Daily associations between cannabis use and alcohol use among people who use cannabis for both medicinal and nonmedicinal reasons: Substitution or complementarity?

Objective: People who use cannabis for medicinal (versus nonmedicinal) reasons report greater cannabis use and lower alcohol use, which may reflect a cannabis–alcohol substitution effect in this population. However, it is unclear whether cannabis is used as a substitute or complement to alcohol at the day level among people who use cannabis for both medicinal and nonmedicinal reasons. This study used ecological momentary assessment (EMA) to examine this question. Method: Participants (N = 66; 53.1% men; mean age 33 years) completed daily surveys assessing previous-day reasons for cannabis use (medicinal versus nonmedicinal), cannabis consumption (both number of different types of cannabis used and grams of cannabis flower used), and number of standard drinks consumed. Results: Multilevel models revealed that, in general, greater cannabis consumption on a given day was associated with greater same-day alcohol use. Further, days during which cannabis was used for medicinal (versus exclusively nonmedicinal) reasons were associated with reduced consumption of both cannabis and alcohol. Finally, the day-level association between medicinal reasons for cannabis use and lower alcohol consumption was mediated by using fewer grams of cannabis on medicinal cannabis use days. Conclusions: Day-level cannabis-alcohol associations may be complementary rather than substitutive among people who use cannabis for both medicinal and nonmedicinal reasons, and lower (rather than greater) cannabis consumption on medicinal use days may explain the link between medicinal reasons for cannabis use and reduced alcohol use. Still, these individuals may use greater amounts of both cannabis and alcohol when using cannabis for exclusively nonmedicinal reasons.This research was supported by grants from the Canadian Institutes of Health Research Canadian HIV Trials Network (CTN PT037; PIs: Jeffrey D. Wardell and Sergio Rueda) and from the Canadian Institutes of Health Research (159754; PIs: Jeffrey D. Wardell and Christian S. Hendershot). The views expressed herein do not necessarily represent the official policy of the Canadian Institutes of Health Research. Sergio Rueda holds an Innovator Award from the Ontario HIV Treatment Network

Forages for Horses Revamped

The Forages for Horses program began in Ohio in1998 as a collaboration between the Ohio Forages & Grasslands Council and Ohio State University Extension. Over time, additional collaborations with the Natural Resources Conservation Service, Ohio Department of Agriculture and local Soil and Water Conservation Districts expanded the program. At its inception, one to three educators would partner to provide eight hours of in-person lectures followed by a pasture walk to better the management practices of equine enthusiasts. From 2021 through 2022, the curriculum was adapted for a hybrid classroom and included three 90-minute live webinars featuring nine different presentations followed by online social events. The modifications to the curriculum were made to improve access to equine resources and grazing education across Ohio. The Forages for Horses resources were also updated as part of the process. Learning modules posted in Canvas (an online learning management system) provided additional information that expanded upon the original curriculum. In 2022, 41 students from Ohio and surrounding states registered for the online course and webinars. Participants were able to hear directly from educators - more than in past iterations of the program– to expand their depth of knowledge and increase opportunities for participation without the location of the class posing a barrier for attendance. This program will continue to be revised over the coming years to remain relevant and accessible to Ohioans

Ohio Pastures for Profit Online

The Pastures for Profit program is an established course created through a collaboration between Ohio State University Extension, Central State University, USDA-Natural Resources Conservation Service, Ohio Federation of Soil and Water Conservation Districts, Ohio Department of Agriculture, and the Ohio Forage and Grasslands Council. In 2021, due to COVID-19, the Pastures for Profit curriculum was adapted to a virtual classroom setting and was offered again in 2022. The virtual experience consisted of three live webinars pairing with corresponding modules in Scarlet Canvas. Enrolled students were also mailed traditional course materials for personal use. Module content was newly developed and compiled to compliment the traditional materials and included videos, quizzes, additional presentations, and technical resources. The course materials were organized and taught by a team of over 50 collaborators. During the three live webinars, nearly 20 speakers presented on topics including the basics of grazing, plant and animal science, and grazing plans. A total of 168 people enrolled in Scarlet Canvas in the two-year time frame from over 15 states and included producers, educators, technical service providers, and government agency staff. Each live session was recorded and made available to the class for access at their convenience. Those who completed the course obtained a signed certificate of completion. This platform allowed for an expanded audience reach than in the past

Locomotor adaptability in persons with unilateral transtibial amputation

Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Developing a method to derive alcohol-attributable fractions for HIV/AIDS mortality based on alcohol's impact on adherence to antiretroviral medication

<p>Abstract</p> <p>Background</p> <p>Alcohol consumption is causally linked to nonadherence to antiretroviral treatment that in turn causes an increase in HIV/AIDS mortality. This article presents a method to calculate the percentage of HIV/AIDS deaths attributable to alcohol consumption and the associated uncertainty.</p> <p>Methods</p> <p>By combining information on risk relations from a number of published sources, we estimated alcohol-attributable fractions (AAFs) of HIV/AIDS in a stepwise procedure. First, we estimated the effect of alcohol consumption on adherence to antiretroviral treatment, and then we combined this estimate with the impact of nonadherence on death. The 95% uncertainty intervals were computed by estimating the variance of the AAFs using Taylor series expansions of one and multiple variables. AAFs were determined for each of the five Global Burden of Disease regions of Africa, based on country-specific treatment and alcohol consumption data from 2005.</p> <p>Results</p> <p>The effects of alcohol on HIV/AIDS in the African Global Burden of Disease regions range from 0.03% to 0.34% for men and from 0% to 0.17% for women, depending on region and age category. The detrimental effect of alcohol consumption was statistically significant in every region and age category except for the North Africa/Middle East region.</p> <p>Conclusions</p> <p>Although the method has its limitations, it was shown to be feasible and provided estimates of the impact of alcohol use on the mortality outcome of HIV/AIDS.</p

The PhenX Toolkit: Get the Most From Your Measures

The potential for genome-wide association studies to relate phenotypes to specific genetic variation is greatly increased when data can be combined or compared across multiple studies. To facilitate replication and validation across studies, RTI International (Research Triangle Park, North Carolina) and the National Human Genome Research Institute (Bethesda, Maryland) are collaborating on the consensus measures for Phenotypes and eXposures (PhenX) project. The goal of PhenX is to identify 15 high-priority, well-established, and broadly applicable measures for each of 21 research domains. PhenX measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The selected measures are then made freely available to the scientific community via the PhenX Toolkit. Thus, the PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies. PhenX measures will have the most impact when included at the experimental design stage. The PhenX Toolkit also includes links to standards and resources in an effort to facilitate data harmonization to legacy data. Broad acceptance and use of PhenX measures will promote cross-study comparisons to increase statistical power for identifying and replicating variants associated with complex diseases and with gene-gene and gene-environment interactions

Searching for DNA Lesions: Structural Evidence for Lower- and Higher-Affinity DNA Binding Conformations of Human Alkyladenine DNA Glycosylase

To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search the million-fold excess of unmodified DNA bases to find a handful of DNA lesions. Such a search can be facilitated by the ability of glycosylases, like AAG, to interact with DNA using two affinities: a lower-affinity interaction in a searching process and a higher-affinity interaction for catalytic repair. Here, we present crystal structures of AAG trapped in two DNA-bound states. The lower-affinity depiction allows us to investigate, for the first time, the conformation of this protein in the absence of a tightly bound DNA adduct. We find that active site residues of AAG involved in binding lesion bases are in a disordered state. Furthermore, two loops that contribute significantly to the positive electrostatic surface of AAG are disordered. Additionally, a higher-affinity state of AAG captured here provides a fortuitous snapshot of how this enzyme interacts with a DNA adduct that resembles a one-base loop.National Institutes of Health (U.S.) (grant no. P30-ES002109)National Institutes of Health (U.S.) (grant no. GM65337)National Institutes of Health (U.S.) (grant no. GM65337-03S2)National Institutes of Health (U.S.) (grant no. CA055042)National Institutes of Health (U.S.) (grant no. CA092584)Repligen Corporation (KIICR Graduate Fellowship