Application of Kombucha Fermentation Broth for Antibacterial, Antioxidant, and Anti-Inflammatory Processes.

Treatment for sepsis and its complications in the clinic is primarily in the forms of antibiotics, anti-inflammatory agents, and antioxidant drugs. Kombucha, a traditional fermented beverage rich in tea polyphenols and organic acids, offers several benefits including bacteriostasis, anti-inflammation ability, and boosting the immune system. Currently, research on kombucha is primarily focused on its antibacterial and antioxidant properties; however, in-depth exploration of the involved mechanisms is lacking. Herein, turmeric, Paeoniae alba, and black tea were used as fermentation substrates to detect the bacteriostatic and antioxidant activities of the fermentation broth and evaluate its anti-inflammatory effects on RAW264.7 cells stimulated by lipopolysaccharides (LPSs). The results showed that fermentation enhanced the antibacterial activity of turmeric against E. coli and S. aureus and that of Paeoniae alba against S. aureus. Turmeric black tea exhibited the highest antioxidant activity. The fermentation broth of turmeric and turmeric black tea significantly reduced the expression of inflammatory cytokines induced by LPSs. Our results showed that using turmeric and Paeoniae alba culture media as substrates can enhance the anti-inflammatory effects of fermentation broth and provide a new strategy for developing anti-inflammatory substances.

Generation and Characterization of Recombinant Pseudorabies Virus Delivering African Swine Fever Virus CD2v and p54.

African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections.

Onsite buprenorphine inductions at harm reduction agencies to increase treatment engagement and reduce HIV risk: Design and rationale.

BACKGROUND: Despite dramatic increases in opioid use disorder (OUD) and overdose deaths, the U.S. has been unable to consistently deliver OUD treatment to those who need it. Syringe services programs (SSPs) can engage an out-of-treatment population of people with OUD that has elevated overdose risk. Buprenorphine treatment is safe and effective, and US regulations allow for prescribing from diverse locations, including SSPs. This study's objective is to test buprenorphine treatment initiation at SSPs. We hypothesize that offering onsite buprenorphine treatment initiation will improve OUD treatment engagement without reducing buprenorphine treatment effectiveness or safety. METHODS: We will recruit 250 out-of-treatment SSP participants with OUD in a large urban area. Participants will be randomized to onsite buprenorphine treatment initiation or enhanced referral. Over 2 weeks, participants in the onsite treatment arm will see a buprenorphine provider twice at the SSP, receive weekly medication packs, and then their care will be transferred to a community health center for treatment continuation. In the control arm, within one week, participants will receive an appointment at the same community health center as in the intervention arm for buprenorphine initiation and continuation. Participants will be assessed with urine drug tests, questionnaires, and medical record review. The primary outcome will be engagement in buprenorphine treatment at 30 days. Secondary outcomes include buprenorphine diversion, opioid-free urine drug tests, and intervention cost-effectiveness. DISCUSSION: Our study will contribute to the growing literature on SSPs as a conduit to OUD treatment. SSPs hold promise to deliver needed care to people with OUD.

Socio-ecological and pharmacy-level factors associated with buprenorphine stocking at pharmacies in New York City.

BACKGROUND: Research is lacking on community and pharmacy-level factors that are associated with stocking buprenorphine. To address these gaps, this study applied a socio-ecological framework to estimate the association between community- and pharmacy-level factors and buprenorphine stocking among a sample of pharmacies in New York City. METHODS: A telephone survey recruitment strategy was used to administer surveys to 662 pharmacies on the New York City Naloxone Standing Order Pharmacy list in 2018. The survey assessed pharmacy-level factors of private spaces to consult with pharmacists, type of pharmacy (chain/independent), size of pharmacy, having buprenorphine in stock and being open on nights and weekends. Socio-ecological variables drawn from census tract and public health data consisted of racial and ethnic composition, rates of poverty, rates of people without insurance, and rates of overdose. Mixed effects logistic regression estimated odds ratios (OR) of carrying buprenorphine in stock after adjusting for socio-ecological and pharmacy-level factors. RESULTS: Fewer than half of the pharmacies reported having buprenorphine in stock (43.81% n = 290). Logistic regression analyses indicate that several pharmacy-level factors - the number of private spaces (aOR=1.67 95% CI=1.20, 2.32 p=.002), large size of the pharmacy (aOR=1.52 95% CI=1.04, 2.22, p=.032), having naloxone in stock (aOR=1.54, 95%CI=1.03, 2.32 p=.037), as well as neighborhood-level factors of higher rates of poverty (aOR=2.07 95%CI=1.07, 4.02 p<.001) and higher rates of uninsured residents were associated with carrying buprenorphine (aOR=0.23 95%CI=0.14,.38). CONCLUSIONS: Using a socio-ecological framework, this study identified inequities in pharmacy stocking of buprenorphine by neighborhood rates of health insurance. At the pharmacy level, increasing private spaces for consultation and encouraging co-stocking of naloxone with buprenorphine stocking may reduce inequalities in buprenorphine availability.

Culturally adapted evidence-based treatments for adults with substance use problems: A systematic review and meta-analysis.

BACKGROUND: This systematic review/meta-analysis aimed to synthesize empirical evidence from randomized controlled trials on the efficacy of culturally adapted interventions (CAIs) for substance use and related consequences for adults of color. METHODS: Six electronic databases were searched to identify eligible studies. Two reviewers independently screened studies, extracted data, and assessed risks of bias. We used robust variance estimation in meta-regression to synthesize effect size estimates and conduct moderator analyses. RESULTS: Twenty-two studies met the inclusion criteria and were included in the review. The overall effect size was 0.23 (95 % Confidence Interval [CI] = 0.12, 0.35). The subgroup effect sizes for comparing CAIs with inactive controls and with active controls were 0.31 (CI = 0.14, 0.48) and 0.14 (CI=-0.02, 0.29), respectively. The effect sizes for alcohol use, illicit drug use, unspecified substance use outcomes, and substance use related consequences were 0.25 (CI = 0.08, 0.43), 0.35 (CI =-0.30, 1.00), 0.22 (CI=-0.17, 0.62), and 0.02 (CI=-0.11, 0.16), respectively. Moderator analysis showed that CAIs' effects might not vary significantly by treatment model, dose, country, follow-up assessment timing, participant age, or gender/sex. CONCLUSIONS: Research on substance use interventions that are culturally adapted for people of color is growing, and more high-quality studies are needed to draw definitive conclusions about CAIs' treatment effects. Our study found CAIs to be a promising approach for reducing substance use and related consequences. We call for more efficacy/effectiveness and implementation research to further advance the development and testing of evidence-based CAIs that meet the unique needs and sociocultural preferences of diverse populations.

Socio-ecological and pharmacy-level factors associated with naloxone stocking at standing-order naloxone pharmacies in New York City.

BACKGROUND: Research on socio-ecological factors that may impede or facilitate access to naloxone in pharmacies remains limited. This study investigated associations between socio-ecological factors, pharmacy participation in the naloxone cost assistance program (NCAP), pharmacy characteristics and having naloxone in stock among pharmacies in New York City. METHODS: Phone interviews were conducted with 662 pharmacies selected from the New York City Naloxone Standing Order List. Multi-level generalized linear modeling estimated associations between neighborhood racial and ethnic composition, poverty rates, overdose fatality rates, pharmacy participation in N-CAP, having private physical spaces within the pharmacy, knowledge of where to refer people to obtain naloxone and adjusted relative risk (aRR) that the pharmacy would have naloxone in stock. RESULTS: Findings from this study supported several of the hypotheses. Greater neighborhood poverty was associated with a lower likelihood of carrying naloxone compared to neighborhoods with less poverty (aRR = .79, CI95 % = .69, .90, p < .001). Pharmacies that provided a private window for consultations (aRR = 1.34, CI95 % = 1.19, 1.51, p < .001), a private room (aRR = 1.42, CI95 % = 1.30, 1.56, p < .001), and a private area (aRR = 1.42, CI95 % = 1.30, 1.56, p < .001) were associated with a higher likelihood of carrying naloxone compared than those that did not. CONCLUSIONS: Findings from this study suggest that community-level socioeconomic marginalization is a contributor to disparities in naloxone availability among pharmacies in New York City. Findings support harm reduction interventions tailored to the built environment of pharmacies that respect privacy to those seeking naloxone.