Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency

Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI), and ACAD9 mutations are recognized as a frequent cause of CI deficiency. ACAD9 also retains enzyme ACAD activity for long-chain fatty acids in vitro, but the biological relevance of this function remains controversial partly because of the tissue specificity of ACAD9 expression: high in liver and neurons and minimal in skin fibroblasts. In this study, we hypothesized that this enzymatic ACAD activity is required for full fatty acid oxidation capacity in cells expressing high levels of ACAD9 and that loss of this function is important in determining phenotype in ACAD9-deficient patients. First, we confirmed that HEK293 cells express ACAD9 abundantly. Then, we showed that ACAD9 knockout in HEK293 cells affected long-chain fatty acid oxidation along with Cl, both of which were rescued by wild type ACAD9. Further, we evaluated whether the loss of ACAD9 enzymatic fatty acid oxidation affects clinical severity in patients with ACAD9 mutations. The effects on ACAD activity of 16 ACAD9 mutations identified in 24 patients were evaluated using a prokaryotic expression system. We showed that there was a significant inverse correlation between residual enzyme ACAD activity and phenotypic severity of ACAD9-deficient patients. These results provide evidence that in cells where it is strongly expressed, ACAD9 plays a physiological role in fatty acid oxidation, which contributes to the severity of the phenotype in ACAD9-deficient patients. Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fatty acid oxidation dysfunction

Public knowledge, attitude and practice towards antibiotics use and antimicrobial resistance in Saudi Arabia: A web-based cross-sectional survey

Background: Antimicrobial resistance is a global issue that causes significant morbidity and mortality. Therefore, this study aims to assess knowledge, attitudes, and practices (KAP) of the general Saudi populations toward antibiotics use. Design and methods: A cross-sectional, anonymous online survey was conducted from January 1 to May 11, 2020, across five major regions of Saudi Arabia. Participants (aged ≥18 years) were invited through social media to complete an online self-structured questionnaire. All data were analyzed by Statistical Package (SPSS v.25). Descriptive statistics, Pearson's Chi-squared, t-tests, one-way analysis of variance (ANOVA), and Pearson correlation analyses were conducted. Results: Out of 443 participants, the majority (n=309, 69.8%) were females, 294 (64.4%) were married, 176 (39.7%) were 25-34 years of age, 338 (76.3%) were living in the Eastern Province, 313 (70.7%) had college or higher education, 139 (31.4%) were not working, and 163 (36.8%) had a monthly income of USD 800-1330. Overall, most participants demonstrated good knowledge and practice (88% and 85.6%, respectively).  However, 76.8%had inadequate attitude score levels towards antibiotics use. Of all the respondents, 74.9% knew that not completing a full course of antibiotics may cause antibiotics resistance, 91.33% did not agree that antibiotics should be accessed without a prescription, and 94.04% will not hand over leftover antibiotics to family members. Factors associated with adequate knowledge were female, medical jobs, and higher income (p<0.05). Conclusions: Our findings revealed that while most participants were aware of antibiotics use and demonstrated good knowledge, good practices, they had negative attitudes towards antibiotics use

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Neurological Complications following Blood Transfusions in Sickle Cell Anemia

In Sickle Cell Anemia (SCA) patient blood transfusions are an important part of treatment for stroke and its prevention. However, blood transfusions can also lead to complications such as Reversible Posterior Leukoencephalopathy Syndrome (RPLS). This brief report highlights two cases of SCA who developed such neurological complications after a blood transfusion. RLPS should be considered as the cause of neurologic finding in patients with SCA and hypertension following a blood transfusion

Nurse Practitioner: Is It Time to Have a Role in Saudi Arabia?

Low recruitment of Saudi nationals into the nursing profession, coupled with a growing population, has led to a severe nursing shortage in Saudi Arabia, particularly of nurses with advanced qualifications in clinical nursing. While the role of nurse practitioner has been successfully integrated into the healthcare systems of the U.S., Canada, the UK and Australia for decades, the advanced practice registered nurse (APRN), which includes nurse practitioners and clinical nursing specialists, is still not being implemented effectively in Saudi Arabia due to a variety of regulatory, institutional and cultural barriers. The author looks at some of those barriers and offers recommendations of how they might be overcome. Given that in many parts of the world, nurse practitioners are considered an essential component to meeting healthcare demands, the author considers the question of whether APRNs can find a role in Saudi Arabia’s healthcare system

The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening

Tyrosinemia type I (TT1) is an inborn error of tyrosine metabolism with features including liver dysfunction, cirrhosis, and hepatocellular carcinoma; renal dysfunction that may lead to failure to thrive and bone disease; and porphyric crises. Once fatal in most infantile-onset cases, pre-symptomatic diagnosis through newborn screening (NBS) protocols, dietary management, and pharmacotherapy with nitisinone have improved outcomes. Succinylacetone provides a sensitive and specific marker for the detection of TT1 but is not universally utilized in screening protocols for the disease. Here, we report an infant transferred to our facility for evaluation and management of hyperinsulinism who subsequently developed acute-onset liver, respiratory, and renal failure around one month of life. She was found to have TT1 caused by novel pathogenic variant in fumarylacetoacetate hydrolase (c.1014 delC, p.Cys 338 Ter). Her NBS, which utilized tyrosine as a primary marker, had been reported as normal, with a tyrosine level of 151 &micro;mol/L (reference: &lt;280 &micro;mol/L). Retrospective analysis of dried blood spot samples via tandem mass spectrometry showed detectable succinylacetone ranging 4.65&ndash;10.34 &micro;mol/L. To our knowledge, this is the first patient with TT1 whose initial presenting symptom was hyperinsulinemic hypoglycemia. The case highlights the importance of maintaining a high suspicion for metabolic disease in critically ill children, despite normal NBS. We also use the case to advocate for NBS for TT1 using succinylacetone quantitation

Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency

Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI), and ACAD9 mutations are recognized as a frequent cause of CI deficiency. ACAD9 also retains enzyme ACAD activity for long-chain fatty acids in vitro, but the biological relevance of this function remains controversial partly because of the tissue specificity of ACAD9 expression: high in liver and neurons and minimal in skin fibroblasts. In this study, we hypothesized that this enzymatic ACAD activity is required for full fatty acid oxidation capacity in cells expressing high levels of ACAD9 and that loss of this function is important in determining phenotype in ACAD9-deficient patients. First, we confirmed that HEK293 cells express ACAD9 abundantly. Then, we showed that ACAD9 knockout in HEK293 cells affected long-chain fatty acid oxidation along with Cl, both of which were rescued by wild type ACAD9. Further, we evaluated whether the loss of ACAD9 enzymatic fatty acid oxidation affects clinical severity in patients with ACAD9 mutations. The effects on ACAD activity of 16 ACAD9 mutations identified in 24 patients were evaluated using a prokaryotic expression system. We showed that there was a significant inverse correlation between residual enzyme ACAD activity and phenotypic severity of ACAD9-deficient patients. These results provide evidence that in cells where it is strongly expressed, ACAD9 plays a physiological role in fatty acid oxidation, which contributes to the severity of the phenotype in ACAD9-deficient patients. Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fatty acid oxidation dysfunctions