Systems genetics identifies miRNA-mediated regulation of host response in COVID-19.

BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.

Protective effects of Fumaria parviflora L. on lead-induced testicular toxicity in male rats.

In recent years, the clinical importance of herbal drugs has received considerable attention in reducing free radical-induced tissue injury. Oxidative stress has been proposed as a possible mechanism involved in lead toxicity that causes reproductive system failure in both human and animals. Fumaria parviflora L., a traditional herb, has been used to cure various ailments in Persian folk medicine. This study was carried out to investigate whether ethanolic extract of F. parviflora leaves could protect the male rats against lead-induced testicular oxidative stress. Adult Wistar rats were treated with 0.1% lead acetate in drinking water with or without 200 mg kg day(-1) F. parviflora extract via gavage for 70 days. Lead acetate treatment resulted in significant reduction in testis weight, seminiferous tubules diameter, epididymal sperm count, serum testosterone level, testicular content of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Moreover, significant elevation was observed in content of malondialdehyde (MDA) in lead-treated rats. However, co-administration of F. parviflora extract showed a significant increase in selected reproductive parameters in lead-treated rats. The results indicated that ethanolic extract of F. parviflora leaves has a potential to restore the suppressed reproduction associated with lead exposure and prevented lead-induced testicular toxicity in male Wistar rats.

Gynecology and obstetrical conditions requiring intensive care admission.

OBJECTIVE: Gynecological admissions to the surgical intensive care unit vary from the obstetrical cases. Pregnant women are of prime age and can tolerate the pregnancy and delivery well. There are certain rare conditions or complications, which make the pregnant women's life pass through a critical time. These are dealt with in a high dependency area, which is short of the intensive care unit. In King Khalid University Hospital there is no such arrangement, so the mildly affected and critically ill patients together are cared for in the surgical intensive care unit. The objective of this study is to study the gynecological and obstetrical conditions requiring intensive care admission in King Khalid University Hospital, surgical intensive care unit. METHODS: All obstetrical and gynecological patients who were admitted to the surgical intensive care unit were included. The demographic particulars, reason for admission, the course of the surgical intensive care unit stay and outcome were studied. RESULTS: During the study period of 3 years, there were 83, (100%) obstetrical and gynecological admissions to the surgical intensive care unit. Two (2%) cases were due to anesthesia complications. The majority of causes of admissions were due to obstetrical (n=63, 76%) complications or combination of medical and surgical conditions. Gynecological admissions comprised only 18 (22%) cases. There was no mortality in the group studied. CONCLUSION: Management of major obstetrical emergencies and gynaecological patients require an understanding of medical conditions' influence on the patients, and the physiological changes of normal and abnormal pregnancies. Intensive care unit management is an essential part in raising the level of patient care; health personnel training and continuing health care education may be improved.

Placental migration and mode of delivery in placenta previa: transvaginal sonographic assessment during the third trimester.

BACKGROUND: The objective of this study was to assess the role of serial transvaginal sonography (TVS) in predicting placental migration and mode of delivery in pregnancy complicated by placenta previa during the third trimester. PATIENTS AND METHODS: In this prospective observational study, all the cases had confirmed diagnosis of placenta previa before 32 weeks' gestation. TVS was performed between 28 and 32 weeks' gestation for 287 patients with either clinical suspicion or previous sonographic diagnosis of placenta previa. The lower placental edge was found to cover the internal cervical os, or was found to be within 3 cm from it in 63 patients. A two-weekly TVS was performed for every patient until delivery, or until migration of the lower placental edge to a distance of more than 3 cm from the internal cervical os was observed. Detailed information on the placental position, its distance from the internal cervical os, and its relation to the presenting part were recorded at each examination. RESULTS: Placental migration to a distance of more than 3 cm from the internal cervical os occurred in 24 patients (38%) by 36 weeks' gestation. Of the 63 patients, 19 (30.2%) delivered vaginally. The last scan of these patients revealed that the distance between the internal cervical os and the lower placental margin were more than 2 cm and 3 cm in the anterior and posterior placenta previa, respectively, and the presenting parts were below the placental margin. Placental migration was not observed sonographically in any of the eight patients with posterior placenta previa when its lower edge was initially located within 1 cm from the internal os. It was also not observed in either the 16 patients with total placenta previa, or in any of the other patients beyond 36 weeks' gestation. CONCLUSION: Posterior placenta previa lying within 1 cm from the internal cervical os and total placenta previa do not migrate during the third trimester. On the other hand, other types of placenta previa may migrate but not beyond 36 weeks' gestation. The mode of delivery does not depend only on the placental degree but also on the placental position (anterior or posterior), and the relationship between the presenting part and the lower placental edge.

Abdomino-pelvic packing to control severe haemorrhage following caesarean hysterectomy.

Surgically uncontrollable peri-operative obstetric haemorrhage associated with coagulopathy, developed in five women who were managed by emergency caesarean hysterectomy. All women had a morbidly adherent anterior placenta praevia and a previous lower segment caesarean section scar. Conventional medical and surgical therapy to control bleeding from pelvic and abdominal raw surfaces were unsuccessful. Abdomino-pelvic packing was performed with 10-12 dry laparotomy pads applied firmly over bleeding sites. The abdomen was closed after observation of the cessation of bleeding for 5-10 minutes. Following correction of coagulation and haemodynamic disorders relaparotomy for pack removal was performed 34-48 hours later. One patient developed small bowel obstruction on the 5th post-operative day, however, there was no long term gynaecological morbidity in any of the cases. Abdomino-pelvic packing achieved complete haemostasis in all of the five women which we believe may have been impossible using alternative measures.