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.

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.

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.

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.

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.

Genomic Surveillance of Streptococcus pyogenes Strains Causing Invasive Disease, United States, 2016-2017.

BACKGROUND: Streptococcus pyogenes is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common. Understanding the current prevalence and dynamics of S. pyogenes lineages could inform vaccine development and disease control strategies. METHODS: We used whole-genome sequencing (WGS) to characterize all invasive S. pyogenes isolates obtained through the United States Center for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) in 2016 and 2017. We determined the distribution of strain features, including emm type, antibiotic resistance determinants, and selected virulence factors. Changes in strain feature distribution between years 2016 and 2017 were evaluated. Phylogenetic analysis was used to identify expanding lineages within emm type. RESULTS: Seventy-one emm types were identified from 3873 isolates characterized. The emm types targeted by a 30-valent M protein-based vaccine accounted for 3230 (89%) isolates. The relative frequencies of emm types collected during the 2 years were similar. While all isolates were penicillin-susceptible, erythromycin-resistant isolates increased from 273 (16% of 2016 isolates) to 432 (23% of 2017 isolates), mainly driven by increase of the erm-positive emm types 92 and 83. The prevalence of 24 virulence factors, including 11 streptococcal pyrogenic toxins, ranged from 6 to 90%. In each of three emm types (emm 49, 82, and 92), a subgroup of isolates significantly expanded between 2016 and 2017 compared to isolates outside of the subgroup (P-values < 0.0001). Specific genomic sequence changes were associated with these expanded lineages. CONCLUSIONS: While the overall population structure of invasive S. pyogenes isolates in the United States remained stable, some lineages, including several that were antibiotic-resistant, increased between 2016 and 2017. Continued genomic surveillance can help monitor and characterize bacterial features associated with emerging strains from invasive infections.

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.

Hematological Parameters in Native Highlanders of Ladakh Aged 4-19 Years.

Hematological adaptations to high altitude (HA) are long studied but are focused either on lowlanders visiting HA or native highlanders from Andes and Tibet. The literature on native highlanders from the Indian subcontinent or paediatric highlanders is scarce. We aimed at assessing hematological parameters in native highlanders of Ladakh, India, aged 4-19 years and derive nomograms in an age stratified manner specific to these native highlanders. A total of 335 self-reported healthy native highlanders of Ladakh, without any known comorbidities and not on hematinic nor any drugs in the age group of 4-19 years were included in the study. Complete hemogram including red cell indices was measured. R ver 3.4.0 was used to compare the hematological parameters based on gender/age stratification, pubertal and nutritional status. The hematological reference ranges were created for various parameters in the paediatric population. The mean (SD) haemoglobin (Hb) concentration was 14.74 (2.07) gm/dL. The mean hematocrit (Hct) was 40.43 (5.57%) %, mean corpuscular volume (MCV) was 81.87 (7.22) fL, white blood cell (WBC) count was 7596 (2172) cells/µL and platelets was 378.4 (152.8) × 103/µL. Hct and MCV increased with age. Hb concentration, Hct, and MCV in girls was significantly lower than boys. Severely underweight subjects (body mass index < 16) showed significantly higher platelet counts compared to their nourished counterparts. The hematological nomograms for the native paediatric highlanders from Ladakh, India have been reported in this study.

A study of acute kidney injury in hospitalized preterm neonates in NICU.

OBJECTIVES: This study was carried out to determine the incidence, clinical features, etiology and outcome of functional and intrinsic acute kidney injury (AKI) in preterm neonates. METHODS: This is a prospective observational study on premature infants admitted to the neonatal intensive care unit (NICU) over an eight month period. All biochemical parameters of renal function tests were monitored and statically analyzed. RESULTS: The study included 450 infants; of them 300 were inborn and 150 infants were outborn and transported to the NICU. Mean gestational age, weight, and age at the time of AKI diagnosis were 32.3 weeks, 1.66 kg and 3.23 days respectively. The male: female ratio was 1.84:1. Incidence of AKI was higher in low birth weight babies. Sluggishness and refusal for feed were most common symptoms. Birth asphyxia and septicemia were the most common early and late cause of AKI. Hyponatremia was the most common electrolyte disturbance. The incidences of AKI, functional renal failure, and intrinsic renal failure were 12%, 48.14%, and 51.85% respectively. CONCLUSIONS: AKI is not uncommon in preterm infants. The early recognition and aggressive management of episodes of shock which often precede AKI could be life-saving.

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).

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).

Transurethral Bougie-guided Placement of Suprapubic Catheter Over Guide Wire Monorail in Females: A Novel Technique.

OBJECTIVE: To assess the safety and effectiveness of a novel transurethral bougie-guided monorail technique for suprapubic catheterization in females with vesicovaginal fistula. METHODS: Patients undergoing transvaginal vesicovaginal fistula repair from February 2013 to December 2013 were selected. Suprapubic catheter was placed using this technique and assessment was done in terms of time taken, intraprocedural dislodgement or entanglement of catheter during the procedure, bleeding from the anterior abdominal wall or urethra, or any other intraoperative difficulty. RESULTS: All patients were catheterized smoothly without any intraoperative difficulty, with a mean time of 6 minutes. CONCLUSION: We describe a new technique of performing suprapubic cystostomy in patients, especially where the bladder cannot be distended. It is safe and easy to perform.

Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies.

In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.

Second stage after initial hybrid palliation for hypoplastic left heart syndrome: Arterial or venous shunt?

OBJECTIVE: Hybrid palliation for hypoplastic left heart syndrome has been developed as an alternative to neonatal Norwood surgery. At the second stage, a source of pulmonary blood flow has to be established. Options include an arterial modified Blalock-Taussig or a venous superior cavopulmonary shunt. METHODS: We retrospectively reviewed patients who received second-stage palliation after the initial hybrid. Patients were stratified according to the source of pulmonary blood supply into the arterial shunt (n = 17 patients) or venous shunt (n = 26 patients). RESULTS: Age and weight at second stage were lower in the arterial group (85 [45-268] days vs 152.5 [61-496] days, P = .001 and 3.6 [2.7-9.4] kg vs 5.1 [2.97-9.4] kg, P = .001, respectively). All recorded surgical times were shorter in the arterial group. Mechanical ventilation and intensive care stay were shorter in the venous group (5.82 [2.01-14.9] days vs 2.42 [0.56-13.67] days, P = .005 and 8.5 [3.6-23.7] vs 5.75 [0.8-17.6] days, P = .036, respectively) There was no difference in mortality (2/17 vs 5/26; P = .685) or incidence of complications between the 2 groups. There was a tendency toward a higher need for intervention in the immediate postoperative period in the venous group, but this did not reach significance (6/17 vs 13/26, P = .342). The arterial group has shown better development of the branch pulmonary arteries with a higher lower lobe index (158.38 ± 39.43 mm(2)/m(2) vs 113.33 ± 43.96 mm(2)/m(2), respectively, P = .037). CONCLUSIONS: Both arterial and venous shunts are viable options with mortality and morbidity results comparable to those in the literature. The arterial shunt pathway (2-stage Norwood I) may offer better pulmonary arterial growth than the venous shunt (comprehensive/combined Norwood I and II).

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.