Objective: This cross-sectional, prospective surveillance study sought to determine the prevalence of novel respiratory viruses among domestic ducks in Central Luzon that are known to have frequent contact with wild avian species. Such contact may lead to novel virus spillover events that may harm domestic poultry as well as humans. Methods: From March 2019 to January 2020, cross-sectional and prospective surveillance for viruses among domestic ducks (Anas luzonica) was conducted by periodically collecting oropharyngeal swabs from ducks on 54 farms across three municipalities within Central Luzon (Region III). A flock of 30 sentinel domestic ducks was also sampled four times after being confined in the Candaba swamp. The resultant 1740 swab samples were pooled (5 samples/pool, 348 pools) by site and screened with molecular assays for respiratory viruses from multiple viral families. Results: Two farms yielded samples positive for avian influenza virus in Candaba, where adolescent ducks are known to freely mix with wild birds as they graze in rice fields. Overall, the prevalence of avian influenza virus was 2.3% (8/348 pools). Sequencing revealed three pools with highly pathogenic avian influenza H5N6, one with low pathogenicity H5N8, and one with H5 with an unspecified neuraminidase. All the pooled specimens tested were negative for influenza C, adenoviruses, coronaviruses and enteroviruses. Discussion: Although this study had several limitations, it found supportive evidence that domestic ducks are acquiring avian influenza viruses from wild bird species. These findings underscore recommendations that duck farmers should seek to prevent domestic ducks from mixing with wild avian species.

Objective: With the development of novel antibody-drug conjugates (ADCs), folate receptor alpha (FOLR1) is a promising therapeutic target for the treatment of platinum-resistant tuboovarian carcinomas. The main aims of this study were to assess FOLR1 protein expression in a large cohort of ovarian carcinoma histotypes. To inform future clinical trial design we identified molecular correlates of FOLR1 expression in low-grade serous carcinoma (LGSC). Methods: One thousand five hundred forty-seven ovarian carcinoma samples from 5 different Canadian cohorts were successfully evaluated by immunohistochemistry for FOLR1 expression using the PS2+ system. Statistical analyses with clinicopathological parameters, LGSC molecular subtypes, and overall survival (OS) were performed. Results: High FOLR1 expression was detected in 44% of high-grade serous carcinomas, and in 30% LGSC, 8% clear cell, 6% endometrioid, and 0% mucinous and/or mesonephrictype adenocarcinomas. In 160 LGSC cases, FOLR1 expression was more frequent in cases with normal MAPK pathway status (37% MAPK wild type vs. 14% canonical MAPK pathway mutations; p=0.002), low progesterone receptor (PR) expression (41%) vs. 23% (Allred score >2; p=0.02), and p16 loss (48% p16 absent vs. 26% normal; p=0.03). Canonical MAPK mutation status and PR expression remained significant on multivariable analysis. No significant associations between OS and FOLR1 expression were observed. Conclusion A significant proportion of LGSC express high FOLR1 levels supporting the development of clinical trials to investigate ADCs targeting FOLR1 as novel agents for treating this disease. In LGSC, high FOLR1 expression was associated with fewer MAPK pathway alterations, low PR expression, and p16 loss.

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.

Humans ; Colonoscopy ; Colorectal Neoplasms/pathology*

COVID-19 ; Heart Diseases ; Humans ; Incidence ; SARS-CoV-2 ; Singapore/epidemiology*

Humans ; Infant ; Prevalence ; Risk Factors ; Vitamin D Deficiency/epidemiology*

Abscess/diagnosis* ; Cardiac Tamponade/etiology* ; Humans ; Klebsiella Infections/diagnosis* ; Klebsiella pneumoniae ; Mediastinal Diseases/diagnostic imaging*

Aims: This study aimed to evaluate the effect of electroporation on the growth characteristics and antimicrobial activity of lactic acid bacteria (LAB) including Bifidobacterium longum ATCC 15707, Lactobacillus acidophilus ATCC 314, Lactobacillus casei ATCC 393 and Lactobacillus fermentum ATCC 14931. Methodology and results: Electroporation with the strength of electric field at 1.0–3.0 kV/cm for 2-4 millisecond were applied on the bacterial cultures. All bacterial cultures showed significant (P<0.05) increased in cell viability (40%-325%) upon electroporation. Such treatment also increased the acidity of the cell where the pH of cells decreased upon treatment. In tandem with the increased viability, electroporated bacterial cultures also showed higher proteolytic activity compared to the control (P<0.05). The electroporation treatment also increased (P<0.05) the bacteriocin activity of treated cells compared to the control. However, the molecular weight of bacteriocins produced were not affected by electroporation. Treated cells also possessed better antimicrobial activity. According to the results collected, all treated LAB strains showed 11.5%-113.8% higher (P<0.05) inhibitory activity compared to untreated control against tested pathogenic bacteria, Escherichia coli and Listeria monocytogenes that commonly associated with food contamination. Microarray data analysis showed that electroporation regulated the entities encoding for surface protein and transporter. Conclusion, significance and impact of study The results from this study suggested that electroporation could enhance the growth characteristics and antimicrobial activity of LAB by modifying the surface regions of the cells. This result may serve as the reference for food manufacturers to opt for effective biopreservation method and produce food with extended shelf life.
Electroporation ; Lactobacillales

Introduction:The management of musculoskeletal tumours is complex and requires a multi-disciplinary approach. Preoperative embolisation can be often employed to reduce intra-operative blood loss and complication rates from surgery. We report our experience with the safety, technical success and efficacy of pre-operative embolisation in musculoskeletal tumours. Materials and Methods:Thirteen consecutive patients who underwent pre-operative embolisation of a musculoskeletal tumour followed by surgical intervention at our institution from May 2012 to January 2016 were enrolled into the study. Patient demographics, tumour characteristics, embolisation techniques and type of surgery were recorded. Technical success of embolisation, amount of blood loss during surgery and transfusion requirements were estimated. Results: There were five female and eight male patients who underwent pre-operative embolisation during the study period. The age ranged between 16 to 68 years, and the median age was 54. Technical success was achieved in all patients. Mean intra-operative blood loss was 1403ml, with a range of 150ml to 6900ml. Eight patients (62%) required intra-operative blood products of packed red blood cells and fresh frozen plasma. No major complications occurred during embolisation. Conclusion: Pre-operative trans-arterial embolisation is feasible and safe for a variety of large and hypervascular musculoskeletal tumours. Our small series suggests that preoperative embolisation could contribute to the reduction of the intra-operative and post-operative blood product transfusion. It should be considered as a pre-operative adjunct for major tumour resections with a high risk of bleeding. The use of the haemoglobin gap complemented the assessment of perioperative blood loss.