Orbital atherectomy of calcified coronary ostial lesions.

OBJECTIVES: To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions. BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long-term outcome data. METHODS: Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high-volume PCI centers. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day, 1-year, and 2-year freedom-from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST). RESULTS: A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30-day, 1-year, and 2-year, a high FF-MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively. CONCLUSIONS: This study represents the largest real-world experience of coronary OA use in heavily calcified ostial lesions with long-term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.

Computer-aided generation and lung deposition modeling of nano-scale particle aggregates.

The study sets its main focus on the introduction of a random-walk-based model for the generation of variably shaped particle aggregates consisting of a predefined number of spherical components. With the help of a well-defined algorithm, the user is enabled to select between isodimensional, chain-like and platelet-like aggregates, for which related aerodynamic parameters (dynamic shape factors, volume-equivalent diameters, aerodynamic diameters) are determined automatically. The theoretical approach for random aggregate construction is directly connected with the previously developed stochastic particle transport and deposition model. Thereby, individually shaped aggregates may be provided for each random-walk scenario taking place in the almost realistic lung structure. Preliminary application of the aggregate generation model was carried out by assuming single components with a constant diameter of 1 nm and unit-density (1 g cm-3) and variably shaped aggregates consisting of 10, 100 and 1000 components. Inhalation of the aggregate-loaded aerosol into lungs of average size (FRC = 3300 mL) was supposed to take place under sitting, light-exercise and heavy-exercise conditions. Results obtained from deposition modeling clearly show that, independent of aggregate geometry, total deposition declines with increasing number of components included in the particulate construct, but experiences a continuous enhancement with rising inhalation flow rate. Among the predefined geometric categories, platelet-like aggregates are distinguished by lowest deposition and isodimensional clusters by highest. While isodimensional aggregates preferentially deposit in the extrathoracic and bronchial airways, chain-like and platelet-like aggregates exhibit a significantly increased tendency to hit the alveolar walls.

Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis.

BACKGROUND: High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC). METHODS AND RESULTS: A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer. Levels of RBC-bound KC were also increased by HFD. These effects of HFD were abolished in DARC(-/-) mice. In RBCs from HFD-fed wild-type and DARC(-/-) mice, levels of membrane cholesterol and phosphatidylserine externalization were increased, fostering RBC-macrophage inflammatory interactions and promoting macrophage phagocytosis in vitro. When labeled ex vivo and injected into wild-type mice, RBCs from HFD-fed mice exhibited ≈3-fold increase in splenic uptake. Finally, RBCs from HFD-fed mice induced increased macrophage adhesion to the endothelium when they were incubated with isolated aortic segments, indicating endothelial activation. CONCLUSIONS: RBC dysfunction, analogous to endothelial dysfunction, occurs early during diet-induced obesity and may serve as a mediator of atherosclerosis. These findings may have implications for the pathogenesis of atherosclerosis in obesity, a worldwide epidemic.

A stochastic model of carbon nanotube deposition in the airways and alveoli of the human respiratory tract.

CONTEXT: In the past two decades, possible exposure of workers to nanoparticles has excited the attention of occupational medicine, resulting in the conception of related risk assessments. Although most nanoparticles have been categorized as hazardous substances in the meantime, their behavior in the human respiratory tract still bears some enigmas, which require clarification. OBJECTIVES: The study pursues the goal to provide detailed theoretical lung deposition data of carbon nanotubes (CNT) with various diameters and lengths. Besides a quantification of total and regional deposition, also airway generation-specific deposition has been subjected to the modeling process. METHODS: Theoretical approach of CNT deposition in the human lungs has been conducted by assuming a stochastic structure of the bronchial network, within which particle transport takes place along randomly selected paths. Fluid-dynamic particle characteristics have been simulated by application of a rigid fiber model, which considers diverse forces and torques acting on the particles during their translocation within the inhaled air. Particle deposition in the entire lungs has been approximated by using the aerodynamic/thermodynamic diameter concept and related empirical deposition formulae. RESULTS: Theoretical deposition data reflect a significant dependence of CNT deposition on (a) the effective size of the particles and (b) the conditions, under which they are taken up into the respiratory tract. Extremely small CNT (∼1 nm) are primarily filtered in the extrathoracic airways, intermediately sized CNT (∼10 nm) exhibit a preference to deposit in the alveoli, and large CNT (∼100 nm) are marked by minimum deposition. CONCLUSION: Pulmonary deposition of CNT is subject to a partly remarkable variation. According to the model of this study, particles of intermediate size seem to bear highest potential to act as hazardous substances.

Improved isobaric tandem mass tag quantification by ion mobility mass spectrometry.

RATIONALE: Isobaric tandem mass tags are an attractive alternative to mass difference tags and label-free approaches for quantitative proteomics due to the high degree of multiplexing that can be performed with their implementation. A drawback of tandem mass tags are that the co-isolation and co-fragmentation of labeled peptide precursors can result in chimeric tandem mass (MS/MS) spectra that can underestimate the fold-change expression of each peptide. Ion mobility (IM) separations coupled to quadrupole time-of-flight (Q-TOF) instruments have the potential to mitigate MS/MS spectra chimeracy since IM-MS has the ability to separate ions based on charge, m/z, and collision cross section (CCS). METHODS: Two complex protein mixtures, labeled with DiLeu isobaric tandem mass tags in opposite ratios, were mixed together and analyzed by data-dependent LC/IM-MS/MS. The accuracy of reporters from interfering pairs was compared with and without IM separation. RESULTS: IM separation was able to mitigate isobaric interference from differentially charged interfering ion pairs, as well as pairs of the same charge. Of the eight example precursors shown, only one had reporters that remained compressed below the significance threshold after IM separation. CONCLUSIONS: The results of this investigation demonstrate proof-of-principle that IM separation of tagged precursors prior to MS/MS fragmentation can help mitigate quantitative inaccuracies caused by isobaric interference. Future improvements of the method would include software for automated correction and use of higher resolution IM instrumentations.

Mass spectrometric evaluation of neuropeptidomic profiles upon heat stabilization treatment of neuroendocrine tissues in crustaceans.

Tissue heat stabilization is a vital component in successful mammalian neuropeptidomic studies. Heat stabilization using focused microwave irradiation, conventional microwave irradiation, boiling, and treatment with the Denator Stabilizor T1 have all proven effective in arresting post-mortem protein degradation. Although research has reported the presence of protein fragments in crustacean hemolymph when protease inhibitors were not added to the sample, the degree to which post-mortem protease activity affects neuropeptidomic tissue studies in crustacean species has not been investigated in depth. This work examines the need for Stabilizor T1 or boiling tissue stabilization methods for neuropeptide studies of Callinectes sapidus (blue crab) pericardial organ tissue. Neuropeptides in stabilized and nonstabilized tissue were extracted using acidified methanol or N,N-dimethylformamide (DMF) and analyzed by MALDI-TOF and nanoLC-ESI-MS/MS platforms. Post-mortem fragments did not dramatically affect MALDI analysis in the range m/z 650-1600, but observations in ESI MS/MS experiments suggest that putative post-mortem fragments can mask neuropeptide signal and add spectral complexity to crustacean neuropeptidomic studies. The impact of the added spectral complexity did not dramatically affect the number of detected neuropeptides between stabilized and nonstabilized tissues. However, it is prudent that neuropeptidomic studies of crustacean species include a preliminary experiment using the heat stabilization method to assess the extent of neuropeptide masking by larger, highly charged molecular species.

Nonproteolytic properties of murine alternatively spliced tissue factor: implications for integrin-mediated signaling in murine models.

This study was performed to determine whether murine alternatively spliced tissue factor (masTF) acts analogously to human alternatively spliced tissue factor (hasTF) in promoting neovascularization via integrin ligation. Immunohistochemical evaluation of a spontaneous murine pancreatic ductal adenocarcinoma model revealed increased levels of masTF and murine full-length tissue factor (mflTF) in tumor lesions compared with benign pancreas; furthermore, masTF colocalized with mflTF in spontaneous aortic plaques of Ldlr(-/-) mice, indicating that masTF is likely involved in atherogenesis and tumorigenesis. Recombinant masTF was used to perform in vitro and ex vivo studies examining its integrin-mediated biologic activity. Murine endothelial cells (ECs) rapidly adhered to masTF in a ß3-dependent fashion. Using adult and embryonic murine ECs, masTF potentiated cell migration in transwell assays. Scratch assays were performed using murine and primary human ECs; the effects of masTF and hasTF were comparable in murine ECs, but in human ECs, the effects of hasTF were more pronounced. In aortic sprouting assays, the potency of masTF-triggered vessel growth was undistinguishable from that observed with hasTF. The proangiogenic effects of masTF were found to be Ccl2-mediated, yet independent of vascular endothelial growth factor. In murine ECs, masTF and hasTF upregulated genes involved in inflammatory responses; murine and human ECs stimulated with masTF and hasTF exhibited increased interaction with murine monocytic cells under orbital shear. We propose that masTF is a functional homolog of hasTF, exerting some of its key effects via ß3 integrins. Our findings have implications for the development of murine models to examine the interplay between blood coagulation, atherosclerosis and cancer.

Morphology and ultrastructure of the accessory glands in the female genital tract of the house cricket, Acheta domesticus.

The accessory glands in the genital tract of female Acheta domesticus L. (Orthoptera: Gryllidae) were investigated in detail. The glands are situated within the 7(th) and 8(th) abdominal segment and lead to the genital chamber lateral to the terminal papilla of the ductus receptaculi. The shape of the gland is characterized by a complex system of tubules, including numerous ramifications. The gland's size ranges from 2 to 4 mm. The epithelium is constructed according to a simple scheme and consists of a cuticular intima at the luminal side, one layer of gland cells, and a basallamina at the outermost side. The observed morphology of the accessory glands widely corresponds with that in other cricket species (e.g., Teleogryllus commodus). This is also true for the structure of a single gland cell, which can be subdivided into a basal part with nucleus and intracellular cisternae, as well as an apical part with all those compartments responsible for the production of the secretion. The secretion itself may be classified as lipophilic and is produced for the first time 4 to 6 days after the imaginai moult. Several endogenic functions of the secretion are discussed (lubricant for oviposition, support for introducing the tube of the spermatophore into the ductus receptaculi, etc.).

Assessing readiness factors for implementation of LGBTQ+ affirmative primary care initiatives: Practice implications from a mixed-method study.

Introduction: Access and utilization barriers in primary care clinics contribute to health disparities that disproportionately affect lesbian, gay, bisexual, transgender, and queer (LGBTQ+) people. Implementing inclusive practice guidelines in these settings may decrease disparities. The purpose of this exploratory/developmental study is to identify key issues affecting the readiness of primary care clinics to implement such guidelines. Methods: Using a concurrent mixed-method research design, we conducted surveys, interviews, and focus groups with 36 primary care personnel in clinics in New Mexico, USA, to examine readiness to implement LGBTQ+ inclusive guidelines, analyzing factors affecting motivation, general organizational capacity, and innovation-specific capacity. We supplemented these data by documenting LGBTQ+ inclusive policies and practices at each clinic. We undertook descriptive analyses and between-subscale comparisons controlling for within-rater agreement of the survey data and iterative coding and thematic analysis of the qualitative data. Results: Quantitatively, participants reported significantly more openness toward adopting guidelines and attitudinal awareness for developing LGBTQ+ clinical skills than clinical preparedness, basic knowledge, and resources to facilitate implementation. Six themes derived from the qualitative findings corroborate and expand on these results: (1) treating all patients the same; (2) addressing diversity in and across LGBTQ+ populations; (3) clinic climates; (4) patient access concerns; (5) insufficient implementation support; and (6) leadership considerations. Conclusion: This study demonstrates that personnel in primary care clinics support initiatives to enhance service environments, policies, and practices for LGBTQ+ patients. However, drawing on Iris Young's theory of structural injustice, we found that neutralizing discourses that construct all patients as the same and time/resource constraints may diminish motivation and capacity in busy, understaffed clinics serving a diverse clientele and reinforce inequities in primary care for LGBTQ+ people. Efforts are needed to build general and innovation-specific capacities for LGBTQ+ initiatives. Such efforts should leverage implementation teams, organizational assessments, education, leadership support, community engagement, and top-down incentives.

Regional Systems of Care in ST Elevation Myocardial Infarction.

ST-segment elevation myocardial infarction is a medical emergency with significant health care delivery challenges to ensure rapid triage and treatment. Several developments over the past decades have led to improved care delivery, decreased time to reperfusion, and decreased mortality. Still, significant challenges remain to further optimize the delivery of care for this patient population.

Orbital Atherectomy for Treatment of Severely Calcified Coronary Artery Bifurcation Lesions: A Multicenter Analysis.

OBJECTIVE: This study evaluated the safety and efficacy of orbital atherectomy (OA) for the treatment of severely calcified coronary artery bifurcation lesions. BACKGROUND: Percutaneous coronary intervention (PCI) of severely calcified coronary artery lesions is associated with lower procedural success and higher rates of target lesion failure compared to non-calcified lesions. OA is an effective treatment for calcified coronary artery lesions prior to stent implantation. However, there is little data regarding the safety and efficacy of OA in patients with coronary artery bifurcation lesions. METHODS: Data were obtained from analysis of patients with severe coronary artery calcification who underwent OA and coronary stent implantation at ten high-volume institutions. Data were pooled and analyzed to assess peri-procedural outcomes and 30-day major adverse cardiac events (MACE). RESULTS: A total of 1156 patients were treated with OA and PCI. 363 lesions were at a coronary artery bifurcation. There were no statistically significant differences in baseline characteristics between the bifurcation and non-bifurcation groups. In the bifurcation group, treatment involved the left anterior descending artery and its branches more frequently and right coronary artery less frequently. After propensity score matching, the 30-day freedom from MACE was not statistically significant between the two groups. CONCLUSION: In this multicenter cohort analysis, patients with severely calcified coronary bifurcation lesions had low rates of MACE and target vessel revascularization at 30 days at rates comparable to non-bifurcation lesions. This analysis demonstrates that OA is safe and effective for complex coronary lesions at both bifurcation and non-bifurcation locations.

Theoretical models for dynamic shape factors and lung deposition of small particle aggregates originating from combustion processes.

A theoretical model was developed which allows the generation of irregularly shaped aggregate particles due to the stepwise joining of spherical components with variable diameters. The mathematical approach is mainly thought to act as a supporting tool for the simulation of the transport and deposition behaviour of combustion aerosols in the atmosphere and the human respiratory tract. In combination with aggregate construction essential particle parameters (dynamic shape factor χ, aerodynamic diameter d(ae)) are computed using the model. As a main result of aggregate generation, an increasing particle size, expressed by an increasing number of spherical components, leads to an enhancement of χ and d(ae), whereby values of the first parameter range from 2 to 70. Deposition of small aggregates (sizes between 2 and 200nm) in the human respiratory tract is commonly marked by high rates of bronchial particle accumulation (40-60%) and declined rates of extrathoracic (20-30%) and alveolar accumulation (2-15%). Concerning aggregate deposition by airway generation, increased cluster size causes a significant decrease of particle accumulation in the proximal airways, whilst accumulation in the intermediate to distal airways is dramatically enhanced. The model was validated using experimental deposition data of tobacco smoke. An excellent correspondence between experimental and theoretical results was found.

Enhancing primary care services for diverse sexual and gender minority populations: a developmental study protocol.

INTRODUCTION: Compared with heterosexual, cisgender populations, sexual and gender minority (SGM) people are more likely to suffer from serious health conditions and insufficient access to health services. Primary care is at the frontlines of healthcare delivery; yet, few clinics have resources or mechanisms in place to meet SGM patient needs. This developmental study protocol focuses on reducing health disparities among SGM patients by identifying, adapting and developing SGM practice guidelines/recommendations and implementation strategies for primary care clinics in urban and rural New Mexico. Using input from patients, healthcare advocates and providers, and researchers, the study will pilot a practice parameter and implementation toolkit to promote SGM-specific cultural competence at multiple service delivery levels. METHODS AND ANALYSIS: We will recruit providers/staff from four Federally Qualified Health Centers (FQHCs) serving ethnically and geographically diverse communities. Incorporating the Implementation of Change Model and an intersectionality perspective, data collection includes a systematic review of SGM-specific practice guidelines/recommendations, focus groups and semistructured interviews, quantitative surveys and the Nominal Group Technique (NGT) with providers/staff. We will categorise guidelines/recommendations identified through the review by shared elements, use iterative processes of open and focused coding to analyse qualitative data from focus groups, interviews and the NGT, and apply descriptive statistics to assess survey data. Findings will provide the foundation for the toolkit. Focus groups with SGM patients will yield supplemental information for toolkit refinement. To investigate changes in primary care contexts following the toolkit's pilot, we will undertake systematic walkthroughs and document review at the FQHCs, analysing these data qualitatively to examine SGM inclusiveness. The structured data-informed Plan-Do-Study-Act method will enable further revision of the toolkit. Finally, focus groups, interviews and quantitative surveys with providers/staff will highlight changes made in the FQHCs to address SGM patient needs, barriers to sustainment of changes, satisfaction, acceptability, usability and feasibility of the toolkit. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Pacific Institute for Research and Evaluation Institutional Review Board. Informed consent will be obtained from all participants before their involvement in research activities begins. Study results will be actively disseminated through peer-reviewed journals, conference presentations, social media and the internet, and community/stakeholder engagement activities.

Orbital Atherectomy for Treatment of Complex Severely Calcified Coronary Artery Lesions: Insights from a Veterans Affairs Cohort.

BACKGROUND: Coronary artery calcification remains a significant challenge to successful percutaneous coronary intervention (PCI). Orbital atherectomy (OA) is an effective treatment for severely calcified coronary artery lesions during PCI, but few data are available in the Veterans Affairs (VA) system which has an increasingly complex subset of patients. METHODS: Data were obtained from retrospective analysis of patients with severe coronary artery calcification who underwent OA followed by stent implantation from February of 2015 to July of 2018 at a single VA Medical Center. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day and 1-year freedom from major adverse cardiac events [MACE: Cardiac Death, myocardial infarction (MI), or target vessel revascularization (TVR)]. RESULTS: Among 151 patients, baseline comorbidities included diabetes (57%), prior PCI (51%), congestive heart failure (36.4%), and prior coronary artery bypass grafting (23.2%). The most common indication for intervention was stable angina (54.3%). Seventeen percent of cases required hemodynamic support. Angiographic complication rates were low. Overall freedom from MACE was 96% at 30 days and 87.7% at 1 year. CONCLUSION: This single-center VA cohort demonstrates that patients with severely calcified and anatomically complex coronary artery lesions treated with OA had a low rate of angiographic complications and a high rate of one-year freedom from MACE. Moreover, this study included demographics underrepresented in clinical trials, including those with acute myocardial infarction, left main coronary artery disease, and bifurcation lesions.

Immunoaffinity-based mass spectrometric characterization of the FMRFamide-related peptide family in the pericardial organ of Cancer borealis.

The tetrapeptide, FMRFamide, was first discovered in 1977 in the molluscan nervous system and was found to affect the contractile force of molluscan cardiac muscle and other muscles. Since then, numerous FMRFamide-related peptides (FaRPs) have been reported in both invertebrate and vertebrate species. We have previously reported the detection and identification of numerous FaRPs in Cancer borealis pericardial organs (POs), one of the major neurosecretory structures in the crustaceans. Here, we have developed two immunoaffinity-based methods, immunoprecipitation (IP) and immuno-dot blot screening assay, for the enrichment of FaRPs in C. borealis POs. A combined mass spectrometry (MS)-based approach involving both matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) and nanoscale liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry (nanoLC-ESI-QTOF MS/MS) is used for a more comprehensive characterization of the FaRP family by utilizing high mass accuracy measurement and efficient peptide sequencing. Overall, 17 FMRFamide-related peptides were identified using these two complementary immuno-based approaches. Among them, three novel peptides were reported for the first time in this study.

[Theoretical calculations of the deposition of non-spherical particles in the upper airways of the human lung]. / Modellrechnungen zur Deposition nicht-sphärischer Teilchen in den oberen Luftwegen der menschlichen Lunge.

In the contribution presented here a computer model for the description of non-spherical particle deposition in the upper human respiratory tract is introduced. The theoretical approach is mainly based on the principle of the aerodynamic diameter, whose calculation was carried out according to most current scientific findings. With the help of this parameter deposition patterns for various particle categories (fibers and oblate disks) and breathing conditions (sitting, light-work and hard-work breathing) were simulated. Concerning cylindrical fibers with a diameter > or = 1 microm, an increase of the aspect ratio beta (i.e. particle length/particle diameter) causes a significant enhancement of deposition in the uppermost regions of the respiratory tract (oropharynx, larynx, trachea). This effect is additionally intensified by an increase of the inhalative flow. Regarding the oblate disks with a diameter > or = 1 microm, any decrease of the aspect ratio leads to an enhancement of deposition in the deeper lung regions, representing an effect contrary to that observed for fibers. An increase of the inhalative flow only induces a limited decrease of the effect.

Structural competency in emergency medicine services for transgender and gender non-conforming patients.

In this formative qualitative research, we draw upon the concepts of structural vulnerability and structural competency to examine how transgender and gender non-conforming (TGGNC) patients and healthcare personnel experience service delivery in Emergency Departments (EDs), and how this experience can be improved upon. Between October 2016 and June 2017, we undertook 31 semi-structured interviews with TGGNC patients (n = 11) and physicians (n = 6), nurses (n = 7), and non-clinical staff (n = 7) in four community-based EDs in New Mexico. Our iterative coding and analysis process resulted in eight sets of findings: (1) reasons why TGGNC patients seek care from EDs; (2) perceptions about and experiences of TGGNC patients; (3) relevance of gender identity and sex at birth; (4) bureaucracy and communication; (5) spatial considerations; (6) preparing providers and staff to care for TGGNC patients; (7) the lack of resources for structural prescriptions; and (8) respect, humanity, and sameness. Findings suggest that structural issues adversely impact the health and wellbeing of TGGNC patients and service-delivery practices in the ED. We describe study implications for training ED personnel and modifying this practice setting to prevent delayed care and ensure appropriate services for TGGNC patients in need of structurally competent emergency medicine.

Semi-empirical stochastic model of aerosol bolus dispersion in the human lung.

Aerosol bolus dispersion, that is, the broadening of an inhaled narrow aerosol bolus upon exhalation, was simulated by Monte Carlo methods using a stochastic, asymmetric morphometric model of the human lung. Physical mechanisms considered to contribute to bolus dispersion were (1) axial diffusion in conductive airways, approximated by effective diffusivities, (2) convective mixing at airway bifurcation sites, (3) differences in inspiratory and expiratory velocity profiles, (4) mixing with residual air in alveoli, and (5) inhomogeneous ventilation of the lung lobes due to asymmetric flow spitting at bifurcations and asymmetric and asynchronous filling of the five lung lobes. Theoretical predictions of the bolus dispersion model were compared to experimental data for 79 healthy volunteers, which provide detailed information on statistical bolus parameters (half-width, standard deviation, skewness, and mode shift) and total bolus deposition as a function of the depth of bolus penetration into the airway system. Predicted bolus dispersion and deposition data show excellent agreement with the published experimental data, suggesting that axial diffusion in conductive airways and convective mixing in alveoli, resulting in irreversible particle transport, are the major determinants of bolus dispersion. The variability and asymmetry of the branching airway network, leading to asymmetric flow splitting at airway bifurcations, greatly enhances the effect of irreversibility and the resulting dispersion of the inhaled bolus.

Morphology and histology of the ductus receptaculi and accessory glands in the reproductive tract of the female cricket, Teleogryllus commodus.

The morphology and histology of the ductus receptaculi and accessory glands in females of the black field cricket, Teleogryllus commodus Walker (Orthoptera: Gryllidae) are described. Both are reproductive organs situated in the 7(th) and 8(th) abdominal segment that join the posterior part of the genital chamber. The ductus receptaculi is a long (up to 25 mm) homogeneous tube, and the accessory glands (total length: 4 to 12 mm) are a complex system of tubes and end lobes with various numbers of ramifications. Based on their external shapes the accessory glands may be subdivided into three distinct regions, a distal region mainly producing the gland's secretion, a middle conducting region, and a basal region serving for the storage and release of the secretory substances into the genital chamber of the female. In histological respects, both organs have an outer muscle coat followed by a basal lamina, one or two cell layers, the cuticular intima, and the inner lumen. The ductus receptaculi is subdivided into three histologically different regions. The region located adjacent to the receptaculum and the region neighbouring the terminal papilla consist of a single, epithelial cell layer that is not secretory. The epithelium of the middle region contains two cell layers, glandular cells and cuticula-forming cells, which are responsible for the production of the cuticular intima. The secretion of the gland cells is released into an extracellular cavity, through which it reaches the lumen via a complex network of canals running through the intima. The histology of the accessory glands is rather homogeneous among the different regions, as one layer of epithelial cells produces both the secretion and the cuticular intima. Histological variations in the distal, middle, and basal gland sections mainly concern the height of the epithelium, the thickness of the basal lamina and the cuticular intima as well as the variable presence of the outer muscle coat. In contrast to the ductus receptaculi, secretory substances produced by the accessory gland cells accumulate in the lumen by a diffusive permeation of the intima.

A Multifaceted Mass Spectrometric Method to Probe Feeding Related Neuropeptide Changes in Callinectes sapidus and Carcinus maenas.

Food intake is regulated by various neuromodulators, including numerous neuropeptides. However, it remains elusive at the molecular and cellular level as to how these important chemicals regulate internal processes and which regions of the neuronal organs are responsible for regulating the behavior. Here we report a comparative neuropeptidomic analysis of the brain and pericardial organ (PO) in response to feeding in two well-studied crustacean physiology model organisms, Callinectes sapidus and Carcinus maenas, using mass spectrometry (MS) techniques. A multifaceted MS-based approach has been developed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and PO. The method employs stable isotope labeling of brain and PO extracts for relative MS quantitation, capillary electrophoresis (CE)-MS for fractionation and high-specificity analysis, and mass spectrometric imaging (MSI) for in-situ molecular mapping of peptides. A number of neuropeptides, including RFamides, B-type allatostatins (AST-B), RYamides, and orcokinins exhibit significant changes in abundance after feeding in this investigation. Peptides from the AST-B family found in PO tissue were shown to have both altered expression and localization changes after feeding, indicating that they may be a class of vital neuropeptide regulators involved in feeding behavior. Graphical Abstract ᅟ.