Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

Nouran B AbdAllah,1 Essam Al Ageeli,2 Abdullah Shbeer,3 Jawaher A Abdulhakim,4 Eman A Toraih,5,6 Doaa O Salman,6 Manal S Fawzy,7,8 Sanaa S Nassar1 1Department of Pediatrics, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 2Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 3Anesthesiology and Intensive Care, Department of Surgery, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 4Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia; 5Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA; 6Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 8Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi ArabiaCorrespondence: Manal S Fawzy, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, Email [email protected] Eman A Toraih, Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA, Email [email protected]: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype.Patients and Methods: This case–control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the clinic-laboratory data.Results: The three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: − 0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p-values < 0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p-values < 0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15– 10.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02– 6.05, p=0.044) were at a higher risk of mortality.Conclusion: Circulatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.Keywords: neonatal sepsis, long non-coding RNAs, MALAT1, ANRIL, HOTAIR, surviva

Quality of life measurement in alopecia areata. Position statement of the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes

New treatment options may lead to an increased interest in using reliable and sensitive instruments to assess health-related quality of life in people with alopecia areata (AA). The purpose of this paper is to present current knowledge about quality of life assessment in AA. The dermatology-specific Dermatology Life Quality Index (DLQI) was the most widely reported health-related quality of life instrument used in AA. Three AA-specific (Alopecia Areata Symptom Impact Scale, Alopecia Areata Quality of Life Index and Alopecia Areata Patients' Quality of Life) and three hair disease-specific instruments (Hairdex, Scalpdex and ‘hair-specific Skindex-29’) were identified with a range of content and validation characteristics: there is little evidence yet of the actual use of these measures in AA. Scalpdex is the best-validated hair disease-specific instrument. Further extensive validation is needed for all of the AA-specific instruments. The European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes recommends the use of the dermatology-specific DLQI questionnaire, hair disease-specific Scalpdex and the alopecia areata-specific instruments the Alopecia Areata Symptom Impact Scale or Alopecia Areata Quality of Life Index, despite the limited experience of their use. We hope that new treatment methods will be able to improve both clinical signs and health-related quality of life in patients with AA. In order to assess the outcomes of trials on these new treatment methods, it would be helpful when further development and validation of AA-specific instruments is being encouraged and also conducted