Publications by authors named "A J Marian"
Causes and consequences of DNA double-stranded breaks in cardiovascular disease.
Mol Cell Biochem
October 2024
Article Synopsis
- The genome is constantly exposed to both internal and external factors that can cause DNA damage, with an estimated 10 to 10 lesions occurring in mammalian cells daily, necessitating a balance between damage and repair to maintain stability.
- During transcription, DNA strands unwind to allow RNA polymerase II to synthesize RNA, which creates supercoils that topoisomerases resolve by introducing double-stranded breaks (DSBs), making DSBs a normal part of gene expression despite their risks.
- When transcription is impeded by damaged DNA or proteins, it leads to transcription stress, resulting in the risk of aberrant RNA, accumulation of DSBs, and activation of DNA damage response pathways that may trigger senescence and inflammation,
Article Synopsis
- The GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is identified as a common cause of amyotrophic lateral sclerosis (ALS), leading to motor neuron degeneration and paralysis.
- A zebrafish model expressing glycine-proline dipeptide repeats (GP DPR) reveals that both gain- and loss-of-function effects contribute to nerve cell damage and autophagy deficits, with poly(GP) levels similar to those found in ALS patient tissues.
- Potential treatments involving autophagy activators like rapamycin or urolithin A show promise in alleviating motor deficits and offer new therapeutic options for ALS patients by addressing key disease mechanisms.
"The unbearable lightness" of the primary end point in clinical trials.
Mol Cell Biochem
August 2024
In this Perspective, I discuss the limitations of a soft primary endpoint that is used in some of the recent randomized phase II/III clinical trials. Unfortunately, many clinicians and investigators do not interpret the data critically to recognize the limitations of such findings. I advise against over-interpreting the effects of an intervention on a soft primary endpoint.
View Article and Find Full Text PDFIntroduction: Prolonged times to tracheal extubation are intervals from the end of surgery to extubation ≥15 minutes. We examined why there are associations with the end-tidal inhalational agent concentration as a proportion of the age‑adjusted minimum alveolar concentration (MAC fraction) at the end of surgery.
Methods: The retrospective cohort study used 11.
Background: Prolonged times to tracheal extubation (≥15 minutes from dressing on the patient) are consequential based on their clinical and economic effect. We evaluated the variability among anesthesia practitioners in their goals for the age-adjusted end-tidal minimum alveolar concentration of sevoflurane (MAC) at surgery end and achievement of their goals.
Methods: We prospectively studied a cohort of 56 adult patients undergoing general anesthesia with sevoflurane as the sole anesthetic agent, scheduled operating room time of at least 3 hours, and non-prone positioning.