Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients who received ketamine had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain. The analysis also revealed that patients who took ketamine had significantly lower frequency of reports of pain and opioid induced side effects, implying ketamine's potential to act as a beneficial adjunct agent in pain management pharmacotherapy. Further, the Inverse-Frequency Analysis methodology provides robust statistical support for the antidepressant action of other currently approved therapeutics including diclofenac and minocycline

Retrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids.

Tramadol is one of the most commonly used analgesics worldwide, classified as having a low abuse potential by U.S. Drug Enforcement Agency, and often recommended in pain management guidelines. Its pain-relieving mechanism of action is attributed to mild μ-opioid receptor agonism, serotonin and norepinephrine mediated nociception modulation, and N-methyl-D-aspartate receptor, NMDAR, antagonism. However, recent case reports and case-control studies have shown an association between tramadol use and hypoglycemia. The growing concern over increasing tramadol use and unexpected side effects warranted a further comparative and quantitative analysis of tramadol adverse reactions. In this study we analyzed over twelve million reports from United States Food and Drug Administration Adverse Event Reporting System and provided evidence of increased propensity for hypoglycemia in patients taking tramadol when compared to patients taking other opioids, serotonin-norepinephrine reuptake inhibitors, and drugs affecting NMDAR activity. Additionally, we identified that only methadone from the opioid cohort behaves similarly to tramadol and has an association with hypoglycemia

Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory.

Proton-pump inhibitors, PPIs, are considered effective therapy for stomach acid suppression due to their irreversible inhibition of the hydrogen/potassium pump in the gastric parietal cells. They are widely prescribed and are considered safe for over-the-counter use. Recent studies have shown an association between PPI use and Alzheimer dementia, while others have disputed that connection. We analyzed over ten million United States Food and Drug Administration Adverse Event Reporting System reports, including over forty thousand reports containing PPIs, and provided evidence of increased propensity for memory impairment among PPI reports when compared to histamine-2 receptor antagonist control group. Furthermore, we found significant associations of PPI use with a wide range of neurological adverse reactions including, migraine, several peripheral neuropathies, and visual and auditory neurosensory abnormalities

Alleviation of cold stress in vegetable crops

Low temperature is a major environmental factor that limits crop productivity of plants. Cold stress is a serious threat to the sustainability of crop yields. Low temperature has a huge impact on the survival and geographical distribution of plants. It negatively affects cellular components and metabolism, and temperature extremes impose stresses of variable severity that depend on the intensity and duration of the stress. Low temperature (less than minimum) leads to chlorosis, necrosis, membrane damage, changes in cytoplasm viscosity, and changes in enzyme activities leading to death of plant. Cold stress disrupts the integrity of intracellular organelles, leading to the loss of compartmentalization. It also causes reduction and impairing of photosynthesis, protein assembly and general metabolic processes. Moreover, cold stress during anthesis induces flower dropping, sterility of pollen, pollen tube distortion, ovule abortion and reduced fruit set, which leads to declined growth and lower yield. A number of approaches are being used to mitigate the deleterious effects of cold stress which threatens the successful vegetable crop production, application of plant growth regulators (salicylic acid, abscisic acid, jasmonic acid, Gibberellin and brassinosteroids) and unitization of genetics tools and plant breeding is one of the strategies to alleviate the low temperature stress in vegetable crops. Plant growth regulators play a greater role in improving the cold stress tolerance. In this paper, the effects of cold stress on vegetable growth, productivity and physiological activities were discussed, and some effective techniques for the mitigation of cold stress that help sustainable vegetable production under fluctuating climate is presented

Publisher Correction: Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper

Risk of respiratory depression with opioids and concomitant gabapentinoids.

Introduction:The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. Methods:This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group. Results:A total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group. Conclusion:There was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours

Character Design in Al-Inju School of Persian Miniature Painting in the Eighth Century (Study Samples: Shāhnāmeh 733 AH and Samak-e Ayyār Illustrated Manuscripts

Problem Definition: Among the schools of miniature paintings, those paintings left from the Shiraz school of the eighth century AH are significant and unique due to the preservation of the artistic traditions of ancient Iran and their expressive approach. Considering that the composition of the paintings based on the arrangement of the figures was one of the main features of the Shiraz school of miniature painting in the Al-Inju period, this study aimed to study and compare the method of characterization in the paintings of two illustrated manuscripts left from the Shiraz school, namely Samak-e Ayyār with 80 images and the Shāhnāmeh 733 AH with 52 images. In addition, it provides explanations about the characterization and design of the figures in Al-Inju miniature paintings and addresses the similarities and differences between the images of these two illustrated manuscripts.Objective: The present study aimed to identify and investigate the characterization of the Shiraz school of miniature painting through the visual analysis of the two illustrated manuscripts of Shāhnāmeh 733 (St. Petersburg) and Samak-e Ayyār (Oxford).Research Method: This research is qualitative in terms of the nature of data and is fundamental considering the purpose. Data collection is a library-based approach, and various instruments such as observation and checklist have been used in compiling the data and writing the research results.Results: The characters in the studied paintings can be divided into six groups based on their social status: kings, court women, non-court women, female Ayyār, servants, and warriors. The results of this study indicate that each of these six groups differs in following the visual conventions in terms of the type of costume and their physical placement mode in the paintings; the style and position of the characters in the two versions of paintings show their personality traits and social status in each story. In this way, the appearance and design of human characters are the same in both manuscripts, but the way the painter deals with the characters in each version is different. The painter of the Samak-e Ayyār illustrated manuscript has provided more painting space for high-ranking characters, including kings. He portrayed kings, both good and evil, sitting on thrones while the painter of Shāhnāmeh 733 AH manuscript has considered the throne as a place to show royal oppression; the kings were not depicted seated on the throne in Shāhnāmeh manuscript unless they were on the side of evil

Advancing Pharmacist Collaborative Care within Academic Health Systems.

INTRODUCTION:The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY:We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS:The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system