Amentoflavone mediated hepatoprotection to counteract paraquat instigated hepatotoxicity via modulating Nrf2/keap1 pathway: A biochemical, inflammatory, apoptotic and histopathological study.

Paraquat (PQ) is a ubiquitous and water-soluble herbicide which has potential to cause systematic poisoning. PQ intoxication is known to be associated with various clinical complications including hepatotoxicity. Amentoflavone (AMF) is an active phenolic compound that exhibits a broad range of biological as well as pharmacological activities. This study was designed to determine the hepato-protective potential of AMF against PQ instigated hepatotoxicity in rats. Forty-eight rats were distributed into four groups such as control group, PQ-treated group (5 mg/kg), PQ (5 mg/kg) + AMF (40 mg/kg) exposed group and AMF (40 mg/kg) only supplemented group. It was revealed that PQ exposure reduced nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidative genes expression whereas increase the expression of Kelch-like ECH-associated protein 1(Keap1). Besides, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), glutathione peroxidase (GPx), Heme- oxygenase-1 (HO-1) & glutathione (GSH) content. Furthermore, the levels of reactive oxygen species (ROS) & malondialdehyde (MDA) were increased. In addition, PQ significantly increased the hepatic serum enzymes including alkaline phosphatase (ALP), aspartate transaminase (AST), & alanine transaminase (ALT) along with inflammatory biomarkers levels such as tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin-6 (IL-6), interleukin 1beta (IL-1ß), & cyclo­oxygenase-2 (COX-2) activity. PQ intoxication increased the expressions of pro-apoptotic markers i.e., Bcl-2-associated X protein (Bax) & Cysteine-aspartic protease-3 (Caspase-3) while reducing the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Furthermore, PQ intoxication prompted various histopathological impairments. However, the co-administration of AMF significantly improved the abovementioned hepatic damages induced by PQ. The present study indicated that AMF may be an effective therapeutic candidate to mitigate PQ provoked hepatic impairments due to its anti-apoptotic, antioxidant & anti-inflammatory properties.

Prevalence and services for the treatment of chronic pain at residential substance treatment centers.

Introduction: Studies suggest that a large proportion of patients with substance use disorders (SUDs) also have underlying chronic pain. There is limited data on prevalence of chronic pain treatment as a component of residential substance use treatment. This initiative sought to investigate the prevalence and type of chronic pain services offered at these residential programs.Methods: This study was a retrospective review of information obtained from residential substance use treatment facility websites contained in SAMHSA's treatment navigator. Nine hundred-fifty out of 2952 websites were randomly selected for analysis. The primary outcome was prevalence of facilities that had chronic pain programs. Services offered were specified as available. Descriptive statistics were used to summarize data.Results: Nine-hundred nine websites (95.7%, [94,97]) were accessible. Twenty-six facilities (2.9%,[1.9,4.2]) had a chronic pain program and of these 22 (84.6%, [64.3,95.0]) specified services offered. Common services included physical therapy (6, 27.3%), massage (12, 54.6%), and acupuncture (10, 45.5%). Of the remaining sites, 630 (69.3%, [66.2,72.3]) specified services offered, including yoga (122, 19.4%) and exercise (199, 31.6%).Conclusion: Our study demonstrated that despite most facilities offering adjunctive services, few had chronic pain programs. This suggests that there is a possible need for better updating of facility websites or possibly an area for improvement in residential substance use treatment settings.

Factors Associated With the Presence of Co-occurring Pain and Substance Use Disorder Programs in Substance Use Treatment Facilities.

OBJECTIVES: The rise in deaths related to substance use has caused a push toward linking patients to pharmacological maintenance treatment and, when appropriate, to residential substance use treatment facilities. One of the underlying issues in a subset of patients with substance use disorder (SUD) is chronic pain. We evaluated the prevalence and characteristics of those facilities that offer treatment programs tailored for patients with co-occurring pain and SUD. METHODS: This study was a retrospective review of data collected by the National Survey of Substance Abuse Treatment Services in 2019. The National Survey of Substance Abuse Treatment Services is sent annually to all substance use treatment facilities and collects information on their characteristics and services. We calculated prevalence of chronic pain programs, reported characteristics, and did a binomial logistic regression to determine predictors of a facility offering such a program. RESULTS: Of 15,945 respondents, 2990 (18.8%) of facilities offered a tailored program for patients with co-occurring pain and SUDs. Characteristics that were best predictors included the following: facility has a tailored program for veterans ( P < 0.001), serves only clients with opioid use disorder ( P = 0.03), and provides maintenance services with methadone or buprenorphine for treating opioid use disorder ( P = 0.009). CONCLUSION: As of 2019, only a small percentage of substance use treatment facilities reported having a program that treats patients with co-occurring pain and SUD. Given the known high prevalence of co-occurring pain and SUD, further understanding of the role of these programs and barriers to implementation may enhance acceptance in treatment programs.

Comparison of two validated evidence-based medicine assessments: Do they correlate?

Evidence-based medicine (EBM) has been defined as a process involving five actions: asking, acquiring, appraising, applying, and assessing. Several attempts have been made to create and validate tools to assess EBM aptitude. The newest testing instrument, the ACE tool, which is a 15-question true/false exam, has not been directly compared to the more established Fresno test, which is composed of 12 in-depth short-answer questions. Although both were designed to test Steps 1-4 of the five-step EBM process, it is unclear whether they examine the same things or whether one is superior. To our knowledge there is not a widely used standard for EBM assessment despite the broad requirements for inclusion of EBM in both undergraduate and graduate medical education. Hypotheses: It was hypothesized that these instruments do not correlate between one another, based on inherent differences between them, including assessment format, grading method, and scoring range. The authors sought to examine whether a correlation between the results of these two instruments exists in a population of U.S. medical students. Methods: A retrospective cohort study of 158 fourth-year U.S. medical students in academic year 2018-2019 was conducted. All students were exposed to a focused EBM curriculum, consisting of three guided discussions of separate journal articles clinically relevant to the practice of emergency medicine. Outcomes measured included scores on both the ACE tool and Fresno test using descriptive statistics. Spearman's rho was used to determine the correlation between the ACE and Fresno scores for each student among the entire group. A subgroup analysis was performed to assess for correlations at more extreme data points. Results: The median scores on the ACE tool and Fresno test were 66.7% and 62.7%. There was no statistically significant correlation between the results of these two assessments (Spearman's rho 0.023, p = 0.774) in our population. The scores from the subgroup of advanced performers on the Fresno test showed a weak statistically significant positive correlation (p = 0.045) to advanced scores on the ACE tool. No other subgroups showed statistically significant correlation. Conclusions: In our population of U.S. medical students, the results of two known EBM assessment instruments do not correlate with one another. The assessments may differ in what categories of learning they measure or in generalizability or perhaps in what depth of understanding they test overall. Further study is needed to determine what each instrument is measuring and whether there is demonstrable variation across populations.

Acute coronary syndrome and transient global amnesia with sumatriptan.

Triptans are potent serotoninergic vasoconstrictors. They are generally avoided in elderly patients age greater than 65 or in patients with a history of CAD. Although there are reported cases of Acute Coronary Syndrome (ACS) or Transient Global Amnesia (TGA) in patients after ingesting therapeutic doses of triptan or dihydroergotamine, this is the first case report, up to our knowledge, of a patient, who had no previous cardiac history, that was diagnosed with both ACS and TGA. A 59-year-old woman with a long-standing history of migraine, gastroesophageal reflux disease, and hypothyroidism, presented to the Emergency Department (ED) complaining of amnesia, chest pain, and left arm numbness after ingesting a single dose of oral sumatriptan approximately 1-2 h prior to arrival. She had no recollection of the events that occurred after taking sumatriptan. No acute laboratory abnormalities were found except for an elevated troponin, which continued to trend upwards. Her EKG had no ST-T wave abnormalities. She was diagnosed with Acute Coronary Syndrome (ACS), non-ST elevation MI. She had a negative noncontrast CT head. Neurology was consulted for her amnesia and diagnosed her with Transient Global Amnesia (TGA). They recommended discontinuing sumatriptan and beginning topiramate as a prophylactic therapy. There is an increasing number of reports delineating sumatriptan's adverse effects. Emergency medicine physicians should promptly recognize the toxic effects and adverse reactions from triptans. Sumatriptan-induced vasoconstriction may lead to cardiac and cerebral ischemic events.