Microvascular maturation of the septal capillary layers takes place in parallel to alveolarization in human lungs.

Primary and secondary septa formed during lung development contain a double-layered capillary network. To improve gas exchange, the capillary network is remodeled into a single-layered one, a process that is called microvascular maturation (MVM). It takes place during classical and continued alveolarization. Classical alveolarization is defined as a formation of new septa from immature septa and continued alveolarization as a formation from mature septa. Until now, MVM was never quantitatively evaluated in human lungs. To correlate alveolarization and MVM, and to determine the transition point from classical to continued alveolarization, the degree of MVM was stereologically estimated. In 12 human lungs (0.1-15 yr), the alveolar surface area of immature and mature septa was estimated stereologically by intersection counting. An MVM-quotient (RMVM) was defined as the mature alveolar surface area over total alveolar surface area. The MVM-quotient increased logarithmically over age and showed a biphasic increase similar to alveolarization. It did not reach 100% maturity in these samples. A linear correlation between the MVM-quotient and the logarithm of the number of alveoli was observed. We conclude that MVM increased logarithmically and biphasically in parallel to alveolarization until alveolarization ceased. However, at 2-3 yr of age three-quarters of the alveolar microvasculature are mature. This result may explain a previous postulate that MVM is finished at this age. We hypothesize that as long as alveolarization takes place, MVM will take place in parallel. We propose that the transition from classical to continued alveolarization takes place between the ages of 1-3 yr in humans.NEW & NOTEWORTHY Newly formed alveolar septa contain a double-layered capillary network. To optimize gas exchange, the two layers fuse to a single-layered capillary network during microvascular maturation. Because its timing is unknow in humans, microvascular maturation was stereologically estimated throughout postnatal human lung development. It is shown that maturation of the microvascular and alveolar septa takes place in parallel to alveolarization. At an age of 2-3 yr three-quarters of the septa are mature.

Differential Immunomodulatory Effects of Head and Neck Cancer-Derived Exosomes on B Cells in the Presence of ATP.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy. Tumor-derived exosomes (TEX) have immunoregulatory properties. Adenosine triphosphate (ATP) and its immunosuppressive precursor adenosine (ADO) have been found in cancerous tissue. We investigated the effect of TEX on B cells in the presence of ATP. TEX were isolated from human HNSCC cell line (PCI-13) cultures and co-cultured with peripheral blood B cells of healthy donors, with or without TEX in different concentrations and with or without a low (20 µM) or high (2000 µM) ATP dose. We were able to demonstrate that TEX inhibit B-cell proliferation. The addition of TEX to either ATP concentration showed a decreasing trend in CD39 expression on B cells in a dose-dependent manner. High ATP levels (2000 µM) increased apoptosis and necrosis, and analysis of apoptosis-associated proteins revealed dose-dependent effects of ATP, which were modified by TEX. Altogether, TEX exhibited dual immunomodulatory effects on B cells. TEX were immunosuppressive by inhibiting B-cell proliferation; they were immunostimulatory by downregulating CD39 expression. Furthermore, TEX were able to modulate the expression of pro- and anti-apoptotic proteins. In conclusion, our data indicate that TEX play an important, but complex, role in the tumor microenvironment.

The Quality of Life, Patient Satisfaction and Rehabilitation in Patients With a Low Energy Fracture-Part III of an Observational Study.

INTRODUCTION: Due to the aging population the incidence of Low Energy Fractures (LEF) increases. LEF have high mortality and morbidity rates and often cause elderly to lose independence. Patient-reported outcomes, such as Quality of Life (QoL) and patient satisfaction (PS) are needed to evaluate treatment, estimate cost-benefit analyses, and to improve clinical decision-making and patient-centered care. OBJECTIVE: The primary goal was to evaluate QoL and PS in patients with LEF, and to compare QoL scores to the community dwelling population. Second, we observed the amount and type of physiotherapy (PT) sessions the patients conducted. METHODS: A single-center cohort study was conducted in Switzerland. Patients between 50 and 85 years, who were treated in the hospital for LEF, were followed 1 year after initial fracture. Data on QoL were obtained through the Euroqol-5-Dimension questionnaire-3-Level (EQ-5D-3L) and the EQ VAS (visual analog scale). PS was measured by a VAS on satisfaction with treatment outcome. Data on PT sessions, mobility and use of analgesics were collected by telephone interviews and written surveys. Results were compared between the different fracture locations and subgroup analyses were performed for age categories. RESULTS: 411 patients were included for analysis. The median scores of the EQ-5D-3L index-VAS and PS were 0.90 (0.75-1.0), 90 (71.3-95) and 100 (90-100). Significant differences in all scores were found between fracture location (P < .05), with hip fracture patients and patients with a malleolar fracture scoring lowest in all measures. QoL index in hip fracture patients was 0.76 (0.70-1.00), QoL VAS 80 (70-90), and PS 95 (80-100). Median amount of PT sessions in all patients was 18 (9-27) and a significant difference was found between fracture locations. Patients with a fracture of the humerus received the highest amount of PT sessions 27 (18-36), hip fracture patients had a median of 18 (9-27) sessions. CONCLUSION: At follow-up, QoL throughout all patients with a LEF was comparable to a normal population. Remarkably, though hip fracture patients seem to suffer from a clinically relevant loss of QoL, they received fewer PT sessions and performed fewer long-lasting home training than patients with a humerus fracture. Intensive, progressive rehabilitation with a high frequency of supervised training is recommended after hip fracture. The low frequency of PT sessions found in this study is unsatisfying. In hip fracture patients and in patients with a malleolar fracture, especially when aged over 75 years, more efforts are required to improve rehabilitation and subsequently QoL.

Fear of Falling, Recurrence of Falls, and Quality of Life in Patients with a Low Energy Fracture-Part II of an Observational Study.

Background and objective: Falls in elderly cause injury, mortality, and loss of independence, making Fear of Falling (FoF) a common health problem. FoF relates to activity restriction and increased fall risk. A voluntary intervention including fall risk assessment and prevention strategies was implemented to reduce falls in elderly patients with low energy fractures (LEF). The primary purpose of this study was to evaluate FoF and the number of subsequent falls in trauma patients one year after a LEF. The secondary aim was to examine how FoF affects patients' lives in terms of Quality of Life (QoL), mobility, and activity levels. Finally, participation in the voluntary fall prevention program (FPP) was evaluated. Materials and Methods: Observational cohort study in one Swiss trauma center. LEF patients, treated between 2012 and 2015, were analyzed one year after injury. Primary outcomes were Falls-Efficacy Score-International (FES-I) and number of subsequent falls. Secondary outcomes were EuroQoL-5-Dimensions-3-Levels (EQ5D-3L), mobility, activity levels, and participation in the FPP. Subgroup analysis was performed for different age categories. Results: 411 patients were included for analysis. Mean age was 72 ± 9.3, mean FES-I was 21.1 ± 7.7. Forty percent experienced FoF. A significant negative correlation between FoF and QoL (R = 0.64; p < 0.001) was found. High FoF correlated with lower activity levels (R= -0.288; p < 0.001). Six percent visited the FPP. Conclusions: At follow-up, 40% suffered from FoF which seems to negatively affect patients' QoL. Nevertheless, participation in the FPP was low. Simply informing patients about their susceptibility to falls and recommending participation in FPPs seems insufficient to motivate and recruit patients into FPPs. We suggest implementing repeated fall risk- and FoF screenings as standard procedures in the follow-up of LEF, especially in patients aged over 75 years.

Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis.

Prognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinical significance of PD-1 and PD-L1 expression in gastric and esophageal adenocarcinomas, particularly in non-Asian patients, is still unclear. Three tissue microarrays including 190 clinically annotated esophageal (n = 31) and gastric (n = 159) adenocarcinomas and 58 paired mucosa specimens, were stained with PD-1, PD-L1, and CD8-specific reagents in indirect immunohistochemistry assays. PD-L1 expression was detectable in 23.2% of cancer specimens. High PD-1 expression was detectable in 37.3% of cases and high CD8+ infiltration in 76%. PD-L1 and high PD1 expression significantly correlated with each other (r s = 0.404, P < 0.0001) and both significantly correlated with CD8+ infiltration (r s = 0.435, P = 0.0003, and r s = 0.444; P = 0.0004, respectively). CD8+ lymphocyte infiltration correlated with improved survival in univariate (P = 0.009), but not multivariate analysis. Most interestingly, multivariate analysis and Kaplan-Meier curves indicate that combined low PD-1/PD-L1 expression and low CD8+ lymphocyte infiltration significantly correlate with poor prognosis. Our data document the clinical significance of a microenvironmental signature including PD-1/PD-L1 expression and CD8+ lymphocyte infiltration in gastric and esophageal adenocarcinomas and contribute to identify a patients' subset requiring more aggressive peri-operative treatments.

Application of a SSR-GBS marker system on investigation of European Hedgehog species and their hybrid zone dynamics.

By applying second-generation sequencing technologies to microsatellite genotyping, sequence information is produced which can result in high-resolution population genetics analysis populations and increased replicability between runs and laboratories. In the present study, we establish an approach to study the genetic structure patterns of two European hedgehog species Erinaceaus europaeus and E. roumanicus. These species are usually associated with human settlements and are good models to study anthropogenic impacts on the genetic diversity of wild populations. The short sequence repeats genotyping by sequence (SSR-GBS) method presented uses amplicon sequences to determine genotypes for which allelic variants can be defined according to both length and single nucleotide polymorphisms (SNPs). To evaluate whether complete sequence information improved genetic structure definition, we compared this information with datasets based solely on length information. We identified a total of 42 markers which were successfully amplified in both species. Overall, genotyping based on complete sequence information resulted in a higher number of alleles, as well as greater genetic diversity and differentiation between species. Additionally, the structure patterns were slightly clearer with a division between both species and some potential hybrids. There was some degree of genetic structure within species, although only in E. roumanicus was this related to geographical distance. The statistically significant results obtained by SSR-GBS demonstrate that it is superior to electrophoresis-based methods for SSR genotyping. Moreover, the greater reproducibility and throughput with lower effort which can be obtained with SSR-GBS and the possibility to include degraded DNA into the analysis, allow for continued relevance of SSR markers during the genomic era.

A spatio temporal spectral framework for plant stress phenotyping.

BACKGROUND: Recent advances in high throughput phenotyping have made it possible to collect large datasets following plant growth and development over time, and those in machine learning have made inferring phenotypic plant traits from such datasets possible. However, there remains a dirth of datasets following plant growth under stress conditions along with methods for inferring them using only remotely sensed data, especially under a combination of multiple stress factors such as drought, weeds and nutrient deficiency. Such stress factors and their combinations are commonly encountered during crop production and being able to accurately detect and treat such stress conditions in an automated and timely manner can provide a major boost to farm yields with minimal resource input. RESULTS: We present a generic framework for remote plant stress phenotyping that consists of a dataset with spatio-temporal-spectral data following sugarbeet crop growth under optimal, drought, low and surplus nitrogen fertilization, and weed stress conditions, along with a machine learning based methodology for systematically inferring these stress conditions from the remotely measured data. The dataset contains biweekly color images, infra-red stereo image pairs and hyperspectral camera images along with applied treatment parameters and environmental factors like temperature and humidity, collected over two months. We present a plant agnostic methodology for deriving plant trait indicators such as canopy cover, height, hyperspectral reflectance and vegetation indices along with a spectral 3D reconstruction of the plants from the raw data to serve as a benchmark. Additionally, we provide fresh and dry weight measurements for both the above (canopy) and below (beet) ground biomass at the end of the growing period to serve as indicators of expected yield. We further describe a data driven, machine learning based method to infer water, Nitrogen and weed stress using the derived plant trait indicators. We use the plant trait indicators to evaluate 8 different classification approaches from which the best classifier achieved a mean cross validation accuracy of ≈ 93, 76 and 83% for drought, nitrogen and weed stress severity classification respectively. We also show that our multi-modal approach significantly improves classifier performance over using any single modality. CONCLUSION: The presented framework and dataset can serve as a valuable reference for creating and comparing processing pipelines which extract plant trait indicators and infer prevalent stress factors from remote sensing data under a variety of environments and cropping conditions. These techniques can then be deployed on farm machinery or robots enabling automated, precise and timely corrective interventions for maximising yield.

Experiences of general practitioners, home care nurses, physiotherapists and seniors involved in a multidisciplinary home-based fall prevention programme: a mixed method study.

BACKGROUND: The feasibility of effective fall prevention programmes (FPPs) for use in daily clinical practice needs to be assessed in the specific healthcare settings. The aim of this study was to explore the perceived benefits and barriers of an evidence-based, home-based pilot FPP among the involved seniors, general practitioners (GPs), home care nurses (HCNs) and physiotherapists (PTs), in order to develop tailored implementation strategies. METHODS: The study was a mixed method study using an 'exploratory sequential design'. In the initial qualitative sequence, semi-structured interviews were performed with four participants from each group and analysed using a deductive content analysis. In the successive quantitative sequence, target group specific postal surveys were conducted with all participants. The triangulation of both steps allowed merging the in-depth experiences from the interviews with the general findings from the survey. RESULTS: In this evaluation study participated 17 seniors (mean age 79.7 (SD +/-6.2) years). 40 GPs, 12 HCNs and four PTs. All were satisfied with the organization and processes of the FPP. The main benefit, perceived by each target group, was the usefulness of the FPP in detecting risk of falling at the senior's home. A low number of recruiting GPs and HCNs, divergent opinions of the health professionals towards the aim of the FPP as well as no perceived need for changes by the seniors were the most important barriers to the participation of (more) seniors. CONCLUSIONS: Multidisciplinary home-based fall prevention is a useful approach to detect the risk of falling in seniors. The barriers identified need to be resolved through tailored strategies to facilitate the successful nationwide implementation of this pilot FPP.

High spatio-temporal resolution video with compressed sensing.

We present a prototype compressive video camera that encodes scene movement using a translated binary photomask in the optical path. The encoded recording can then be used to reconstruct multiple output frames from each captured image, effectively synthesizing high speed video. The use of a printed binary mask allows reconstruction at higher spatial resolutions than has been previously demonstrated. In addition, we improve upon previous work by investigating tradeoffs in mask design and reconstruction algorithm selection. We identify a mask design that consistently provides the best performance across multiple reconstruction strategies in simulation, and verify it with our prototype hardware. Finally, we compare reconstruction algorithms and identify the best choice in terms of balancing reconstruction quality and speed.