Small Lungs Research Articles

Endothelial Chromatin-Remodeling Enzymes Regulate the Production of Critical ECM Components During Murine Lung Development.

The chromatin-remodeling enzymes BRG1 (brahma-related gene 1) and CHD4 (chromodomain helicase DNA-binding protein 4) independently regulate the transcription of genes critical for vascular development, but their coordinated impact on vessels in late-stage embryos has not been explored. In this study, we genetically deleted endothelial Brg1 and Chd4 in mixed background mice (Brg1fl/fl;Chd4fl/fl;VE-Cadherin-Cre), and littermates that were negative for Cre recombinase were used as controls. Tissues were analyzed by immunostaining, immunoblot, and flow cytometry. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression, and chromatin immunoprecipitation revealed gene targets of BRG1 and CHD4 in cultured endothelial cells. We found Brg1/Chd4 double mutants grew normally but died soon after birth with small and compact lungs. Despite having normal cellular composition, distal air sacs of the mutant lungs displayed diminished ECM (extracellular matrix) components and TGFβ (transforming growth factor-β) signaling, which typically promotes ECM synthesis. Transcripts for collagen- and elastin-related genes and the TGFβ ligand Tgfb1 were decreased in mutant lung endothelial cells, but genetic deletion of endothelial Tgfb1 failed to recapitulate the small lungs and ECM defects seen in Brg1/Chd4 mutants. We instead found several ECM genes to be direct targets of BRG1 and CHD4 in cultured endothelial cells. Collectively, our data highlight essential roles for endothelial chromatin-remodeling enzymes in promoting ECM deposition in the distal lung tissue during the saccular stage of embryonic lung development.

Development of a low priming volume hydrodynamic test bench for isolated ex vivo perfusion of small animal lungs

Development of a low priming volume hydrodynamic test bench for isolated ex vivo perfusion of small animal lungs

Comparison of safety and anxiety/depression in computed tomography-guided hook-wire localization versus electromagnetic navigation bronchoscopy-guided localization: a retrospective cohort study.

The utilization of computed tomography (CT)-guided localization and electromagnetic navigation bronchoscopy (ENB)-guided localization has gained significant traction in the localization of pulmonary nodules before video-assisted thoracoscopic surgery (VATS). This study aimed to ascertain the precision and safety of the two groups in the preoperative resection of isolated nodules in small peripheral lungs. Furthermore, we examined the subsequent outcomes pertaining to the decline in lung function and alterations in anxiety and depression following resection utilizing both localization techniques. A total of 177 patients with small-sized pulmonary nodules, scheduled to undergo video-assisted thoracoscopic limited resection, were enrolled in this study. The study involved the examination and comparison of pertinent findings obtained through the utilization of CT-guided hook-wire or ENB injection techniques. The nodules were localized by ENB in 57 patients and by CT guidance in 120 patients. There were no significant complications in ENB-guided localization group (0/57). CT-guided hook-wire localization group had more complications (61/120, P<0.001). There was no disparity observed in pulmonary function decline 3 months post-operation between the two cohorts. The analysis of postoperative Hospital Anxiety and Depression Scale (HADS) scores indicated that the CT-guided localization group exhibited higher anxiety and depression scores on the initial day and 2 weeks following surgery. ENB-guided and CT-guided localization can effectively identify solitary pulmonary nodules. ENB-guided localization has fewer complications, lower incidence of adverse events, and less impact on postoperative anxiety or depression, suggesting that this is a promising, safe, and feasible method for localization of solitary pulmonary nodules.

Establishment of an Animal Model Scheme of Strongyloides stercoralis-Infected Meriones meridianus.

Studying parasitic nematodes, which generate a massive hazard to animal health, is more difficult than studying free-living nematodes as appropriate animal models are essential, and the relationship between parasites and hosts is extremely complex. Strongyloides stercoralis is an intestinal nematode parasite that mainly infects dogs, humans and other primates. Currently, S. stercoralis worms needed for research mainly rely on their natural host, the dog. This study explored a method of using Meriones meridianus as a model for S. stercoralis. The immunosuppressed M. meridianus were infected with S. stercoralis subcutaneously, and post-parasitic, first-stage larvae (PP L1) were detected in the faeces, with more larvae in female gerbils. In addition, parasitic females (PFs), third-stage larvae (L3s) and rhabditiform larvae were found primarily in the small intestines and lungs of infected gerbils. The PFs and auto-infective third-stage larvae (aL3s) obtained from M. meridianus are morphologically identical to those obtained from beagles and Meriones unguiculatus. Moreover, the infection of S. stercoralis caused changes to biochemical indicators in the serum and in the physiology of M. meridianus. The results demonstrated that M. meridianus can be infected by S. stercoralis, and this model provides a great tool for exploring the biological processes of this parasite and its interaction with the host.

Tissue expression of the SARS-CoV-2 cell receptor gene ACE2 in children.

Coronavirus disease 2019 (COVID-19) has become a significant global public health problem. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the disease, utilizes angiotensin-converting enzyme II (ACE2) as a major functional receptor to enter host cells. No study has systematically assessed ACE2 expression in multiple tissues in children. This study investigated ACE2 expression and ACE2 protein's histological distribution in various organs in paediatric patients (the small intestine, thymus, heart and lungs). Our study revealed that ACE2 was highly expressed in enterocytes of the small intestine and widely expressed in the myocardium of heart tissues. The most notable finding was the positive staining of ACE2 in the Hassall's corpuscles epithelial cells. Negligible ACE2 expression in the lung tissues may contribute to a lower risk of infection and fewer symptoms of pneumonia in children than in adults with COVID-19 infection. These findings provide initial evidence for understanding SARS-CoV-2 pathogenesis and prevention strategies in paediatric clinical practice, which should be applicable for all children worldwide.

Development of a new low-volume oxygenator and creation of a hydrodynamic test bench for ex vivo lung perfusion in small animals

Small animal models are widely used in basic research. However, experimental hydrodynamic test benches, which include extracorporeal circuits, often have limitations associated with the size and filling volume of equipment. Thus, we aimed at developing and validating a miniature oxygenator as well as a low-volume hydrodynamic system for ex vivo perfusion of small animal lungs. A series of low-volume membrane oxygenators (n = 10) with 90–100 aligned microporous polypropylene hollow fibers, placed inside a sheath that is sealed at both ends to isolate the perfusing solution, was designed and manufactured. This design makes gas to flow through the hollow fibers and perfusate to circulate around the fibers. A low-volume hydrodynamic test bench was designed and assembled for isolated ex vivo lung perfusion and for evaluation of the performance characteristics of the oxygenators: gas and perfusate flow, perfusion pressure and temperature at 5–70 ml/min flow range.

#5592 THE SODIUM PHOSPHATE COTRANSPORTER NAPI-IIB IS UPREGULATED AND EXPRESSED DE NOVO IN KIDNEYS OF PATIENTS WITH CHRONIC KIDNEYS DISEASE

Abstract Background and Aims Renal reabsorption of phosphate is mediated by 3 main transporters located in the luminal brush border membrane of the proximal tubule, namely NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit2 (SLC20A2). The expression of all three proteins has been shown to be reduced in animal models of kidney disease [1]. Recently, we demonstrated that NaPi-IIb, a paralogue of the SLC34 subfamily that is mostly expressed in small intestine and lungs, is also expressed in the loop of Henle. Its mRNA expression is enhanced in rodent models of kidney injury. However, the expression of NaPi-IIb has not been characterized in humans and it is unknown whether NaPi-IIb is also upregulated in chronic kidney disease (CKD). Method In this study, we examined the localization of NaPi-IIa, IIb, and IIc in kidneys of control healthy individuals (kidney donors) (eGFR: 111.6 ± 22.9 ml/min/1.73m2) and patients with diabetic nephropathy (eGFR: 31.9 ± 7.7 ml/min/1.73m2), anti-glomerular basement membrane nephritis (anti-GMB) (eGFR: 27.2 ± 22.6 ml/min/1.73m2), and hypertensive nephropathy (eGFR: 31.5 ± 5.3 ml/min/1.73m2) by immunofluorescence. Moreover, we analyzed data from various transcriptome data bases from healthy individuals and patients with CKD. Results In kidneys from healthy donors, NaPi-IIb staining was restricted to thin and thick limbs of the loop of Henle, while AQP1 was observed in proximal tubules and descending thin limbs. NaPi-IIc was abundantly found in proximal tubule cells. In biopsies from patients, NaPi-IIb signal was also found in addition to thin and thick limbs in cells of the collecting duct and in many proximal tubules. In contrast, the staining of NaPi-IIc was reduced in all groups of patients with CKD. RNA expression data from the European Renal cDNA Bank (ERCB) confirmed our immunofluorescence findings. SLC34A2 (NaPi-IIb) mRNA was progressively more expressed in kidneys of patients with kidney disease of tubulointerstitial origin from CKD stages 1 to 5, while it was strongly upregulated from stage 4 onwards in CKD of glomerular origin. Single cell RNA sequencing data of patients with acute kidney injury and CKD [2] showed elevation of SLC34A2 expression in injured thick ascending limb, degenerative proximal tubule cells (14x higher, adj. p≪0.0001) (de novo expression), and descending thin limb (3.7x higher, adj. p≪0.0001). SLC34A1 (NaPi-IIa) expression levels were reduced in whole kidneys (ERCB data) and SLC34A1 and SLC34A3 expression also decreased in proximal tubule cells of patients with CKD. Conclusion The phosphate transporter NaPi-IIb is highly upregulated in kidneys from patients with various etiologies of CKD and its expression spreads to proximal tubule and collecting duct. In contrast, the expression of the main physiological phosphate transporters NaPi-IIa and NaPi-IIc is reduced in CKD. These findings may have implications for the development and maintenance of hyperphosphatemia in CKD patients and limit the use of specific NaPi-IIa and/or NaPi-IIc inhibitors in patients with CKD.

Worldwide organ allocation systems for pediatric lung transplantation.

Pediatric lung transplantation (LTX) remains limited by the scarcity of small donor lungs, particularly in less populated parts of the world. Optimal organ allocation, including the prioritization and ranking of pediatric LTX candidates, and the appropriate matching of pediatric donors to recipients have been crucial elements in improving pediatric LTX outcomes. We aimed to elucidate the various pediatric lung allocation practices worldwide. A global survey of current pediatric solid organ transplantation deceased donation allocation practices was conducted by the International Pediatric Transplant Association (IPTA), and these policies were subsequently analyzed if publicly available, with focus on pediatric lung transplantation. Significant variation was found in lung allocation systems worldwide both in terms of prioritization and distribution for children. Definition of pediatrics varied from <12 years of age to <18 years of age. While several countries performing LTX for young children do not have a formal system to prioritize pediatric candidates, many countries that perform LTX at higher rates do offer prioritization methods for children: including the United States, United Kingdom, France, Italy, Australia, and countries serviced by Eurotransplant. Certain lung allocation practices for pediatrics are highlighted herein, including the newly instituted Composite Allocation Score (CAS) system in the United States, pediatric matching with Eurotransplant, and pediatric prioritization in Spain. The systems highlighted here explicitly aim to provide judicious and high quality LTX care for children.

Generalized Eosinophilia Following Moderna COVID-19 Vaccine Administration: A Case Report.

Coronavirus disease 19 (COVID-19) vaccination is considered an important part in improving health outcomes globally. While various adverse events following vaccination against COVID-19 have been reported, eosinophilic diseases have rarely been documented in the literature and are poorly understood. Although vaccination is lauded as being "safe," it has become apparent that adverse reactions related to the vaccines can have detrimental health effects for certain individuals. We present a case of a death related to multiple severe preexisting comorbidities, complicated by new-onset gastrointestinal complaints which were temporally associated with recent COVID-19 vaccination and did not subside, but worsened prior to death. Autopsy revealed evidence of eosinophilic enteritis, associated with ascites, as well as eosinophilic inflammation elsewhere, including the lungs and heart. Histological examination revealed abundant eosinophils in tissues, including the small intestines, epicardium, and lungs. Whether or not the eosinophilic inflammatory process was caused by the recent vaccination cannot be stated with certainty; however, the temporal association between vaccination, symptom onset/progression, and death, and the literature which suggests a possible association between coronavirus vaccination and eosinophilic reactions leads to the conclusion that this death might have been related to an adverse reaction to COVID-19 vaccination.

A knockout-first model of H3f3a gene targeting leads to developmental lethality.

Histone variant H3.3 is encoded by two genes, H3f3a and H3f3b, which can be expressed differentially depending on tissue type. Previous work in our lab has shown that knockout of H3f3b causes some neonatal lethality and infertility in mice, and chromosomal defects in mouse embryonic fibroblasts (MEFs). Studies of H3f3a and H3f3b null mice by others have produced generally similar phenotypes to what we found in our H3f3b nulls, but the relative impacts of the loss of either H3f3a or H3f3b have varied depending on the approach and genetic background. Here we used a knockout-first approach to target the H3f3a gene for inactivation in C57BL6 mice. Homozygous H3f3a targeting produced a lethal phenotype at or before birth. E13.5 null embryos had some potential morphological differences from WT littermates including smaller size and reduced head size. An E18.5 null embryowas smaller than its control littermates with several potential defects including small head and brain size as well as small lungs, which would be consistent with a late gestation lethal phenotype. Despite a reduction in H3.3 and total H3 protein levels, the only histone H3 post-translational modification in the small panel assessed that was significantly altered was the unique H3.3 mark phospho-Serine31, which was consistently increased in null neurospheres. H3f3a null neurospheres also exhibited consistent gene expression changes including in protocadherins. Overall, our findings are consistent with the model that there are differential, cell-type-specific contributions of H3f3a and H3f3b to H3.3 functions in epigenetic and developmental processes.

Effects of Notch signaling pathway inhibition by dibenzazepine in acute experimental toxoplasmosis

Notch signaling pathway plays a crucial role in cellular fate across species, being important for the differentiation and development of several cell types. The aim of this study was to evaluate the effect of Notch inhibition pathway by dibenzazepine (DBZ) in histological and inflammatory alterations and, tissue parasitism in acute Toxoplasma gondii infection. For this, C57BL/6 mice were treated with DBZ before infection with T. gondii, and the small intestine, lungs and liver were analyzed. The genes related to Notch signaling pathway were assayed through qPCR in the organs, and cytokine measurement was performed in serum samples. In the small intestine, T. gondii infection impaired the Hes1 and Math1 mRNA expressions, increased the inflammation and decreased goblet and Paneth cell numbers. The DBZ-treatment was able to partially preserve these cells, however, the parasitism and inflammation were not altered. In parallel, the high IL-2, IL-6, TNF and, IFN-γ levels induced by infection were not changed with the DBZ treatment, with the IFN-γ levels even higher. In contrast, in the liver and lungs, the DBZ-treatment diminished parasitism and inflammation. Our results highlight that Notch pathway inhibition in T.gondii infection results in different parasitological and inflammatory outcomes depending on the organ analyzed.

298 Late Gestational Nutrient Restriction of Primiparous Beef Heifers Decreases Neonatal Calf Body Weight and Organ Mass

Abstract We hypothesized that late gestational nutrient restriction (NR) would decrease organ mass in neonatal calves. Fall-calving crossbred beef heifers (BW: 466 ± 30 [SD] kg; BCS: 5.4 ± 0.5) bred to a single sire were individually fed 100% (control; n = 10) or 70% (nutrient restricted; NR; n = 12) of NASEM metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to calving. Diets were based on chopped sorghum sudan hay and supplemented to meet targeted nutritional planes. Calves were removed immediately post-calving and fed colostrum and milk replacer relative to BW until euthanasia (48.7 ± 0.4 h of age) for organ mass determination. Nutritional plane was a fixed effect, and maternal sire, calf sex (when P &amp;lt; 0.25), and date of study initiation were covariates. Post-calving, NR dams were 62 kg BW and 2.1 BCS less (P &amp;lt; 0.001) than controls. Calf BW, liver, large intestine, omental/mesenteric fat, kidney, and heart weights were less (P ≤ 0.05) and carcass, rumen/reticulum/omasum, stomach complex, and total gastrointestinal tract weights tended to be less (P ≤ 0.09) in offspring from NR dams. Maternal nutrient restriction did not affect (P ≥ 0.11) weights of the small intestine, pancreas, abomasum, spleen, perirenal fat, adrenals, lungs, femur, and brain. Expressed per BW, lung weight was greater (P = 0.05), and brain and femur weight tended to be greater (P ≤ 0.10) in calves from NR dams, but other organ masses were unaffected (P ≥ 0.15). Expressed relative to brain weight, liver and large intestine weights were less (P ≤ 0.04) and carcass, total gastrointestinal tract, omental/mesenteric fat, and kidney weights tended to be less (P ≤ 0.08) in NR. In summary, late gestational NR decreased some organ masses in neonatal calves while sparing other tissues via asymmetric growth.

Rectal administration of butyrate ameliorates pulmonary fibrosis in mice through induction of hepatocyte growth factor in the colon via the HDAC-PPARγ pathway

Butyrate, given by oral administration or in drinking water, has been shown to improve experimental pulmonary fibrosis (PF) in mice despite of very low bioavailability. The pharmacokinetic-pharmacodynamics disconnection attracts us to explore its anti-PF mechanism in view of the intestinal expression of anti-PF factors. In bleomycin-induced PF in mice, rectal administration of butyrate (500 mg/kg) exhibited a significant anti-PF effect, with a maximum plasma concentration largely lower than the minimum effective concentration (1 mM) at which butyrate inhibited the expression of pro-inflammatory factors by lung epithelial cells and the production of extracellular matrix by lung fibroblasts. The rectal administration of butyrate significantly upregulated the mRNA expression of hepatocyte growth factor (HGF) in the colons of PF mice, but showed no significant effect on the mRNA expression of HGF in the small intestines, lungs and livers. In colon epithelial cells, the monocarboxylate transporter inhibitor α-cyano-4-hydroxycinnamic acid (CHC) abrogated butyrate-induced expression of HGF, indicating that butyrate functions through entering into cells. Butyrate showed no significant effect on the histone acetylation in the promoter region of HGF, suggesting that it promotes HGF expression not by directly affecting the histone deacetylation of HGF but by other pathways. GW9662, the inhibitor of PPARγ, significantly attenuated the effect of butyrate to promote the mRNA expression of HGF. Butyrate was able to enhance the acetylation of PPARγ, and a targeted mutation of lysine at the position 240 (K240) of PPARγ markedly diminished the induction of butyrate on HGF expression, suggesting that butyrate promoted HGF expression in colon epithelial cells by upregulating PPARγ K240 acetylation.In summary, rectal administration of butyrate promotes the expression of HGF in colonic epithelial cells through upregulating PPARγ acetylation via inhibition of HDAC activity. The findings of the present study provide a reasonable explanation for the anti-PF action mode of butyrate based on the ‘lung-gut axis’, and found that intestine-derived butyrate and HGF may be involved in the modulation of the occurrence and progression of PF.

Overview and analysis of internal radiation dose estimates in experimental animals in a framework of international studies of the sprayed neutron-induced 56Mn radioactive microparticles effects.

The aim of overview is to present the pooled data of published internal dose estimates and the results of corresponding analysis of internal irradiation features of experimental mice and rats after exposure to sprayed neutron activated radioactive 56MnO2. These dose estimates were conducted in a framework of multicenter international study to investigate biological effects as a result of exposure to sprayed radioactive 56MnO2 microparticles. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main gamma-beta emitters during the first hours after neutron activation of soil following nuclear explosion. It was concluded that there are three groups of organs of mice and rats, the radiation doses of which differ by approximately an order of magnitude: the group with the highest radiation doses (large and small intestine, stomach, skin and lungs), the group with lowered radiation doses (eyes, esophagus, trachea), the group with the lowest radiation doses (liver, heart, kidneys). The radiation doses to organs are proportional to the activity of the sprayed radioactive powder. The distribution of internal radiation doses among organs of experimental mice of different strains but of the same age was practically the same in case of exposure to the same activity of sprayed 56MnO2 powder. Doses of internal irradiation of experimental mice substantially exceed the doses of internal irradiation of experimental rats exposed to the same activities of the sprayed 56MnO2 powder. The data presented in the overview can be helpful for further investigation and for interpretation of the biological effects of this type of irradiation.

H151, A SMALL MOLECULE INHIBITOR OF STING AS A NOVEL THERAPEUTIC IN INTESTINAL ISCHEMIA-REPERFUSION INJURY.

Intestinal ischemia-reperfusion (I/R) injury is a severe disease associated with high mortality. Stimulator of interferon genes (STING) is an intracellular protein that is activated by cytosolic DNA and is implicated in I/R injury, resulting in transcription of type I interferons (IFN-α and IFN-β) and other proinflammatory molecules. Extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, induces STING activation. H151 is a small molecule inhibitor of STING that has not yet been studied as a potential therapeutic. We hypothesize that H151 reduces inflammation, tissue injury, and mortality after intestinal I/R. Methods: In vitro, RAW264.7 cells were pretreated with H151 then stimulated with recombinant murine (rm) CIRP, and IFN-β levels in the culture supernatant were measured at 24 hours after stimulation. In vivo, male C57BL/6 mice were subjected to 60-minute intestinal ischemia via superior mesenteric artery occlusion. At the time of reperfusion, mice were intraperitoneally instilled with H151 (10 mg/kg BW) or 10% Tween-80 in PBS (vehicle). Four hours after reperfusion, the small intestines, lungs, and serum were collected for analysis. Mice were monitored for 24 hours after intestinal I/R to assess survival. Results: In vitro, H151 reduced rmCIRP-induced IFN-β levels in a dose-dependent manner. In vivo, intestinal levels of pIRF3 were increased after intestinal I/R and decreased after H151 treatment. There was an increase in serum levels of tissue injury markers (lactate dehydrogenase, aspartate aminotransferase) and cytokine levels (interleukin 1β, interleukin 6) after intestinal I/R, and these levels were decreased after H151 treatment. Ischemia-reperfusion-induced intestinal and lung injury and inflammation were significantly reduced after H151 treatment, as evaluated by histopathologic assessment, measurement of cell death, chemokine expression, neutrophil infiltration, and myeloperoxidase activity. Finally, H151 improved the survival rate from 41% to 81% after intestinal I/R. Conclusions: H151, a novel STING inhibitor, attenuates the inflammatory response and reduces tissue injury and mortality in a murine model of intestinal I/R. H151 shows promise as a potential therapeutic in the treatment of this disease.

Patient reported outcomes in adult patients with neuroendocrine neoplasms.

e24122 Background: Neuroendocrine neoplasm (NEN) is a broad term that includes both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). These rare malignancies most often occur in the gastrointestinal tract, pancreas, lung, adrenal medulla, and thyroid. Clinical symptoms depend upon several factors including tumor location, length of time since diagnosis, secretion of hormones, and tumor growth. Physical symptoms may include fatigue, gastrointestinal complaints, shortness of breath, and fluctuations in blood pressure, weight, and appetite. Patient reported outcomes (PROs) are critical in understanding the clinical spectrum of patients with NENs including their physical and social-emotional response to disease course and treatments. The aim of the current study was to assess physical, social, and emotional domains of PROs amongst a cohort of adult participants with NENs over time. Methods: Patients were enrolled on an ongoing NIH natural history study (NCT03739827). Annual PROs were electronically administered to adult participants (≥18 years) using the PRO Measurement Information System (PROMIS) forms for Anxiety, Depression, Fatigue, Mobility, Upper Extremity, Pain Interference, Cognitive Function, and Emotional Support ( www.nihpromis.org ). PROMIS forms are standardized on a T-Scale with a mean of 50 and a standard deviation of 10. Pain intensity was assessed from 0 (no pain) to 10 (worst pain imaginable) using the Numeric Rating Scale for Pain (NRS) (Wolters, 2013). The Pain Interference Index (PII) was used to assess the impact of pain on daily functioning on a 7-point Likert scale (Martin et al., 2015). Results: A total of 49 out of 85 patients provided completed PROs: 47 NET and 2 NEC. Mean (M) age was 58.8 years and 61.2% of the sample was female. Amongst NET patients (n = 47), primary tumor locations were the small bowel (45.7%), pancreas (21.7%), and lungs (13.0%). Other primary sites (19.6%) included the appendix, rectum, thyroid, kidney, and prostate. 46.8% had metastatic disease. Fatigue was the primary symptom complaint; 34% of NET patients reported fatigue in the moderate to severe range (Mean: 54.1; Standard Deviation: 11.2). Self-perceived mobility (M:47.4; SD: 9.1) and pain interference (M: 51.8; SD: 9.0) were a moderate concern for 19.1% and 17.0% of patients, respectively. At follow-up, 24 patients have returned PROs to date. Fatigue and mobility remained prevalent concerns; 29.1% of patients reported moderate to severe fatigue and 25% reported moderate concerns with mobility. Challenges with upper extremity mobility were endorsed by 20.8% of the sample. Conclusions: Our prospective and comprehensive PRO assessment confirms previously reported fatigue as the most prevalent symptom in patients with NET. Assessment of PROs over time will inform the development of clinical interventions and assessment of their impact on patient quality of life and functioning.

Perspectives on the Structure and Function of the Avian Respiratory System: Functional Efficiency Built on Structural Complexity

Among the air-breathing vertebrates, regarding respiratory efficiency, the avian respiratory system rests at the evolutionary zenith. Structurally, it is separated into a lung that serves as a gas exchanger and air sacs that mechanically ventilate the lung continuously and unidirectionally in a caudocranial direction. Largely avascular, the air sacs are delicate, transparent, compliant and capacious air-filled spaces that are not meaningfully involved in gas exchange. The avian lungs are deeply and firmly attached to the vertebrae and the ribs on the dorsolateral aspects, rendering them practically rigid and inflexible. The attachment of the lung to the body wall allowed extreme subdivision of the exchange tissue into minuscule and stable terminal respiratory units, the air capillaries. The process generated a large respiratory surface area in small lungs with low volume density of gas exchange tissue. For the respiratory structures, invariably, thin blood-gas barrier, large respiratory surface area and large pulmonary capillary blood volume are the foremost adaptive structural features that confer large total pulmonary morphometric diffusing capacities of O2. At parabronchial level, the construction and the arrangement of the airway- and the vascular components of the avian lung determine the delivery, the presentation and the exposure of inspired air to capillary blood across the blood-gas barrier. In the avian lung, crosscurrent-, countercurrent- and multicapillary serial arterialization systems that stem from the organization of the structural parts of the lung promote gas exchange. The exceptional respiratory efficiency of the avian respiratory system stems from synergy of morphological properties and physiological processes, means by which O2uptake is optimized and high metabolic states and capacities supported. Given that among the extant animal taxa insects, birds and bats (which accomplished volancy chronologically in that order) possess structurally much different respiratory systems, the avian respiratory system was by no means a prerequisite for evolution of powered flight but was but one of the adaptive solutions to realization of an exceptionally efficient mode of locomotion.

Catastrophic antiphospholipid syndrome (Asherson’s syndrome) caused by a suspected intestinal neuroendocrine tumor: a case report

Background. Every year, the number of people with rare forms of the disease is increasing worldwide. One of these is the catastrophic antiphospholipid syndrome — Asherson’s syndrome. To date, it is being actively studied, but the pathophysiological mechanisms of its development have not yet been fully investigated. Our work is the first attempt to describe Asherson’s syndrome on the example of a clinical case in Ukraine. Objective: to determine the factors and mechanisms that led to the death of a patient with Asherson’s syndrome in Ukraine. Materials and methods. The structural-logical analysis and the clinical-statistical method were used. Results. Based on clinical and laboratory criteria, our medical team established a clinical diagnosis of systemic lupus erythematosus complicated by a catastrophic antiphospholipid syndrome (CAPS). Despite treatment with glucocorticoids and anticoagulants according to international guidelines, the patient died. The autopsy results showed that the immediate cause of death was a large blood clot that blocked the pulmonary artery and its main branches. Histological examination revealed thrombosis of small vessels of the kidneys and brain; a neuroendocrine tumor (G2; pT3pNxpM1b) of the small intestine with metastases to the liver, brain, myocardium and kidneys was suspected. An additional immunohistochemical study was performed to clarify the histological diagnosis. The morphological picture and results of immunohistochemical study mostly correspond to the moderately differentiated (G2) non-keratinizing squamous cell carcinoma (ICD-O code: 8070/3) with damage to the walls of the small intestine, liver, lungs, kidneys, myocardium and brain. Conclusions. These data emphasize that despite the rarity of Asherson’s syndrome, it is always necessary to consider its probability in the presence of signs of multiple thrombosis and multiple organ failure. Because its development is the result of serious diseases, including connective tissue diseases, malignancies, infections, the etiotropic and pathogenetic treatment can prevent the development of CAPS and death.

Features of bioaccumulation and toxic effects of copper (II) oxide nanoparticles under the oral route of intake into the body

Introduction. Active use in various spheres of economic activity and the large-scale nature of production determine the relevance of studying the effects of copper (II) oxide nanoparticles (CuO NPs) on the body during the oral route of intake. Material and methods. Particle size was determined by scanning electron microscopy and dynamic laser light scattering; specific surface area - Brunauer, Emmett and Teller; total pore volume - Barrett, Joyner and Khalenda. Acute oral toxicity of CuO NPs was studied in Wistar rats in accordance with GOST 32644-2014, multiple oral toxicity was studied by the Lim method. After repeated exposure, the biochemical and hematological parameters of the blood, the concentration of copper in the organs, and pathomorphological changes in the tissues of the organs were determined. Results. The size of CuO NPs in the composition of the native powder was 45.86 nm, in the aqueous suspension - 307.40 nm, the specific surface area was 17.70 m2/g, and the total pore volume was 0.056 cm3/g. According to the results of a single oral exposure, the LD50 value was &gt; 2000 mg / kg body weight, which corresponds to 3 (GOST 12.1.007-76) and 4 (GOST 32644-2014) hazard classes. With repeated oral exposure, an increase in the levels of activity of ALT, AST, ALP, LDH, amylase, AOA and MDA was noted; the relative number of segmented neutrophils is increased, the number of leukocytes is increased, the relative number of lymphocytes is reduced. The concentration of copper under the action of NPs increases in the lungs, liver, stomach, intestines, kidneys, brain and blood. Pathomorphological changes in the tissues of the liver, kidneys, stomach, small and large intestines and lungs were established. Conclusion. The results obtained prove the presence of toxic properties of CuO NPs and can be used in the development of preventive measures for workers and consumers in contact with products containing CuO NPs.

Digestive Morphology of Native Pig Supplemented by Different Levels of Fermented Vigna radiata L.

Enhancing feed efficiency in converting feed mass into pig body mass is a critical phase for the profit in producing pig. To improve the metabolic utilization of dietary nutrients, it relies heavily on a healthy gut or gastrointestinal tract, and only a healthy digestive can result in better feed digestion and better nutrient absorption. Thus, the study investigates the growth performance, the response of the digestive morphology of native pigs, which treatment will stretch higher output and variations under different levels of fermented mungbean. The experimental research design was employed to determine the response of the three (3) pigs treated with mungbean for 70 days. The growth performance of pigs treated with different levels of fermented mungbean has a total gain weight of 7.50kg for Treatment 1; Treatment 2 is 9.00kg and, Treatment 3 is 6.50kg and is observed no significant difference on the final weight and the total weight with a p-value of &gt; 0. 050; the response on digestive morphology such as small intestine, large intestine, heart, stomach, liver, lungs, esophagus, spleen, and kidney of pigs shows no variations on their length, width, and weight with a p-value of &gt;0.050 under the different level of fermented mungbean; and resulted with high output treated with different level of fermented mungbean is observed on Treatment 2 with a lowest feed conversion efficiency of 3.89 for feeds and 1.39 for mungbean. Treatment 2 has the highest gain weight among the treated sample; the intestinal morphology of pigs was comparable under the three treatments; treatment 2 has the lowest feed conversion efficiency.