Autofluorescence Detection of Bronchial Tumors With the D-Light/AF

We present a newly developed diagnostic system combining a conventional light source (white light mode and two different fluorescence excitation modes), a bronchoscope and optionally a highly sensitive camera (Baumgartner et al., Photochem. Photobiol. 1987; 46(5): 759–763). Routine diagnostics can be performed with the autofluorescence bronchoscopy (AFB) and the white light bronchoscopy (WLB) in one diagnostic procedure. The image is visible directly with the naked eye. The system was evaluated in a pilot study including 60 patients. Two hundred and sixty-four biopsies were taken to detect premalignant and malignant findings (Stanzel et al., Contribution to 10th World Congress for Bronchology, June 1998). The sensitivity of the combination of WLB and AFB was 2.8 times higher than that of the conventional WLB. The specificity decreased from 94% (WLB) to 89% (WLB + AFB). The results of this preliminary pilot study are being confirmed in a multicenter study, which will begin at seven European centers

Longitudinal Profiles of Girls' Irritable, Defiant and Antagonistic Oppositional Symptoms: Evidence for Group Based Differences in Symptom Severity

Three subdimensions of ODD symptoms have been proposed -angry/irritable (IR), argumentative/defiant (DF) and antagonism (AN). This study tested whether longitudinal symptom trajectories could be identified by these subdimensions. Group-based trajectory analysis was used to identify developmental trajectories of IR, DF and AN symptoms. Multi-group trajectory analysis was then used to identify how subdimension trajectories were linked together over time. Data were drawn from the Pittsburgh Girls Study (PGS; N = 2450), an urban community sample of girls between the ages of five--eight at baseline. We included five waves of annual data across ages five-13 to model trajectories. Three trajectories were identified for each ODD subdimension: DF and AN were characterized by high, medium and low severity groups; IR was characterized by low, medium stable, and high increasing groups. Multi-trajectory analysis confirmed these subdimensions were best linked together based on symptom severity. We did not identify girls' trajectory groups that were characterized predominantly by a particular subdimension of ODD symptoms. Membership in more severe symptom groups was significantly associated with worse outcomes five years later. In childhood and early adolescence girls with high levels of ODD symptoms can be identified, and these youth are characterized by a persistently elevated profile of IR, DF and AN symptoms. Further studies in clinical samples are required to examine the ICD-10 proposal that ODD with irritability is a distinct or more severe form of ODD

LaDIVA: A neurocomputational model providing laryngeal motor control for speech acquisition and production

Many voice disorders are the result of intricate neural and/or biomechanical impairments that are poorly understood. The limited knowledge of their etiological and pathophysiological mechanisms hampers effective clinical management. Behavioral studies have been used concurrently with computational models to better understand typical and pathological laryngeal motor control. Thus far, however, a unified computational framework that quantitatively integrates physiologically relevant models of phonation with the neural control of speech has not been developed. Here, we introduce LaDIVA, a novel neurocomputational model with physiologically based laryngeal motor control. We combined the DIVA model (an established neural network model of speech motor control) with the extended body-cover model (a physics-based vocal fold model). The resulting integrated model, LaDIVA, was validated by comparing its model simulations with behavioral responses to perturbations of auditory vocal fundamental frequency (fo) feedback in adults with typical speech. LaDIVA demonstrated capability to simulate different modes of laryngeal motor control, ranging from short-term (i.e., reflexive) and long-term (i.e., adaptive) auditory feedback paradigms, to generating prosodic contours in speech. Simulations showed that LaDIVA’s laryngeal motor control displays properties of motor equivalence, i.e., LaDIVA could robustly generate compensatory responses to reflexive vocal fo perturbations with varying initial laryngeal muscle activation levels leading to the same output. The model can also generate prosodic contours for studying laryngeal motor control in running speech. LaDIVA can expand the understanding of the physiology of human phonation to enable, for the first time, the investigation of causal effects of neural motor control in the fine structure of the vocal signal.Fil: Weerathunge, Hasini R.. Boston University; Estados UnidosFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Cler, Gabriel J.. University of Washington; Estados UnidosFil: Guenther, Frank H.. Boston University; Estados UnidosFil: Stepp, Cara E.. Boston University; Estados UnidosFil: Zañartu, Matías. Universidad Técnica Federico Santa María; Chil

Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice

Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The long-term hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II–mediated hypertension. Taken together, our findings suggest that overexpression of 11β-HSD1 in fat is sufficient to cause salt-sensitive hypertension mediated by an activated RAS. The potential role of adipose 11β-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder

Mental Models of Soil Management for Food Security in Peri-Urban India

Agricultural development during the Green Revolution brought India food sovereignty but food insecurity persists. Increased crop production was promoted without considering the more holistic impact on food security. Scientists, extension agents, and farmers have different perspectives on how soil health relates to food security. Understanding stakeholders’ perspectives is essential to improving extension communication and mitigating consequences. This study uses qualitative interviews to construct mental models of soil health for food security. The study site is a peri-urban watershed, which is currently participating in the Integrated Farmer Participatory Watershed Management Model (IFPWM). Our study details and defines stakeholders’ mental models of soil health, soil nutrient management, soil sodicity, and food security. A triad belief held by farmers shows the strongly perceived causal relationship between soil health, plant health, and human health. Healthy soil produces healthy food and humans that eat such food will be healthy. Scientists only perceive one condition to achieving food security in the community—food quantity. However, all other stakeholders perceived another risk to food security—food quality. Eating poor quality food is perceived as linked to human health problems in the community. This research suggests the importance of including a fifth dimension of food security, cultural acceptability, within agricultural technology development and dissemination

Uveitis-mediated immune cell invasion through the extracellular matrix of the lens capsule.

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune resolution is occurring at D26. 3D surface rendering image analytics of confocal z-stacks and scanning electron microscopy imaging of the lens surface show the degradation of the lens capsule as these lens-associated immune cells integrate with and invade the lens capsule, with a subset infiltrating both epithelial and fiber cell regions of lens tissue, abrogating its immune privilege. Those immune cells that remain on the surface often become entwined with a fibrillar net-like structure. Immune cell invasion of the lens capsule in uveitis has not been described previously and may play a role in induction of lens and other eye pathologies associated with autoimmunity

Uveitis-mediated immune cell invasion through the extracellular matrix of the lens capsule

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune resolution is occurring at D26. 3D surface rendering image analytics of confocal z-stacks and scanning electron microscopy imaging of the lens surface show the degradation of the lens capsule as these lens-associated immune cells integrate with and invade the lens capsule, with a subset infiltrating both epithelial and fiber cell regions of lens tissue, abrogating its immune privilege. Those immune cells that remain on the surface often become entwined with a fibrillar net-like structure. Immune cell invasion of the lens capsule in uveitis has not been described previously and may play a role in induction of lens and other eye pathologies associated with autoimmunity

Anatomic Optical Coherence Tomography (aOCT) for Evaluation of the Internal Nasal Valve

Objectives/Hypothesis: To establish the utility of anatomic optical coherence tomography (aOCT) in evaluating internal nasal valve (INV). Study Design: Anatomic specimen imaging study. Methods: Fresh-harvested human specimen heads were evaluated using both computed tomography (CT) imaging as well as using aOCT. Scans were performed at three time points: 1) After septoplasty for cartilage harvest, 2) after placement of butterfly graft (BFG), and 3) after placement of bilateral spreader grafts (SG). Imaging data were then converted into 3D models of the nasal airway. CT- and aOCT-generated models were compared by both static volumetric analysis and computational fluid dynamics (CFD) to predict nasal resistance and pressure. Results: Scans using aOCT showed comparable results to CT in terms of volumetric parameters both before and after intervention. Analysis of aOCT data by CFD demonstrated decrease in pressure after SG or BFG intervention. No statistically significant difference was observed when comparing CT- and aOCT-generated calculations of pressure or resistance. Conclusion: The INV can be imaged in a static fashion using aOCT technology. Advantages over traditional CT imaging include lack of exposure to radiation and rapid scan time. In addition, in-office use is possible as aOCT technology develops. Further investigation will be necessary to define the role of aOCT in the dynamic evaluation of this vital component of the nasal airway. Level of Evidence: III Laryngoscope, 2021

Protective role of Cav-1 in pneumolysin-induced endothelial barrier dysfunction

Pneumolysin (PLY) is a bacterial pore forming toxin and primary virulence factor of Streptococcus pneumonia, a major cause of pneumonia. PLY binds cholesterol-rich domains of the endothelial cell (EC) plasma membrane resulting in pore assembly and increased intracellular (IC) Ca2+ levels that compromise endothelial barrier integrity. Caveolae are specialized plasmalemma microdomains of ECs enriched in cholesterol. We hypothesized that the abundance of cholesterol-rich domains in EC plasma membranes confers cellular susceptibility to PLY. Contrary to this hypothesis, we found increased PLY-induced IC Ca2+ following membrane cholesterol depletion. Caveolin-1 (Cav-1) is an essential structural protein of caveolae and its regulation by cholesterol levels suggested a possible role in EC barrier function. Indeed, Cav-1 and its scaffolding domain peptide protected the endothelial barrier from PLY-induced disruption. In loss of function experiments, Cav-1 was knocked-out using CRISPR-Cas9 or silenced in human lung microvascular ECs. Loss of Cav-1 significantly enhanced the ability of PLY to disrupt endothelial barrier integrity. Rescue experiments with re-expression of Cav-1 or its scaffolding domain peptide protected the EC barrier against PLY-induced barrier disruption. Dynamin-2 (DNM2) is known to regulate caveolar membrane endocytosis. Inhibition of endocytosis, with dynamin inhibitors or siDNM2 amplified PLY induced EC barrier dysfunction. These results suggest that Cav-1 protects the endothelial barrier against PLY by promoting endocytosis of damaged membrane, thus reducing calcium entry and PLY-dependent signaling

Structure and photophysics of indigoids for singlet fission: Cibalackrot

We report an investigation of structure and photophysics of thin layers of cibalackrot, a sturdy dye derived from indigo by double annulation at the central double bond. Evaporated layers contain up to three phases, two crystalline and one amorphous. Relative amounts of all three have been determined by a combination of X-ray diffraction and FT-IR reflectance spectroscopy. Initially, excited singlet state rapidly produces a high yield of a transient intermediate whose spectral properties are compatible with charge-transfer nature. This intermediate more slowly converts to a significant yield of triplet, which, however, does not exceed 100% and may well be produced by intersystem crossing rather than singlet fission. The yields were determined by transient absorption spectroscopy and corrected for effects of partial sample alignment by a simple generally applicable procedure. Formation of excimers was also observed. In order to obtain guidance for improving molecular packing by a minor structural modification, calculations by a simplified frontier orbital method were used to find all local maxima of singlet fission rate as a function of geometry of a molecular pair. The method was tested at 48 maxima by comparison with the ab initio Frenkel-Davydov exciton model. Published under license by AIP Publishing