Phytochemical analysis of water and ethanol liquid extracts prepared using freshly harvested leaves of Mitragyna speciosa (Korth.).

Mitragyna speciosa, also known as kratom, has been reported to have a broad range of pharmacological properties. Freshly harvested leaves and their water extracts are consumed in Southeast Asia while preparations made from dried leaf material are consumed in Western countries. Our study evaluated the phytochemical composition of freshly harvested kratom leaves using LCMS/MS analysis of water and ethanol liquid extracts. Mitragynine and its congeners, including 7-hydroxymitragynine, speciocilliatine, speciogynine, paynantheine, as well as bioactive phenolics including chlorogenic acid, o-coumaric acid, quercitrin, and rutin were identified. However, 7-hydroxymitragynine was detected solely in the water-liquid extract. Currently, unknown compounds were also present in the chromatograms and mass spectra. The study results support that 7-hydroxymitragynine is a post-harvest oxidative derivative or metabolite of mitragynine. Further rigorous and comprehensive evaluations of the phytochemical composition of freshly harvested kratom leaves utilising advanced spectrometric methods are needed to establish the full spectrum of phytochemicals within the plant.

Research and publication gaps on kratom and kratom products: a scoping review of current literature.

PURPOSE OF REVIEW: Kratom plant, products derived from the plant, and plant phytochemicals are of great interest among researchers, clinicians, and consumers. However, there is a paucity of rigorously collected scientific data on their risk/safety profile and public health impact. This scoping review discusses original research articles published between 2022 and 2023. It focuses on identifying publication gaps on topics related to epidemiology, public health, and risk/safety profiles comparing evidence collected by researchers from Southeast Asia and the West. RECENT FINDINGS: Our review of the Scopus database identified a total of 55 publications, including clinical case reports and case series reports, surveys, studies enrolling human participants, and publications based on large-scale national surveys or large-scale national or international health system database records. SUMMARY: Overall, there is dearth of reliable data on key epidemiological factors, including the prevalence rates, and on objective and reliable indices of the risk/safety profiles. Rigorous and systematic studies including improved epidemiological surveillance, human laboratory, and controlled clinical studies are urgently needed to advance our understanding of public health consequences of consuming kratom and kratom-derived products and to improve our understanding of their risk/safety profile and additional analytical studies to better inform development of needed regulatory oversight.

Short 2'-O-methyl/LNA oligomers as highly-selective inhibitors of miRNA production in vitro and in vivo.

MicroRNAs (miRNAs) that share identical or near-identical sequences constitute miRNA families and are predicted to act redundantly. Yet recent evidence suggests that members of the same miRNA family with high sequence similarity might have different roles and that this functional divergence might be rooted in their precursors' sequence. Current knock-down strategies such as antisense oligonucleotides (ASOs) or miRNA sponges cannot distinguish between identical or near identical miRNAs originating from different precursors to allow exploring unique functions of these miRNAs. We here develop a novel strategy based on short 2'-OMe/LNA-modified oligonucleotides to selectively target specific precursor molecules and ablate the production of individual members of miRNA families in vitro and in vivo. Leveraging the highly conserved Xenopus miR-181a family as proof-of-concept, we demonstrate that 2'-OMe/LNA-ASOs targeting the apical region of pre-miRNAs achieve precursor-selective inhibition of mature miRNA-5p production. Furthermore, we extend the applicability of our approach to the human miR-16 family, illustrating its universality in targeting precursors generating identical miRNAs. Overall, our strategy enables efficient manipulation of miRNA expression, offering a powerful tool to dissect the functions of identical or highly similar miRNAs derived from different precursors within miRNA families.

Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats.

Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.

Implementation Facilitation to Promote Emergency Department-Initiated Buprenorphine for Opioid Use Disorder.

Importance: Emergency department (ED)-initiated buprenorphine for the treatment of opioid use disorder (OUD) is underused. Objective: To evaluate whether provision of ED-initiated buprenorphine with referral for OUD increased after implementation facilitation (IF), an educational and implementation strategy. Design, Setting, and Participants: This multisite hybrid type 3 effectiveness-implementation nonrandomized trial compared grand rounds with IF, with pre-post 12-month baseline and IF evaluation periods, at 4 academic EDs. The study was conducted from April 1, 2017, to November 30, 2020. Participants were ED and community clinicians treating patients with OUD and observational cohorts of ED patients with untreated OUD. Data were analyzed from July 16, 2021, to July 14, 2022. Exposure: A 60-minute in-person grand rounds was compared with IF, a multicomponent facilitation strategy that engaged local champions, developed protocols, and provided learning collaboratives and performance feedback. Main Outcomes and Measures: The primary outcomes were the rate of patients in the observational cohorts who received ED-initiated buprenorphine with referral for OUD treatment (primary implementation outcome) and the rate of patients engaged in OUD treatment at 30 days after enrollment (effectiveness outcome). Additional implementation outcomes included the numbers of ED clinicians with an X-waiver to prescribe buprenorphine and ED visits with buprenorphine administered or prescribed and naloxone dispensed or prescribed. Results: A total of 394 patients were enrolled during the baseline evaluation period and 362 patients were enrolled during the IF evaluation period across all sites, for a total of 756 patients (540 [71.4%] male; mean [SD] age, 39.3 [11.7] years), with 223 Black patients (29.5%) and 394 White patients (52.1%). The cohort included 420 patients (55.6%) who were unemployed, and 431 patients (57.0%) reported unstable housing. Two patients (0.5%) received ED-initiated buprenorphine during the baseline period, compared with 53 patients (14.6%) during the IF evaluation period (P < .001). Forty patients (10.2%) were engaged with OUD treatment during the baseline period, compared with 59 patients (16.3%) during the IF evaluation period (P = .01). Patients in the IF evaluation period who received ED-initiated buprenorphine were more likely to be in treatment at 30 days (19 of 53 patients [35.8%]) than those who did not 40 of 309 patients (12.9%; P < .001). Additionally, there were increases in the numbers of ED clinicians with an X-waiver (from 11 to 196 clinicians) and ED visits with provision of buprenorphine (from 259 to 1256 visits) and naloxone (from 535 to 1091 visits). Conclusions and Relevance: In this multicenter effectiveness-implementation nonrandomized trial, rates of ED-initiated buprenorphine and engagement in OUD treatment were higher in the IF period, especially among patients who received ED-initiated buprenorphine. Trial Registration: ClinicalTrials.gov Identifier: NCT03023930.

Missed Opportunities for HIV and Hepatitis C Screening Among Emergency Department Patients With Untreated Opioid Use Disorder.

OBJECTIVE: We assessed the frequency of emergency department (ED) HIV and hepatitis C (HCV) screening in a high-risk cohort of ED patients with untreated opioid use disorder (OUD). METHODS: This analysis used data from a prospective, observational study of English-speaking adults with untreated OUD enrolled from April 2017 to December 2018 in 4 urban, academic EDs. Two cohorts were defined for this analysis by self-reported negative/unknown status for HIV (cohort 1) and HCV (cohort 2). Sites featured structured screening programs throughout the entire enrollment period for HIV and during at least part of the enrollment period for HCV. We calculated the proportion tested for HIV and HCV during the study enrollment ED visit. RESULTS: Among 394 evaluated ED patients, 328 of 394 (83.2%) were not tested for HIV or HCV and 244 of 393 (62.1%) lacked a usual medical care provider. In cohort 1, 375 reported negative or unknown HIV status; 59/375 (15.7%) overall and 33/218 (15.1%) of those reporting recent injection drug use were tested for HIV. In cohort 2, 231 reported negative of unknown HCV status; 22/231 (9.5%) overall and 9/98 (9.2%) of those reporting recent injection drug use were tested for HCV. The proportion tested by the ED ranged from 3% to 25% for HIV and 4% to 32% for HCV across study sites. CONCLUSIONS: Emergency department HIV and HCV screening remains infrequent among patients with untreated OUD, including those who inject drugs, even in EDs committed to screening. Targeted HIV/HCV screening should be considered as an adjunct strategy until the ideal of universal screening is more fully achieved.

Analgesic effects of main indole alkaloid of kratom, mitragynine in acute pain animal model.

Mitragynine exerts its analgesic effect mainly via opioid receptors activation. Additionally, the effect may be mediated via mitragynine's anti-inflammatory property and non-opioid receptor pain pathways, namely through the TRPV1 receptor. No studies identify hitherto, hence, the current study aimed to investigate the mitragynine's analgesic effect via the anti-inflammatory property, non-opioid receptor (TRPV1) and the effective dose (ED) to alleviate pain. Male and female Sprague Dawley rats were pre-treated intraperitoneally with either mitragynine (1, 5, 10, 13, 15 or 30 mg/kg), vehicle, or indomethacin (1 mg/kg) 30 min before inducing inflammatory pain using acetic acid. The writhes and pain-related withdrawal behaviour occurrence were counted within a 1-h duration. Percentage of writhes inhibition, pain-related withdrawal behaviour aggregate, ED50 and ED95 were determined. The body temperature was recorded and TRPV1 expression in the rats' brains was measured. Mitragynine (except 1 mg/kg) significantly reduced the number of writhes compared with the vehicle administered group. Mitragynine (30 mg/kg) demonstrated 99.5% inhibition of writhing behaviour and low withdrawal behaviour score compared with vehicle and indomethacin and successfully blocked the hypothermia induced by acetic acid. The overall ED50 and ED95 values of mitragynine were 3.62 and 20.84 mg/kg, respectively. The percentage of writhing inhibition and withdrawal behaviour were similar in both genders. Mitragynine (15 and 30 mg/kg) significantly reduced the TRPV1 expression in the brain of the rats. Mitragynine alleviated pain-like behaviour and showed analgesic effects via anti-inflammatory and non-opioid receptor pathways. The findings also suggest that mitragynine might regulate some physiological functions of the rat.

Fighting Food Waste by Law: Making Sense of the Chinese Approach.

The Standing Committee of the National People's Congress adopted the Anti-food Waste Law of the People's Republic of China in April 2021 to guarantee grain security, conserve resources, and protect the environment. We pursue three research questions: Why has China implemented a law with sanctions to reduce food waste, and why now? Why does the law target the catering industry? To answer these questions, we collected primary data through semi-structured interviews with government officials, as well as secondary data through recorded interviews available online with officials of the Legislative Affairs Commission of the Standing Committee of the National People's Congress (NPCSC) and food waste activists, as well as NPCSC conference reports. We find a legal approach with sanctions was necessary since cultural aspects, specifically conventional Chinese dining habits and pop culture, are difficult to regulate through instruments without sanctions. In addition, we find the Chinese law focuses on the catering industry for a few reasons: (1) More waste is generated by the catering industry than households, (2) waste from the catering industry is easier to monitor than household waste, and (3) this was a response to citizen requests collected during the Anti-food Waste Law public consultation process.

Continuous electrocoagulation of Chlorella vulgaris in a novel channel-flow reactor: A pilot-scale harvesting study.

The most frequently used method to harvest microalgae on an industrial scale is centrifugation, although this has very high energy costs. To reduce these costs, a continuous electrocoagulation process for harvesting Chlorella vulgaris was developed and tested using a pilot-scale 111 L working volume device consisting of an electrolyser with iron electrodes, aggregation channel and lamellar settler. The flow rate of the microalgal suspension through the device was 240 L/h. When using controlled cultivation and subsequent electrocoagulation, a high harvesting efficiency (above 85%), a low Fe contamination in the harvested biomass (<4 mg Fe/g dry biomass, a harvested biomass complied with legislative requirements for food) and significant energy savings were achieved. When comparing electrocoagulation and subsequent centrifugation with the use of centrifugation alone, energy savings were 80 % for a biomass harvesting concentration of 0.23 g/L. Electrocoagulation was thus proven to be a feasible pre-concentration method for harvesting microalgae.