A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

INTRODUCTION: Child sexual abuse (CSA) adversely affects a child's growth and well-being. This study aimed to describe the profile of children presenting to a tertiary paediatric emergency department(ED) with CSA. METHODS: Children 0-16 years old presenting to KK Women's and Children's Hospital ED from June 2016 to August 2020 with sexual abuse were retrospectively reviewed. We performed a secondary analysis on girls and stratified them by age <13 and ≥13 years old. RESULTS: There were 790 patients who made 833 visits for CSA. Victims were predominantly girls (747, 94.8%) and perpetrators were predominantly men (763, 96.6%). The abuse first occurred before the age of 13 years in 315 victims (39.9%). For 468 (59.2%), more than one incident occurred before presentation. Compared to girls ≥13 years old, girls <13 years old were more frequently abused by a family member (47.7% versus 8.0%, CONCLUSION The findings highlight common characteristics of CSA cases, and can aid the future identification and protection of vulnerable children. The fact that most children presented after more than one incident suggests the need to more closely monitor and protect potentially at-risk children.
Adolescent ; Child ; Child Abuse ; Child Abuse, Sexual ; Child, Preschool ; Emergency Service, Hospital ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Parents ; Retrospective Studies

BACKGROUND/AIMS: Surveillance for hepatocellular carcinoma (HCC) with ultrasound in high-risk populations is generally believed to improve opportunities for treatment. However, tumors are still missed due to various factors. This study explores success versus failure of HCC surveillance. METHODS: This is a retrospective study of 1,125 HCC cases. Categories considered for successful detection were largest tumor ≤3.0 cm, single tumors ≤3.0 cm and ≤2.0 cm, and adherence to Milan criteria. Examined factors were age <60 years, gender, rural residence, body-mass index (BMI), hepatitis infection, smoking, diabetes, hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10. RESULTS: HCC was found on surveillance in 257 patients with a mean tumor size of 3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases involving a largest tumor ≤3.0 cm, with BMI ≥35 negatively affecting detection (odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR 2.31, P=0.036). Ultrasound detected 19.1% of single tumors ≤2.0 cm with ascites improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan criteria occurred in 75.1% of cases, revealing negative associations with diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08). CONCLUSIONS: Although surveillance is recommended for HCC, not all surveillance ultrasound are ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and ascites and is achieved in 19.1–75% of cases depending on the definition of success. Closer follow-up or additional imaging might be necessary for some patient subgroups.
Ascites ; Carcinoma, Hepatocellular* ; Early Detection of Cancer ; Fibrosis ; Follow-Up Studies ; Hepatitis ; Humans ; Hyperlipidemias ; Liver Diseases ; Male ; Population Surveillance ; Retrospective Studies ; Smoke ; Smoking ; Ultrasonography

OBJECTIVE: Angioplasty and Stenting of intracranial atherosclerotic lesions have a higher complication rate and a large proportion of this is attributable to side branch arterial occlusion from forceful displacement of the atheroma into the ostia or snowplowing effect. This can result in severe disabilities when it result in small infarcts involving eloquent areas in the posterior circulation or the motor tracts. MATERIALS AND METHODS: We present a series of 6 cases utilizing a new dual catheter technique for maintaining the patency of at-risk vessels during angioplasty and stenting. There are several methods previously described to help reduce the incidence of stroke but because they do not have a physical presence in the ostia to protect it, they are unable to guarantee the patency of the vessel. RESULTS: All 6 patients underwent angioplasty and stenting with the technique. The patients were assessed for complications with post-procedure magnetic resonance imaging and no complications were found. CONCLUSION: In this preliminary series, the dual catheter technique appears to safe and effective in preventing occlusion of the adjacent branch arteries. This technique may facilitate the use of the Wingspan stent in the treatment of intracranial atherosclerotic stenotic segments by reducing the risk of peri-procedural stroke.
Angioplasty* ; Arteries ; Catheters* ; Humans ; Incidence ; Magnetic Resonance Imaging ; Plaque, Atherosclerotic ; Stents* ; Stroke