Higher tumor histopathologic grade was associated with occult metastasis (P = .004). While undergoing END did not affect significantly survival, those with occult metastasis had poorer survival (P < .001).

END should be considered in cT1-T2 N0 glottic cancers with poorly differentiated or undifferentiated tumor histopathology. While END itself may not improve overall survival, identification of occult nodal metastasis is an important finding for prognostication.

Level 3 Laryngoscope, 2020.

Level 3 Laryngoscope, 2020.

Novel therapies are urgently needed for pediatric patients with relapsed acute myeloid leukemia (AML).

To determine whether the histone deacetylase inhibitor panobinostat could be safely given in combination with intensive chemotherapy, a phase 1 trial was performed in which 17 pediatric patients with relapsed or refractory AML received panobinostat (10, 15, or 20 mg/m

) before and in combination with fludarabine and cytarabine.

All dose levels were tolerated, with no dose-limiting toxicities observed at any dose level. Pharmacokinetic studies demonstrated that exposure to panobinostat was proportional to the dose given, with no associations between pharmacokinetic parameters and age, weight, or body surface area. Among the 9 patients who had sufficient (>2%) circulating blasts on which histone acetylation studies could be performed, 7 demonstrated at least 1.5-fold increases in acetylation. Although no patients had a decrease in circulating blasts after single-agent panobinostat, 8 of the 17 patients (47%), including 5 of the 6 patients treated at dose level 3, achieved complete remission. Among the 8 complete responders, 6 (75%) attained negative minimal residual disease status.

Panobinostat can be safely administered with chemotherapy and results in increased blast histone acetylation. This suggests that it should be further studied in AML.

Panobinostat can be safely administered with chemotherapy and results in increased blast histone acetylation. This suggests that it should be further studied in AML.

To determine predictors of increased drain output following type I thyroplasty for glottic insufficiency.

Retrospective chart review.

A retrospective review was conducted for patients who underwent type I thyroplasty for glottic insufficiency from 2014-2019. The primary outcome was 24-hour drain output. Increased drain output was defined as >50th percentile for the sample. Univariate logistic regression models and linear regression models were used.

There were 84 patients with a mean age of 58.9 (SD 16.9) years. Twenty-four-hour drain output ranged from 0 to 29 mL with a mean of 9.47 (SD 6.49) mL. Patients with a history of tobacco use (OR 3.33; 95% CI, 1.24-8.95; P = .017) and prior neck surgery (OR 3.52; 95% CI, 1.26 to 9.83; P = .016) were significantly more likely to have increased drain output following surgery; these patients had a mean increase in 24-hour drain output of 3.51 mL (95% CI, 0.52 to 6.51; P = .022) and 1.74 mL (95% CI, -1.41 to 4.89; P = .274), respectively. Type of implant (Gore-Tex vs. Silastic; P = .425) and operative technique (unilateral vs. bilateral; P = .506) were not significantly associated with drain output.

History of tobacco use and prior surgery of the neck predict increased drain output following type I thyroplasty surgery. These patients may derive the most benefit from surgical drain placement. More research is needed to confirm these findings and elucidate potential mechanisms.

4 Laryngoscope, 2020.

4 Laryngoscope, 2020.Cyclobutane pyrimidine dimer (CPD) is a photoproduct formed by two stacked pyrimidine bases through a cycloaddition reaction upon irradiation. Owing to its close association with skin cancer, the mechanism of CPD formation has been studied thoroughly. Among many aspects of CPD, its formation involving 5-methylcytosine (5mC) has been of special interest because the CPD yield is known to increase with C5-methylation of cytosine. In this work, high-level quantum mechanics/molecular mechanics (QM/MM) calculations are used to examine a previously experimentally detected pathway for CPD formation in hetero (thymine-cytosine and thymine-5mC) dipyrimidines, which is facilitated through intersystem crossing in thymine and formation of a triplet biradical intermediate. A DNA duplex model system containing a core sequence TmCG or TCG is used. The stabilization of a radical center in the biradical intermediate by the methyl group of 5mC can lead to increased CPD yield in TmCG compared with its non-methylated counterpart, TCG, thereby suggesting the existence of a new pathway of CPD formation enhanced by 5mC.Sense of community and well-being are considered core tenets in the field of community psychology, acting as focal points for theory, research, and action. This integrative review synthesizes the empirical literature on sense of community and well-being with respect to four research questions focused on the relationships between these variables, the methodologies used to study those relationships, and how future research might expand upon the current literature. A search of the available literature produced 30 articles that met the search criteria, based primarily on conceptualizations and measurement of both sense of community and hedonic and eudaimonic well-being. This review suggests a general consensus across the literature of a positive relationship between sense of community and well-being among both youth and adults in a variety of settings, and discusses the strengths and limitations of this area of research, pointing to the need for more nuanced, ecologically valid research that incorporates more qualitative and critical methodologies. We hope that this review can promote a more thorough understanding of how sense of community and individual well-being relate to each other, and that ongoing research in this area can be a catalyst for action research and interventions that are applied to pressing contemporary issues as well as strengths-based approaches focused on how to foster and support the well-being of individuals within their community contexts.In this work we benefited from recent advances in tools for crystal-structure analysis that enabled us to describe an exotic nanoscale phenomenon in structural chemistry. The Mn0.60 Ni0.40 As sample of the Mn1-x Nix As solid solution, exhibits an incommensurate compositional modulation intimately coupled with positional modulations. The average structure is of the simple NiAs type, but in contrast to a normal solid solution, we observe that manganese and nickel segregate periodically at the nano-level into ordered MnAs and NiAs layers with thickness of 2-4 face-shared octahedra. The detailed description was obtained by combination of 3D electron diffraction, scanning transmission electron microscopy, and neutron diffraction. The distribution of the manganese and nickel layers is perfectly described by a modulation vector q=0.360(3) c*. Displacive modulations are observed for all elements as a consequence of the occupational modulation, and as a means to achieve acceptable Ni-As and Mn-As distances. This modulated evolution of magnetic MnAs and non-magnetic NiAs-layers with periodicity at approximately 10 Å level, may provide an avenue for spintronics.

In animal studies of vocal fold scarring and treatment, imaging-based evaluation is most often conducted by tissue slicing and histological staining. Given variation in anatomy, injury type, severity, and sacrifice timepoints, planar histological sections provide limited spatiotemporal details of tissue repair. Three-dimensional (3D) virtual histology may provide additional contextual spatial information, enhancing objective interpretation. The study’s aim was to evaluate the suitability of magnetic resonance imaging (MRI), microscale computed tomography (CT), and nonlinear laser-scanning microscopy (NM) as virtual histology approaches for rabbit studies of vocal fold scarring.

A unilateral injury was created using microcup forceps in the left vocal fold of three New Zealand White rabbits. Animals were sacrificed at 3, 10, and 39 days postinjury. ex vivo imaging of excised larynges was performed with MRI, CT, and NM modalities.

The MRI modality allowed visualization of injury location and morphological internal features with 100-μm spatial resolution. The CT modality provided a view of the injury defect surface with 12-μm spatial resolution. The NM modality with optical clearing resolved second-harmonic generation signal of collagen fibers and two-photon autofluorescence in vocal fold lamina propria, muscle, and surrounding cartilage structures at submicrometer spatial scales.

Features of vocal fold injury and wound healing were observed with MRI, CT, and NM. The MRI and CT modalities provided contextual spatial information and dissection guidance, whereas NM resolved extracellular matrix structure. The results serve as a proof of concept to motivate incorporation of 3D virtual histology techniques in future vocal fold injury animal studies.

NA Laryngoscope, 2020.

NA Laryngoscope, 2020.

Cardiac specificity provides an advantage in correlating heart failure (HF) biomarker plasma levels with indices of cardiac function and remodelling, as shown for natriuretic peptides. Using bioinformatics, we explored the cardiac specificity of secreted proteins and investigated in more detail the relationship of Dickkopf-3 (DKK3) gene expression and DKK3 plasma concentrations with cardiac function and remodelling in (pre)clinical studies.

The cardiac specificity of secreted proteins was determined using RNAseq data for a large panel of organs and tissues. This showed that natriuretic peptides (NPPA and NPPB) are highly cardiac-specific (>99%), whereas other HF biomarkers, including galectin-3 (Gal-3, LGALS3) and growth differentiation factor-15 (GDF-15), lack cardiac specificity (<4%). DKK3 was cardiac-enriched (44%), warranting further investigation. In three different HF mouse models, cardiac Dkk3 expression was altered, but DKK3 plasma concentrations were not. In humans, DKK3 plasma concentrations were higher in HF patients (n= 2090) in comparison with age- and sex-matched controls without HF (n= 240) (46.4 ng/mL vs. 36.3 ng/mL; P < 0.001). Multivariate regression analysis revealed that DKK3 was strongly associated with HF risk factors and comorbidities, including age, kidney function and atrial fibrillation. After correction for existing prediction models, DKK3 did not independently predict HF outcome [all-cause mortality/HF hospitalization, hazard ratio 1.13 (0.79-1.61) per DKK3 doubling; P= 0.503].

Of actively secreted HF biomarkers, only natriuretic peptides showed high cardiac specificity. Despite a cardiac specificity of 44%, secreted DKK3 had limited additional diagnostic and prognostic value.

Of actively secreted HF biomarkers, only natriuretic peptides showed high cardiac specificity. Despite a cardiac specificity of 44%, secreted DKK3 had limited additional diagnostic and prognostic value.

Ventricular tachycardia (VT) is a common arrhythmia in heart failure with reduced ejection fraction but its incidence, predictors, and significance have not been determined in heart failure with preserved ejection fraction (HFpEF).

We performed a retrospective review of arrhythmias in two cohorts of patients with an HFpEF diagnosis. Patients in cohort 1 (n=40) underwent routine arrhythmia surveillance with a 14-day ambulatory electrocardiogram (ECG) monitor. Patients in cohort 2 (n=85) had cardiac pacemakers and underwent routine device interrogations.

In cohort 1, 13 patients (32.5%) had one or more episodes of nonsustained VT (NSVT) on ambulatory ECG. In cohort 2, 38 patients (44.7%) had NSVT on cardiac pacemaker interrogations. During a median (interquartile range) follow-up of 3.0 (1.6 to 5.1) years, 15 (12%) patients died (20% of patients with NSVT versus 6.8% of those without NSVT; P=.03). In logistic regression analysis, NSVT was associated with a 3.4-fold higher odds of death (95% confidence interval 1.