The Effects of Ayahuasca on Psychological Disorders: A Systematic Literature Review.

Ayahuasca is an original Amazonian brew made from the vines and leaves of Psychotroa viridis and Banisteriopsis caapi. Both P. viridis and B. caapi give this brew its unique psychedelic properties which have been revered over centuries. In recent years, ayahuasca has gained attention as a potential therapeutic tool for mental health disorders, including substance abuse and depression. The uniqueness of ayahuasca's therapeutic potential is that it is an amalgamation of its biochemical makeup and the ritual guided by a shaman, along with the interpretation of the participant of their experience. The boom of "ayahuasca tourism" has brought forth testimonies of feeling "cured" of depression, and substance abuse and an improvement in overall well-being. This systematic literature review focuses on summarizing the recently available research on the effectiveness of ayahuasca as a treatment for depression, anxiety, substance abuse, eating disorders, and post-traumatic stress disorder. It also focuses on understanding the effects it has on personality traits that play a significant role in the manifestation of the above-listed mental health conditions effects. Additionally, the review investigates the importance and role the ritual itself plays, often described as the "mystical experience". This systematic literature review aims to explore the current state of knowledge regarding the use of ayahuasca for numerous mental health conditions by analyzing medical research papers published no earlier than September 2017 to no later than May 2023 from Google Scholar and PubMed. A total of 43 articles met the criteria and were used for detailed analysis. This review will synthesize the findings of the studies, examining the potential therapeutic effects of ayahuasca on multiple mental health disorders, the significance of the "mystical experience," and the mechanisms of action underlying its effects. Through the review, ayahuasca proves to be a worthwhile therapeutic tool that if used in the right setting influences mind, body, and spirit. It is important to note that most studies used in this article relied on surveys and self-reporting proving to be a limitation as no clear standard has been achieved to test the efficacy of ayahuasca. The respect for the culture and origin needs to be retained as Western medicine dwells deeper into ayahuasca's benefits.

Curative intent resection for loco-regionally recurrent colon cancer: Cleveland clinic experience.

BACKGROUND: Locoregional colon cancer recurrence occurs in around 10% of patients following initial curative intent primary resection. We hypothesized oncological results can vary based on the recurrence site. Our aim was to determine outcomes for patients undergoing resection with curative intent for locally recurrent colon cancer. METHODS: Patients with locoregional recurrence after curative intent resection for colon cancer were identified (1999-2017). Demographics, operative details and outcome data were recorded. Kaplan-Meier method was used to compare survival differences. RESULTS: Fifty-two patients (mean age, 62) were included. The most common recurrence site was primary anastomosis (48%). R0 resection was obtained in 68%. Major morbidity occurred in 37%. Patients with anastomotic recurrence had a statistically significant overall survival compared to other sites (71.6 vs. 40.8 months respectively with a P value of 0.05). CONCLUSIONS: Excellent outcomes are possible for curative intent recurrent colon cancer surgery. The site of loco-regional recurrence plays a significant role in outcomes. Table of Contents Summary: Colon cancer recurrence can be treated surgically with optimal outcomes. Anastomotic recurrence is associated with improved survival.

Phylogenetic sequence analysis and functional studies reveal compensatory amino acid substitutions in loop 2 of human ribonucleotide reductase.

Eukaryotic class I ribonucleotide reductases (RRs) generate deoxyribonucleotides for DNA synthesis. Binding of dNTP effectors is coupled to the formation of active dimers and induces conformational changes in a short loop (loop 2) to regulate RR specificity among its nucleoside diphosphate substrates. Moreover, ATP and dATP bind at an additional allosteric site 40 Å away from loop 2 and thereby drive formation of activated or inactive hexamers, respectively. To better understand how dNTP binding influences specificity, activity, and oligomerization of human RR, we aligned >300 eukaryotic RR sequences to examine natural sequence variation in loop 2. We found that most amino acids in eukaryotic loop 2 were nearly invariant in this sample; however, two positions co-varied as nonconservative substitutions (N291G and P294K; human numbering). We also found that the individual N291G and P294K substitutions in human RR additively affect substrate specificity. The P294K substitution significantly impaired effector-induced oligomerization required for enzyme activity, and oligomerization was rescued in the N291G/P294K enzyme. None of the other mutants exhibited altered ATP-mediated hexamerization; however, certain combinations of loop 2 mutations and dNTP effectors perturbed ATP's role as an allosteric activator. Our results demonstrate that the observed compensatory covariation of amino acids in eukaryotic loop 2 is essential for its role in dNTP-induced dimerization. In contrast, defects in substrate specificity are not rescued in the double mutant, implying that functional sequence variation elsewhere in the protein is necessary. These findings yield insight into loop 2's roles in regulating RR specificity, allostery, and oligomerization.