The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks.

Introduction: Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states. Methods: Infants with SVHD in the interstage period were compared to similar-age healthy controls. Serum samples were collected, stored at -80°C, and run on a panel of 1,500 proteins in single batch analysis (Somalogic Inc., CO). Partial Least Squares-Discriminant Analysis (PLS-DA) was used to compare the proteomic profile of cases and controls and t-tests to detect differences in individual proteins (FDR <0.05). Protein network analysis with functional enrichment was performed in STRING and Cytoscape. Results: PLS-DA readily discriminated between SVHD cases (n = 33) and controls (n = 24) based on their proteomic pattern alone (Accuracy = 0.96, R2 = 0.97, Q2 = 0.80). 568 proteins differed between groups (FDR <0.05). We identified 25 up-regulated functional clusters and 13 down-regulated. Active biological systems fell into six key groups: angiogenesis and cell proliferation/turnover, immune system activation and inflammation, altered metabolism, neural development, gastrointestinal system, and cardiac physiology and development. Conclusions: We report a clear differentiation in the circulating proteome of patients with SVHD and healthy controls with >500 circulating proteins distinguishing the groups. These proteomic data identify widespread protein dysregulation across multiple biologic systems with promising biological plausibility as drivers of SVHD morbidity.

Women's knowledge, perception, practice, and experience of using of skin-lightening products in the United Arab Emirates (UAE): A cross-sectional survey.

Background: Skin lightening products (SLPs) are popular among women for medical and non-medical reasons. Therefore, this study aimed to determine the extent of SLP use among women, identify their sources of information, explore factors associated with SLP use and SLP related knowledge, attitudes, and practices (KAP) among women in the UAE. Methods: A structured questionnaire in English and Arabic was distributed to women in the UAE. The questionnaire included demographic characteristics, knowledge (10 items), attitudes (10 items), practices (9 items), and four additional questions on SLP use. Adequate KAP scores were defined as a score of ≥70% out of the maximum score for each KAP section. Chi-square tests were used to test associations between demographic characteristics, dichotomized KAP scores, and SLP use. Results: The study included 370 participants, 50% of the respondents were aged 18-24, and 40% were from the Middle East, 64.8% were unmarried, 91% had university degrees, and 50% had healthcare related profession. Among the respondents 25% use SLPs, the majority use SLPs for non-medical reasons. Employment status is significantly associated with SLP use. The percentage of participants with a knowledge, attitude, and practice score of ≥70% is 66.48%, 76.75%, and 74.72% respectively. Type of profession was significantly associated knowledge and practice. In addition, nationality was also associated with practice. Conclusion: This study highlighted knowledge, attitude and practice gaps and varied levels of SLP-related KAP among women in the UAE. To promote the rational use of SLPs, educational campaigns and stricter regulations are necessary.

Diagnosis and management of acute pharyngotonsillitis among pediatric patients at Ribat Teaching Hospital: a prospective audit (2021-2022).

Diagnosis of pharyngotonsillitis is challenging due to the wide range of symptoms and signs. Sudan Federal Ministry of Health and Sudanese Association of Paediatricians, along with Sudan Heart Society reached a consensus about the clinical prediction rule which aids in diagnosing and managing bacterial pharyngotonsillitis. This audit aimed to assess doctors' knowledge and practice regarding diagnosis and management of bacterial pharyngotonsillitis at Ribat Teaching Hospital, Khartoum, Sudan. This audit was done at Pediatric Department, Ribat Teaching Hospital, and data collection was done over 2 weeks either in the first or the second cycle. Inclusion criteria were children who presented at the emergency room and were diagnosed with acute pharyngotonsillitis. The criteria used in this audit were from Sudan guidelines for prevention, diagnosis and management of rheumatic heart disease. Regular training sessions were done between the first and second cycles. There were 19 patients in the first cycle, 17 of them (89.4%) were diagnosed clinically with bacterial pharyngotonsillitis, and 8 of these 17 (47%) were fitting the criteria. Regarding the management of bacterial pharyngotonsillitis, no patient was given the recommended antibiotics in the guidelines (0.00%). In the second cycle, there were 21 patients, of whom 11 patients were diagnosed clinically with bacterial pharyngotonsillitis (52%). Of those 11, 8 patients were fitting the criteria (72.7%), and the recommended antibiotics were given in 9 of them (82%). The current practice toward acute pharyngotonsillitis management revealed a lack of doctors' knowledge about local guidelines which can be improved by simple ways such as posters, lectures, and focused group discussions.

Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury.

Acute kidney injury (AKI) is a common cause of morbidity after congenital heart disease surgery. Progress on diagnosis and therapy remains limited, however, in part due to poor mechanistic understanding and a lack of relevant translational models. Metabolomic approaches could help identify novel mechanisms of injury and potential therapeutic targets. In the present study, we used a piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB/DHCA) and targeted metabolic profiling of kidney tissue, urine, and serum to evaluate metabolic changes specific to animals with histological acute kidney injury. CPB/DHCA animals with acute kidney injury were compared with those without acute kidney injury and mechanically ventilated controls. Acute kidney injury occurred in 10 of 20 CPB/DHCA animals 4 h after CPB/DHCA and 0 of 7 control animals. Injured kidneys showed a distinct tissue metabolic profile compared with uninjured kidneys (R2 = 0.93, Q2 = 0.53), with evidence of dysregulated tryptophan and purine metabolism. Nine urine metabolites differed significantly in animals with acute kidney injury with a pattern suggestive of increased aerobic glycolysis. Dysregulated metabolites in kidney tissue and urine did not overlap. CPB/DHCA strongly affected the serum metabolic profile, with only one metabolite that differed significantly with acute kidney injury (pyroglutamic acid, a marker of oxidative stress). In conclusion, based on these findings, kidney tryptophan and purine metabolism are candidates for further mechanistic and therapeutic investigation. Urine biomarkers of aerobic glycolysis could help diagnose early acute kidney injury after CPB/DHCA and warrant further evaluation. The serum metabolites measured at this early time point did not strongly differentiate based on acute kidney injury.NEW & NOTEWORTHY This project explored the metabolic underpinnings of postoperative acute kidney injury (AKI) following pediatric cardiac surgery in a translationally relevant large animal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Here, we present novel evidence for dysregulated tryptophan catabolism and purine catabolism in kidney tissue and increased urinary glycolysis intermediates in animals who developed histological AKI. These pathways represent potential diagnostic and therapeutic targets for postoperative AKI in this high-risk population.

Nanoparticles for active combination radio mitigating agents of zinc coumarate and zinc caffeinate in a rat model.

Zinc coumarate and zinc caffeinate nanoparticles (ZnCoNPs, ZnCaNPs) affect different biological processes. This study aimed to evaluate the mitigating action of ZnCoNPs in combination with ZnCaNPs against liver damage induced by gamma rays (γ-rays). Rats were exposed to 7 Gy of γ-rays and then injected intraperitoneally (i.p) with ZnCoNPs [2U/rat/day (5 mg/kg)] and ZnCaNPs [2U/rat/day (15 mg/kg)] for 7 consecutive days. The results showed that irradiated rats treated with ZnCoNPs (5 mg/kg/body weight) in combination with ZnCaNPs (15 mg/kg/body weight) for 7 days had a significant increases in body weight, antioxidant levels, T helper cell 4 (cluster of differentiation 4 (CD4)), and T cytotoxic cell 8 (cluster of differentiation 8 (CD8)), associated with a marked decrease in lipid peroxidation (LP), nitric oxide(NOx), total free radicals concentrate (TFRC), and DNA fragmentation. There were positive alterations in the morphological state, hematological parameters and the cell cycle phases. Additionally, the histopathological study demonstrated an improvement in the liver tissue of irradiated rats after treatment. Thus, ZnCoNPs and ZnCaNPs could be used as natural mitigating agents to reduce the hazards of ionizing radiation.

Association Between Myasthenia Gravis and Systemic Lupus Erythematosus as a Comorbid State.

Systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune states which have presentational similitude. Both conditions test serologically positive for anti-nuclear antibodies and require exceptional differential diagnostic acumen to segregate one from the other. The hypothesized factors provoking these diseases may be immunological, genetic, hormonal, or environmental and can be better understood by large-scale controlled epidemiological studies. Biochemical factors such as variation in CXC (an α chemokine subfamily), CXCL13, and granulocyte-macrophage colony-stimulating factor levels are assumed to play a pivotal role in the pathogenesis of SLE and MG; however, further studies are required to understand their exact mechanism and effect on the underlying autoimmune diseases. Following this, another precipitating factor for this overlap is believed to be thymectomy which is performed to eliminate MG symptoms. Although thymectomy is the effective treatment modality in MG patients, other findings and data support the view that this procedure may lead to the development of other autoimmune states such as SLE. It is evident from previously published data and case reports that patients with one autoimmune disease who underwent thymectomy contracted SLE and became more susceptible to other autoimmune diseases compared to the general population. Post-thymectomy follow-up of patients provides us with mechanistic clues for understanding the development of SLE-MG overlap; hence, in MG patients who have undergone thymectomy, any clinical and immune serological SLE suspicion should be carefully evaluated.

Risk Assessment Using the Association Between Renin-Angiotensin Genes Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a multifactorial disease that involves genetic and environmental interaction. In addition to the well-known CAD risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, and atherosclerosis, it has a genetic component that predisposes to its occurrence even in young people. One of the most commonly studied genes that increase the susceptibility to CAD is renin-angiotensin system (RAS) genes polymorphisms mainly angiotensin-converting enzyme gene (ACE) polymorphisms, angiotensinogen polymorphisms, angiotensin- II type 1 receptor gene polymorphisms, and many other genes. These genetic polymorphisms have a direct association with CAD development or indirect association through causing atherosclerosis and hypertension which, in turn, are complicated by CAD later on. The difference between genetic mutations and polymorphisms lies in the frequency of the abnormal genotype. If the frequency is 1% and more in the general population, it is called polymorphism and if it is less than 1%, then it is called a mutation. According to our findings, after thorough searching, which support the association of RAS genes polymorphisms with premature CAD, hypertension, hypertrophic cardiomyopathy, and atherosclerosis, we recommend additional studies in the form of clinical trials and meta-analyses aiming to create a specific diagnostic tool for CAD risk assessment and discovering the high-risk people as early as possible. Targeted gene therapy, being the future of medicine, needs to be taken into researchers' consideration. It can have promising results in these cases.

Physiological Effects of High-Flow Nasal Cannula Therapy and Its Use in Acute Cardiogenic Pulmonary Edema.

High-flow nasal cannula (HFNC) is an open oxygen delivery system, which provides heated and humidified oxygen at a high flow (up to 60 L/min). This effect can improve mucociliary function, airway clearance, and level of comfort to the patient. It can provide controlled and adequate fraction of inspired oxygen (FiO2) between 21% and 100%. Generation of end-expiratory pressure helps in carbon dioxide washout, reduction of anatomical dead space, and recruitment of collapsed alveoli, ultimately improving tissue oxygenation. The use of HFNC in acute hypoxemic respiratory failure, post-extubation period, pre-intubation period, respiratory infection, and obstructive airway disease has been extensively studied, but there are very few studies regarding its use in cardiogenic pulmonary edema. This review provides the current understanding of the physiological effect of HFNC and its application in acute cardiogenic pulmonary edema (ACPE). We conducted a literature search on PubMed using appropriate terms and reviewed relevant articles published within the last 10 years. We found that initial therapy with HFNC in ACPE patients can improve oxygenation and respiratory rate. HFNC can potentially be an alternative to non-invasive positive-pressure ventilation in terms of initial oxygen therapy in patients with ACPE. There is a need for larger prospective studies to evaluate and develop guidelines to consider the use of HFNC in patients with ACPE. We also highlight the fact that if there is no improvement in arterial blood gas parameters after HFNC therapy, initiation of invasive ventilation should not be delayed.

Can Big Data and Machine Learning Improve Our Understanding of Acute Respiratory Distress Syndrome?

Acute respiratory distress syndrome (ARDS) accounts for 10% of all diagnoses in the Intensive Care Unit, and about 40% of the patients succumb to the disease. Clinical methods alone can result in the under-recognition of this heterogeneous syndrome. The purpose of this study is to evaluate the role that big data and machine learning (ML) have played in understanding the heterogeneity of the disease and the development of various prediction algorithms. Most of the work in the field of ML in ARDS has been in the development of prediction models that have comparable efficacies to that of traditional models. Prediction algorithms have been useful in identifying new variables that may be important to consider in the future, supplementing the unknown information with the help of available noninvasive parameters, as well as predicting mortality. Phenotype identification using an unsupervised ML algorithm has been pivotal in classifying the heterogeneous population into more homogenous classes. Big data generated from ventilators in the form of ventilator waveform analysis and images in the form of radiomics have also been leveraged for the identification of the syndrome and can be incorporated into a clinical decision support system. Although the results are promising, lack of generalizability, "black box" nature of algorithms and concerns about "alarm fatigue" should be addressed for more mainstream adoption of these models.

Epidemiology of Substance Use among University Students in Sudan.

Background. Youth populations are vulnerable to substance use particularly in developing countries where circumstances may be favorable for it. There is no published data on substance use among the youth in Sudan other than on tobacco use. Objectives. The aim of this study was to investigate the prevalence, circumstances, and factors associated with substance use. Methods. An institution-based survey was conducted on a sample of 500 students. Data was collected using a questionnaire designed by the WHO for student drug surveys and analyzed using IBM SPSS version 20. Results. The overall prevalence of substance use is 31%. The current prevalence of tobacco, cannabis, alcohol, amphetamines, tranquilizers, inhalants, opiates, cocaine, and heroin use was 13.7%, 4.9%, 2.7%, 2.4%, 3.2%, 1%, 1.2%, 0.7%, and 0.5%, respectively. Curiosity (33.1%) was the main reason for initiation of substance use. The main adverse effects reported were health problems (19.7%) and theft (19.7%). Peers (40.9%) were the prime source of substance use. On multivariate analysis, male sex was the principle predictor for substance use (AOR: 5.55; 95% CI: 3.38, 9.17). Conclusion. Strategies to control substance use should encompass the role of the university and parents in observing and providing education to improve awareness of substances and their consequences.