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Arguably, the most important parameter in treating cognitive decline associated with Alzheimer's disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy, resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvements in patients with cognitive decline, but long-term follow-up (>5 years) has not been reported previously. Therefore, here, we report sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols. [ABSTRACT FROM AUTHOR]

Although next-generation sequencing (NGS) has been instrumental in determining the genomic sequences of emerging RNA viruses, de novo sequence determination often lacks sufficient coverage of the 5′ and 3′ ends of the viral genomes. Since the genome ends of RNA viruses contain the transcription and genome replication promoters that are essential for viral propagation, a lack of terminal sequence information hinders the efforts to study the replication and transcription mechanisms of emerging and re-emerging viruses. To circumvent this, we have developed a novel method termed ViBE-Seq (Viral Bona Fide End Sequencing) for the high-resolution sequencing of filoviral genome ends using a simple yet robust protocol with high fidelity. This technique allows for sequence determination of the 5′ end of viral RNA genomes and mRNAs with as little as 50 ng of total RNA. Using the Ebola virus and Marburg virus as prototypes for highly pathogenic, re-emerging viruses, we show that ViBE-Seq is a reliable technique for rapid and accurate 5′ end sequencing of filovirus RNA sourced from virions, infected cells, and tissue obtained from infected animals. We also show that ViBE-Seq can be used to determine whether distinct reverse transcriptases have terminal deoxynucleotidyl transferase activity. Overall, ViBE-Seq will facilitate the access to complete sequences of emerging viruses. [ABSTRACT FROM AUTHOR]

Simple Summary: Mannan-rich fraction (MRF) is a natural extract of Saccharomyces cerevisiae and can be classified into the emerging functional category of products termed postbiotics. Dietary supplementation with MRF has been extensively investigated in poultry as a natural alternative to in-feed antibiotics due to its efficacy in improving immune response, nutrient digestion, and absorption. This present study provides a comprehensive meta-analytic review of the effect of dietary MRF on broiler performance parameters and carbon footprint (CFP) of chicken production via a life cycle assessment model. The results showed that the supplementation of broiler diets with MRF improved growth performance parameters and reduced mortality. Dietary MRF had an equivalent effect to in-feed antibiotics on broiler performance, suggesting that MRF can be used in broiler nutrition as a natural alternative to in-feed antibiotics. Additionally, feeding MRF lowered the environmental impact by reducing feed and total emission intensities, on average, by −2.4% and −2.1%, respectively, contributing to sustainable chicken production. Dietary supplementation of yeast-derived mannan-rich fraction (MRF) could improve the gastrointestinal health and production efficiency of broilers, and, consequently, lower the environmental impacts of chicken production. The objective of this meta-analysis was to quantify the retrospective effects of feeding MRF (Actigen®, Alltech Inc., Nicholasville, KY) on the production performance of broilers. The meta-analysis database included 27 studies and consisted of 66 comparisons of MRF-supplemented diets vs. basal (i.e., negative control) and antibiotic-supplemented (i.e., positive control) diets. A total of 34,596 broilers were involved in the comparisons and the average final age of the birds was 35 days. Additionally, the impact of feeding MRF on the carbon footprint (feed and total emission intensities) of chicken production was evaluated using the meta-analysis results of broiler performance (MRF vs. basal diets) to develop a scenario simulation that was analyzed by a life cycle assessment (LCA) model. A database of all trials (MRF vs. basal and antibiotic diets) indicated that feeding MRF increased (p < 0.01) average daily feed intake (ADFI; +3.7%), final body weight (FBW; +3.5%), and average daily gain (ADG; 4.1%) and improved (p < 0.01) feed conversion ratio (FCR; −1.7%) without affecting (p > 0.05) mortality. A subdatabase of MRF vs. basal diets indicated that dietary MRF increased ADFI (+4.5%), FBW (+4.7%), and ADG (+6.3%) and improved FCR (−2.2%) and mortality (−21.1%). For the subdatabase of MRF vs. antibiotic diets, both treatments exhibited equivalent effects (p > 0.05) on broiler performance parameters, suggesting that MRF could be an effective alternative to in-feed antibiotics. Subgroup analysis revealed that different study factors (year of study, breed/strain, production challenges, and MRF feeding duration) influenced the effect of dietary MRF on broiler performance. Simulated life cycle analysis (LCA) indicated that feeding MRF decreased feed and total emission intensities, on average, by −2.4% and −2.1%, respectively. In conclusion, these results demonstrate that dietary MRF is an effective nutritional solution for improving broiler performance, an effective alternative to in-feed antibiotic growth promoters, and reduces the environmental impact of poultry meat production. [ABSTRACT FROM AUTHOR]

AimsTo examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.MethodsThis multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events.ResultsNo group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events.ConclusionsBuprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.