Continued Increase of Erythromycin Nonsusceptibility and Clindamycin Nonsusceptibility Among Invasive Group A Streptococci Driven by Genomic Clusters, United States, 2018-2019.

We analyzed 9630 invasive GAS surveillance isolates in the USA. From 2015-2017 to 2018-2019, significant increases in erythromycin-nonsusceptibility (18% vs 25%) and clindamycin-nonsusceptibility (17% vs 24%) occurred, driven by rapid expansions of genomic subclones. Prevention and control of clustered infections appear key to containing antimicrobial resistance.

Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016- April 2017.

BACKGROUND: The genomic features and transmission link of circulating Group A Streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood. METHODS: We used whole-genome sequencing to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017. RESULTS: The GAS isolates were cultured from 236 invasive and 417 pharyngitis infections. Whole-genome sequencing identified 34 emm types. Compared with pharyngitis isolates, invasive isolates were more likely to carry the erm family genes (23% vs 7.4%, P<.001), which confer resistance to erythromycin and clindamycin (including inducible resistance), and covS gene inactivation (7% vs 0.5%, P<.001). Whole-genome sequencing identified 97 genomic clusters (433 isolates; 2-65 isolates per cluster) that consisted of genomically closely related isolates (median single-nucleotide polymorphism=3 [interquartile range, 1-4] within cluster). Thirty genomic clusters (200 isolates; 31% of all isolates) contained both pharyngitis and invasive isolates and were found in 11 emm types. CONCLUSIONS: In the Denver metropolitan population, mixed disease types were commonly seen in clusters of closely related isolates, indicative of overlapping transmission networks. Antibiotic-resistance and covS inactivation was disproportionally associated with invasive disease.

A low threshold for neonatal intervention yields a high rate of biventricular outcomes in pulmonary atresia with intact ventricular septum.

AIMS: Management strategies for pulmonary atresia with intact ventricular septum are variable and are based on right ventricular morphology and associated abnormalities. Catheter perforation of the pulmonary valve provides an alternative strategy to surgery in the neonatal period. We sought to assess the long-term outcome in terms of survival, re-intervention, and functional ventricular outcome in the setting of a 26-year single-centre experience of low threshold inclusion criteria for percutaneous valvotomy. METHODS AND RESULTS: Retrospective analysis of patients diagnosed with pulmonary atresia with intact ventricular septum from 1990 to 2016 at a tertiary referral centre, was performed. Of 71 patients, 48 were brought to the catheterisation laboratory for intervention. Catheter valvotomy was successful in 45 patients (94%). Twenty-three patients (51%) also underwent ductus arteriosus stenting. The length of intensive care and hospital stay was significantly shorter, and early re-interventions were significantly reduced in the catheterisation group. There were eight deaths (17%); all within 35 days of the procedure. Of the survivors, only one has required a Fontan circulation. Twenty-eight patients (74%) have undergone biventricular repair and nine patients (24%) have one-and-a-half ventricle circulation. Following successful valvotomy, 80% of patients required further catheter-based or surgical interventions. CONCLUSIONS: A low threshold for initial interventional management yielded a high rate of successful biventricular circulations. Although mortality was low in patients who survived the peri-procedural period, the rate of re-intervention remained high in all groups.

Erythropoietin and ferritin response in native highlanders aged 4-19 years from the Leh-Ladakh region of India.

The pivotal role of erythropoietin (EPO) in hypoxic adaptation has led to various studies assessing the EPO and ferritin response in native highlanders from Andes and Tibet. We assessed the relationship between EPO, haemoglobin and ferritin in 335 native highlanders (172 boys and 163 girls, aged 4 to 19 years) from Leh-Ladakh, India, who had no history of travel to lowland areas. Complete blood counts, serum EPO and ferritin levels were measured. We stratified study subjects based on age, gender, pubertal status and analysed the EPO and ferritin levels between the stratified groups respectively. The mean EPO level in boys was lower than girls. The mean ferritin level in boys was significantly higher (P = 0·013) than in girls. There was no significant variation in the EPO and ferritin levels amongst the various age groups in our study. Near normal EPO levels since childhood with a negative correlation with haemoglobin is suggestive of a robust adaptive mechanism to high altitude from the early years of life. Low ferritin levels are indicative of decreased iron stores in these native highlanders.

Description of Lunatimonas salinarum sp. nov.

A Gram-stain-negative, crescent-shaped, non-motile, aerobic bacterium was isolated from a saltern at Nari along the Bhavnagar coast, Gujarat, India. The strain designated JC344T was oxidase- and catalase-positive. The 16S rRNA gene sequence analysis and sequence comparison data indicated that JC344T represented a member of the genus Lunatimonas and was closely related to the only species of the genus, Lunatimonas lonarensis AK24T (95.5 %). The DNA G+C content of JC344T was 43 mol%. JC344T has phosphatidylethanolamine (PE) and four unidentified polar lipids. MK-7 is the only respiratory quinone. The major (>10 %) fatty acids of strain JC344T are iso-C15 : 0, anteiso-C15 : 0 and summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl). On the basis of physiological, genotypic, phylogenetic and chemotaxonomic analyses, we conclude that JC344T represents a novel species of the genus Lunatimonas, for which the name Lunatimonas salinarum sp. nov. is proposed. The type strain is JC344T (=KCTC 42988T=LMG 29259T).

Salinicoccus amylolyticus sp. nov., isolated from a saltern.

A Gram-stain-positive coccus, strain JC304T, was isolated from a saltern of Nari along the Bhavnagar Coast, Gujarat, India. The 16S rRNA gene sequence analysis and sequence comparison data indicated that JC304T represented a member of the genus Salinicoccus and was most closely related to Salinicoccus roseus 9T (99.6 %), Salinicoccus luteus YIM 70202T (97.0 %), Salinicoccus hispanicus J-82T (97.0 %) and the remaining species of the genus Salinicoccus (<97 %). Genome relatedness based on DNA-DNA hybridization of JC304T with the type strains of the most closely related species was less than 46 % and the ΔTmwas >5 °C indicating that the strain represents a novel species of the genus Salinicoccus. Independent and concatenated phylogenetic analysis of recA/fusA gene translated product showed a clear distinction of JC304T from its phylogenetic neighbors. Diphosphotidylglycerol, phosphatidylglycerol, an unidentified glycolipid and three unidentified lipids (L1, L2 and L3) were the polar lipids of JC304T. Iso-C15 : 0 and anteiso-C15 : 0 were the major (>10 %) fatty acids in strain JC304T. The cell-wall amino acids were l-lysine and d-glycine. Hopanoids were not detected. The major isoprenoid quinone was menaquinone (MK-6). The DNA G+C content of JC304T was 48 mol%. On the basis of physiological, genotypic, phylogenetic and chemotaxonomic analyses, strain JC304T is considered to represent a novel species of the genus Salinicoccus, for which the name Salinicoccusamylolyticus sp. nov. is proposed. The type strain is JC304T (=KCTC 33661T=LMG 28757T).

Description of Jeotgalibacillus alkaliphilus sp. nov., isolated from a solar salt pan, and Jeotgalibacillus terrae sp. nov., a name to replace 'Jeotgalibacillus soli' Chen et al. 2010.

A Gram-stain-positive, non-motile, rod-shaped bacterium (strain JC303T) isolated from a salt pan was identified based on 16S rRNA gene sequence analysis as a member of the genus Jeotgalibacillus. It was related most closely to Jeotgalibacillus salarius ASL-1T (99.1 % similarity), Jeotgalibacillusalimentarius YKJ-13T (97.9 %), Jeotgalibacillussoli JSM 081008 (97.9 %), Jeotgalibacillusmalaysiensis D5T (97.8 %), Jeotgalibacillusmarinus DSM 1297T (96.3 %), Jeotgalibacilluscampisalis SF-57T (96.1 %) and J. soli P9T (94.9 %). Genomic relatedness based on DNA-DNA hybridization of strain JC303T with the type strains of the closest related species was less than 40 %. Diphosphatidylglycerol, three aminophospholipids, an unidentified aminoglycolipid, two unidentified phospholipids and an unidentified lipid were the polar lipids of strain JC303T. Major (>10 %) fatty acids were anteiso-C15 : 0, iso-C15 : 0 and iso-C14 : 0. Cell-wall amino acids contained peptidoglycan with l-lysine as the diagnostic diamino acid. Strain JC303T contained MK-7 as the predominant (96 %) menaquinone with the presence of a significant amount (4 %) of MK-8. The DNA G+C content was 43 mol%. On the basis of morphological, physiological, genotypic, phylogenetic and chemotaxonomic analyses, strain JC303T is considered to represent a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus alkaliphilus sp. nov. is proposed. The type strain is JC303T (=KCTC 33662T=LMG 28756T). In addition, we propose to rename J. soli (Chen et al., 2010), an illegitimate homonym of the validly published name Jeotgalibacillus soli(Cunha et al., 2012) as Jeotgalibacillus terrae sp. nov. with type strain JSM 081008T (=DSM 22174T=KCTC 13528T).

Long-term follow-up is not indicated after routine interventional closure of persistent arterial ducts.

BACKGROUND: Little is known about the necessity for long-term follow-up after interventional closure of persistent arterial duct (PDA). Potential side effects and complications include residual shunts, haemolysis, device embolization, and obstruction to flow in the adjoining vessels. METHODS: Single centre retrospective study of paediatric patients undergoing interventional PDA occlusion. RESULTS: 315 patients who underwent interventional occlusion of a PDA between November 2002 and September 2013 were included. Of these, eight needed re-intervention (three for device embolization, five for residual shunt). Seven had mild obstruction to flow in the adjoining vessels, but did not require any intervention. All sequelae were found latest at the first follow-up appointment after the procedure (usually within 3 months); whilst none developed during further follow-up. CONCLUSION: Complications of interventional closure of PDA were apparent immediately after the procedure or by three months of follow-up. Long-term follow-up is not indicated in cases when no complications are seen early after the procedure.

Obstructive sleep apnea: awakening the hidden truth.

Obstructive sleep apnea (OSA) is a common type of sleep apnea and is caused by obstruction of upper airway. Sleep apnea is clinically defined as frequent episodes of apnea, hypopnea and symptoms of functional impairment, which could be life-threatening and associated with extreme daytime hyper somnolence, dysfunction, discrements in health-related quality of life, automobile accidents, and cardiovascular morbidity and mortality. Etiopathogenic factors that contribute to OSA include reduced upper-airway dilator muscle activity during sleep, upper-airway anatomical features, ventilatory control insufficiency, lung volume, and rostral fluid shifts. The presence of risk factors such as age, gender and obesity increases the incidence of OSA. The repetitive nocturnal hypoxemia experienced by patients with OSA is associated with activation of a number of neural, humoral, thrombotic, metabolic, and inflammatory disease mechanisms, all of which have also been implicated in the pathophysiology of various systemic diseases. This article summarizes the etiopathogenesis, epidemiology, associated systemic diseases such as cardiovascular diseases, diabetes, and dental diseases with OSA and the influence of tongue on oropharyngeal airway in OSA patients.

Rhodoplanes oryzae sp. nov., a phototrophic alphaproteobacterium isolated from the rhizosphere soil of paddy.

A Gram-stain-negative, rod-shaped, phototrophic bacterium, strain JA793(T), was isolated from rhizosphere soil of paddy. The strain was capable of growing phototrophically and chemotrophically. Bacteriochlorophyll-a and carotenoids of the spirilloxanthin series were present as photosynthetic pigments. The major fatty acid of strain JA793(T) was C18 : 1ω7c/C18 : 1ω6c (>65.7%), with minor amounts of C16 : 0, C16 : 1ω7c/C16 : 1ω6c, C20 : 2ω6,9c, C16 : 0 3-OH, C14 : 0 and C18 : 0 also present. Ubiquinone-10 and rhodoquinone-10 were present as primary quinones. Phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine were the major polar lipids, while minor amounts of amino lipids and unidentified lipids were also present. The G+C content of genomic DNA of strain JA793(T) was 68.7 mol%. 16S rRNA gene-based EzTaxon-e blast search analysis of strain JA793(T) indicated highest sequence similarity with members of the genus Rhodoplanes in the family Hyphomicrobiaceae of the class Alphaproteobacteria. Strain JA793(T) had high sequence similarity with Rhodoplanes elegans AS130(T) (98.6%), Rhodoplanes roseus 941(T) (98%), Rhodoplanes pokkaliisoli JA415(T) (97.5%) and Rhodoplanes piscinae JA266(T) (97.3%) and other members of the genus Rhodoplanes (<97%). However, strain JA266(T) was related by <59% (based on DNA-DNA hybridization) to Rhodoplanes elegans DSM 11907(T) ( = AS130(T)), Rhodoplanes roseus DSM 5909(T) ( = 941(T)), Rhodoplanes pokkaliisoli JA415(T) and Rhodoplanes piscinae JA266(T). The genomic information was well supported by phenotypic and chemotaxonomic data to classify strain JA793(T) as a representative of a novel species in the genus Rhodoplanes, for which the name Rhodoplanes oryzae sp. nov. is proposed. The type strain is JA793(T) ( = NBRC 109406(T) = KCTC 15260(T)).

Rhodovulum salis sp. nov. and Rhodovulum viride sp. nov., phototrophic Alphaproteobacteria isolated from marine habitats.

Two strains (JA746(T) and JA756(T)) having yellowish brown-to-green pigment were isolated from a solar saltern and a pink pond, respectively. While both strains were non-motile and shared the presence of bacteriochlorophyll-a, major cellular fatty acids (C18 : 1ω7c, C16 : 0, C18 : 0), quinone (Q-10), polar lipids and hopanoids, they differed from each other in their carotenoid composition. The G+C content of genomic DNA of strains JA746(T) and 756(T) was 62.4 and 63.3 mol%, respectively. The 16S rRNA gene-based EzTaxon-e blast search analysis of strains JA746(T) and 756(T) indicated highest sequence similarity with members of the genus Rhodovulum in the family Rhodobacteraceae of the class Alphaproteobacteria. Strain JA746(T) has high sequence similarities with Rhodovulum visakhapatnamense JA181(T) (97.3 %), Rhodovulum steppense A-20s(T) (97.3 %), Rhodovulum phaeolacus JA580(T) (97 %), Rhodovulum strictum MB-G2(T) (97 %) and other members of the genus Rhodovulum (<97 %). Strain JA756(T) has high sequence similarities with Rhodovulum visakhapatnamense JA181(T) (99.8 %), Rhodovulum sulfidophilum Hansen W4(T) (99.1 %), Rhodovulum kholense JA297(T) (97.9 %) and other members of the genus Rhodovulum (<97 %). The sequence similarity between strains JA746(T) and JA756(T) was 97.5 %. However, these strains are not closely related to each other or to their phylogenetic neighbours since the DNA-DNA reassociation values were less than 56 %. The genomic information was also supported by phenotypic and chemotaxonomic results, leading us to classify strains JA746(T) ( = NBRC 108898(T) = KCTC 15180(T)) and JA756(T) ( = NBRC 109122(T) = KCTC 15223(T)) as the type strains of two novel species of the genus Rhodovulum, for which the names Rhodovulum salis sp. nov. and Rhodovulum viride sp. nov. are proposed, respectively.

Computational modeling and uncertainty prediction of hyperelastic constitutive responses of damaged brain tissue under different temperature and strain rates.

The effect of strain rate and temperature on the hyperelastic material stress-strain characteristics of the damaged porcine brain tissue is evaluated in this present work. The desired constitutive responses are obtained using the commercially available finite element (FE) tool ABAQUS, utilizing 8-noded brick elements. The model's accuracy has been verified by comparing the results from the previously published literature. Further, the stress-strain behavior of the brain tissue is evaluated by varying the damages at various strain rates and temperatures (13, 20, 27, and 37°C) under compression test. Additionally, the sensitivity analysis of the model is computed to check the effect of input parameters, that is, the temperature, strain rate, and damages on the material properties (shear modulus). The modeling and discussion sections enumerate the inclusive features and model capabilities.

Growth capacity of a Wharton's Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets.

Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy. Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry. Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded. Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

Underlying factors determining grain morphologies in high-strength titanium alloys processed by additive manufacturing.

In recent research, additions of solute to Ti and some Ti-based alloys have been employed to produce equiaxed microstructures when processing these materials using additive manufacturing. The present study develops a computational scheme for guiding the selection of such alloying additions, and the minimum amounts required, to effect the columnar to equiaxed microstructural transition. We put forward two physical mechanisms that may produce this transition; the first and more commonly discussed is based on growth restriction factors, and the second on the increased freezing range effected by the alloying addition coupled with the imposed rapid cooling rates associated with AM techniques. We show in the research described here, involving a number of model binary as well as complex multi-component Ti alloys, and the use of two different AM approaches, that the latter mechanism is more reliable regarding prediction of the grain morphology resulting from given solute additions.

Rhodovulum bhavnagarense sp. nov., a phototrophic alphaproteobacterium isolated from a pink pond.

An oval to rod-shaped, Gram-stain-negative, phototrophic bacterium, strain JA738(T), was isolated from a sediment sample collected from a pink pond. Strain JA738(T) was non-motile and had vesicular-type intracellular photosynthetic membranes. Bacteriochlorophyll a and carotenoids of the spheroidene series were present as the major photosynthetic pigments. Strain JA738(T) required thiamine and pantothenate for growth. The major cellular fatty acids were C(18 : 1)ω7c, C(18 : 1)ω5c, C(18 : 0) and C(18 : 1)ω7c11-methyl; minor amounts of C(10 : 0) 3-OH and C(16 : 0) were also present. The major quinone was Q-10 and major polar lipids were phosphatidylglycerol, phosphatidylethanolamine and two unidentified sulfolipids (SL1-2). Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that strain JA738(T) clustered with species of the genus Rhodovulum in the class Alphaproteobacteria. Strain JA738(T) was most closely related to Rhodovulum adriaticum DSM 2781(T) (96.4 % 16S rRNA gene sequence similarity) and other members of the genus Rhodovulum (<96.1 %). On the basis of phenotypic and molecular genetic evidence, it is proposed that strain JA738(T) should be classified as a novel species of the genus Rhodovulum for which the name Rhodovulum bhavnagarense sp. nov. is proposed. The type strain is JA738(T) ( = DSM 24766(T) = KCTC 15110(T)).

Georgenia satyanarayanai sp. nov., an alkaliphilic and thermotolerant amylase-producing actinobacterium isolated from a soda lake.

A Gram-stain-positive, oxidase-negative, starch-hydrolysing, actinobacterium (strain JC82(T)) was isolated from a soda lake in Lonar, India. Based on 16S rRNA gene sequence similarity studies, strain JC82(T) belonged to the genus Georgenia and was most closely related to Georgenia muralis 1A-C(T) (96.8 %) and other members of the genus Georgenia (<96.5 %). The DNA G+C content of strain JC82(T) was 73.4 mol%. The cell-wall amino acids were alanine, glutamic acid and lysine with peptidoglycan type A4α. Polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, an unidentified lipid (L1) and an unidentified glycolipid (GL3). The predominant isoprenoid quinone was menaquinone MK-8(H(4)). Anteiso-C(15 : 0) was the predominant fatty acid and significant proportions of iso-C(14 : 0), C(14 : 0), C(16 : 0), iso-C(15 : 0) and iso-C(16 : 0) were also detected. Strain JC82(T) produced thermostable alkaline amylase. The results of physiological and biochemical tests allowed a clear phenotypic differentiation of strain JC82(T) from all other members of the genus Georgenia. Based on these data, strain JC82(T) represents a novel species of the genus Georgenia, for which the name Georgenia satyanarayanai sp. nov. is proposed. The type strain is JC82(T) ( = KCTC 19802(T) = NBRC 107612(T)).

Fluorescent uranyl ion lidded cucurbit[5]uril capsule.

A novel fluorescent complex {(UO(2))(2)(CB5)}(NO(3))(4)·4HNO(3).3H(2)O (U2CB5) is obtained from cucurbit[5]uril (CB5) and uranyl nitrate under ambient temperature conditions. The crystal structure revealed that two uranyl ions are coordinated to the two open portals of CB5 giving a closed molecular capsule, which further connected through CB5 molecules to give two-dimensional frameworks. The U2CB5 complex was further investigated by NMR, FTIR and TGA techniques. The Fluorescence of uranyl ion was found to be enhanced due to complexation with cucurbituril.

Repeated dose dermal toxicity study of nano zinc oxide with Sprague-Dawley rats.

CONTEXT: In light of the increased use of zinc oxide nanoparticles in cosumer products such as sunscreens, there is a need for screening the potential dermal toxicity of these nanoparticles. OBJECTIVE: The aim of this study is to identify the risk associated with the nano zinc oxide at realistic exposure levels through dermal route. This study is to understand the toxic potential of nano zinc oxide through repeated dermal exposure for a period of 28 days. MATERIALS AND METHODS: Six- to 8-week-old Sprague-Dawley rats were applied with three different doses (75, 180, and 360 mg/kg body weight) of nano zinc oxide (20 nm) at 5 days/week basis for a period of 28 days. The dose levels were calculated taking into consideration the percentage of nanomaterial in the sunscreen, number of application times, and average weight of the consumer in order to assess the realistic risk related to it. Control group animals were applied with distilled water alone. The collagen content was estimated in skin and tail of all the treated and control animals. RESULTS: The content was significantly decreased in all the nano zinc oxide-treated groups with an inverse dose relationship. DISCUSSION AND CONCLUSION: The percentage collagen loss was high in skin when compared with tail. This may be due to the site of application where in the nano zinc oxide may be passed through skin due to their small size and may induce oxidative stress. Hence, we suggest that regulators and industry need to address the toxicity of nanomaterials with a realistic exposure assessment rather following conventional dose measurements following existing protocols.

Wharton's Jelly-Mesenchymal Stem Cell-Engineered Conduit for Pulmonary Artery Reconstruction in Growing Piglets.

Surgical treatment of congenital heart defects affecting the right ventricular outflow tract often requires complex reconstruction and multiple reoperations. With a randomized controlled trial, we compared a novel tissue-engineered small intestine submucosa-based graft for pulmonary artery reconstruction (seeded with mesenchymal stem cells derived from Wharton's Jelly) with conventional small intestine submucosa in growing piglets. Six months after implantation, seeded grafts showed integration with host tissues at cellular level and exhibited growth potential on transthoracic echocardiography and cardiovascular magnetic resonance. Our seeded graft is a promising biomaterial for pulmonary artery reconstruction in pediatric patients with right ventricular outflow tract abnormalities.

Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes.

The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA's blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft's growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.