Field-tuned ferroquadrupolar quantum phase transition in the insulator TmVO4.

We report results of low-temperature heat-capacity, magnetocaloric-effect, and neutron-diffraction measurements of TmVO4, an insulator that undergoes a continuous ferroquadrupolar phase transition associated with local partially filled 4f orbitals of the thulium (Tm[Formula: see text]) ions. The ferroquadrupolar transition, a realization of Ising nematicity, can be tuned to a quantum critical point by using a magnetic field oriented along the c axis of the tetragonal crystal lattice, which acts as an effective transverse field for the Ising-nematic order. In small magnetic fields, the thermal phase transition can be well described by using a semiclassical mean-field treatment of the transverse-field Ising model. However, in higher magnetic fields, closer to the field-tuned quantum phase transition, subtle deviations from this semiclassical behavior are observed, which are consistent with expectations of quantum fluctuations. Although the phase transition is driven by the local 4f degrees of freedom, the crystal lattice still plays a crucial role, both in terms of mediating the interactions between the local quadrupoles and in determining the critical scaling exponents, even though the phase transition itself can be described via mean field. In particular, bilinear coupling of the nematic order parameter to acoustic phonons changes the spatial and temporal fluctuations of the former in a fundamental way, resulting in different critical behavior of the nematic transverse-field Ising model, as compared to the usual case of the magnetic transverse-field Ising model. Our results establish TmVO4 as a model material and electronic nematicity as a paradigmatic example for quantum criticality in insulators.

Local structure of Sr2CuO3.3, a 95 K cuprate superconductor without CuO2 planes.

The local structure of the highly "overdoped" 95 K superconductor Sr2CuO3.3 determined by Cu K X-ray absorption fine structure (XAFS) at 62 K in magnetically oriented samples shows that 1) the magnetization is perpendicular to the c axis; 2) at these levels of precision the Cu sublattice is tetragonal in agreement with the crystal structure; the O sublattice has 3) continuous -Cu-O- chains that orient perpendicular to an applied magnetic field; 4) approximately half-filled -Cu-O- chains that orient parallel to this field; 5) a substantial number of apical O vacancies; 6) O ions at some apical positions with expanded Cu-O distances; and 7) interstitial positions that imply highly displaced Sr ions. These results contradict the universally accepted features of cuprates that require intact CuO2 planes, magnetization along the c axis, and a termination of the superconductivity when the excess charge on the CuO2 Cu ions exceeds 0.27. These radical differences in charge and structure demonstrate that this compound constitutes a separate class of Cu-O-based superconductors in which the superconductivity originates in a different, more complicated structural unit than CuO2 planes while retaining exceptionally high transition temperatures.

Nonadiabatic coupling of the dynamical structure to the superconductivity in YSr2Cu2.75Mo0.25O7.54 and Sr2CuO3.3.

A crucial issue in cuprates is the extent and mechanism of the coupling of the lattice to the electrons and the superconductivity. Here we report Cu K edge extended X-ray absorption fine structure measurements elucidating the internal quantum tunneling polaron (iqtp) component of the dynamical structure in two heavily overdoped superconducting cuprate compounds, tetragonal YSr2Cu2.75Mo0.25O7.54 with superconducting critical temperature, Tc = 84 K and hole density p = 0.3 to 0.5 per planar Cu, and the tetragonal phase of Sr2CuO3.3 with Tc = 95 K and p = 0.6. In YSr2Cu2.75Mo0.25O7.54 changes in the Cu-apical O two-site distribution reflect a sequential renormalization of the double-well potential of this site beginning at Tc, with the energy difference between the two minima increasing by ∼6 meV between Tc and 52 K. Sr2CuO3.3 undergoes a radically larger transformation at Tc, >1-Šdisplacements of the apical O atoms. The principal feature of the dynamical structure underlying these transformations is the strongly anharmonic oscillation of the apical O atoms in a double-well potential that results in the observation of two distinct O sites whose Cu-O distances indicate different bonding modes and valence-charge distributions. The coupling of the superconductivity to the iqtp that originates in this nonadiabatic coupling between the electrons and lattice demonstrates an important role for the dynamical structure whereby pairing occurs even in a system where displacements of the atoms that are part of the transition are sufficiently large to alter the Fermi surface. The synchronization and dynamic coherence of the iqtps resulting from the strong interactions within a crystal would be expected to influence this process.

Local lattice distortions and dynamics in extremely overdoped superconducting YSr2Cu2.75Mo0.25O7.54.

A common characteristic of many "overdoped" cuprates prepared with high-pressure oxygen is Tc values ≥ 50 K that often exceed that of optimally doped parent compounds, despite O stoichiometries that place the materials at the edge or outside of the conventional boundary between superconducting and normal Fermi liquid states. X-ray absorption fine-structure (XAFS) measurements at 52 K on samples of high-pressure oxygen (HPO) YSr2Cu2.75Mo0.25O7.54, Tc = 84 K show that the Mo is in the (VI) valence in an unusually undistorted octahedral geometry with predominantly Mo neighbors that is consistent with its assigned substitution for Cu in the chain sites of the structure. Perturbations of the Cu environments are minimal, although the Cu X-ray absorption near-edge structure (XANES) differs from that in other cuprates. The primary deviation from the crystal structure is therefore nanophase separation into Mo- and Cu-enriched domains. There are, however, indications that the dynamical attributes of the structure are altered relative to YBa2Cu3O7, including a shift of the Cu-apical O two-site distribution from the chain to the plane Cu sites. Another effect that would influence Tc is the possibility of multiple bands at the Fermi surface caused by the presence of the second phase and the lowering of the Fermi level.

Automated detection of glottic laryngeal carcinoma in laryngoscopic images from a multicentre database using a convolutional neural network.

OBJECTIVE: Little is known about the efficacy of using artificial intelligence (AI) to identify laryngeal carcinoma from images of vocal lesions taken in different hospitals with multiple laryngoscope systems. This multicentre study aimed to establish an AI system and provide a reliable auxiliary tool to screen for laryngeal carcinoma. STUDY DESIGN: Multicentre case-control study. SETTING: Six tertiary care centres. PARTICIPANTS: Laryngoscopy images were collected from 2179 patients with vocal fold lesions. OUTCOME MEASURES: An automatic detection system of laryngeal carcinoma was established and used to distinguish malignant and benign vocal lesions in 2179 laryngoscopy images acquired from 6 hospitals with 5 types of laryngoscopy systems. Pathological examination was the gold standard for identifying malignant and benign vocal lesions. RESULTS: Out of 89 cases in the malignant group, the classifier was able to correctly identify laryngeal carcinoma in 66 patients (74.16%, sensitivity). Out of 640 cases in the benign group, the classifier was able to accurately assess the laryngeal lesion in 503 cases (78.59%, specificity). Furthermore, the region-based convolutional neural network (R-CNN) classifier achieved an overall accuracy of 78.05%, with a 95.63% negative predictive value and a 32.51% positive predictive value for the testing data set. CONCLUSION: This automatic diagnostic system has the potential to assist clinical laryngeal carcinoma diagnosis which may improve and standardise the diagnostic capacity of laryngologists using different laryngoscopes.

Chaos Behavior Analysis of Alaryngeal Voices Including Esophageal and Tracheoesophageal Voices.

HYPOTHESIS/OBJECTIVES: This study's objective was to develop a method to evaluate the chaotic characteristic of alaryngeal speech. The proposed method will be capable of distinguishing between normal and alaryngeal voices, including esophageal (SE) and tracheoesophageal (TE) voices. It has been previously shown that alaryngeal voices exhibit chaotic characteristics due to the aperiodicity of their signals. The proposed method will be applied for future use to quantify both chaos behavior (CB) and the difference between SE and TE voices. STUDY DESIGN: A total of 74 voice recordings including 34 normal and 40 alaryngeal (26 SE and 14 TE) were used in the study. Voice samples were analyzed to distinguish alaryngeal voices from normal voices and to investigate different chaotic characteristics of SE and TE speech. METHODS: A chaotic distribution detection-based method was used to investigate the CB of alaryngeal voices. This CB was used to detect the difference between SE and TE voice types. Quantification of the CB parameter was performed. Statistical analyses were used to compare the results of the CB analysis for both the SE and TE voices. RESULTS: Statistical analysis revealed that CB effectively differentiated between all normal and alaryngeal voice types (p < 0.01). Subsequent multiclass receiver operating characteristic (ROC) analysis demonstrated that CB (area under the curve) possessed the greatest classification accuracy relative to correlation dimension (D2). CONCLUSIONS: The CB metric shows strong promise as an accurate, useful metric for objective differentiation between all normal and alaryngaeal, SE and TE voice types. The CB calculations showed expected results, as SE voices have significantly more CB than TE voices, constituting substantial improvement over previous methods and becoming the first SE and TE classification method. This metric can help clinicians obtain additional acoustic information when monitoring the efficacy of treatment for patients undergoing total laryngectomies.

Microbes vs. chemistry in the origin of the anaerobic gut lumen.

The succession from aerobic and facultative anaerobic bacteria to obligate anaerobes in the infant gut along with the differences between the compositions of the mucosally adherent vs. luminal microbiota suggests that the gut microbes consume oxygen, which diffuses into the lumen from the intestinal tissue, maintaining the lumen in a deeply anaerobic state. Remarkably, measurements of luminal oxygen levels show nearly identical pO2 (partial pressure of oxygen) profiles in conventional and germ-free mice, pointing to the existence of oxygen consumption mechanisms other than microbial respiration. In vitro experiments confirmed that the luminal contents of germ-free mice are able to chemically consume oxygen (e.g., via lipid oxidation reactions), although at rates significantly lower than those observed in the case of conventionally housed mice. For conventional mice, we also show that the taxonomic composition of the gut microbiota adherent to the gut mucosa and in the lumen throughout the length of the gut correlates with oxygen levels. At the same time, an increase in the biomass of the gut microbiota provides an explanation for the reduction of luminal oxygen in the distal vs. proximal gut. These results demonstrate how oxygen from the mammalian host is used by the gut microbiota, while both the microbes and the oxidative chemical reactions regulate luminal oxygen levels, shaping the composition of the microbial community throughout different regions of the gut.

The integrity and barrier function of porcine vocal fold epithelium: its susceptibility to damage by deoxycholic acid compared with pepsin.

PURPOSE: In this study, we aim to systematically evaluate the damaging role of gastric (pepsin and acid) and duodenal ingredients (bile acids) on vocal fold epithelium in excised porcine larynges. METHODS: Fresh ex vivo porcine larynges were exposed to one of five experimental conditions for 1 h. These conditions will be referred to as alkaline deoxycholic acid, acidic pepsin, acid pH3 only, acid pH5 only, and control, respectively. A Franz diffusing cell was used to evaluate the barrier function of vocal fold epithelium by measuring the permeability to fluorescein isothiocyanate dextran of 4 kDa. Histological changes were observed using transmission electron microscopy. RESULTS: After immersing the fresh porcine larynges in the five solution groups, we found that the vocal fold epithelium in the deoxycholic acid group had more permeability to FD4 than the pepsin group (P < 0.001). Fragmentation and desquamation of dead cell layers were observed in both the pepsin and deoxycholic acid groups, but were more severe in the deoxycholic acid group than the pepsin group. The thickness of the dead epithelial cell layer gradually increased with increasing acid concentration (P < 0.05). Additionally, the thickness of the dead epithelial cell layer in the deoxycholic acid group was significantly higher than that in the pepsin group (P < 0.01). CONCLUSION: Deoxycholic acid in a weakly acidic condition is more likely than pepsin to induce apoptosis in ex vivo porcine vocal fold epithelium, destroy the link proteins between epithelial cells, and affect their integrity and barrier function.

Study of spatiotemporal liquid dynamics in a vibrating vocal fold by using a self-oscillating poroelastic model.

The main purpose of this study is to investigate the spatiotemporal interstitial fluid dynamics in a vibrating vocal fold. A self-oscillating poroelastic model is proposed to study the liquid dynamics in the vibrating vocal folds by treating the vocal fold tissue as a transversally isotropic, fluid-saturated, porous material. Rich spatiotemporal liquid dynamics have been found. Specifically, in the vertical direction, the liquid is transported from the inferior side to the superior side due to the propagation of the mucosal wave. In the longitudinal direction, the liquid accumulates at the anterior-posterior midpoint. However, the contact between the two vocal folds forces the accumulated liquid out laterally in a very short time span. These findings could be helpful for exploring etiology of some laryngeal pathologies, optimizing laryngeal disease treatment, and understanding hemodynamics in the vocal folds.

FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.

BACKGROUND & AIMS: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor, affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analogue and farnesoid X receptor agonist, on the intestinal microbiomes of humans and mice. METHODS: We performed a phase I study in 24 healthy volunteers given OCA (5, 10, or 25 mg/d for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun meta-genomic sequencing. A Uniref90 high-stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavage fed daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S-tagged sequencing. Culture experiments were performed to determine the taxonomic-specific effects of bile acids and OCA on bacterial growth. RESULTS: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of gram-positive bacteria that are found in the small intestine and are components of the diet and oral microbiota. We found that bile acids decreased proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had lower endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared with mice fed water or vehicle. CONCLUSIONS: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that farnesoid X receptor activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. ClinicalTrials.gov, NCT01933503.

Wound-healing effects of 635-nm low-level laser therapy on primary human vocal fold epithelial cells: an in vitro study.

Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief for skin and oral applications. However, there is no corresponding literature reporting on vocal fold wound healing. Our purpose was to assess the potential wound-healing effects of LLLT on primary human vocal fold epithelial cells (VFECs). In this study, normal vocal fold tissue was obtained from a 58-year-old male patient who was diagnosed with postcricoid carcinoma without involvement of the vocal folds and underwent total laryngectomy. Primary VFECs were then cultured. Cells were irradiated at a wavelength of 635 nm with fluences of 1, 4, 8, 12, 16, and 20 J/cm2 (50 mW/cm2), which correspond to irradiation times of 20, 80, 160, 240, 320, and 400 s, respectively. Cell viability of VFECs in response to varying doses of LLLT was investigated by the Cell Counting Kit-8 (CCK-8) method. The most effective irradiation dose was selected to evaluate the cell migration capacity by using the scratch wound-healing assay. Real-time polymerase chain reaction (RT-PCR) was used to detect the gene expression of TGF-ß1, TGF-ß3, EGF, IL-6, and IL-10. Irradiation with doses of 8 J/cm2 resulted in 4% increases in cell proliferation differing significantly from the control group (p < 0.05). With subsequent doses at 48 and 72 h after irradiation, the differences between the experimental and the control groups became greater, up to 9.8% (p < 0.001) and 19.5% (p < 0.001), respectively. It also increased cell migration and the expression of some genes, such as EGF, TGF-ß1, TGF-ß3, and IL-10, involved in the tissue healing process. This study concludes that LLLT at the preset parameters was capable of stimulating the proliferation and migration of human vocal fold epithelial cells in culture as well as increase the expression of some genes involved in tissue healing process. Additionally, successive laser treatments at 24 h intervals have an additive beneficial effect on the healing of injured tissues.

Effects of a simulated system of straw phonation on the complete phonatory range of excised canine larynges.

PURPOSE: This study investigated the effects of straw phonation therapy on the aerodynamic and acoustic parameters of the vocal folds at different levels of elongation and subglottal pressure. METHODS: 20 excised canine larynges were used in both experimental (straw phonation therapy simulation) and control conditions. Aerodynamic parameters, including phonation threshold pressure (PTP), phonation instability pressure (PIP), phonation pressure range (PPR), phonation threshold flow (PTF), phonation instability flow (PIF), phonation flow range (PFR), were obtained at different levels of vocal fold elongation (0%, 10%, 20%). Acoustic parameters, including fundamental frequency (F0), jitter, shimmer, signal noise ratio (SNR) were detected at different levels of vocal fold elongation (0%, 10%, 20%) and subglottal pressure (15 cmH2O, 20 cmH2O, 25 cmH2O). RESULTS: Significant decreases in PTP and PTF and significant increases in PIP, PIF, PPR, and PFR occurred in experimental condition at all levels of elongation when compared with control condition. However, no significant changes of acoustic parameters were obtained between conditions at all levels. CONCLUSION: At different levels of vocal fold elongation, straw phonation not only lowered the onset of normal voice, but also elevated the onset of chaotic voice, indicating a better voice economy and voice control. Moreover, the improved phonatory range demonstrated that straw phonation had the potential to prevent voice users who have high voice demand from voice fatigue and vocal damage.

Establishment of a novel and effective reflux laryngitis model in rabbits: a preliminary study.

PURPOSE: To establish a novel and effective reflux model with a modified nasogastric aspiration tube and to investigate the association between different types of nasogastric aspiration tubes and reflux laryngitis, we conducted this study. METHODS: Thirty-eight healthy New Zealand albino rabbits (2.5-3.5 kg) were divided into three groups: control (CTR, n = 6)-non-intubated; normal nasogastric intubation (NNI, n = 16)-intubated with 4#, 6#, 8#, and 10# normal nasogastric aspiration tubes; and modified nasogastric intubation (MNI, n = 16)-intubated with 4#, 6#, 8#, and 10# modified nasogastric aspiration tubes. The laryngoscopy, body weight, and pH values at the esophageal entrance were recorded before and 1, 2, and 4 weeks after intubation. After the final laryngoscopy, the animals in groups with a pH below 4 were sacrificed to obtain histological and gene expression analysis results. RESULTS: The reflux finding score (RFS) after 4 weeks showed that there was a statistically significant difference in the 8# NNI group (7 ± 0.816, P < 0.001), the 8# MNI group (11.5 ± 2.517, P < 0.001) and the 10# MNI (12.75 ± 1.893, P < 0.001) group compared with the control group (1.83 ± 1.602). The pH values of these three groups were lower than 4. However, the weight loss of the rabbits in the 10# NNI and 10# MNI groups was more obvious. Submucous gland hyperplasia and inflammation were significantly increased in the 8# NNI group, 8# MNI group and the 10# MNI group, but in the level of some pro-inflammatory cytokines and COX-2, the MNI group was significantly higher than the NNI group (8# NNI × 8# MNI, P < 0.01; 8# MNI × 10# MNI, P < 0.01). CONCLUSION: This study showed that 8# modified nasogastric intubation (MNI) produces effective reflux laryngitis in the rabbits.

Prolonged phonation impairs the integrity and barrier function of porcine vocal fold epithelium: a preliminary study.

PURPOSE: Voice abuse is known to be a common risk factor of voice disorders and prolonged; high-intensity phonation has been shown to damage the vocal fold epithelium. We aim to evaluate the effects of phonation on the integrity and barrier function of vocal fold epithelium using a porcine laryngeal model. METHODS: Ex vivo porcine larynges were phonated at low intensity or high intensity for 15, 30, or 60 min within 4 h after harvest. Vocal fold epithelium was visualized using transmission electron microscopy (TEM). The barrier function of vocal fold epithelium was evaluated by measuring the permeability to model molecules, fluorescein (376 Da), and fluorescein isothiocyanate (FITC)-dextrans of 4000 and 10,000 Da (FD4, FD10), in a Franz diffusing cell. RESULTS: Cell death and dilated intercellular space after phonation were observed using TEM. Thickness of vocal fold epithelium was significantly reduced after low-intensity phonation for 30 and 60 min and high-intensity phonation for 15, 30, and 60 min. Epithelial permeability to fluorescein was significantly increased after low-intensity phonation for 30 and 60 min, and high-intensity phonation. Permeability to FD4 was significantly increased after high-intensity phonation for 30 and 60 min. Phonation did not alter the permeability to FD10 significantly. CONCLUSION: Long-duration phonation destroys the integrity and barrier function of vocal fold epithelium. These effects likely make vocal folds more vulnerable to other environmental irritants, such as tobacco smoke, reflux components, allergens, and inhaled pollutants. Destroyed barrier function may be an important factor in the pathogenesis of voice lesions related to voice abuse.

Evaluation of an asymmetric anterior glottic web in an excised canine larynx model.

The main objective of the study is to model asymmetry within anterior glottic webs in excised larynges using sutures and apply aerodynamic and acoustic analyses. Anterior glottic webs (AGW) were modeled in eight excised larynges using sutures secured at the level of the glottis to mimic the scar tissue of the web. Each of the eight larynges were tested under three different pressure increments for each of the three models of AGW: symmetric, vertically asymmetric, and laterally asymmetric. Phonation threshold pressure (PTP) and flow (PTF) differed significantly across AGW conditions (p = 0.006 and p = 0.005, respectively). Additionally, vocal efficiency was significantly different among conditions (p = 0.005) as well as significantly lower in the asymmetric groups (p = 0.015 and p = 0.007). Perturbation measures were not significantly different across conditions. Correlation dimension (D2) was significantly different at PTP, 1.25 × PTP, and 1.5 × PTP (p = 0.003, p = 0.010, and p < 0.001, respectively) as well as significantly higher in the asymmetric groups at each pressure increment. The increased PTP, PTF, and D2 values as well as decreased vocal efficiency among the asymmetric conditions indicates a significant decrease in vocal function, and thus represents that asymmetries could be a contributing factor to the pathological symptoms associated with glottic webs.

Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma.

PURPOSE: Margin status can often be difficult to assess intraoperatively, particularly during partial nephrectomy given the time constraints related to renal hilar clamping. We hypothesized that a targeted molecular imaging approach could be used during surgery to identify tumor margins and confirm disease clearance. MATERIALS AND METHODS: EC17, a novel tracer targeting FRα, was used in murine models of renal cell carcinoma to identify positive margins after surgery. Positive margins were detected due to elevated tumor-to-background ratios of the tumor compared to surrounding normal tissues. We performed a pilot study in 4 patients using EC17 preoperatively with intraoperative imaging during the operation. RESULTS: FRα was highly expressed in 65% of clear cell renal cell carcinomas harvested from the operating room. In the murine model intraoperative imaging of renal cell carcinoma revealed a mean ± SD tumor-to-background ratio of 8.2 ± 1.1 in the RCC10, 11.2 ± 1.1 in the 786-0 and 4.3 ± 1.1 in the UMRC2 cell line. Compared to visual inspection intraoperative imaging of the surgical resection bed identified residual disease in 24% more animals. In the human pilot study targeted molecular imaging identified 2 of 4 renal cell carcinomas and had no false-positive results. In these 2 cases the tumor-to-background ratio was 3.7 and 4.6, respectively. In each case we confirmed disease clearance and tumor fluorescence did not correlate with nodule size or tumor grade. CONCLUSIONS: To our knowledge this is the first demonstration in humans of identifying renal cell carcinoma during surgery using a targeted molecular contrast agent. This approach may lead to a superior method of identifying malignancy and tumor borders in the intraoperative setting.

Identification of breast cancer margins using intraoperative near-infrared imaging.

BACKGROUND AND OBJECTIVES: Current methods of intraoperative breast cancer margin assessment are labor intensive, not fully reliable, and time consuming; therefore novel strategies are necessary. We hypothesized that near infrared (NIR) intraoperative molecular imaging using systemic indocyanine green (ICG) would be helpful in discerning tumor margins. METHODS: A mammary cancer cell line, 4T1, was used to establish tumors in mouse flanks (n = 60). Tumors were excised 24 hr after intravenous ICG. Assessment of residual tumor in the wound bed was performed using a combination of NIR imaging and traditional method (by visual inspection and palpation) versus traditional method alone. Next we performed a clinical trial to evaluate the role of NIR imaging after systemic ICG for the margin assessment of 12 patients undergoing breast-conserving surgery. RESULTS: Traditional margin assessment identified 30% of positive margins while NIR imaging identified 90% of positive margins. In our clinical trial, all tumors were detected by NIR imaging and there was fluorescent evidence of residual tumor in the tumor bed in 6 of the 12 patients. None of these patients had positive margins on pathology. CONCLUSIONS: Systemic ICG reliably accumulates in breast cancers in murine models as well as human breast cancer. While NIR imaging is helpful for detection of retained tumor margins in our animal model, intraoperative imaging for precise margin detection will need further refinement before clinical value can be obtained. J. Surg. Oncol. 2016;113:508-514. © 2016 Wiley Periodicals, Inc.

The Protective Role of Autophagy in Human Vocal Fold Fibroblasts under Cigarette Smoke Extract Exposure: A New Insight into the Study of Reinke's Edema.

BACKGROUND/AIMS: Reinke's edema (RE), one of the most common benign lesions of the human vocal folds, has been associated with cigarette smoking. We have observed an abundant number of autophagosomes in the cytoplasm of fibroblasts in the lamina propria of human vocal folds under transmission electron microscopy in RE tissue. Thus, we conducted a study about autophagy induced by cigarette smoke extract (CSE) exposure in cultured human vocal fold fibroblasts (hVFFs). METHODS: Sampled tissues were cultured and exposed to varying levels of CSE. Immunochemistry staining and Western blot analyses were then performed on the cultures. RESULTS: We demonstrated that CSE significantly promoted intracellular reactive oxygen species accumulation and reduced the viability of hVFFs in a concentration-dependent manner. Both immunocytochemistry and Western blot analysis showed increased expression of the autophagy marker type II-membrane-associated light chain 3 in fibroblasts following 24 h of CSE exposure, indicating the upregulation of autophagy activity. Furthermore, the results demonstrate that the induction of autophagy played a protective role in hVFFs exposed to CSE. CONCLUSION: Autophagy can be induced by CSE in hVFFs, and it is a protective response of hVFFs to the exposure of CSE. This study provides a new insight into the process involved in the development of RE.

Molecular imaging to identify tumor recurrence following chemoradiation in a hostile surgical environment.

Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a "hostile" field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

Management of thoracic esophageal perforation.

BACKGROUND: The aim of this study was to characterize an optimal strategy in managing thoracic esophageal perforation, focusing on the differential diagnosis and treatment of patients with contained versus noncontained perforations and on the importance of the time interval between injury and repair and how that affects the outcome of a primary repair. METHODS: A retrospective study was conducted. A strict definition of contained or noncontained perforation was based on a combination of esophagography, chest CT scan, and endoscopy as well as monitoring systemic symptoms. Management options for our cohort included conservative therapy, primary repair and debridement, esophagectomy, and mesh-covered stents. Patients were stratified into two groups according to the time interval after injury: ≤ 48-h group and >48-h group. RESULTS: Between January 1997 and January 2013, a total of 66 consecutive patients (47 males and 19 females, mean age = 49.1 ± 16.2 years) were treated for thoracic esophageal perforation. Perforation was confirmed by esophagography in 51 patients and by endoscopy in 15 patients. Eighteen patients were assigned to the contained perforation group. All these patients were successfully cured without surgery. The noncontained group included 48 patients; its mortality rate was 7.7 % (3/39) with surgery and 55.6 % (5/9) with stent placement. Compared with the contained group, the noncontained group had a significantly longer length of stay (LOS) (16 ± 3.2 vs. 26.3 ± 18.7 days; p < 0.05) and a higher mortality rate (0 vs. 22.9 %, p < 0.05). In the two time-interval groups, patient characteristics, including age, gender, and comorbidities, etiologic cause, length and location of the perforation, and the incidence of using tissue buttress were similar (p > 0.05). The incidence of postoperative leak was significantly higher in >48-h group (0 in ≤ 48-h group vs. 37.5 % in >48-h group; p < 0.01). In addition, the >48-h group had a significantly longer LOS (18.0 ± 9.1 days in ≤ 48-h group vs. 31.5 ± 18.6 days in >48-h group; p < 0.01). The two deaths occurred in the >48-h group (0 in ≤ 48-h group vs. 12.5 % in >48-h group; p > 0.05) due to postoperative leaks. CONCLUSIONS: Contained or noncontained perforation should be rigorously differentiated. Then, for a contained perforation, conservative therapy coupled with repeated imaging is reasonable treatment. For a noncontained perforation, a primary repair can be safely performed within 48 h after injury. After that, a primary repair is still reasonable but is associated with an increased risk of postoperative leaks.