RESUMO
The influence of various risk factors such as aging, intricate cellular molecular processes, and lifestyle factors like smoking, alcohol consumption, caffeine intake, and occupational factors has received increased focus in relation to the risk and development of Parkinson's disease (PD). Limited research has been conducted on the assessment of lifestyle impact on kynurenine 3-monooxygenase (KMO) gene in PD. A total of 164 subjects, including 82 PD cases and 82 healthy individuals, were recruited based on specific inclusion and exclusion criteria. The severity of PD and clinical assessment were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY) scaling. Sanger sequencing was performed to analyse the KMO gene in the recruited subjects, and case-control studies were conducted. The UPDRS assessment revealed significant impairments in smell, tremors, walking, and posture instability in the late-onset PD cohorts. The HY scaling indicated a higher proportion of late-onset cohorts in stage 2. Moreover, both alcoholic and non-alcoholic groups showed significantly increased levels of 3-HK in late-onset PD. Gene analysis identified missense variants at position g.241593373 T > A (rs752312199) and intronic variants at positions g.241592623A > G (rs640718), g.241592800C > A (rs990388262), g.241592802A > C (rs1350160268), g.241592808 T > C (rs1478255936), and g.241592812G > T (rs948928931). The alterations in the KMO gene were found to influence the levels of kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). Genomic analysis revealed a high prevalence of missense mutations in the late-onset PD groups, leading to a decline in 3-HK levels in patients. This leads to the reduction of the progression of disease in late-onset groups which shows that this mutation may lead to the protective effect on the PD subjects. This study suggests the use of KYNA and 3-HK as potential biomarkers in analysing the progression of disease. This study is limited by its small sample size. To overcome this limitation, a larger study involving in greater number of participants is needed to thoroughly investigate the KMO gene and KP metabolites, to enhance our understanding of Parkinson's disease progression, and to enhance diagnostic capabilities.
RESUMO
Background: Maternal infection by SARS-CoV-2 may lead to adverse pregnancy outcomes and causes pathological changes in the placenta. However, consensus regarding characteristic pathological features is lacking. Researchof the placental histopathology in a cohort of women from Mizoram, India, was conducted to relate the SARS-CoV-2 infection's effectswith pregnancy and its outcome. Materials and methods: The characteristics of 72 pregnant women diagnosed positive for SARS-CoV-2 who eventually delivered at Zoram Medical College Hospital, Mizoram, neonates' well-being, and histopathological features of placentas were studied. Results: Of 72 women in this study, 59 (81.9%) gave birth at full term. Among these births, 5 were normal vaginal deliveries, while the remaining 67 (93.1%) were delivered via cesarean section. The reasons for cesarean delivery were either related to SARS-CoV-2 infection (n â= â49), existing obstetric problems (n â= â15) or fetal-distress (n â= â5). All deliveries resulted in live births of COVID-negative babies, with 80.6% (n â= â58) of the newborns having a birth weight of over 2.5 âkg. APGAR scores ranged from 4 to 6 in 61 (84.7%) of the babies, and 10 neonates required resuscitation, of which 8 were managed in the neonatal intensive care unit (NICU). The placental histopathology showed increased fibrin thrombi in 8 cases (11.1%), while 20 cases (28%) showed focal infarction, microcalcification levels were elevated in 16 cases (22.2%), and a small percentage of cases (1.4%) exhibited small fibrotic villi and inter-villus agglutination. Placental chorioangiosis was detected in 28 (38.9%) of the cases, while avascular villi were seen in 6 cases. Meconium-stained liquor was observed in a single case. Intervillous hemorrhage was found in 42 cases, whileintervillous inflammation and increased syncytial knots were present in 14 and 5 cases, respectively. The placenta pathology of 10 neonates who required resuscitation/NICU admission was not significantly different from that of the 62 neonates who did not require it. However, a higher proportion of placenta from the asymptomatic group showed no abnormality compared to the symptomatic group (p â= â0.046). Conclusion: SARS-CoV-2 infection causes a range of morphological changes and lesions in the placenta, including chorangiosis, villositis, chorioamnionitis, fetal vascular malperfusion/thrombosis, fibrin-deposition, increased syncytial-knotting, increased microcalcification, increased villous agglutination, focal infarct, intervilloushemorrhage as well as inflammation. Placental histopathological findings from this study can provide additional information to the existing literature on the subject.
