Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review

Oxidative stress has a recognized role in the pathophysiology of asthma. Recently, interest has increased in the assessment of pH and airway oxidative stress markers. Collection of exhaled breath condensate (EBC) and quantification of biomarkers in breath samples can potentially indicate lung disease activity and help in the study of airway inflammation, and asthma severity. Levels of oxidative stress markers in the EBC have been systematically evaluated in children with asthma; however, there is no such systematic review conducted for adult asthma. A systematic review of oxidative stress markers measured in EBC of adult asthma was conducted, and studies were identified by searching MEDLINE and SCOPUS databases. Sixteen papers met the inclusion criteria. Concentrations of exhaled hydrogen ions, nitric oxide products, hydrogen peroxide and 8‐isoprostanes were generally elevated and related to lower lung function tests in adults with asthma compared to healthy subjects. Assessment of EBC markers may be a noninvasive approach to evaluate airway inflammation, exacerbations, and disease severity of asthma, and to monitor the effectiveness of anti‐inflammatory treatment regimens. Longitudinal studies, using standardized analytical techniques for EBC collection, are required to establish reference values for the interpretation of EBC markers in the context of asthma.     

The prevalence of non-syndromic orofacial clefts and associated congenital heart diseases of a tertiary hospital in Riyadh,Saudi Arabia

BackgroundOrofacial clefts are considered one of the most common birth defects and are frequently associated with other malformations. Congenital heart disease is one of the most prevalent congenital malformation.ObjectiveTo investigate the prevalence of congenital heart diseases associated with non-syndromic orofacial clefts in the Saudi population.MethodsElectronic files of non-syndromic orofacial cleft patients who visited the Oral and Maxillofacial Surgery Department in King Abdulaziz Medical City of Riyadh, Saudi Arabia from January 2015 to December 2018 were retrospectively reviewed. Data were recorded in an excel sheet and analyzed using SPSS via frequency tests.ResultsIn the cleft children identified, the prevalence of non-syndromic orofacial clefts was (77%). Orofacial clefts showed a male predominance (62%). The most common orofacial phenotype was unilateral cleft lip and palate (34%). The prevalence of associated congenital malformations with orofacial clefts was (41%). The most prevalent congenital malformation was congenital heart disease (35%), mainly found in unilateral cleft lip and palate patients (33%). The prevalence of associated congenital heart disease with orofacial clefts was (19%). The most frequent type of congenital heart disease was atrial septal defect (37%).ConclusionThis study highlights the recognition of the associated congenital heart disease with non-syndromic orofacial cleft patients. Global screening protocols designed for newborns with non-syndromic orofacial cleft are needed to eliminate late diagnosis of critical congenital heart diseases which might present operative risks of anesthesia and/or surgical procedures.     

Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma

Liposarcoma (LPS) can be divided into 4 different subtypes, of which well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) are the most common. WDLPS is typically low grade, whereas DDLPS is high grade, aggressive, and carries a worse prognosis. WDLPS and DDLPS frequently co-occur in patients. However, it is not clear whether DDLPS arises independently from WDLPS, or whether epigenomic alterations underly the histopathological differences of these subtypes. Here, we profiled 9 epigenetic marks in tumor samples from 151 patients with LPS and showed elevated trimethylation of histone H3 at Lys9 (H3K9me3) levels in DDLPS tumors. Integrated ChIP-seq and gene expression analyses of patient-derived cell lines revealed that H3K9me3 mediates differential regulation of genes involved in cellular differentiation and migration. Among these, Kruppel-like factor 6 (KLF6) was reduced in DDLPS, with increased H3K9me3 at associated regulatory regions. Pharmacologic inhibition of H3K9me3 with chaetocin decreased DDLPS proliferation and increased expression of the adipogenesis-associated factors PPARγ, CEBPα, and CEBPβ, suggesting that increased H3K9me3 may mediate DDLPS-associated aggressiveness and dedifferentiation properties. KLF6 overexpression partially phenocopied chaetocin treatment in DDLPS cells and induced phenotypic changes that were consistent with adipocytic differentiation, suggesting that the effects of increased H3K9me3 may be mediated through KLF6. In conclusion, we provide evidence of an epigenetic basis for the transition between WDLPS and DDLPS.     

Prospects of Establishing a Saudi Version of the United States Food and Drug Administration Orange Book

BackgroundThe recent incidents of generic drug recalls have shaken the public confidence in the quality of generic drugs in Saudi Arabia. Therefore, many clinicians and health policymakers are calling for the establishment of a national reference or formulary that rates different generic drugs based on their therapeutic equivalence to the listed reference drugs, such as the Orange Book of the United States Food and Drug Administration (USFDA).MethodTo explore the prospects of establishing a Saudi version of the USFDA Orange Book, the Saudi discussion group of the American Association of Pharmaceutical Scientists (AAPS) called for a group meeting to discuss the issue with stakeholders representing different sectors (regulatory, industry, purchasing and supply chain, and patient safety). The meeting was audio-recorded and transcribed verbatim. Thereafter, the text was reviewed and analyzed.ResultsThe participants agreed that there is no national guide or reference that can be used in generic substitution. Moreover, it was indicated that the Saudi Food and Drug Authority (SFDA) is working on establishing a Saudi version of the USFDA Orange Book, which will help in choosing the right generic drugs whenever medication substitution is performed to ensure patient safety.ConclusionThe establishment of a Saudi version of the USFDA Orange Book would help healthcare providers in choosing the right generic drug for their patients, which will hopefully improve health outcomes.