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.

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.

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.

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.

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.

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.

Inhalation of nanoplatelets - Theoretical deposition simulations.

Primary objective of the contribution was the theoretical prediction of nanoplatelet deposition in the human respiratory tract. Modeling was founded on the hypothetical inhalation of graphene nanoplatelets (GNP) measuring 0.01 and 0.1µm in thickness and adopting a projected area diameter of 1-30µm. Particle uptake was assumed to take place with inhalation flow rates of 250, 500, 750, and 1000cm3s-1, respectively. For an appropriate description of pulmonary particle behavior, transport of GNP in a stochastic lung structure and deposition formulae based on analytical and numerical studies were presupposed. The results obtained from the theoretical approach clearly demonstrate that GNP with a thickness of 0.01µm deposit in the respiratory tract by 20-50%, whereas GNP with a thickness of 0.1µm exhibit a deposition of 20-90%. Larger platelets deposit with higher probability than small ones. Increase of inhalation flow rate is accompanied by decreased deposition in the case of thin GNP, whilst thicker GNP are preferably accumulated in the extrathoracic region. Generation-specific deposition ranges from 0.05 to 7% (0.01µm) and from 0.05 to 9%, with maximum values being obtained in airway generation 20. In proximal airway generations (0-10), deposition is increased with inhalation flow rate, whereas in intermediate to distal generations a reverse effect may be observed. Health consequences of GNP deposition in different lung compartments are subjected to an intense debate.

Theoretical diagnosis of emphysema by aerosol bolus inhalation.

BACKGROUND: The present contribution deals with the theoretical description of aerosol bolus dispersion in lungs being affected by different manifestations of emphysema. The work constructs the hypothesis that each manifestation of emphysema exhibits specific properties with regard to the dispersion of inhaled and exhaled aerosol boluses as well as the deposition of particles from the aerosol pulse. METHODS: For an appropriate simulation of single emphysematous manifestations, a previously developed model assuming (I) a random variation of alveolar diameters, (II) an exact localization of diseased structures, and (III) a realistic balance between alveolar air volume and number of air sacs was applied. Dispersion of inhaled and exhaled aerosol boluses was simulated by using the mathematical concept of effective diffusivities. Computations were conducted for an average adult lung (FRC =3,300 mL), symmetric breath-cycles with a length 8 s, and inhalation flow rates of 250 mL/s. Particles used for the model predictions had a uniform diameter of 0.84 µm and a density of 1 g/cm3. RESULTS: According to the theoretical data obtained from the model highest aerosol bolus dispersion may be observed in lungs affected by panacinar and bullous emphysema, whereas centriacinar and paraseptal emphysema cause a significant reduction of the phenomenon. Also other statistical parameters exhibit partly remarkable differences among the studied manifestations. Particle deposition in lungs affected by bullous emphysema falls below that of lungs impaired by the other types of emphysema by 2%-50%. CONCLUSIONS: From the hypothetical results presented in this study it may be concluded that aerosol bolus inhalation bears a certain potential for the diagnosis of emphysematous structures and, if applied with sufficient accuracy, also for the distinction of single manifestations of emphysema. For a successful use of the technique, however, all statistical bolus parameters and particle deposition have to be subjected to a detailed evaluation.

Bioaerosols in the lungs of subjects with different ages-Part 2: clearance modeling.

BACKGROUND: The present contribution deals with theoretical aspects regarding biogenic particle clearance from various lung structures of probands with different ages (1, 5, 15, 20 y). With reference to part 1 of the study, particles varying in size and shape are subject to a detailed analysis. The main goal of the investigation consists in an increase of our knowledge concerning the clearance behaviour of bioparticles and its dependence upon various physiological and anatomical factors. METHODS: Theoretical clearance of biogenic particles was subdivided into four main phases, namely fast bronchial clearance, slow bronchial clearance, fast alveolar clearance, and slow alveolar clearance. All of these phases were simulated by using a well validated stochastic modeling approach, where the main focus is set on the randomly varied particle mass transfer between main compartments of the human respiratory tract. Whilst effects of particle geometry on clearance were approximated by application of the projective-diameter concept, age dependence of the particle removal process was expressed by the experimentally proven relationship between bronchial mucus velocities and morphometry of the airway tree. RESULTS: According to the results of the theoretical simulations efficiency of fast bronchial clearance, expressed by the 24-h-retention value, exhibits a negative correlation with proband's age, whereas the other clearance phases are characterized by a rather conservative behaviour among the different age categories. Highest clearance rates may be observed for very fine (<0.01 µm) and very coarse particles (>5 µm) preferentially deposited in the upper bronchial airways, whilst large particles accumulated in the alveoli may be stored there for several months to years. CONCLUSIONS: The study comes to the conclusion that infants and children dispose of an enhanced bronchial clearance efficiency with respect to adolescents and adults, which results in a faster removal of particulate substances accumulated in the upper bronchial regions. Particles escaping from the natural filtering process in the upper airways and undergoing alveolar deposition are subject to identical clearance scenarios among the age groups and may represent remarkable health hazards.

Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues.

Local lung deposition of ultrafine particles in healthy adults: experimental results and theoretical predictions.

BACKGROUND: Ultrafine particles (UFP) of biogenic and anthropogenic origin occur in high numbers in the ambient atmosphere. In addition, aerosols containing ultrafine powders are used for the inhalation therapy of various diseases. All these facts make it necessary to obtain comprehensive knowledge regarding the exact behavior of UFP in the respiratory tract. METHODS: Theoretical simulations of local UFP deposition are based on previously conducted inhalation experiments, where particles with various sizes (0.04, 0.06, 0.08, and 0.10 µm) were administered to the respiratory tract by application of the aerosol bolus technique. By the sequential change of the lung penetration depth of the inspired bolus, different volumetric lung regions could be generated and particle deposition in these regions could be evaluated. The model presented in this contribution adopted all parameters used in the experiments. Besides the obligatory comparison between practical and theoretical data, also advanced modeling predictions including the effect of varying functional residual capacity (FRC) and respiratory flow rate were conducted. RESULTS: Validation of the UFP deposition model shows that highest deposition fractions occur in those volumetric lung regions corresponding to the small and partly alveolated airways of the tracheobronchial tree. Particle deposition proximal to the trachea is increased in female probands with respect to male subjects. Decrease of both the FRC and the respiratory flow rate results in an enhancement of UFP deposition. CONCLUSIONS: The study comes to the conclusion that deposition of UFP taken up via bolus inhalation is influenced by a multitude of factors, among which lung morphometry and breathing conditions play a superior role.

Morphology and development of the accessory glands in various female cricket species.

The study presents new results with regard to the morphometric and ultrastructural development of the accessory glands in females of the three cricket species Gryllus bimaculatus, Gryllus assimilis, and Acheta domesticus. Furthermore, possible age-dependence of secretory productivity of single organs was analyzed by application of the ligature technique introduced in a previous contribution. Within the first 12 days of the adult phase, the accessory glands of all investigated cricket species exhibit a significant increase in length and width which assumes values between 50 and 100%. This gland growth is rather the result of a continuous increase in cellular volume and less that of mitotic cell propagation. In all species height and width of single gland cells increase by 60-80% within the studied time interval. These changes in morphometry are commonly accompanied by ultrastructural modifications. Total glandular secretion is subject to an increase from the 5th to the 12th day of adult age. This development corresponds well with the number of eggs contemporaneously oviposited into the substrate and thus underlines the hypothesis, according to which the main function of the secretion consists in acting as a lubricant for the facilitated transport of the oocytes through the ovipositor.

HRMS using a Q-Exactive series mass spectrometer for regulated quantitative bioanalysis: how, when, and why to implement.

High-resolution MS (HRMS) has seen an uptake in use for discovery qual/quan workflows, however, its utilization in late discovery/development has been slow. Past reports comparing HRMS to triple quadrupole (QQQ) instrumentation to date have indicated that HRMS instruments are capable of producing data acceptable for regulated bioanalysis, however lack the sensitivity required for sub ng/ml LLOQ assays. Recent advances in HRMS instrumentation have closed the sensitivity gap with QQQ and have even provided improved selectivity and sensitivity over QQQ SRM assays. Herein, the authors will describe how, when, and why HRMS (specifically Q-Exactive series mass spectrometers) should be considered for implementation in regulated quantitative bioanalysis assays.

Total deposition of ultrafine particles in the lungs of healthy men and women: experimental and theoretical results.

BACKGROUND: Inhaled ultrafine particles (UFP) may induce greater adverse respiratory effects than larger particles occurring in the ambient atmosphere. Due to this potential of UFP to act as triggers for diverse lung injuries medical as well as physical research has been increasingly focused on the exact deposition behavior of the particles in lungs of various probands. Main purpose of the present study was the presentation of experimental and theoretical data of total, regional, and local UFP deposition in the lungs of men and women. METHODS: Both experiments and theoretical simulations were carried out by using particle sizes of 0.04, 0.06, 0.08, and 0.10 µm [number median diameters (NMD)]. Inhalation of UFP took place by application of predefined tidal volumes (500, 750, and 1,000 mL) and respiratory flow rates (150, 250, 375, and 500 mL·s(-1)). For male subjects a functional residual capacity (FRC) of 3,911±892 mL was measured, whereas female probands had a FRC of 3,314±547 mL. Theoretical predictions were based on (I) a stochastic model of the tracheobronchial tree; (II) particle transport computations according to a random walk algorithm; and (III) empirical formulae for the description of UFP deposition. RESULTS: Total deposition fractions (TDF) are marked by a continuous diminution with increasing particle size. Whilst particles measuring 0.04 µm in size deposit in the respiratory tract by 40-70%, particles with a size of 0.10 µm exhibit deposition values ranging from 20% to 45%. Except for the largest particles studied here TDF of female probands are higher than those obtained for male probands. Differences between experimental and theoretical results are most significant for 0.10 µm particles, but never exceed 20%. Predictions of regional (extrathoracic, tracheobronchial, alveolar) UFP deposition show clearly that females tend to develop higher tracheobronchial and alveolar deposition fractions than males. This discrepancy is also confirmed by airway generation-specific deposition, which is permanently higher in women than in men. CONCLUSIONS: From the experimental data and modeling predictions it can be concluded that females bear a slightly higher potential to develop lung insufficiencies after exposure to UFP than males. Besides higher deposition fractions occurring in female subjects, also total lung deposition dose is noticeably enhanced.

Bioaerosols in the lungs of subjects with different ages-part 1: deposition modeling.

BACKGROUND: In this contribution the inhalation and deposition of bioaerosols including particles with various shapes and sizes were investigated for probands with different ages (1, 5, 15 and 20 y). The study should help to increase our knowledge with regard to the behavior of variably shaped and sized particles in lungs being subject to different developmental stages. METHODS: Simulation of particle transport and deposition in single structures of the respiratory tract was conducted by using a stochastic model of the tracheobronchial tree and well-validated analytical and empirical deposition formulae. Possible effects of particle geometry on deposition were taken into consideration by application of the aerodynamic diameter concept. Age-dependent lung morphometry and breathing parameters were computed by using appropriate scaling factors. RESULTS: Theoretical simulations came to the result that bioparticle deposition in infants and children clearly differs from that in adolescents and adults insofar as the amount of deposited mass exhibits a positive correlation with age. Nose breathing results in higher extrathoracic deposition rates than mouth breathing and, as a consequence of that, lower particle amounts are enabled to enter the lung structures after passing the nasal airways. Under sitting breathing conditions highest alveolar deposition rates were calculated for particles adopting aerodynamic diameters of 10 nm and 4 µm, respectively. CONCLUSIONS: The study comes to the conclusion that bioparticles have a lower chance to reach the alveoli in infants' and children's lungs, but show a higher alveolar deposition probability in the lungs of adolescents and adults. Despite of this circumstance also young subjects may increasingly suffer from biogenic particle burden, when they are subject to a long-term exposure to certain bioaerosols.

Antibody-based targeting of alternatively spliced tissue factor: a new approach to impede the primary growth and spread of pancreatic ductal adenocarcinoma.

Alternatively spliced Tissue Factor (asTF) is a secreted form of Tissue Factor (TF), the trigger of blood coagulation whose expression levels are heightened in several forms of solid cancer, including pancreatic ductal adenocarcinoma (PDAC). asTF binds to ß1 integrins on PDAC cells, whereby it promotes tumor growth, metastatic spread, and monocyte recruitment to the stroma. In this study, we determined if targeting asTF in PDAC would significantly impact tumor progression. We here report that a novel inhibitory anti-asTF monoclonal antibody curtails experimental PDAC progression. Moreover, we show that tumor-derived asTF is able to promote PDAC primary growth and spread during early as well as later stages of the disease. This raises the likelihood that asTF may comprise a viable target in early- and late-stage PDAC. In addition, we show that TF expressed by host cells plays a significant role in PDAC spread. Together, our data demonstrate that targeting asTF in PDAC is a novel strategy to stem PDAC progression and spread.