cosmological argument has been one of the most significant philosophical and theological arguments in religious traditions of different religions. in the western theo-philosophical tradition, there have been both different interpretations and numerous criticisms presented about this argument. in this article, the most important of those arguments and their criticisms are both taken into conside...

Randomised controlled trials (RCTs) sometimes recruit participants who are desperate to receive the experimental treatment. This paper defends the practice against three arguments that suggest it is unethical first, desperate volunteers are not in equipoise. Second clinicians, entering patients onto trials are disavowing their therapeutic obligation to deliver the best treatment; they are follo...

Despite therapeutic advancement, multiple myeloma (MM) remains incurable with drug resistance being one of the main challenges in the clinic. Myeloma cells possess high protein secretory load, leading to increased intracellular endoplasmic reticulum (ER) stress. Hence, they are vulnerable to further perturbation to its protein homeostasis. In studying the therapeutic mechanism of PRIMA-1 (mutan...

Self-deception is a special kind of motivational dominance in belief-formation. We develop criteria which set paradigmatic self-deception apart from related phenomena of auto-manipulation such as pretense and motivational bias. In self-deception rational subjects defend or develop beliefs of high subjective importance in response to strong counter-evidence. Self-deceivers make or keep these bel...

Malpractice insurance rates have created a crisis in American medicine. Rates are rising and reimbursements are not keeping pace. In response, physicians in the states hardest hit by this crisis are feeling compelled to take political action, and the current action of choice seems to be physician strikes. While the malpractice insurance crisis is acknowledged to be severe, does it justify the e...

PRIMA-1met (APR-246) is a methylated derivative and structural analog of PRIMA-1 (p53 re-activation and induction of massive apoptosis). PRIMA-1met has been reported to restore both the wild type (wt) structure and function of mutant p53. Here, we show that PRIMA-1met is highly effective at limiting the growth of CRC cells regardless of p53 status. However, PRIMA-1met induces robust apoptosis o...

Raanan Gillon is a noted defender of the four principles approach to healthcare ethics. His general position has always been that these principles are to be considered to be both universal and prima facie in nature. In recent work, however, he has made two claims that seem to present difficulties for this view. His first claim is that one of these four principles, respect for autonomy, has a sp...

There is an intensive need for the development of novel drugs for the treatment of epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy due to the high recurrence rate. TP53 mutation is a common event in EOC, particularly in high-grade serous ovarian cancer, where it occurs in more than 90% of cases. Recently, PRIMA-1 and PRIMA‑1MET (p53 reactivation and induction of massive ...

PRIMA-1Met is the methylated PRIMA-1 (p53 reactivation and induction of massive apoptosis) and could restore tumor suppressor function of mutant p53 and induce p53 dependent apoptosis in cancer cells harboring mutant p53. However, p53 independent activity of PRIMA-1Met remains elusive. Here we reported that PRIMA-1Met attenuated colorectal cancer cell growth irrespective of p53 status. Kinase p...

Presenilin-1 (PS1) is the catalytic component of the γ-secretase complex. In this study, we explore if PS1 participates in the processing of the cholinergic acetylcholinesterase (AChE). The major AChE variant expressed in the brain is a tetramer (G(4)) bound to a proline-rich membrane anchor (PRiMA). Overexpression of the transmembrane PRiMA protein in Chinese hamster ovary cells expressing ACh...