PC and priority status (PS). We included adult first-time heart transplant candidates and recipients from the UNOS registry during a 19-month period before and after the PC. We compared clinical characteristics and performed competing risks and survival analyses stratified by PC and PS. There was a dependence of PC and PS on waitlist death/deterioration with an interaction sub-distribution hazard ratio (adjusted sdHR) of 0.59 (0.45-0.78), p-value < .001. There was a trend toward a benefit of PC on waitlist death/deterioration (adjusted sdHR: 0.86 [0.73-1.01]; p = .07) and an increase in heart transplantation (adjusted sdHR: 1.08 [1.02-1.14], p = .007) for low-priority patients. There was no difference in 1-year post-transplant survival (log-rank p = .22) when stratifying by PC and PS. PC did not negatively affect waitlisted or transplanted low-priority patients. High-priority, post-PC patients had a targeted reduction in waitlist death/deterioration and did not come at the expense of worse post-transplant survival.

Association of pepper intake with all-cause and specific cause mortality - A systematic review and meta-analysis.

OBJECTIVE: To conduct a comprehensive systematic review and meta-analysis to compare mortality and other clinical outcomes associated with chili pepper (CP) consumption versus no/rare consumption of CP. METHODS: A comprehensive search was performed using Ovid, Cochrane, Medline, EMBASE, and Scopus from inception till January 16, 2020. Observational studies and randomized controlled trials were included, while pediatric/animal studies, letters/case reports, reviews, abstracts, and book chapters were excluded. All-cause mortality was studied as the primary outcome. Cardiovascular mortality, cancer-related deaths and cerebrovascular accidents were studied as secondary outcomes. RESULTS: From 4729 studies, four studies met the inclusion criteria. Random effects pooled analysis showed that all-cause mortality among CP consumers was lower, compared to rare/non-consumers, with a hazard ratio (HR) of 0.87 [95% CI: 0.85-0.90; p<0.0001; I 2=1%]. HR for cardiovascular mortality was 0.83 [95% CI: 0.74-0.95; p = 0.005, I 2=66%] and for cancer-related mortality as 0.92 [95% CI: 0.87-0.97; p = 0.001; I 2=0%]. However, the HR for CVA was 0.78 [95% CI: 0.56-1.09; p = 0.26; I2 =60%]. The mode and amount of CP consumption varied across the studies, and data were insufficient to design an optimal strategy guiding its intake. CONCLUSION: Regular CP consumption was associated with significantly lower all-cause, cardiovascular, and cancer-related mortalities. However, based on current literature, it is difficult to derive a standardized approach to guide the optimal mode and amount of CP consumption. This warrants well-designed prospective studies to further investigate the potential health benefits of CP consumption.

A colorimetric sensor array for rapid discrimination of edible oil species based on a halogen ion exchange reaction between CsPbBr3 and iodide.

Peroxides in edible oils, whose amounts are measured using the peroxide value, are closely related to human health. Long-term consumption of edible oils with high peroxide values can lead to a variety of human diseases, which highlights the significance of examining oil types and their corresponding peroxide values. For identifying a wide range of edible oils, we established a colorimetric sensor array based on the halogen ion exchange between CsPbBr3 and two iodides (octadecylammonium iodide (ODAI) and ZnI2). Different kinds of edible oils contain distinct peroxidic substances that have the distinct ability to oxidize iodides. After specific types of edible oils react with excess iodides (ODAI and ZnI2), different amounts of residual iodides are left for further halogen exchange with CsPbBr3, resulting in various colorimetric responses, measured in RGB (red/green/blue) values, under fluorescent light. Based on RGB pattern analysis as fingerprints using two anion exchangers (ODAI and ZnI2), our proposed colorimetric sensor array was proved by linear discriminant analysis (LDA) to have an ability to accurately distinguish edible oils at a minimal volumetric concentration of 6.67% in seven real samples.

Noninvasive methods to reduce cardiac complications postheart transplant.

PURPOSE OF REVIEW: Long-term success of heart transplantation is limited by allograft rejection and cardiac allograft vasculopathy (CAV). Classic management has relied on frequent invasive testing to screen for early features of rejection and CAV to allow for early treatment. In this review, we discuss new developments in the screening and prevention of allograft rejection and CAV. RECENT FINDINGS: Newer noninvasive screening techniques show excellent sensitivity and specificity for the detection of clinically significant rejection. New biomarkers and treatment targets continue to be identified and await further studies regarding their utility in preventing allograft vasculopathy. SUMMARY: Noninvasive imaging and biomarker testing continue to show promise as alternatives to invasive testing for allograft rejection. Continued validation of their effectiveness may lead to new surveillance protocols with reduced frequency of invasive testing. Furthermore, these noninvasive methods will allow for more personalized strategies to reduce the complications of long-term immunosuppression whereas continuing the decline in the overall rate of allograft rejection.

Prognostic implications and outcomes of cardiac arrest among contemporary patients with STEMI treated with PCI.

BACKGROUND: Cardiac arrest (CA) complicating ST-elevation myocardial infarction (STEMI) is associated with a disproportionately higher risk of mortality. We described the contemporary presentation, management, and outcomes of CA patients in the era of primary percutaneous coronary intervention (PCI). METHODS: We reviewed 1,272 consecutive STEMI patients who underwent PCI between 1/1/2011-12/31/2016 and compared characteristics and outcomes between non-CA (N = 1,124) and CA patients (N = 148), defined per NCDR definitions as pulseless arrest requiring cardiopulmonary resuscitation and/or defibrillation within 24-hr of PCI. RESULTS: Male gender, cerebrovascular disease, chronic kidney disease, in-hospital STEMI, left main or left anterior descending culprit vessel, and initial TIMI 0 or 1 flow were independent predictors for CA. CA patients had longer door-to-balloon-time (106 [83,139] vs. 97 [74,121] minutes, p = 0.003) and greater incidence of cardiogenic shock (48.0% vs. 5.9%, p < 0.001), major bleeding (25.0% vs. 9.4%, p < 0.001), and 30-day mortality (16.2% vs. 4.1%, p < 0.001). Risk score for 30-day mortality based on presenting characteristics provided excellent prognostic accuracy (area under the curve = 0.902). However, over long-term follow-up of 4.5 ± 2.4 years among hospital survivors, CA did not portend any additional mortality risk (HR: 1.01, 95% CI: 0.56-1.82, p = 0.97). CONCLUSIONS: In a contemporary cohort of STEMI patients undergoing primary PCI, CA occurs in >10% of patients and is an important mechanism of mortality in patients with in-hospital STEMI. While CA is associated with adverse outcomes, it carries no additional risk of long-term mortality among survivors highlighting the need for strategies to improve the in-hospital care of STEMI patients with CA.

Effect of High-Density Lipoprotein Cholesterol Levels on Overall Survival and Major Adverse Cardiovascular and Cerebrovascular Events.

Several studies designed to augment high density lipoprotein (HDL) levels have so far been unsuccessful in reducing rates of major adverse cardiovascular and cerebrovascular events (MACCE). In this study, we report the effect of HDL-C levels on overall survival outcomes and rates of MACCE following percutaneous coronary intervention (PCI). We reviewed patients who underwent PCI at the Cleveland Clinic from 2005 to 2017 and followed them through the end of 2018. Restricted cubic splines incorporated into Cox proportional hazard regression models were used to assess the outcomes. The HDL-C level associated with the lowest mortality was used as a reference value.15,633 patients underwent PCI during the study period, of which 70% were male, 81% were white, and 73% were on statins. The mean age at the time of procedure was 65.8 ± 11.8 years. After adjusting for demographics, co-morbidities, lipid profile, statin use, and date of procedure, our model demonstrated a U-shaped association between HDL-C and overall mortality, with HDL-C levels of 30-50 mg/dl associated with the most favorable outcomes, and HDL-C levels < 30 mg/dl or > 50 mg/dl associated with worse outcomes. A sensitivity analysis in men yielded a similar U-shaped association. In conclusion, our study shows that both low and high levels of HDL-C are associated with worse overall survival, with no effect on rates of MACCE in PCI patients. Further studies are required to understand the mechanism of this association between elevated HDL-C levels with increased overall mortality in patients with atherosclerotic cardiovascular disease (ASCVD).

Implementation of a Comprehensive ST-Elevation Myocardial Infarction Protocol Improves Mortality Among Patients With ST-Elevation Myocardial Infarction and Cardiogenic Shock.

Mortality in patients with STEMI-associated cardiogenic shock (CS) is increasing. Whether a comprehensive ST-elevation myocardial infarction (STEMI) protocol (CSP) can improve their care delivery and mortality is unknown. We evaluated the impact of a CSP on incidence and outcomes in patients with STEMI-associated CS. We implemented a 4-step CSP including: (1) Emergency Department catheterization lab activation; (2) STEMI Safe Handoff Checklist; (3) immediate catheterization lab transfer; (4) and radial-first percutaneous coronary intervention (PCI). We studied 1,272 consecutive STEMI patients who underwent PCI and assessed for CS incidence per National Cardiovascular Data Registry definitions within 24-hours of PCI, care delivery, and mortality before (January 1, 2011, to July 14, 2014; n = 723) and after (July 15, 2014, to December 31, 2016; n = 549) CSP implementation. Following CSP implementation, CS incidence was reduced (13.0% vs 7.8%, p = 0.003). Of 137 CS patients, 43 (31.4%) were in the CSP group. CSP patients had greater IABP-Shock II risk scores (1.9 ± 1.8 vs 2.8 ± 2.2, p = 0.014) with otherwise similar hemodynamic and baseline characteristics, cardiac arrest incidence, and mechanical circulatory support use. Administration of guideline-directed medical therapy was similar (89.4% vs 97.7%, p = 0.172) with significant improvements in trans-radial PCI (9.6% vs 44.2%, p < 0.001) and door-to-balloon time (129.0 [89:160] vs 95.0 [81:116] minutes, p = 0.001) in the CSP group, translating to improvements in infarct size (CK-MB 220.9 ± 156.0 vs 151.5 ± 98.5 ng/ml, p = 0.005), ejection fraction (40.8 ± 14.5% vs 46.7 ± 14.6%, p = 0.037), and in-hospital mortality (30.9% vs 14.0%, p = 0.037). In conclusion, CSP implementation was associated with improvements in CS incidence, infarct size, ejection fraction, and in-hospital mortality in patients with STEMI-associated CS. This strategy offers a potential solution to bridging the historically elusive gap in their care.

Combining solid dispersion-based spray drying with cyclodextrin to improve the functionality and mitigate the beany odor of pea protein isolate.

The beany flavor of pea protein limits its application in the food industry. This study aimed at addressing this problem by combining the advantages of solid-based spray drying technique and the ability of cyclodextrins (CD) to entrap volatiles. Pea protein isolates (PPI) was extracted by alkaline extraction-isoelectric precipitation, followed by co-spray drying with CD. The resulted PPI-CD showed no major structure changes. HS-SPME-GC-MS coupled to untargeted metabolomics successfully identified 23 aroma compounds that represent the different odorants among PPI-control, physically mixed PPI-CD, and co-spray dried PPI-CD samples. Heat map analysis also showed a remarkable beany odor mitigation effect upon the addition of CD, which was further proved to be due to CD entrapping aroma compounds during spray drying. In the meantime, the functional attributes of PPI-CD were not adversely impacted by the addition of CD.

Radiation induced cardiovascular disease: An odyssey of bedside-bench-bedside approach.

The journey to Mars will be an ambitious, yet arduous task as it will entail culmination of all the information we have gathered over many decades. While the mission is of utmost importance, preservation of astronaut's well-being is paramount also. To that end, mitigation of radiation risk especially afflicting cardiovascular disease (CVD) is of great interest and challenge. Current data from astronauts on low earth orbit and Apollo missions provides insight on the risk of CVD from radiation exposure. However, data is limited given the small cohort size of astronauts who embarked on just nine prolonged missions. Therefore, a cerebral approach to understanding and mitigating risks are essential. This paper discusses the need for a predictive preclinical model to help understand and mitigate the effects of radiation on astronauts. We will discuss strengths and limitations of preclinical models and the methods of validating and constructing a model to predict human clinical outcomes. Our bedside-bench-bedside approach focuses on adapting the preclinical model through common investigative tools used between humans and animals. The result will be an optimization of preclinical model to a point of being a surrogate clinical model capable of predicting CVD outcomes in astronauts exposed to radiation.

Improving the Thermostability and Catalytic Efficiency of the d-Psicose 3-Epimerase from Clostridium bolteae ATCC BAA-613 Using Site-Directed Mutagenesis.

d-Psicose is a highly valuable rare sugar because of its excellent physiological properties and commercial potential. d-Psicose 3-epimerase (DPEase) is the key enzyme catalyzing the isomerization of d-fructose to d-psicose. However, the poor thermostability and low catalytic efficiency are serious constraints on industrial application. To address these issues, site-directed mutagenesis of Tyr68 and Gly109 of the Clostridium bolteae DPEase was performed. Compared with the wild-type enzyme, the Y68I variant displayed the highest substrate-binding affinity and catalytic efficiency, and the G109P variant showed the highest thermostability. Furthermore, the double-site Y68I/G109P variant was generated and exhibited excellent enzyme characteristics. The Km value decreased by 17.9%; the kcat/Km increased by 1.2-fold; the t1/2 increased from 156 to 260 min; and the melting temperature (Tm) increased by 2.4 °C. Moreover, Co(2+) enhanced the thermostability significantly, including the t1/2 and Tm values. All of these indicated that the Y68I/G109P variant would be appropriate for the industrial production of d-psicose.

Taste Masking of Griseofulvin and Caffeine Anhydrous Using Kleptose Linecaps DE17 by Hot Melt Extrusion.

The objective of this project was to investigate the potential of Kleptose Linecaps DE17 (KLD) in masking the unpleasant/bitter taste of therapeutic agents by hot melt extrusion (HME). Griseofulvin (GRI) and caffeine anhydrous (CA) were used as a bitter active pharmaceutical ingredient (API) model drugs. Thermogravimetric studies confirmed the stability of GRI, CA, and KLD at the employed extrusion temperatures. The differential scanning calorimetry (DSC) studies revealed a characteristic melting endotherm of GRI at 218-220°C and CA at 230-232°C in the physical mixtures as well as in all extrudates over the period of study, indicating the crystalline nature of drug. HME of KLD was achieved only in the presence of plasticizer. Among the several plasticizers investigated, xylitol showed improved processability of KLD at 15% w/w concentration. Dissolution studies of HME extrudates using simulated salivary medium exhibited ∼threefold less release compared to physical mixture at the end of 5 min (the lesser drug release, better the taste masking efficiency). Furthermore, the results from the sensory evaluation of products in human panel demonstrated strong bitter taste in the case of physical mixture compared to the HME formulation, suggesting the potential of Kleptose Linecaps DE17 as taste masking polymer in melt extruded form.

Engineering of Alicyclobacillus hesperidum L-arabinose isomerase for improved catalytic activity and reduced pH optimum using random and site-directed mutagenesis.

A mutation, D478N, was obtained by an error-prone polymerase chain reaction using the L-arabinose isomerase (L-AI) gene from Alicyclobacillus hesperidum URH17-3-68 as the template. The mutated isomerase showed higher activity for D-galactose isomerization. The mutation site obtained from random mutagenesis was then introduced as a single-site mutation using site-directed mutagenesis. Single-site variants, D478N, D478Q, D478A, D478K, and D478R, were constructed. The optimum temperatures were all higher than 60 °C. D478A, D478N, and D478Q retained more than 80 % of the maximum relative activity of the wild-type L-AI at 75 °C. With the exception of the D478A variant, all variants showed decreased optimum pH values in the acidic range (6.0-6.5). All of the variant L-AIs could be significantly activated by the addition of Co(2+) and Mn(2+). D478N and D478Q showed higher catalytic efficiencies (k cat/K m) toward D-galactose than that of wild-type L-AI. In addition, the D478N and D478Q variants exhibited a much higher conversion ratio of D-galactose to D-tagatose at 6.0 than the wild-type L-AI. According to the molecular model, residue D478 was located on the surface of the enzyme and distant from the active site. It was supposed that the charged state of residue 478 may influence the optimum pH for substrate binding or isomerization.

Characterization of a metal-dependent D-psicose 3-epimerase from a novel strain, Desmospora sp. 8437.

The rare sugar d-psicose is an ideal sucrose substitute for food products, due to having 70% of the relative sweetness but 0.3% of the energy of sucrose. It also shows important physiological functions. d-Tagatose 3-epimerase (DTEase) family enzymes can produce d-psicose from d-fructose. In this paper, a new member of the DTEase family of enzymes was characterized from Desmospora sp. 8437 (GenBank accession no. WP_009711885 ) and was named Desmospora sp. d-psicose 3-epimerase (DPEase) due to its highest substrate specificity toward d-psicose. Desmospora sp. DPEase was strictly metal-dependent and displayed maximum activity in the presence of Co(2+). The optimum pH and temperature were 7.5 and 60 °C, respectively. The enzyme was relatively thermostable below 50 °C, but easily lost initial activity when preincubated at 60 °C. The thermostability property was almost not affected by the addition of Co(2+). Desmospora sp. DPEase had relatively high catalysis efficiency for the substrates d-psicose and d-fructose, which were measured to be 327 and 116 mM(-1) min(-1), respectively. The equilibrium ratio between d-psicose and d-fructose of Desmospora sp. DPEase was 30:70. The enzyme could produce 142.5 g/L d-psicose from 500 g/L of d-fructose, suggesting that the enzyme is a potential d-psicose producer for industrial production.

Stability of benzocaine formulated in commercial oral disintegrating tablet platforms.

Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions.

Characterization of a D-psicose-producing enzyme, D-psicose 3-epimerase, from Clostridium sp.

The gene coding for D-psicose 3-epimerase (DPEase) from Clostridium sp. BNL1100 was cloned and expressed in Escherichia coli. The recombinant enzyme was purified by Ni-affinity chromatography. It was a metal-dependent enzyme and required Co(2+) as optimum cofactor. It displayed catalytic activity maximally at pH 8.0 and 65 °C (as measured over 5 min). The optimum substrate was D-psicose, and the K m, turnover number (k cat), and catalytic efficiency (k cat/K m) for D-psicose were 227 mM, 32,185 min(-1), and 141 min(-1 )mM(-1), respectively. At pH 8.0 and 55 °C, 120 g D-psicose l(-1) was produced from 500 g D-fructose l(-1) after 5 h.

Characterization of a novel metal-dependent D-psicose 3-epimerase from Clostridium scindens 35704.

The noncharacterized protein CLOSCI_02528 from Clostridium scindens ATCC 35704 was characterized as D-psicose 3-epimerase. The enzyme showed maximum activity at pH 7.5 and 60°C. The half-life of the enzyme at 50°C was 108 min, suggesting the enzyme was relatively thermostable. It was strictly metal-dependent and required Mn²âº as optimum cofactor for activity. In addition, Mn²âº improved the structural stability during both heat- and urea-induced unfolding. Using circular dichroism measurements, the apparent melting temperature (T m) and the urea midtransition concentration (C m) of metal-free enzyme were 64.4°C and 2.68 M. By comparison, the Mn²âº-bound enzyme showed higher T m and C m with 67.3°C and 5.09 M. The Michaelis-Menten constant (K m), turnover number (k cat), and catalytic efficiency (k cat/K m) values for substrate D-psicose were estimated to be 28.3 mM, 1826.8 s⁻¹, and 64.5 mM⁻¹ s⁻¹, respectively. The enzyme could effectively produce D-psicose from D-fructose with the turnover ratio of 28%.