A new diphenyl ether from the cultured lichen mycobiont of Graphis cf. handelii.

Lichen is well-known for its various purposes. However, understanding the chemical composition and antimicrobial characteristics of Graphis cf. handelii remains insufficient. In this study, a new compound, graphinone A (1), together with three known compounds, handelone (2), 4-O-methylhiascic acid (3), and ethyl orsellinate (4) were isolated and structurally elucidated. Their chemical structures were established using comprehensive spectroscopic data (1D- and 2D-NMR and HRESIMS). Compounds 1-4 were tested for antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and evaluated for the alpha-glucosidase inhibition.

A longitudinal study assessing the impact of elexacaftor/tezacaftor/ivacaftor on gut transit and function in people with cystic fibrosis using magnetic resonance imaging (MRI).

BACKGROUND: Gastrointestinal (GI) symptoms in cystic fibrosis (CF) are common and disruptive. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the GI tract is not fully understood. The aim was to use magnetic resonance imaging (MRI) to determine if elexacaftor/tezacaftor/ivacaftor (ETI) changed GI function and transit. METHODS: This was an 18 month prospective, longitudinal, observational study. We enrolled 24 people with CF aged 12 years or older to undergo MRI scans before starting ETI and 3, 6, and 18 months after starting ETI. The primary outcome measure was change in oro-caecal transit time (OCTT) at 6 and 18 months. Secondary outcome measures included change in small bowel water content (SBWC), change in the reduction in small bowel water content following a meal (DeltaSBWC) and change in total colonic volume (TCV). RESULTS: A total of 21 participants completed MRI scans at 6 months and 11 completed at 18 months. After 18 months of ETI, median OCTT significantly reduced, from >360 min [IQR 240->360] to 240 min [IQR 180-300] (p = 0.02, Wilcoxon signed-rank). Both SBWC and DeltaSBWC increased after starting ETI. TCV reduced significantly after 18 months (p = 0.005, Friedman). CONCLUSIONS: Our findings suggest an improvement in small bowel transit, small bowel response to food and a reduction in colonic volume after starting ETI. These effects may relate to CFTR activation in the small bowel. To our knowledge this is the first study to show a physiological change in GI transit and function in response to CFTR modulator use through imaging studies.

Discovery of delayed gas production after implantation of a continuous-flow left ventricular assist device and a preliminary exploration of the mechanisms of its occurrence.

Objective: To characterize the gas production phenomenon in the animal model of left ventricular assist device (LVAD), and study its mechanism. Methods: An in vitro bubble precipitation experiment was conducted, and the blood samples of Parma spp. animals were divided into ordinary group and oxygen-enriched group according to whether they were oxygenated or not at the time of blood collection, and a static control group was set up respectively. Blood gases were drawn and analyzed before and after the experiment. Activate the pump, and the number of air bubbles in the loop was measured by ultrasound at different rotational speeds; CFD was applied to simulate the flow field in the blood pump, and pressure, fluid velocity vector and shear force diagrams were plotted, and a thrombus model was constructed and the flow field was simulated and plotted as a cloud diagram. Results: There was a statistical difference in the number of bubbles in the inflow and outflow tubes of the blood pump (P values of 0.04 and 0.023, respectively), and the number of bubbles in the outflow tubes of both groups was significantly higher than the number of bubbles in the inflow tubes. The number of bubbles in the tubes of both the oxygen-enriched and normal groups was significantly higher than that in the inflow group. In both the normal and oxygen-enriched groups, more gas was produced at higher speeds than at lower speeds. Blood gas analysis showed that the reduced gas composition in the blood was mainly oxygen. Flow field simulation results: the high rotation speed group had lower central pressure and greater scalar shear. The thrombus simulation group was more prone to turbulence, sudden pressure changes, and greater shear than the normal group. Conclusion: Blood gas production is associated with higher partial pressures of blood oxygen, higher rotation speed, and intrapump thrombosis, and the mechanism of pump gas production is degassing of dissolved gases rather than cavitation of water, and the gas released is most likely to have oxygen. The degassing phenomenon is an warning factor for pump thrombosis.

Study on Low-Velocity Impact and Residual Compressive Mechanical Properties of Carbon Fiber-Epoxy Resin Composites.

Room temperature drop hammer impact and compression after impact (CAI) experiments were conducted on carbon fiber-epoxy resin (CF/EP) composites to investigate the variation in impact load and absorbed energy, as well as to determine the residual compressive strength of CF/EP composites following impact damage. Industrial CT scanning was employed to observe the damage morphology after both impact and compression, aiding in the study of impact-damage and compression-failure mechanisms. The results indicate that, under the impact load, the surface of a CF/EP composite exhibits evident cratering as the impact energy increases, while cracks form along the length direction on the back surface. The residual compressive strength exhibits an inverse relationship with the impact energy. Impact damage occurring at an energy lower than 45 J results in end crushing during the compression of CF/EP composites, whereas energy exceeding 45 J leads to the formation of long cracks spanning the entire width of the specimen, primarily distributed symmetrically along the center of the specimen.

Analysis of the Impact of Cooling Lubricants on the Tensile Properties of FDM 3D Printed PLA and PLA+CF Materials.

This study investigates the impact of infill density on the mechanical properties of fused deposition modeling (FDM) 3D-printed polylactic acid (PLA) and PLA reinforced with carbon fiber (PLA+CF) specimens, which hold industrial significance due to their applications in industries where mechanical robustness and durability are critical. Exposure to cooling lubricants is particularly relevant for environments where these materials are frequently subjected to cooling fluids, such as manufacturing plants and machine shops. This research aims to explore insights into the mechanical robustness and durability of these materials under realistic operating conditions, including prolonged exposure to cooling lubricants. Tensile tests were performed on PLA and PLA+CF specimens printed with varying infill densities (40%, 60%, 80%, and 100%). The specimens underwent tensile testing before and after exposure to cooling lubricants for 7 and 30 days, respectively. Mechanical properties such as tensile strength, maximum force, strain, and Young's modulus were measured to evaluate the effects of infill density and lubricant exposure. Higher infill densities significantly increased tensile strength and maximum force for both PLA and PLA+CF specimens. PLA specimens showed an increase in tensile strength from 22.49 MPa at 40% infill density to 45.00 MPa at 100% infill density, representing a 100.09% enhancement. PLA+CF specimens exhibited an increase from 23.09 MPa to 42.54 MPa, marking an 84.27% improvement. After 30 days of lubricant exposure, the tensile strength of PLA specimens decreased by 15.56%, while PLA+CF specimens experienced an 18.60% reduction. Strain values exhibited minor fluctuations, indicating stable elasticity, and Young's modulus improved significantly with higher infill densities, suggesting enhanced material stiffness. Increasing the infill density of FDM 3D-printed PLA and PLA+CF specimens significantly enhance their mechanical properties, even under prolonged exposure to cooling lubricants. These findings have significant implications for industrial applications, indicating that optimizing infill density can enhance the durability and performance of 3D-printed components. This study offers a robust foundation for further research and practical applications, highlighting the critical role of infill density in enhancing structural integrity and load-bearing capacity.

Radiation-Induced miRNAs Changes and cf mtDNA Level in Trauma Surgeons: Epigenetic and Molecular Biomarkers of X-ray Exposure.

Exposure to ionizing radiation can result in the development of a number of diseases, including cancer, cataracts and neurodegenerative pathologies. Certain occupational groups are exposed to both natural and artificial sources of radiation as a consequence of their professional activities. The development of non-invasive biomarkers to assess the risk of exposure to ionizing radiation for these groups is of great importance. In this context, our objective was to identify epigenetic and molecular biomarkers that could be used to monitor exposure to ionizing radiation. The impact of X-ray exposure on the miRNAs profile and the level of cf mtDNA were evaluated using the RT-PCR method. The levels of pro-inflammatory cytokines in their blood were quantified using the ELISA method. A significant decrease in miR-19a-3p, miR-125b-5p and significant increase in miR-29a-3p was observed in the blood plasma of individuals exposed to X-ray. High levels of pro-inflammatory cytokines and cf mtDNA were also detected. In silico identification of potential targets of these miRNAs was conducted using MIENTURNET. VDAC1 and ALOX5 were identified as possible targets. Our study identified promising biomarkers such as miRNAs and cf mtDNA that showed a dose-dependent effect of X-ray exposure.

Early detection of hepatobiliary involvement in cystic fibrosis: Biomarkers, radiologic methods, and genetic influences.

Cystic fibrosis-related hepatobiliary involvement (CFHBI) is a term used to describe a spectrum of hepatobiliary involvement ranging from a transient elevation of transaminase levels to advanced cystic fibrosis-associated liver disease (aCFLD). While CFHBI is common among people with cystic fibrosis (PwCF), aCFLD is rare impacting only approximately 5%-10% of the CF population. After respiratory/cardiorespiratory issues and transplant-related complications, aCFLD is now the 4th leading cause of mortality among PwCF. Additionally, aCFLD is an independent predictor of all-cause mortality and is associated with significant morbidity. Despite this recognition, our ability to predict those patients at greatest risk for aCFLD, identify early aCFLD, and monitor the incremental progression of CFHBI is lacking. Here, we review the strengths and weaknesses of the common biomarkers and imaging modalities used in the evaluation and monitoring of CFHBI, as well as the current understanding of genetic modifiers related to aCFLD.

Advanced cystic fibrosis liver disease: Endovascular, endoscopic, radiologic, and surgical considerations.

Up to 90% of people with CF (pwCF) will have some form of hepatobiliary involvement. This manuscript aims to explore the different endovascular, endoscopic, radiological and surgical procedures available to diagnose and manage the most severe form of CF hepatobiliary involvement (CFHBI) known as advanced cystic fibrosis liver disease (aCFLD), seen in 10% of pwCF. These procedures and interventions include liver biopsy, hepatic venous pressure gradient measurement, gastrostomy tube placement to optimize nutrition, paracentesis, endoscopic variceal control of bleeding and portosystemic shunting before liver transplantation. By utilizing advanced diagnostic or surgical techniques, healthcare professionals of pwCF can more effectively manage patients with CFHBI and aCFLD and potentially improve patient outcomes.

Enhanced favipiravir drug degradation using the synergy of PbO2-based anodic oxidation and Fe-MOF-based cathodic electro-Fenton.

Favipiravir (FAV) is a widely utilized antiviral drug effective against various viruses, including SARS-CoV-2, influenza, and RNA viruses. This article aims to introduce a novel approach, known as Linear-Paired Electrocatalytic Degradation (LPED), as an efficient technique for the electrocatalytic degradation of emerging pollutants. LPED involves simultaneously utilizing a carbon-Felt/Co-PbO2 anode and a carbon-felt/Co/Fe-MOF-74 cathode, working together to degrade and mineralize FAV. The prepared anode and cathode characteristics were analyzed using XPS, SEM, EDX mapping, XRD, LSV, and CV analyses. A rotatable central composite design-based quadratic model was employed to optimize FAV degradation, yielding statistically desirable results. Under optimized conditions (pH = 5, current density = 4.2 mA/cm2, FAV concentration = 0.4 mM), individual processes of cathodic electro-Fenton and anodic oxidation with a CF/Co-PbO2 anode achieved degradation rates of 58.9% and 89.5% after 120 min, respectively. In contrast, using the LPED strategy resulted in a remarkable degradation efficiency of 98.4%. Furthermore, a cyclic voltammetric study of FAV on a glassy carbon electrode was conducted to gather additional electrochemical insights and rectify previously published data regarding redox behavior, pH-dependent properties, and adsorption activities. The research also offers a new understanding of the LPED mechanism of FAV at the surfaces of both CF/Co-PbO2 and CF/Co/Fe-MOF-74 electrodes, utilizing data from cyclic voltammetry and LC-MS techniques. The conceptual strategy of LPED is generalizable in order to the synergism of anodic oxidation and cathodic electro-Fenton for the degradation of other toxic and resistant pollutants.

Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis.

Addressing osteoporosis-related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron-overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush-like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self-assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre-osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP/ß-catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron-overloaded osteoporotic rabbits and supported by in vitro validations.

Silence of the lungs: comparing measures of slow and non-communicating lung units from pulmonary function tests with computed tomography.

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of under-ventilated lung units (UVLU). Additionally, we used 2 previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P<0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249ml [95%CI -10796; 580ml] and -203ml [95%CI -997;591ml], respectively). Parameters from both spirometry and body plethysmography were sub-optimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared to the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.

GIS- and Multivariate-Based Approaches for Assessing Potential Environmental Hazards in Some Areas of Southwestern Saudi Arabia.

Soil contamination is a major issue that endangers the ecology in most countries. Total concentrations of As, Cd, Co, Cr, Cu, Mn, Ni, Pb, VFe, and Zn were determined by analyzing soil samples from 32 surface soil samples in southwest Saudi Arabia, including certain areas of Al-Baha. Kriging techniques were used to create maps of the distribution of metal. To assess the levels of soil contamination in the research area, principal component analysis (PCA), contamination factors (CF), and pollution load index were used. The results show the stable model gave the best fit to the As and Zn semivariograms. The circular model fits the Cd, Co, and Ni semivariograms the best, while the exponential model fits the Cr, V, and Fe semivariograms the best. For Ni and Pb, respectively, spherical and Gaussian models are fitted. The findings demonstrated two clusters containing different soil heavy metal concentrations. According to the data, there were two different pollution levels in the research region: 36.58% of it is strongly contaminated, while 63.41% of it has a moderate level of contamination (with average levels of these metals 5.28 ± 5.83, 0.81 ± 0.19, 18.65 ± 6.22, 45.15 ± 23.25, 60.55 ± 23.74, 972.30 ± 223.50, 33.45 ± 14.11, 10.05 ± 5.13, 84.15 ± 30.72, 97.40 ± 30.05, and 43,245.00 ± 8942.95 mg kg-1 for As, Cd, Co, Cr, Cu, Mn, Ni, Pb, V, Fe, and Zn, respectively). The research area's poor management practices are reflected in the current results, which raised the concentration of harmful elements in the soil's surface layers. Ultimately, the outcomes of pollution concentration and spatial distribution maps could aid in informing decision-makers when creating suitable heavy metal mitigation strategies.

Genetic alteration of mRNA editing enzyme APOBEC3B in the pathogenesis of ovarian endometriosis.

RESEARCH QUESTION: What are the specific genetic alterations and associated network in endometriotic cells responsible for the disease pathogenesis? DESIGN: Case control experimental study involving 45 women with endometriosis who underwent laparoscopic surgery (case) and 45 normal samples from women undergoing total abdominal hysterectomy (control). The endometrial samples were subjected to whole exome sequencing (WES) of endometriotic tissue and copy number variation analysis. Validation of gene hits were obtained from WES using polymerase chain reaction techniques, immunological techniques, in-silico tools and transgenic cell line models. RESULTS: Germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from the same patient. APOBEC3B deletions resulted in a hybrid protein that activates A1CF. APOBEC3B deletion can be a major cause of changes in the endometriotic microenvironment, and contributes to the pathogenesis and manifestation of the disease. The effect of APOBEC3B deletion was proved by in-vitro experiments in a cell line model, which displayed endometriosis-like characteristics. APOBEC3B germline deletion plays a major role in the pathogenesis of endometriosis, which is evident by the activation of A1CF, an increase in epithelial to mesenchymal transition, cellular proliferation, inflammation markers and a decrease in apoptosis markers. CONCLUSION: The deleterious effects caused by APOBEC3B deletion in endometriosis were identified and confirmed. These results might provide a base for identifying the complete pathogenetic mechanism of endometriosis, thereby moving a step closer to better diagnosis and treatment options.

Potential ecological risk assessment of microplastics in environmental compartments in Mexico: A meta-analysis.

Microplastic (MP) environmental contamination has been widely studied in Mexico. However, the evaluation of the associated risk to MPs in environmental compartments is scarce. Therefore, this study addresses this issue using diverse indicators such as the Pollution Load Index (PLI), the Polymer Risk Index (PRI), and the Potential Ecological Risk Index (PERI). The results of a meta-analysis revealed high MP contamination levels in most of the studied compartments, which included marine and estuarine waters, beach sand, freshwater, sediments, and biota. Regarding the risk assessment indicators, PLIs indicated low (56%), dangerous (22%), moderate (12%), and high (10%) levels across compartments. Meanwhile, PRIs displayed concerning values, with 36%, 35%, 20%, and 9% exhibiting dangerous, high, moderate, and low levels, respectively. Thus, high PRI values emphasized the significant rise in MP pollution, largely attributed to high-hazard polymer compositions. Otherwise, PERIs showed low (56%), very dangerous (29%), moderate (6%), high (5%), and dangerous (4%) levels. Thus, the ecological risk in Mexico is widespread and mainly linked to MP abundance, polymer type, environmental matrix, and characteristics of organisms. This study represents the first attempt at MP ecological risk assessment in Mexico, providing crucial insights for developing mitigation strategies to address concerns about MP contamination.

An Experimental Study on the Thermomechanical Coupling Effects of Carbon-Fiber-Reinforced Polyetheretherketone under Dynamic Impact.

Carbon-fiber-reinforced polyetheretherketone (CF/PEEK) composites are widely utilized in aerospace, medical devices, and automotive industries, renowned for their superior mechanical properties and high-temperature resistance. Despite these advantages, the thermomechanical coupling behavior of CF/PEEK under dynamic loading conditions is not well understood. This study aims to explore the thermomechanical coupling effects of CF/PEEK at elevated strain rates, employing Hopkinson bar impact tests and scanning electron microscopy (SEM) for detailed characterization. Our findings indicate that an increase in temperature led to significant reductions in the yield strength, peak stress, and specific energy absorption of CF/PEEK, while fracture strain had no significant effect. For instance, at 200 °C, the yield strength, peak stress, and specific energy absorption decreased by 39%, 37%, and 38%, respectively, compared to their values at 20 °C. Furthermore, as the strain rate increased, the yield strength, peak stress, specific energy absorption, and fracture strain all exhibited strain-hardening effects. However, as the strain rate further increased, above 4000 s-1, the enhancing effect of the strain rate on the yield strength and peak stress gradually diminished. The interaction of the temperature and strain rate significantly affected the mechanical performance of CF/PEEK under high-speed impact conditions. While the strain rate generally enhanced these properties, the strain-hardening effect on the yield strength weakened as the temperature increased, and both the temperature and strain rate contributed to the increase in specific energy absorption. Microdamage mechanism analysis revealed that interface debonding and sliding between the fibers and the matrix were more pronounced under static compression than under dynamic compression, thereby diminishing the efficiency of stress transfer. Additionally, higher temperatures caused the PEEK matrix to soften and exhibit increased viscoelastic behavior, which in turn affected the material's toughness and the mechanisms of stress transfer. These insights hold substantial engineering significance, particularly for the optimization of CF/PEEK composite design and applications in extreme environments.

Accuracy of cell-free Mycobacterium tuberculosis DNA testing in pleural effusion for diagnosing tuberculous pleurisy: a multicenter cross-sectional study.

BACKGROUND: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. METHODS: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. RESULTS: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. CONCLUSIONS: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).

THE EFFECT OF A PRE-MEAL SNACK AND/OR POSTPRANDIAL EXERCISE ON BREAKFAST GLYCEMIC EXCURSION IN ADULTS WITH CYSTIC FIBROSIS: A PILOT STUDY.

BACKGROUND & AIMS: Cystic fibrosis (CF)-related diabetes (CFRD), a common comorbidity in CF, is often preceded and characterized with elevated postprandial glycaemia (PPG). In the general population, the consumption of a pre-meal protein snack and/or physical activity (PA) hinder the elevation of PPG levels. Our objective is to evaluate the effect of a pre-meal snack and/or post-meal PA on PPG excursions in CF. METHODS: This is a double-blinded randomized controlled crossover interventional study in 14 adults with CF, with 4 interventions: placebo pre-meal snack + no PA (control: CTL), pre-meal soy snack + no PA (SK), placebo pre-meal snack + PA (PA), and pre-meal soy snack + PA (SK+PA). The pre-meal soy snack or placebo beverage (vanilla flavoured water) is served at 8 am, followed by a standardized breakfast at 9 am and, postprandially, 5 repeated bouts of 3-min walk every 30 mins or sedentary activity. Blood glucose and insulin were measured every 15 to 30 minutes during the interventions. RESULTS: Plasma glucose (PG) was higher 30 mins after snack consumption compared to placebo beverage. One-hour post-breakfast, PG levels were lower during both PA interventions than with sedentary behavior. However, the overall 3h post-breakfast glucose area under the curve (AUC) was similar between interventions. Post-breakfast 3h insulin AUC was significantly lower during the SK+PA intervention compared to the sedentary behavior interventions. CONCLUSION: Repeated short bouts of post-meal physical activity may positively impact PPG control in adults with CF, with or without the addition of a pre-meal soy snack. A pre-meal snack alone does not improve PPG.

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.

BACKGROUND: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. METHODS: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. RESULTS: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term. CONCLUSION: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

Attitudes toward and preparedness for lung transplantation among individuals with cystic fibrosis in the era of highly effective modulators.

BACKGROUND: Outcomes for individuals with cystic fibrosis (CF) have improved due to highly effective modulator therapy (HEMT). However, lung transplant (LTx) remains an important treatment for people with advanced lung disease. This study assessed attitudes and knowledge about LTx in the HEMT era. METHODS: All patients from the University of Washington CF clinic were surveyed March 25-May 30, 2020. Questions addressed self-rated LTx preparedness and knowledge, as well as barriers and facilitators to discussing LTx. Demographic and clinical data were extracted from the electronic health record. RESULTS: There were 159/224 (71%) responses. Respondents had a median forced expiratory volume in one second (FEV1) of 70%, and 142 (89%) were on modulatory therapy. One hundred thirteen (71%) respondents felt that it was moderately or very important to be prepared to make decisions about LTx, though only 56 (35%) felt moderately or very prepared. Only 83 (30%) and 47 (52%) participants correctly answered questions about life expectancy and improved quality of life after LTx, respectively. Respondents with Medicaid insurance less frequently answered questions correctly. The most common barriers to discussing LTx were fear of being a burden on loved ones for 58 respondents (36%) and cost of LTx for 46 (29%). Most participants (94%) trusted their CF doctor, and 75% of participants selected trust as a facilitator for LTx discussions. CONCLUSIONS: Many individuals with CF, especially those with lower socioeconomic status, lacked knowledge and did not feel very prepared for decisions about LTx. Earlier education and discussions about LTx represent an area for improvement in CF care.

Compatibility of Bioinsecticides with Parasitoids for Enhanced Integrated Pest Management of Drosophila suzukii and Tuta absoluta.

Drosophila suzukii and Tuta absoluta are successful biological invaders of agroecosystems. Their integrated pest management (IPM) programs involve the release and/or conservation of natural enemies. Among these, Ganaspis kimorum is a major Asian parasitoid of D. suzukii and has been introduced as a classical biological control agent of this pest in Europe and North America, while Necremnus tutae is a key fortuitous parasitoid of T. absoluta in the Mediterranean region. Bioinsecticides represent key alternatives to chemicals for controlling both pests. This study investigated the potential compatibility of both parasitoids with Beauveria bassiana, Bacillus thuringiensis, garlic essential oil (EO), and spinosad, in comparison to two synthetic insecticides, cyantraniliprole and chlorantraniliprole. The results showed that combining each of the tested insecticides with G. kimorum slightly increased pest mortality compared to the insecticide alone. Necremnus tutae had a significant additive effect on host mortality when combined with insecticides. Beauveria bassiana and B. thuringiensis were most compatible with both parasitoid species. Both garlic EO and chlorantraniliprole impaired the survival of immature N. tutae and showed sublethal toxicity on the reproductive and non-reproductive behaviors of N. tutae. Spinosad exhibited high acute toxicity on both juvenile and adult parasitoids of both species. Overall, these findings provide useful insights into insecticide selectivity toward two key parasitoids and offer new knowledge on the potential of combining natural enemies and bioinsecticides for optimized IPM.