INTRODUCTION

Ventricular tachycardia (VT) storm is a condition characterized by recurrent ventricular arrhythmias within a 24-hour period, requiring a device or pharmacologic intervention. Despite its clinical significance, data on VT storm prevalence and treatment outcomes in the Filipino population remain limited

We present a 69-year-old male with heart failure from non-ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD), who experienced multiple VT episodes unresponsive to amiodarone, lidocaine and mechanical cardioversion. He was initially admitted for catheter ablation but later developed a left ventricular thrombus precluding the procedure. Mexiletine was introduced and successfully suppressed arrhythmia recurrence

This case emphasized the complexity of managing ES, especially in patients with contraindications to ablation. Mexiletine, a class IB antiarrhythmic agent structurally similar to lidocaine, has shown efficacy in refractory VT, especially when standard therapies are ineffective or are contraindicated. Limited data exists on its safety for such cases, particularly in patients with intracardiac thrombus.

Mexiletine may offer a viable treatment option for VT storm in patients ineligible for ablation due to left ventricular thrombus. While it was effective in this case, further studies are needed to validate its safety and long-term outcomes in similar high-risk populations.

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.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

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.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*