Ambulatory Electrocardiography Monitoring for Early Discharge After Minimally Invasive Valve Surgery.

INTRODUCTION: We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS). MATERIALS AND METHODS: We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia. RESULTS: Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662). CONCLUSIONS: Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality.

Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.

A temperature-sensitive, high-adhesion medical tape: a comparative, single-blind clinical trial.

OBJECTIVE: Medical adhesives are used to secure wound care dressings and other critical devices to the skin. While high peel-strength adhesives provide more secure skin attachment, they are difficult to remove from the skin and are correlated with medical adhesive-related skin injuries (MARSI), including skin tears, and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to dressing or device dislodgement and further medical complications. METHOD: This paper reports on the clinical testing of a new, high-adhesion medical tape, ThermoTape (University of Washington, US), designed for low skin trauma upon release. ThermoTape was benchmarked with Tegaderm (3M, US) and Kind Removal Tape (KRT) (3M, US). All three tapes were applied to both the left and right forearm of healthy volunteers and were removed 24 hours later-the right arm without applying heat and the left arm by applying a heat pack for 30 seconds before removal. Tape wear, self-reported pain (0-10 scale) and skin redness 15 minutes after removal were recorded. RESULTS: This was a 53-subject comparative, single-blind clinical trial. There were clinically and statistically significant results supporting reduced pain during removal of ThermoTape with warming, with an average 58% decrease in pain, paired with a statistically significant 45% reduction in skin redness (p<0.01 for both values). In contrast, there were statistically insignificant differences in pain and redness for removal of Tegaderm and KRT with warming. ThermoTape after warming, in comparison with Tegaderm without warming, produced a reduced pain score of >1 on the 0-10 Wong-Baker/Face pain scale, which was statistically significant (p<0.01). CONCLUSION: These results provide compelling evidence that warming ThermoTape prior to removal can reduce pain and injury when compared with standard medical tapes. This could allow for stronger attachment of wound care dressings and critical medical devices while reducing cases of MARSI.

Utilizing ambulatory electrocardiogram monitoring to reduce conduction related death after transcatheter aortic valve replacement.

OBJECTIVE: The purpose of this study is to assess the utility of ambulatory cardiac monitoring (ACM) in detecting delayed advanced conduction abnormalities (DACA) and associated 30-day mortality. BACKGROUND: DACA are well-known complications of TAVR and may be associated with post-discharge mortality within 30-days. METHODS: Between October 2019 and October 2020, TAVR patients who were discharged home without a permanent pacemaker (PPM) were monitored with an ACM device for 14-days. The incidence of DACA at follow up, mortality and readmission within 30-days were investigated. The risk of DACA was assessed in three patient categories based on a composite of their 12-lead electrocardiogram (ECG) data. Group I: Normal pre-TAVR, periprocedural, and discharge ECGs. Group II: Normal pre-TAVR and abnormal subsequent ECGs. Group III. Abnormal baseline and abnormal subsequent ECGs. RESULTS: Among 340 TAVR patients, 248 were discharged home with an ACM device. The overall incidence of DACA was 7% (n = 17), of whom 4% (n = 10) required a PPM. Mortality and readmission between discharge and 30 days was 0% and 8.3%, respectively. Stratification of patients identified 96 (38.7%) patients in Group I: 50 (20%) in Group II, and 102 (41%) in Group III. The incidence of DACA requiring a PPM was 0% in Group I, 4% (n = 2) in Group II, and 8.5% (n = 8) in Group III (p < 0.004). CONCLUSIONS: In TAVR patients who were discharged home with ACM, none died between discharge and 30-days. For those with normal baseline, perioperative and discharge ECG, there were no events of DACA at 14-days.

Outcomes of minimally invasive aortic valve replacement in patients with obese body mass indices.

BACKGROUND: Minimally invasive heart valve surgery has previously been shown to be safe and feasible in obese patients. Within this population, we investigated the effect of obesity class on the patient outcomes of minimally invasive aortic valve replacement (mini-AVR). METHODS: A single-center retrospective cohort study of consecutive patients with obese body mass indices (BMIs) who underwent mini-AVR between 2012 and 2020. Patients were stratified into three groups according to Centers for Disease Control and Prevention adult obesity classifications: Class I (BMI: 30.0-<35.0), Class II (BMI: 35.0-<40.0), and Class III (BMI ≥ 40.0). The primary outcomes were postoperative length of stay (LOS), 30-day mortality, and direct cost. RESULTS: Among 206 obese patients who underwent mini-AVR, LOS (Class I 5 [3-7] vs. Class II 6 [5-7] vs. Class III 6 [5-7] days; p = .056), postoperative 30-day mortality (Class I 2.44% [n = 3] vs. Class II 4.44% [n = 2] vs. Class III 7.89% [n = 3]; p = .200), and costs (Class I $24,118 [$20,237-$29.591] vs. Class II $22,215 [$18,492-$28,975] vs. Class III $24,810 [$20,245-$32,942] USD; p = .683) did not differ between obesity class cohorts. CONCLUSIONS: Mini-AVR is safe and feasible to perform for obese patients regardless of their obesity class. Patients with obesity should be afforded the option of minimally invasive aortic valve surgery regardless of their obesity class.

Prototype Development of a Temperature-Sensitive High-Adhesion Medical Tape to Reduce Medical-Adhesive-Related Skin Injury and Improve Quality of Care.

Medical adhesives are used to secure wound care dressings and other critical devices to the skin. Without means of safe removal, these stronger adhesives are difficult to painlessly remove from the skin and may cause medical-adhesive-related skin injuries (MARSI), including skin tears and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to device dislodgement and further medical complications. This paper outlines the development of a high-adhesion medical tape designed for low skin trauma upon release. By warming the skin-attached tape for 10-30 s, a significant loss in adhesion was achieved. A C14/C18 copolymer was developed and combined with a selected pressure-sensitive adhesive (PSA) material. The addition of 1% C14/C18 copolymer yielded the largest temperature-responsive drop in surface adhesion. The adhesive film was characterized using AFM, and distinct nanodomains were identified on the exterior surface of the PSA. Our optimized formulation yielded 67% drop in adhesion when warmed to 45 °C, perhaps due to melting nanodomains weakening the adhesive-substrate boundary layer. Pilot clinical testing resulted in a significant decrease in pain when a heat pack was used for removal, giving an average pain reduction of 66%.

Impact of risk factors on in-hospital mortality for octogenarians undergoing cardiac surgery.

BACKGROUND: Octogenarians undergoing cardiac surgery have higher mortality than their younger counterparts. OBJECTIVES: To determine if various risk factors have the same effect on mortality in octogenarians as in younger patients. METHODS: The National Inpatient Sample data set from 2004 to 2014 was queried to select patients aged 65 years and older who underwent either coronary artery bypass grafting (CABG), valvular heart surgery (VHS), or both (CABG + VHS) within 10 days of hospital admission. The patients were divided into two groups 65-79 years and 80 years and greater. Hospital mortality, patient demographics, comorbidities, and type of hospital admission was evaluated and compared using χ2 and multivariable logistic regressions. RESULTS: About 397,713 patients were identified including 86,345 (21.7%) aged 80 and above. Octogenarians had higher in-hospital mortality for all procedures: CABG (4.94% vs. 2.39%, p < .001), VHS (5.49% vs. 4.08%, p < .001), and CABG + VHS (7.59% vs. 5.95%, p < .001), and this relationship persisted when gender, race, comorbidities, and type of hospital admission were controlled for: CABG (odds ratio [OR] = 1.71; 95% confidence interval [CI] 1.62-1.81); VHS (OR = 1.18; 95% CI 1.11-1.27); and CABH + VHS (OR = 1.17; 95%CI 1.10-1.26). Female gender, renal, or heart failure, nonelective admission, and CABG + VHS were associated with increased risk of in-hospital mortality. Octogenarians had higher rates of these factors (p < .001). The effect size of renal and heart failure and type of surgery was smaller for octogenarians. CONCLUSIONS: Octogenarians undergoing cardiac surgery have higher rates of nonelective admissions, renal and heart failure, and female gender, which are most strongly associated with in-hospital mortality. Differing effect sizes suggest that certain risk factors, such as renal and heart failure, contribute more to mortality in younger patients.

Effect of fluorescent and nonfluorescent glaze pastes on lithium disilicate pressed ceramic color at different thicknesses.

STATEMENT OF PROBLEM: Materials possessing fluorescent properties are assumed to emit sufficient visible light to change tooth color under daylight illumination. Fluorescent and nonfluorescent glaze pastes are available to finish the surface of a pressed lithium disilicate restoration. However, the effect of a fluorescent-glaze layer on the final color of the restoration remains unclear. PURPOSE: The purpose of this in vitro study was to measure the color dimensions of lithium disilicate glass-ceramic with different thicknesses and different surface treatments under daylight (D65) illumination conditions. MATERIAL AND METHODS: A total of 120 pressed lithium disilicate glass-ceramic disks were fabricated with 4 different thicknesses: 0.7, 1.2, 1.7, and 2.2 mm. In each thickness, 3 different subgroups were created based on the surface treatment performed (n=10): polished (NG), clear glaze (CG), and fluorescent glaze (FG). For the NG group, disks were polished with 180-, 320-, 600-, 800-, and 1400-grit SiC papers and a polishing machine. For the glazed groups, the CG and FG groups, the specimens were polished with 180-grit SiC papers and the same polishing machine. After the polishing sequence, the final thickness was verified in all groups by using digital calipers (0.5, 1.0, 1.5, and 2.0 mm). Additionally, 20 µL of clear glaze or fluorescent glaze was applied on the CG and FL groups by using an electronic positive displacement repeating pipette. The glaze layer was crystallized in a furnace according to the manufacturer recommendations. Color measurements in the CIELab coordinates were made with a spectrometer coupled to an integrating sphere and a standardized photography gray card as a background. Color difference (ΔE) values were calculated by using the CIE76 and CIEDE2000 formulas. The Shapiro-Wilk test revealed that the data were normally distributed. Two-way ANOVA and the Bonferroni test for multiple comparisons were used to analyze the data (α=.05). RESULTS: Statistically significant differences were found among the groups for the L∗, a∗, and b∗ values for the different ceramic thicknesses and surface finishing treatments evaluated (P<.001), except for the b∗ value between the FG and CG groups (P=.988). The L∗ value on the polished group was significantly higher than that on the glazed specimens, followed by the fluorescent-glazed and then by the clear-glazed specimens (P<.001). The ΔE values using the CIE76 formula varied from 0.87 to 2.76 among specimen groups and from 0.32 to 2.34 using the CIEDE2000 among the tested groups. CONCLUSIONS: Ceramic thickness and surface finishing treatment affected all color dimensions (L∗, a∗, and b∗ values) of lithium disilicate ceramic under daylight conditions. These differences resulted in a perceptible but acceptable color mismatch. The value (L∗ color dimension) of the lithium disilicate ceramic was higher on fluorescent-glazed than on not-fluorescent-glazed specimens.

Association between increased-risk donor social behaviors and recipient outcomes after heart transplantation.

BACKGROUND: This study aims to investigate the association between social behaviors of increased-risk donors (IRD) and recipient outcomes after heart transplantation. METHODS: The United Network for Organ Sharing (UNOS) database was queried to identify patients who received a heart transplant between 2004 and 2015. Patients were grouped based on donor's risk status (IRD vs standard risk donor [SRD]). Recipients of IRD were categorized based on donor social behaviors (SB), and recipient survival was assessed. Cox regression analysis was used to identify associations between SB of donors and recipient survival. RESULTS: Out of 22 333 heart transplantations performed during the study period, 2769 (12%) received an IRD graft with the following SB: Unprofessional tattoos or piercings (n = 1722) (63%), cocaine use (n = 916) (33%), heavy smoking (n = 437) (16%), and heavy alcohol abuse (n = 610) (22%). Viral screens detected 72(3%) hepatitis B virus (HBV) positive and 12 (0.4%) hepatitis C virus (HCV) positive at donation. There was no difference in recipient survival based on both donor risk and their social behaviors. Cox regression analysis found only donor HCV infection and non-identical ABO mismatch to be associated with poor recipient survival among recipients of IR grafts. CONCLUSION: Cardiac allografts from IRD, serologically negative for viruses, can safely be used. There is no association between social behaviors of IRD and recipient survival.

Placement of a rapid deployment aortic valve in a patient with severely calcified aortic root homograft.

Significant aortic calcification is a known sequelae of homograft aortic root replacement and creates a treatment challenge if these patients require cardiac reintervention. The standard surgical option for patients requiring an aortic valve replacement in the setting of a calcified aortic homograft has been a Bentall procedure, which is high-risk with extended cross-clamp, cardiopulmonary bypass and operative times. We present a patient with a severely calcified aortic homograft who underwent successful valve replacement using a rapid deployment aortic valve leaving the aortic root and arch intact and avoiding the more extensive redo aortic root replacement. Similar cases in the literature are rare.

Synthesis of Organic Super-Electron-Donors by Reaction of Nitrous Oxide with N-Heterocyclic Olefins.

The reaction of nitrous oxide (N2O) with N-heterocyclic olefins (NHOs) results in cleavage of the N-O bond and formation of azo-bridged NHO dimers. The latter represent very electron-rich compounds with a low ionization energy. Cyclic voltammetry studies show that the dimers can be classified as new organic super-electron-donors, with a reducing power similar to what is found for tetraazafulvalene derivatives. Mild oxidants are able to convert the neutral dimers into radical cations, which can be isolated. Further oxidation gives stable dications.

Surgical pericardial drainage procedures have a limited diagnostic sensitivity.

PURPOSE: Cardiothoracic surgeons are frequently called upon to perform surgical pericardial drainage procedures (pericardial window) for pericardial effusions. These procedures have therapeutic value, but the diagnostic value of such procedures is debated. We set out to determine the sensitivity of pericardial drainage to detect the disease when cytology, microbiology, and pathology are evaluated. METHODS: A retrospective chart review of patients who underwent pericardial windows from 1 July 2011 to 1 January 2018 at a single academic institution was conducted. All patients who had undergone a recent trauma or cardiac procedure were excluded. Cytology, microbiology, and pathology were examined. The charts were then carefully reviewed to determine if a clinical diagnosis was reached. Sensitivity was then calculated for all diseases and for those that should have been able to be detected. RESULTS: One hundred sixty-two patients who had undergone a pericardial drainage procedure were identified; 49 patients were excluded for recent cardiac procedure or trauma. Of the 113 patients who met our inclusion criteria, 56 patients (49.6%) were female with a mean age of 59.7 ± 15.1 years. A diagnosis based on the pathology, microbiology, or cytology was obtained for 27 patients. The most common pathologies detected were adenocarcinoma (11), bacteremia (9), and small cell lung cancer (3); 56 patients had underlying pathologies that would have been possible to detect with either pathology, microbiology, or cytology. The most common detectable diagnoses were adenocarcinoma (20), bacteremia (12), and lymphoma (7). The most common undetectable diagnoses were idiopathic (17), cardiorenal fluid overload (17), and viral (11). The sensitivity of a pericardial drainage procedure for detecting disease was 0.24 for all cases, and 0.48 when restricted to cases where a detectable disease was present. CONCLUSION: Cytology, microbiology, and pathology for pericardial drainage procedures were unable to detect a diagnosis for 76% of all cases and greater than 50% of cases with the theoretically detectable disease. Pericardial drainage procedures have a clear therapeutic value, but they have limited diagnostic utility.

Synthesis of Azo Dyes from Mesoionic Carbenes and Nitrous Oxide.

Covalent adducts of imidazole-based mesoionic carbenes and nitrous oxide (N2 O, "laughing gas") can be converted into azo dyes by reaction with arenes in the presence of AlCl3 or HCl. The azo coupling can be achieved with electron-rich aromatic compounds such as mesitylene, trimethoxybenzene, azulene, or dibenzo-18-crown-6. The latter coupling reaction allows for the easy preparation of a colorimetric sensor for potassium or sodium ions. As a putative intermediate of the reaction with acid, we were able to isolate and structurally characterize a rare diazohydroxide. Using imidazolium compounds with two N2 O groups, it was possible to prepare amine-substituted azo dyes or dyes with two azoarene groups attached to the heterocycle. A triazole-based mesoionic carbene was also found to form a stable covalent adduct with N2 O. The adduct could be used to prepare novel azo triazolium dyes in good yields.

Trimethylsilyl-Induced N-O Bond Cleavage in Nitrous Oxide-Derived Aminodiazotates.

The chemical activation of nitrous oxide (N2O) typically results in O-atom transfer and the extrusion of N2 gas. In contrast, reactions of N-trimethylsilyl (TMS)-substituted amides with N2O give inorganic or organic azides, with concomitant formation of silanols or siloxanes. N-TMS-substituted amides are also able to induce N-O bond cleavage in N2O-derived dialkylaminodiazotates, generating tetrazene salts. These results indicate the potential of silyl groups in devising transformations, in which N2O acts as an N-atom donor.

LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice.

Skeletal dysplasias are a common, genetically heterogeneous cause of short stature that can result from disruptions in many cellular processes. We report the identification of the lesion responsible for skeletal dysplasia and male infertility in the spontaneous, recessive mouse mutant chagun. We determined that Poc1a, encoding protein of the centriole 1a, is disrupted by the insertion of a processed Cenpw cDNA, which is flanked by target site duplications, suggestive of a LINE-1 retrotransposon-mediated event. Mutant fibroblasts have impaired cilia formation and multipolar spindles. Male infertility is caused by defective spermatogenesis early in meiosis and progressive germ cell loss. Spermatogonial stem cell transplantation studies revealed that Poc1a is essential for normal function of both Sertoli cells and germ cells. The proliferative zone of the growth plate is small and disorganized because chondrocytes fail to re-align after cell division and undergo increased apoptosis. Poc1a and several other genes associated with centrosome function can affect the skeleton and lead to skeletal dysplasias and primordial dwarfisms. This mouse mutant reveals how centrosome dysfunction contributes to defects in skeletal growth and male infertility.

CREG1 Interacts with Sec8 to Promote Cardiomyogenic Differentiation and Cell-Cell Adhesion.

Understanding the regulation of cell-cell interactions during the formation of compact myocardial structures is important for achieving true cardiac regeneration through enhancing the integration of stem cell-derived cardiomyocytes into the recipient myocardium. In this study, we found that cellular repressor of E1A-stimulated genes 1 (CREG1) is highly expressed in both embryonic and adult hearts. Gain- and loss-of-function analyses demonstrated that CREG1 is required for differentiation of mouse embryonic stem (ES) cell into cardiomyocytes and the formation of cohesive myocardium-like structures in a cell-autonomous fashion. Furthermore, CREG1 directly interacts with Sec8 of the exocyst complex, which tethers vesicles to the plasma membrane. Site-directed mutagenesis and rescue of CREG1 knockout ES cells showed that CREG1 binding to Sec8 is required for cardiomyocyte differentiation and cohesion. Mechanistically, CREG1, Sec8, and N-cadherin colocalize at intercalated discs in vivo and are enriched at cell-cell junctions in cultured cardiomyocytes. CREG1 overexpression enhances the assembly of adherens and gap junctions. By contrast, its knockout inhibits the Sec8-N-cadherin interaction and induces their degradation. These results suggest that the CREG1 binding to Sec8 enhances the assembly of intercellular junctions and promotes cardiomyogenesis. Stem Cells 2016;34:2648-2660.

Proteolytic Cleavage of AMPKα and Intracellular MMP9 Expression Are Both Required for TLR4-Mediated mTORC1 Activation and HIF-1α Expression in Leukocytes.

LPS-induced TLR4 activation alters cellular bioenergetics and triggers proteolytic cleavage of AMPKα and HIF-1α expression in leukocytes. In human leukocytes, and more specifically neutrophils, AMPKα cleavage yields 55- and 35-kDa protein fragments. In this study, we address the mechanism by which AMPKα is cleaved and its relevance to human health. Our data indicate that AMPKα cleavage is linked to MMP9 expression and that both are required for mammalian target of rapamycin complex-1 and S6K1 activation and HIF-1α expression in LPS-stimulated human and mice leukocytes. Three key observations support this conclusion. First, no changes in AMPKα and TLR4 signaling intermediates (mammalian target of rapamycin complex-1/S6 kinase 1/HIF-1α) were detected in LPS-stimulated MMP9-deficient mice leukocytes. Second, rMMP9 cleaved human AMPKα ex vivo, producing degradation products similar in size to those detected following LPS stimulation. Third, MMP9 inhibitors prevented AMPKα degradation and HIF-1α expression in LPS-activated human leukocytes, whereas AMPK activators blocked MMP9 and HIF-1α expression. Significantly, AMPKα degradation, MMP9, and TLR4 signaling intermediates were all detected in leukocytes from patients with type 2 diabetes mellitus and patients following cardiopulmonary bypass surgery. Plasma from these two patient cohorts induced AMPKα cleavage and TLR4 signaling intermediates in healthy donor leukocytes and either a TLR4 inhibitor or polymyxin prevented these outcomes. Detection of AMPKα degradation, MMP9 expression, and TLR4 signaling intermediates described in this study in leukocytes, the most readily available human cells for clinical investigation, may provide a powerful tool for further exploring the role of TLR4 signaling in human diseases and lead to identification of new, context-specific therapeutic modalities for precision medicine.

Aortic root replacement in a patient following congenital aortico-left ventricular tunnel repair in childhood.

Congenital aortico-left ventricular tunnel requires surgical repair during childhood. Long-term surveillance is essential in these patients given the risk for aortic aneurysm development in adulthood. We describe an aortic root replacement for an aortic aneurysm five decades following the closure of an aortic-left ventricular tunnel.

Neutral Aminyl Radicals Derived from Azoimidazolium Dyes.

The synthesis and characterization of a new class of neutral aminyl radicals is reported. Monoradicals were obtained by reduction of azoimidazolium dyes with potassium. Structural, spectroscopic, and computational data suggest that the spin density is centered on one of the nitrogen atoms of the former azo group. The reduction of a dimeric dye with an octamethylbiphenylene bridge between the azo groups resulted in the formation of a biradical with largely independent unpaired electrons. Both the monoradicals and the biradical were found to display high stability in solution as well as in the solid state.

Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches.

PURPOSE: This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. METHODS: Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C. RESULTS: While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo. CONCLUSIONS: These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.