Background and aim: The ultimate goal of mitral valve surgery in young women is to extend life expectancy and improve quality of life. Mitral valve replacement (MVR) prosthesis in middle-aged women is a difficult choice between the lifelong anticoagulation by mechanical prosthesis versus the limited long-term durability of bioprosthesis. The current trend towards reducing women’s age for selecting bioprosthesis over mechanical prosthesis leads to a dilemma for younger women decision making.1,2 The aim of this study was to compare the safety and freedom from complications in pregnancy and survival rate after mitral valve bioprosthesis versus mechanical prosthesis in young women for whom mitral valve repair is not feasible or unsuitable. Methods: This single-center non randomized prospective propensity-matched comparative study included all female patients undergoing MVR at our center from January 2010 to February 2020. Results: In total, 355 patients underwent MVR at our center, of whom 174 received a bioprosthesis and 181 received a mechanical prosthesis. The use of anticoagulation among young women with mechanical prosthesis was associated with a remarkable risk of postoperative bleeding, abortion, and increased frequency of pregnancy-related complications (p < 0.0001). In contrast, there was a considerable survival benefit for those who received bioprosthesis (p = 0.0001). Conclusions: Our data confirm that the use of mitral bioprosthesis in young women who desire to become pregnant is safe, reduces complications, and increases survival.

ABSTRACT Introduction and Objective: There are various management options for newborns with single ventricle physiology, ventriculoarterial discordance and subaortic stenosis (SOS), classically involving the early pulmonary banding and aortic arch repair, the restricted bulboventriculer foramen(BVF) enlargement or the Norwood and the Damus Kaye Stansel (DKS) procedures. The aim of this study is to evaluate the midterm results of our clinical experience with palliative arterial switch operation (pASO) for this subset of patients. Method: We hereby retrospectively evaluate the charts of patients going through pASO, as initial palliation through Fontan pathway, starting from 2014 till today. Results: 10 patients underwent an initial palliative arterial switch procedure. 8 of 10 patients survived the operation and discharged. 7 of 10 patients completed stage II and 1 patient reached the Fontan completion stage and the other six of ten (6/10) patients are doing well and waiting for the next stage of palliation. There are two mortalities in the series (2/10) and one patient lost to follow-up (1/10). Conclusions: The pASO can be considered as an alternative palliation option for patients with single ventricle physiology, transposition of the great arteries and systemic outflow obstruction. It not only preserves systolic and diastolic ventricular function, but also provides a superior anatomic arrangement for following stages. Keywords: Congenital Heart Disease, Single Ventricle, Arterial Switch Operation

Purpose: To explore the relationship between anti-MDA5 antibody and clinical manifestations of dermatomyositis(DM) and to explain the correlation of prognosis as well. Methods: Retrospective analysis was performed at the Department of Rheumatology and Immunology in Xiangya Hospital, Central South University from April 2017 to February 2019. The clinical data were collected from 109 patients with DM, and then the patients were divided into anti-MDA5 antibody positive group and negative group according to the results of antibody detection, after which statistical analysis was carried out with SPSS 23.0 software. Results: Among the 109 DM patients, the ratio of male to female is 1:2.3, with 58 positive anti-MDA5 antibody and 51 negative anti-MDA5 antibody. There is no difference in gender and age between the two groups, and patients with positive anti-MDA5 have a shorter course. The incidence of clinical symptoms, including Gottron sign, skin ulcer, joint pain, joint swelling, nail erythema, dyspnea, and cough in patients with anti-MDA5-positive DM is significantly higher than those in the anti-MDA5-negative group. Anti-MDA5 antibodies are inversely associated with tumorigenesis. Patients with anti-MDA5-positive DM have less elevation of muscle enzymes and are prone to ILD and RPILD, while patients with anti-MDA5-positive DM have a high mortality rate and poor prognosis. Conclusion: Combined with RP-ILD, the prognosis of DM is poor. When patients have these clinical manifestations and positive MDA5, they must actively undergo lung imaging examination and be alert to RP-ILD.

Allergic sensitization is commonly assessed in patients by performing the skin prick test (SPT) or determining specific IgE levels in blood samples with the ImmunoCAP assay, which measures each allergen and sample separately. This paper explores the possibility to investigate respiratory allergies with a high throughput method, the Meso Scale Discovery (MSD) multiplex immunoassay, measuring IgE levels in low volumes of blood. The MSD multiplex immunoassay, developed and optimized with standards and allergens from Radim, was validated against the SPT and the ImmunoCAP assay. For 18 adults (15 respiratory allergy patients and 3 controls), blood collection and the SPT were performed within the same hour. Pearson correlations and Bland-Altman analysis showed high comparability of the MSD multiplex immunoassay and the ImmunoCAP assay, except for house dust mite. The sensitivity of the MSD multiplexed assay was ≥75% for most allergens compared to the SPT and ImmunoCAP assay. Additionally, the specificity of the MSD multiplex immunoassay was ≥80% - the majority showing 100% specificity. Only the rye allergen had a low specificity when compared to the SPT, probably due to cross-reactivity. The reproducibility of the MSD multiplex immunoassay, assessed as intra- and inter-assay reproducibility and biological variability between different sampling moments, showed significantly high correlations (r=0.943-1) for all tested subjects (apart from subject 13; r=0.65-0.99). The MSD multiplex immunoassay is a reliable method to detect specific IgE levels against respiratory allergens in a multiplexed and high throughput way, using blood samples as small as from a finger prick.

Gli interventi di messa in sicurezza, a differenza di quelli di bonifica che vanno ad eliminare la sorgente di contaminazione, hanno lo scopo di ridurre la mobilità degli inquinanti e la diffusione dei contaminanti dal sito all’ambiente mediante l’isolamento del sito stesso. Il presente lavoro affronta lo studio degli interventi di messa in sicurezza attraverso l’adozione di tecniche di ingegneria ambientale nell’ambito della normativa Italiana ed Inglese. A tal fine, verrà discusso il caso di un sito contaminato a Londra e verranno analizzate le principali tecniche di messa in sicurezza attualmente disponibili.

Objective To determine maternal and neonatal outcomes in pregnant women with COVID-19 Design Retrospective, descriptive study Setting A single-center managing pregnant women with COVID-19 Population or Sample Third-trimester pregnant women with a diagnosis of COVID-19 Methods A retrospective, single-center, descriptive study Main Outcome Measures The maternal and neonatal results of COVID-19 pregnant women were evaluated by looking at the following parameters: the concentrations of D-dimer, complete blood count, ferritin, C-reactive protein, lymphocytes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), neonatal umbilical blood gas analyzes, real-time RT-PCR tests, lung CT imaging, admission to (neonatal) intensive care unit. Results In the third trimester, 40 pregnant women with COVID-19 were included. The most common complaint was cough (50%). The most common symptom that accompanied cough was fever and shortness of breath. Thirty-four patients delivered by cesarean and 6 patients delivered vaginally. Two patients were taken to the intensive care unit because of respiratory distress. There were no maternal and fetal deaths. The patients were hospitalized for an average of 5 days. One patient was followed up without treatment, while all other patients were given hydroxychloroquine. In addition, azithromycin, oseltamivir, or lopinavir/ritonavir were added to some patients in addition to hydroxychloroquine. Conclusions The clinical features of pregnant women with COVID-19 are comparable compared to non-pregnant adults. Long-term results and comparative studies are needed in this regard.

The COVID-19 pandemic has forced the transition of many traditional face-to-face classes into an online format with little time to prepare best practice guidelines. In this article we share ways to adapt a group field activity into an individual lab assignment that can be completed during shelter-in-place restrictions. We address the tactics, difficulties, successes, and ideas for future applications while staying mindful of the ways in which this pandemic has highlighted the inequities of the classroom.

Aim: To assess the characteristics of admissions with diabetic ketoacidosis (DKA) in a specialized children hospital in order to inform appropriate prevention and intervention strategies. Methods: This is a retrospective chart review of DKA admissions of children with T1DM at King Abdullah Specialized Children’s hospital, Riyadh, Saudi Arabia (March 2015- December 2017). Results: A total of 116/562 patients with type 1 diabetes (mean age 8.97±3.08 years, Females n=81 (55.5%)) presented with DKA during the study period. The majority were between 10-14 years of age (p=<0.001). We scrutinized data from (146/311, 47%) DKA events of all inpatient admissions of children with T1D. The frequency of DKA admissions was 26% (n=146/562 of all patients with T1DM, 25% (n= 42/141) were in newly diagnosed and 24.7% (n=104/421) were in previously diagnosed patients). Missing insulin was the main precipitating cause (p=0.001) in previously diagnosed patients. Recurrent episodes (n=30, 20.5% of all episodes) occurred in 15/116 patients and was more common in children 10 years old (P=0.024). The overall mean length of stay (LOS) was 2.67±2.04 days. Increased LOS was significantly associated with DKA severity (P=0.008). Conclusion: Missing insulin remained to be the main cause of DKA in previously diagnosed patients with type 1 diabetes even in advanced settings. Besides awareness campaigns to prevent DKA as an initial presentation of T1DM, intervention and prevention strategies should also focus on vulnerable groups of previously diagnosed patients such as adolescents and those with recurrent episodes of DKA.

Aim: Although medicine misuse is a public health issue, it has multiple meanings in the medical literature. This study aimed to characterize, classify and identify the most appropriate definitions of medicine misuse. Methods: A systematic review was performed in Medline, ISI Web of Science, SocINDEX, PsycInfo, PsycArticles, and Psychological and Behavioral Sciences Collection, using keywords related to misuse, appropriateness, and medicine between November 1st, 2008 and November 1st, 2018. Additional searches were conducted in websites of regulatory agencies and public health institutions. Two authors independently selected studies providing both definitions and examples of misuse, while a third resolved disagreements. Definitions were used to propose a hierarchical classification based on initiator, intent, purpose, and context of medicine misuse. The study is registered on PROSPERO: CRD42018115789. Results: Of 2,901 identified records, 44 were included. A total of 63 definitions and 60 examples of misuse were retrieved. When the prescriber is initiator and according to intent, potential medicine misuse referred to “intentional or unintentional prescribing not in line with clinical evidence”. Based on context, he could prescribe medicines not clinically justified, i.e. “overprescribing”, or prescribe indicated medicines incorrectly, i.e. “misprescribing”. Among other groups of definitions, those overlapping with drug abuse or medication use errors were considered out-of-scope. Conclusion: This systematic review provides a comprehensive overview of the terms and definitions used to characterize medicine misuse and could serve as a basis for a terminology that makes clear distinctions between misuse, abuse, and errors.

Aims: to test the hypothesis that a semi-supervised home physical exercise program improves the functional mobility and quality of life (QOL) of elderly in the community. Methods: This trial was conducted with elderly people (88% female), aged 60 years or older, sedentary and without cognitive decline. Elderly were randomly assigned to an intervention group - IG (home physical exercise and sleep hygiene) and a control group - CG (sleep hygiene). Were applied the International Questionnaire on Physical Activity; mental state mini-exam and the Timed Up and Go test (TUG) before and after the 12-week intervention period. Results: The IG showed an improvement in functional mobility, with a mean reduction in TUG execution time (p <0.01) and improvement in the QOL, (p <0.01) in WHOQOL-OLD. Conclusion: Semi-supervised physical home exercise is effective in improving the functional mobility and the QOL of sedentary elderly in the community. Trial Registration: Registro Brasileiro de Ensaios Clínicos (REBEC) Identifier: RBR-3cqzfy Keywords: Elderly; exercise; functional mobility; quality of life; community; physical activity; home exercise.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has recently emerged as a new public health threat. SARS-CoV-2 is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. At the time of writing, approximately 6.6 million cases have been reported worldwide. Like other coronaviruses, SARS-CoV-2 relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the host receptor Angiotensin-Converting Enzyme2 (ACE2). SARS-CoV-2 infection induces a profound downstream proinflammatory cytokine storm. This release of the proinflammatory cytokines is underpinning lung tissue damage, respiratory failure, and eventually multiple organ failure in COVID-19 patients. The phosphorylation status of ERK1/2 is positively correlated with virus load and ERK1/2 inhibition suppressed viral replication and viral infectivity.Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or damping hyperinflammatory cytokines storm, blocking ERK1/2 phosphorylation have a great potential to inhibit viral entry along with viral infectivity. Herein, we report that the FDA-approved non-peptide opioid antagonist drug, naltrexone suppresses high fat/LPS induced pro-inflammatory cytokine release both from macrophage cells and Adipose Tissue Macrophage (ATM). Moreover, Low Dose Naltrexone (LDN) also showed its activity as an ERK1/2 inhibitor. Notably, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD and thus LDN may be considered as a target as the treatment and (or) adjuvant therapy for coronavirus infection.

Kikuchi-Fujimoto Disease (KFD) is a self-limiting condition that typically presents with lymphadenopathy and fever. It’s autoimmune in nature, and possibly associated with systemic lupus erythematosus (SLE). The case report highlights an unusual case of KFD associated with autoimmune hemolytic anemia and provided a review for other atypical presentations.

As a complication of GV treatment with Histoacryl®, boweel obstruction is not common. However, when the patients with a history of abdominal surgery complain of an abdominal pain after the GV treatment, we should also consider bowel obstruction.

Objective: To gain a deeper understanding of women’s experiences with accessing care for abnormal uterine bleeding (AUB), in order to inform future strategies in early detection of endometrial cancer. Design: We conducted semi-structured interviews with 15 women who attended their first gynaecological specialist consultation for abnormal uterine bleeding at Wellington Regional Hospital between October-December 2019. Inductive thematic analysis was used to decipher facilitators and barriers to care. Results: Thirty women were invited to participate in the study. The medium age of the final participant cohort was 45 years, with women self-identifying as New Zealand European (9/15), Māori (2/15) and Pasifika (4/15). All women had sought investigation for their AUB in primary care, for some women this was over a timeframe of many years. For all women, AUB had a significant and traumatic impact on their quality of life including their relationships and their work or education. Women described how they felt they often received inadequate care for AUB, and negative experiences with their general practitioner. Timely access was further compounded by feelings of embarrassment and that AUB was taboo subject and being able to discuss it with family, friends and their general practitioners. Conclusion: Women in our cohort experienced a multitude of compounding influences that acted as barriers to them having access to appropriate and timely care. Information campaigns that create awareness around ‘abnormal periods’ alongside better health provider practice guidelines for AUB investigation need to be a priority.

Background and Purpose Histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses, but the role of HRF/TCTP remains undefined in rheumatoid arthritis (RA). In this study, we explored the pathogenic significance of HRF/TCTP and evaluated the therapeutic effects of HRF/TCTP blockade in RA. Experimental Approach HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in the sera of RA patients and compared to those with osteoarthritis (OA), ankylosing spondylitis, Behçet’s disease, and healthy controls. HRF/TCTP expression was also assessed in the synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed the effects of HRF/TCTP and dimerized HRF/TCTP-binding peptide-2 (dTBP2), an HRF/TCTP inhibitor, in RA-FLS and CIA mice. Key Results Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were higher in HRF/TCTP TG mice, and lower in KD mice, compared to that in wild-type littermates. HRF/TCTP levels were higher in the sera, synovial fluid, synovium, and FLS of patients with RA than control groups. Serum levels of HRF/TCTP correlated well with disease activity of RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effects in a murine tuberculosis model. Conclusion and Implications Our results indicate that HRF/TCTP is a novel biomarker and therapeutic target for the diagnosis and treatment of RA.

Jejunoileal atresia is a common cause of neonatal intestinal obstruction with high mortality and morbidity in a low resource setting where surgical care is lacking. Herein, a 4-day-old presented with features of acute abdomen and septicaemia, managed with ileostomy diversion and recovered uneventfully.

Skeletal dysplasias are a heterogeneous group of disorders ranging from mild to lethal skeletal defects. We investigated two unrelated families with individuals presenting with a severe skeletal disorder. In family NMD02, affected individuals had a dysostosis multiplex-like skeletal dysplasia and severe short stature (<-8.5 SD). They manifested increasing coarse facial features, protruding abdomens and progressive skeletal changes, reminiscent of mucopolysaccharidosis. The patients gradually lost mobility and the two oldest affected individuals died in their twenties. The affected child in family ID01 had coarse facial features and severe skeletal dysplasia with clinical features similar to mucopolysaccharidosis. She had short stature, craniosynostosis, kyphoscoliosis and hip-joint subluxation. She died at the age of 5 years. Whole-exome sequencing identified two homozygous variants c.133C>T; p.(Arg45Trp) and c.215dupA; p.(Tyr72Ter) respectively, in the two families, affecting an evolutionary conserved gene TMEM251. Immunofluorescence and confocal studies on Human Osteosarcoma cells indicated that TMEM251 localized to the Golgi complex and plasma membrane. However, p.Arg45Trp mutant TMEM251 protein was targeted less efficiently to the membranes and the localization was punctate. Tmem251 knockdown by siRNA induced dedifferentiation of rat primary chondrocytes. Our work implicates TMEM251 in the pathogenesis of a novel disorder and suggests its potential function in chondrocyte differentiation.

Objective: To provide objective data on the impact of COVID-19 crisis on our ENT practice. Design: Cross-sectional study. Setting: Tertiary referral hospital (1038 inpatients beds). Participants: 572 consecutive patients presenting to the ENT clinic and ENT operating theatre from March 16, 2020 to May 3, 2020 were prospectively included. Main outcome measures: Demographic and clinical data, admission time, paraclinic testing, management, outcome and follow’up were recorded. Retrospective search for comparison to past year over the same period of time was carried out. Results: Coronavirus crisis and the strict lockdown rules led to a severe disruption of the ENT service. A drop in overall activity of 91.1% was observed. Mortality rates increased from 0.82% to 4.55%. While some patients in real need may not have been able to be seen, others presented without ground. More than a quarter of admissions (n=157, 27.6%) resulted in no specific ENT treatment. Patient selection improved when patients had a recent ENT history (OR=2.39 [1.50-3.81], p=0.0003) or were referred by a physician (OR=5.30 [3.69-7.61], p<0.0001). Conclusions: Our data suggested impaired healthcare of all ENT patients. Special attention should be paid to non-Covid otolaryngology patients.

Objectives: Salivary gland malignancies are an uncommon and heterogeneous group of cancers. We report our experience of clinicopathological variables that affect survival in patients treated by curative intent with surgery at a UK institution over a period of 15 years. Design: Retrospective cohort study Setting: Single centre study Participants We included 108 patients with malignant salivary gland tumours treated by curative intent with surgery from 2004 to 2019. Main outcome measures: The association between clinicopathological factors and their impact on overall survival (OS) and disease-free survival (DFS). Results: 77 (71.3%) presented with early pT classification and 81 (75%) of were node-negative. The parotid was the commonest site of malignancy (86, 79.6%). Perineural invasion (PNI) was present in 40 (37%) and lymphovascular invasion (LVI) was present in 20 (18.5%). 63 (58.3%) underwent adjuvant therapy. Median follow up was 36 months. Five-year OS and DFS were 81.7% and 71%. Age 50, pT classification 3-4, high tumour grade, PNI, and advanced TNM stage were all associated with worse OS and DFS, and LVI with worse DFS. There was no survival difference between a close (1-<5 mm) or negative (≥5 mm) resection margin. Conclusions: Age >50 years, advanced TNM stage, PNI and LVI are predictors of poor DFS. There was no difference in OS or DFS between patients with negative and close resection margins, indicating that close margins may be adequate for maintaining good oncologic outcomes in this group of patients.

Perfusion processes have gained interest as mammalian cell culture mode. Due to the high complex issues and variability regarding such culture mode, a Principal Component Analysis (PCA) to the data was used to characterize such variable process patterns and to achieve a better understanding. The transfected NS0/1B8 cell line was fermented in a 500 L bioreactor in perfusion culture mode to obtain a desired monoclonal antibody against CD20 molecule. Given the high variability of the process, an exploratory data analysis based on a multivariate analysis technique such as PCA was applied. The variables were selected by a risk model analysis based on the cause-effect matrix, the experience accumulated in the process, over the critical quality attributes, and parameters focus on the fermentation process. As a result, it was obtained that two main components were able to explain more than 95% of the total variance, and it was possible to select between the critical parameters those that have the greatest contribution to the variability of the fermentation process. Furthermore, the practical experiences of the specialists matched with the results and new process recommendations were projected to improve the control strategy for a further Continuous Process Verification. Keywords: Monoclonal antibody, Principal Component Analysis, Fermentation, Critical parameters.

Background Optimal treatment of children who develop appendicitis while undergoing treatment for an oncologic diagnosis has not been defined, in part due to theoretical concerns for an increased risk of post-operative wound complications. We hypothesized that synchronous oncologic diagnosis conferred no increased odds of developing a wound complication in pediatric patients undergoing appendectomy. Methods Retrospective cohort study using the National Surgical Quality Improvement Program, Pediatric (2012-2017) of patients <18 years of age undergoing appendectomy. The main exposure variable was active treatment for an oncologic diagnosis. The primary outcomes of interest were 30-day wound complications (superficial or deep infections or dehiscence, and abscess). For univariate analysis comparison of baseline differences between patients with/without a cancer diagnosis we employed Pearson’s χ2 and two sample t-tests. Multivariate logistic regression was used to evaluate which covariates were independently associated with our outcome. Results We identified 28219 patients who had undergone appendectomy; 95 (0.3%) were undergoing oncologic treatment at time of surgery. Patients in the cancer group were more likely to be receiving steroids, have lower white blood cell counts and have higher American Society of Anesthesiology classes compared to the non-cancer patients. Age, gender, rates of perforation and laparoscopy were similar between the two groups. Patients with an active cancer diagnosis suffered wound complications (measured individually and as an aggregate) at no higher odds than those without a cancer diagnosis. Conclusion Pediatric patients undergoing treatment for cancer do not have increased odds of suffering post-operative wound complications following appendectomy compared to the general population.

Background: The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. We analyzed seasonality of diagnosis in a homogenous Hispanic cohort. Design/Method: Clinical files and electronic databases of consecutive children and adolescents with ALL in Northeast Mexico over 2004-2018 were scrutinized. Data included date of diagnosis, age, sex, and risk group. Patients were divided into children <16 and adolescents 16 to 20 years. Statistical analysis included Chi-square tests for heterogeneity and multiple Poisson regression using parametric harmonic modelling to detect monthly variation. Results: During the fifteen-year study period 394 consecutive patients with ALL were included. There were 323 (81.9%) children, and 71 (18.1%) adolescents. 176 (54.5%) children had high-risk disease. Heterogeneity across months of diagnosis was confirmed (P=0.038). A statistically significant monthly variation in the date of diagnosis documented by Poisson regression was found for the whole group, with a peak on March (P < 0.001). When analyzing by age group, cases of children with ALL predominated in March. Adolescents had a separate peak in July, with a 4.5 : 1 male to female ratio. Conclusions: Seasonality at month of diagnosis in children and adolescents with ALL was identified. Male adolescents had a high July peak suggesting a hormonal influence in ALL development in this age group.

Bright IDEAS Problem-Solving Skills Training (BI) is an evidence-based behavioral intervention that has been utilized extensively with caregivers of children recently diagnosed with cancer. Considerable evidence has shown that BI is acceptable to caregivers and improvements in problem-solving skills mediate reduced symptoms of distress; and it is most effective with single, minority caregivers. A slightly modified version of BI was offered to caregivers of children with sickle cell disease (SCD) in a two-site pilot feasibility trial. BI was modified to reduce barriers to care, logistical challenges, and stigma associated with receiving behavioral health services. Our goal was to establish high rates of recruitment and retention amongst caregivers of children with SCD. Recruitment was acceptable (94%; N = 72) and retention reasonable (48.6%) across both sites with 35 caregivers successfully completing the BI program. Results showed that caregivers of children with SCD, who successfully completed the BI program reported, significant improvements in problem-solving skills immediately and three months post-intervention completion. Interestingly, initial levels of distress were low with few caregivers reporting clinically significant levels of distress; distress remained low over time. Findings are discussed in the context of psychosocial screening and assumptions regarding caregivers of children with SCD.

One of the leading trends in the modern tissue engineering is the development of new effective methods of decellularization aimed at the removal of cellular components from donor tissue reducing its immunogenicity and the risk of rejection. Supercritical CO2 (scCO2) extraction can significantly improve the outcome of decellularization, reduce contamination and time costs. The resulting products can serve as personalized tools for tissue-engineering therapy of various somatic pathologies. However, decellularization of complex 3D structures, such as the aortic root, requires optimization of the parameters, including preconditioning medium composition, type of co-solvent, values of pressure and temperature insight the scCO2 reactor, etc. In our work, using an ovine aortic root model, we performed a comparative analysis of the efficiency of decellularization using approaches based on various combinations of these parameters. The protocols were based on combinations of treatment in alkaline, ethanol or detergent solutions with scCO2 extraction at different modes. Based on a histological analysis, we have selected an optimal protocol for the decellularization of ovine aortic root employing preconditioning in a detergent solution. The positive effects of scCO2 on the decellularization extent, cytotoxicity and histoarchitecture of the tissue were demonstrated.