AGO HITS-CLIP reveals distinct miRNA regulation of white and brown adipose tissue identity.

MicroRNAs (miRNAs) are short, noncoding RNAs that associate with Argonaute (AGO) to influence mRNA stability and translation, thereby regulating cellular determination and phenotype. While several individual miRNAs have been shown to control adipocyte function, including energy storage in white fat and energy dissipation in brown fat, a comprehensive analysis of miRNA activity in these tissues has not been performed. We used high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) to comprehensively characterize the network of high-confidence, in vivo mRNA:miRNA interactions across white and brown fat, revealing >20,000 unique AGO binding sites. When coupled with miRNA and mRNA sequencing, we found an inverse correlation between depot-enriched miRNAs and their targets. To illustrate the functionality of our HITS-CLIP data set in identifying specific miRNA:mRNA interactions, we show that miR-29 is a novel regulator of leptin, an adipocyte-derived hormone that coordinates food intake and energy homeostasis. Two independent miR-29 binding sites in the leptin 3' UTR were validated using luciferase assays, and miR-29 gain and loss of function modulated leptin mRNA and protein secretion in primary adipocytes. This work represents the only experimentally generated miRNA targetome in adipose tissue and identifies multiple regulatory pathways that may specify the unique identities of white and brown fat.

Robotic approach for retromuscular ventral hernia repair may be associated with improved wound morbidity in high-risk patients: a propensity score analysis.

BACKGROUND: Retromuscular sublay (RMS) technique for repair of ventral hernias has gained popularity due to lower risk of recurrence and wound complications. Robotic approaches to RMS have been shown to decrease hospital stay; however, previous studies have failed to show a significant reduction in wound morbidity. Utilizing the Abdominal Core Health Quality Collaborative (ACHQC) database, this study sought to determine the effect of robotic approach on wound morbidity, while specifically focusing on a high-risk population. METHODS: A retrospective review of elective robotic and open RMS repairs in the ACHQC database was performed. Patients deemed to be high-risk for wound complications were included: adult patients with BMI greater than 35 and who were either current smokers or diabetics. A propensity score match was then done to balance covariates between the two groups. Main outcomes of concern were surgical site occurrences (SSO), surgical site infections (SSI), and surgical site occurrence requiring procedural intervention (SSOPI) at 30-day follow-up. RESULTS: A total of 917 patients met inclusion criteria. After propensity score matching, 211 patients matched for each approach. There was no difference in overall SSO (18% for Open vs 23% for Robotic, p = 0.23). Open repair was associated with higher rates of SSI (4% vs 1%, p = 0.032) and SSOPI (9% SSOPI vs 3%, p < 0. 015). As seen in previous studies, there was a higher rate of seroma associated with Robotic RMS repair (87% vs 48%, p < 0.001) in patients that developed an SSO. CONCLUSIONS: In this analysis, a robotic approach was associated with decreased rates of SSI and SSOPI in obese patients who were either current smokers or diabetics. In effort to reduce wound morbidity and the associated physical and economic costs, robotic approach for retromuscular ventral hernia repair should be considered in this patient population.

Spectral resolution enhancement for impulsive stimulated Brillouin spectroscopy by expanding pump beam geometry.

Brillouin microscopy has recently emerged as a powerful tool for mechanical property measurements in biomedical sensing and imaging applications. Impulsive stimulated Brillouin scattering (ISBS) microscopy has been proposed for faster and more accurate measurements, which do not rely on stable narrow-band lasers and thermally-drifting etalon-based spectrometers. However, the spectral resolution of ISBS-based signal has not been significantly explored. In this report, the ISBS spectral profile has been investigated as a function of the pump beam's spatial geometry, and novel methodologies have been developed for accurate spectral assessment. The ISBS linewidth was found to consistently decrease with increasing pump-beam diameter. These findings provide the means for improved spectral resolution measurements and pave the way to broader applications of ISBS microscopy.

Learning curves of robotic extended totally extraperitoneal (eTEP) hernia repair among two surgeons at a high-volume community hospital: a cumulative sum analysis.

INTRODUCTION: Robotic extended totally extraperitoneal hernia (eTEP) repair is a novel technique for minimally invasive ventral hernia repair with retromuscular placement of mesh. This study aimed to evaluate the learning curve for robotic eTEP hernia repair using risk-adjusted cumulative sum (RA-CUSUM) analysis for two general surgeons-one with dedicated fellowship training in robotic eTEP technique (surgeon 2) and another without robotic eTEP-specific training (surgeon 1). METHODS: We conducted a retrospective analysis of 98 patients undergoing robotic eTEP hernia repair from July 2020 to February 2022 for two surgeons. RA-CUSUM method was applied to the overall operative time (OT) in minutes, adjusting for transversus abdominis release (TAR). RESULTS: Figures 3 (surgeon 1) and 4 (surgeon 2) illustrate the three phases in the RA-CUSUM graphs of OT. For surgeon 1, the cases for each phase were determined: phase 1 (1 to 12), phase 2 (13 to 24), and phase 3 (25 to 51). For surgeon 2, the three phases were similarly determined as 1 to 8, 9 to 32, and 33 to 47, respectively. A significant (p = 0.017) difference existed for the OTs between phases 1 (262 ± 69) and 3 (192 ± 63.0) for surgeon 1. OT compared to the risk-adjusted value stabilized after case 12 and decreased after case 24 for surgeon 1; it began to decrease after case 8 for surgeon 2. CONCLUSIONS: The initial learning curve for surgeon 1 reached its plateau after 12 cases, shorter than comparable studies. This was likely due to the surgeon's intentional focus on learning this technique through courses, proctoring, and active mentorship. The flat learning curve seen in surgeon 2's series illustrates the value of experience gained during fellowship training. Our data support that, given the right resources and support, a short learning curve for eTEP is attainable for community surgeons without prior training in the technique.

Dissemination of public health research to prevent non-communicable diseases: a scoping review.

BACKGROUND: Dissemination is a critical element of the knowledge translation pathway, and a necessary step to ensure research evidence is adopted and implemented by key end users in order to improve health outcomes. However, evidence-based guidance to inform dissemination activities in research is limited. This scoping review aimed to identify and describe the scientific literature examining strategies to disseminate public health evidence related to the prevention of non-communicable diseases. METHODS: Medline, PsycInfo and EBSCO Search Ultimate were searched in May 2021 for studies published between January 2000 and the search date that reported on the dissemination of evidence to end users of public health evidence, within the context of the prevention of non-communicable diseases. Studies were synthesised according to the four components of Brownson and colleagues' Model for Dissemination of Research (source, message, channel and audience), as well as by study design. RESULTS: Of the 107 included studies, only 14% (n = 15) directly tested dissemination strategies using experimental designs. The remainder primarily reported on dissemination preferences of different populations, or outcomes such as awareness, knowledge and intentions to adopt following evidence dissemination. Evidence related to diet, physical activity and/or obesity prevention was the most disseminated topic. Researchers were the source of disseminated evidence in over half the studies, and study findings/knowledge summaries were more frequently disseminated as the message compared to guidelines or an evidence-based program/intervention. A broad range of dissemination channels were utilised, although peer-reviewed publications/conferences and presentations/workshops predominated. Practitioners were the most commonly reported target audience. CONCLUSIONS: There is a significant gap in the peer reviewed literature, with few experimental studies published that analyse and evaluate the effect of different sources, messages and target audiences on the determinants of uptake of public health evidence for prevention. Such studies are important as they can help inform and improve the effectiveness of current and future dissemination practices in public health contexts.

Binge and high-intensity drinking-Associations with intravenous alcohol self-administration and underlying risk factors.

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21-28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders.

Intraoperative Oxygen Practices in Cardiac Surgery: A National Survey.

OBJECTIVE: To describe the current nationwide perspectives and practice regarding intraoperative oxygen titration in cardiac surgery. DESIGN: Prospective, observational survey. SETTING: Hospitals across the United States. PARTICIPANTS: Cardiovascular anesthesiologists and perfusionists. INTERVENTIONS: Expert- and consensus-derived electronic surveys were sent to perfusionists and cardiac anesthesiologists to evaluate the current intraoperative practices around oxygen administration. Providers were asked about individual intraoperative oxygen titration practices used at different stages of cardiac surgical procedures. Anonymous responses were collected in the Research Electronic Data Capture (REDCap). MEASUREMENTS AND MAIN RESULTS: A total of 3,335 providers were invited to participate, of whom 554 (317 anesthesiologists and 237 perfusionists) were included in the final analysis (17% response rate). During cardiopulmonary bypass (CPB), perfusionists reported a median (interquartile range [IQR]) target range from 150 (110-220)-to-325 mmHg (250-400), while anesthesiologists reported a significantly lower target range from 90 (70-150)-to-250 mmHg (158-400) (p values <0.0001 and 0.02, respectively). This difference was most pronounced at lower partial pressure of arterial oxygen (PaO2) ranges. The median PaO2 considered "too low" by perfusionists was 100 mmHg (IQR 80-125), whereas it was 60 mmHg (IQR 60-75) for anesthesiologists, who reported for both off and on bypass. The median PaO2 considered "too high" was 375 mmHg (IQR 300-400) for perfusionists and 300 mmHg (IQR 200-400) for anesthesiologists. Anesthesiologists, therefore, reported more comfort with significantly lower PaO2 values (p < 0.0001), and considered a higher PaO2 value less desirable compared with perfusionists (p < 0.0001). CONCLUSIONS: This survey demonstrated there was wide variation in oxygen administration practices between perfusionists and anesthesiologists. Hyperoxygenation was more common while on CPB.

Association between the level of partial foot amputation and gait: a scoping review with implications for the minimum impairment criteria for wheelchair tennis.

OBJECTIVE: This scoping review examines how different levels and types of partial foot amputation affect gait and explores how these findings may affect the minimal impairment criteria for wheelchair tennis. METHODS: Four databases (PubMed, Embase, CINAHL and SPORTDiscus) were systematically searched in February 2021 for terms related to partial foot amputation and ambulation. The search was updated in February 2022. All study designs investigating gait-related outcomes in individuals with partial foot amputation were included and independently screened by two reviewers based on Arksey and O'Malley's methodological framework and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. RESULTS: Twenty-nine publications with data from 252 participants with partial foot amputation in 25 studies were analysed. Toe amputations were associated with minor gait abnormalities, and great toe amputations caused loss of push-off in a forward and lateral direction. Metatarsophalangeal amputations were associated with loss of stability and decreased gait speed. Ray amputations were associated with decreased gait speed and reduced lower extremity range of motion. Transmetatarsal amputations and more proximal amputations were associated with abnormal gait, substantial loss of power generation across the ankle and impaired mobility. CONCLUSIONS: Partial foot amputation was associated with various gait changes, depending on the type of amputation. Different levels and types of foot amputation are likely to affect tennis performance. We recommend including first ray, transmetatarsal, Chopart and Lisfranc amputations in the minimum impairment criteria, excluding toe amputations (digits two to five), and we are unsure whether to include or exclude great toe, ray (two to five) and metatarsophalangeal amputations. TRIAL REGISTRATION: The protocol of this scoping review was previously registered at the Open Science Framework Registry (https://osf.io/8gh9y) and published.

Intoxication Effects on Impulsive Alcohol Choice in Heavy Drinkers: Correlation With Sensation Seeking and Differential Effects by Commodity.

BACKGROUND: The preference for immediate rewards and high sensation seeking are both potent risk factors for alcohol use disorder (AUD), but how they interact during intoxication is poorly understood. To model decision making linked to AUD risk, we tested heavy drinkers for impulsive choice (delay discounting with alcohol:money or money:money) and behavioral sensation seeking using a novel odor choice task. Laboratory tasks measured actual behavior with real contingencies. Our goals were to determine, in heavy drinkers, (i) alcohol's effects on delay discounting, and (ii) how AUD risk factors relate to delay discounting, and (iii) how delay discounting with alcohol choices compares with strictly monetary choices. METHODS: Thirty-five heavy drinkers (≥2 binges per month; age = 22.8 ± 2.2; 20 male; 5.8 ± 2.3 drinks/drinking day) performed cross-commodity discounting (CCD) of immediate alcohol vs. delayed money, a monetary delay discounting (DD), and behavioral sensation-seeking tasks. CCD and DD were performed while sober and during controlled alcohol infusion targeting 0.08 g/dl. The behavioral sensation-seeking task presented binary choices of odorants varying in intensity and novelty, and the risk of exposure to a malodorant. RESULTS: CCD and DD behaviors were highly correlated across conditions, mean r = 0.64. Alcohol increased delayed reward preference in DD, p = 0.001, but did not alter mean CCD, p > 0.16. However, alcohol-induced changes in CCD correlated with behavioral sensation seeking, such that higher sensation seekers' immediate alcohol preference increased when intoxicated, p = 0.042; self-reported sensation seeking was uncorrelated, ps > 0.08. Behavioral sensation seeking also correlated with "want" alcohol following a priming dose targeting 0.035 g/dl, p = 0.021. CCD and DD did not correlate with self-reported drinking problems or other personality risk traits. CONCLUSIONS: Alcohol increased impulsive alcohol choice in high sensation seekers, suggesting an interaction that may underlie impaired control of drinking, at least in a subset of heavy drinkers-consistent with models highlighting high novelty/sensation-seeking AUD subtypes. Discounting behavior overall appears to be a generalized process, and relatively stable across methods, repeated testing, and intoxication. These findings further support the utility of behavioral tasks in uncovering key behavioral phenotypes in AUD.

Effects of moderate alcohol levels on default mode network connectivity in heavy drinkers.

BACKGROUND: It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self-related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol-induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self-initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol-related changes. METHODS: We investigated resting-state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single-blind crossover design. RESULTS: Intranetwork connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus during acute alcohol exposure. Moreover, follow-up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory internetwork connectivity analyses of the DMN with other resting-state networks showed no significant alcohol-induced changes, but suffered from low statistical power. CONCLUSIONS: Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self-referential processes commonly observed during alcohol intoxication. Future resting-state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN-related connectivity changes are associated with alcohol-induced impairments or craving.

Translating preclinical models of alcohol seeking and consumption into the human laboratory using intravenous alcohol self-administration paradigms.

Preclinical models of alcohol use disorder (AUD) have advanced theoretical, mechanistic, and pharmacological study of the human condition. "Liking" and "wanting" behaviors reflect core processes underlying several models of AUD. However, the development and application of translational models of these preclinical approaches are at an incipient stage. The goal of this study was to examine how intravenous free-access and progressive-ratio, operant-response human alcohol self-administration paradigms can be used as translational human model parallels of preclinical "liking" and "wanting." Participants were 40 adults (mean age = 23.7, SD = 2.0; 45% female) of European descent who reported 12.6 drinking days (SD = 5.2) out of the previous 30 (average = 4.1 drinks per drinking day [SD = 1.7]). Individuals diverged in their alcohol self-administration behavior, such that free-access and progressive-ratio paradigm outcomes were not significantly correlated (p = 0.44). Free-access alcohol seeking was related to enjoying alcohol (p < 0.001), but not craving (p = 0.48), whereas progressive-ratio seeking at similar levels of alcohol exposure was related to craving (p = 0.02), but not enjoying (p = 0.30). Family history of alcoholism, venturesomeness traits, and disinhibition traits were unrelated (ps > 0.70) to preferred level of breath alcohol concentration (BrAC) in the free-access session, a measure of liking alcohol. Family history of alcoholism, disinhibition traits, and recent drinking history were significantly related (ps < 0.05) to alcohol seeking in the progressive-ratio paradigm, a measure of wanting alcohol. We conclude that intravenous alcohol self-administration paradigms show promise in modeling behaviors that characterize and parallel alcohol "liking" and "wanting" in preclinical models. These paradigms provide a translational link between preclinical methods and clinical trials.

Efficacy, Use, and Acceptability of a Web-Based Self-management Intervention Designed to Maximize Sexual Well-being in Men Living With Prostate Cancer: Single-Arm Experimental Study.

BACKGROUND: Sexual dysfunction is a frequent side effect associated with different prostate cancer treatment approaches. It can have a substantial impact on men and their partners and is associated with increased psychological morbidity. Despite this, sexual concerns are often not adequately addressed in routine practice. Evidence-based web-based interventions have the potential to provide ongoing information and sexual well-being support throughout all stages of care. OBJECTIVE: The aim of this study is to examine the efficacy of a web-based self-management intervention designed to maximize sexual well-being in men living with prostate cancer and explore user perspectives on usability and acceptability. METHODS: We used a single-arm study design, and participants were provided with access to the 5-step intervention for a period of 3 months. The intervention content was tailored based on responses to brief screening questions on treatment type, relationship status, and sexual orientation. Efficacy was assessed by using two-tailed, paired sample t tests for comparing the mean differences between pre- and postintervention measurements for exploring the participants' self-reported knowledge and understanding, sexual satisfaction, and comfort in discussing sexual issues. Usability and acceptability were determined based on the program use data and a postintervention survey for exploring perceived usefulness. RESULTS: A total of 109 participants were recruited for this study. Significant postintervention improvements at follow-up were observed in the total scores (out of 20) from the survey (mean 12.23/20 points, SD 2.46 vs mean 13.62/20, SD 2.31; t88=9.570; P=.001) as well as in individual item scores on the extent to which the participants agreed that they had sufficient information to manage the impact that prostate cancer had on their sex life (mean 2.31/4 points, SD 0.86 vs mean 2.57/4, SD 0.85; t88=3.660; P=.001) and had the potential to have a satisfying sex life following treatment (mean 2.38/4 points, SD 0.79 vs mean 3.17/4, SD 0.78; t88=7.643; P=.001). The median number of intervention sessions was 3 (range 1-11), and intervention sessions had a median duration of 22 minutes (range 8-77). Acceptable usability scores were reported, with the highest result observed for the question on the extent to which the intervention provided relevant information. CONCLUSIONS: This study provides evidence on the efficacy of a tailored web-based intervention for maximizing sexual well-being in men living with prostate cancer. The results indicate that the intervention may improve one's self-perceived knowledge and understanding of how to manage sexual issues and increase self-efficacy or the belief that a satisfactory sex life could be achieved following treatment. The findings will be used to refine the intervention content before testing as part of a larger longitudinal study for examining its effectiveness.

To Infuse or Ingest in Human Laboratory Alcohol Research.

Human alcohol laboratory studies use two routes of alcohol administration: ingestion and infusion. The goal of this paper was to compare and contrast these alcohol administration methods. The work summarized in this report was the basis of a 2019 Research Society on Alcoholism Roundtable, "To Ingest or Infuse: A Comparison of Oral and Intravenous Alcohol Administration Methods for Human Alcohol Laboratory Designs." We review the methodological approaches of each and highlight strengths and weaknesses pertaining to different research questions. We summarize methodological considerations to aid researchers in choosing the most appropriate method for their inquiry, considering exposure variability, alcohol expectancy effects, safety, bandwidth, technical skills, documentation of alcohol exposure, experimental variety, ecological validity, and cost. Ingestion of alcohol remains a common and often a preferable, methodological practice in alcohol research. Nonetheless, the main problem with ingestion is that even the most careful calculation of dose and control of dosing procedures yields substantial and uncontrollable variability in the participants' brain exposures to alcohol. Infusion methodologies provide precise exposure control but are technically complex and may be limited in ecological validity. We suggest that alcohol ingestion research may not be the same thing as alcohol exposure research; investigators should be aware of the advantages and disadvantages that the choice between ingestion and infusion of alcohol invokes.

Eye safety implications of high harmonic generation in zinc selenide.

Polycrystalline zinc selenide (ZnSe) has been the subject of many nonlinear optics studies for wavelengths under 4.0 µm including sum/difference frequency generation, harmonic generation, and filamentation. In this report, the conversion efficiency of high harmonic generation (HHG) in ZnSe is quantified for mid-infrared wavelengths ranging from 2.7 µm to 8.0 µm. By increasing the fundamental wavelength, we demonstrate that HHG in thick ZnSe targets is limited by the band gap. The high conversion efficiency of mid-infrared to near-infrared light in ZnSe raises concerns of a nonlinear retinal hazard. We contrast the HHG behavior of ZnSe against the observed harmonic generation of calcium fluoride, BK7, and fused silica over the same wavelengths.

Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration Under Similar Systemic Exposures.

BACKGROUND: Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous (IV) alcohol administration techniques, and any differences attributable to the route employed should be understood. Our objective was to test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by IV administration. METHODS: We conducted a 2-session, within-subject study in 44 young adult, healthy, nondependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an IV alcohol infusion rate profile, precomputed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals' baseline-corrected responses at peak BrAC and at half-peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson-product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response. RESULTS: No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations. CONCLUSIONS: The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar.

The Surprising Reach of FDA Regulation of Cannabis, Even After Descheduling.

As more states legalize cannabis, the push to "deschedule" it from the Controlled Substances Act is gaining momentum. At the same time, the Food and Drug Administration (FDA) recently approved the first conventional drug containing a cannabinoid derived from cannabis­cannabidiol (CBD) for two rare seizure disorders. This would all seem to bode well for proponents of full federal legalization of medical cannabis. But some traditional providers are wary of drug companies pulling medical cannabis into the regular small molecule drug development system. The FDA's focus on precise analytical characterization and on individual active and inactive ingredients may be fundamentally inconsistent with the "entourage effects" theory of medical cannabis. Traditional providers may believe that descheduling cannabis would free them to promote and distribute their products free of federal intervention, both locally and nationally. Other producers appear to assume that descheduling would facilitate a robust market in cannabis-based edibles and dietary supplements. In fact, neither of these things is true. If cannabis were descheduled, the FDA's complex and comprehensive regulatory framework governing foods, drugs, and dietary supplements would preclude much of this anticipated commerce. For example, any medical claims about cannabis would require the seller to complete the rigorous new drug approval process, the cost of which will be prohibitive for most current traditional providers. Likely also unexpected to some, there is no pathway forward for conventional foods containing cannabis constituents, with the (probably exclusive) exception of certain hemp seed ingredients, if those foods cross state lines. And it will certainly come as a shock to many that federal law already prohibits the sale of dietary supplements containing CBD--including those already on the market as well as those made from "hemp," which has recently been descheduled under the 2018 Farm Bill. This Article describes in detail the surprising reach of the FDA and then outlines three modest, but legal, pathways forward for cannabis-based products in a world where cannabis has been descheduled.

Z-scan measurements of water from 1150 to 1400 nm.

Understanding the nonlinear properties of water is essential for laser surgery applications, as well as understanding supercontinuum generation in water. Unfortunately, the nonlinear properties of water for wavelengths longer than 1064 nm are poorly understood. We extend the application of the Z-scan technique in water to determine its nonlinear refractive index (n2) and nonlinear absorption (ß) for wavelengths in the 1150-1400 nm range, where linear absorption is also significant. We observe the wavelength-dependent variation of the nonlinear properties of water around the water absorption band.

Sex Differences in Motivation to Self-Administer Alcohol After 2 Weeks of Abstinence in Young-Adult Heavy Drinkers.

BACKGROUND: Studies in animal models document that forced abstinence from usual consumption of alcohol changes subsequent seeking and consumption, with increases or decreases depending on the species, duration of abstinence, number of deprivations, and sex. Human laboratory-based alcohol deprivation studies are rare. METHODS: We conducted a 2-session, within-participant, randomized-order comparison of intravenous, progressive ratio, alcohol self-administration during 2.5 hours of progressive work for alcohol and/or vehicle; once while the participants pursued their usual drinking habits and once after 2 weeks of closely monitored, voluntary outpatient abstinence from alcohol. The schedule of work for rewards and the incremental increases in breath alcohol concentration following completion of an alcohol work-set were identical across participants. Fifty young-adult (27 men), heavy-drinking participants completed both sessions. Our primary hypothesis was that motivation to work for alcohol after 2 weeks of abstinence would be greater in participants with a weekly binge pattern of drinking, compared to those who regularly drink heavily, and we intended to explore associations with biological family history of alcoholism and sex. RESULTS: We detected no change in work for alcohol associated with recent drinking history. However, females, on average, increased their work for alcohol upon resumption after 2 weeks of abstinence (mean ± SEM = +16.3 ± 9.6%), while males decreased that work (-24.8 ± 13.8%). The sex difference was substantial and significant (p < 0.03), with a medium effect size (Cohen's d = 0.63). CONCLUSIONS: We believe a more comprehensive study of mechanisms underlying the sex differences in the human postabstinence response is warranted.

Exposure-Response Relationships during Free-Access Intravenous Alcohol Self-Administration in Nondependent Drinkers: Influence of Alcohol Expectancies and Impulsivity.

Background: Self-administration is a hallmark of all addictive drugs, including alcohol. Human laboratory models of alcohol self-administration have characterized alcohol-seeking behavior and served as surrogate measures of the effectiveness of pharmacotherapies for alcohol use disorders. Intravenous alcohol self-administration is a novel method that assesses alcohol exposure driven primarily by the pharmacological response to alcohol and may have utility in characterizing unique behavioral and personality correlates of alcohol-seeking and consumption. Methods: This study examined exposure-response relationships for i.v. alcohol self-administration, and the influence of impulsivity and alcohol expectancy, in healthy, nondependent drinkers (n=112). Participants underwent a 2.5-hour free-access i.v. alcohol self-administration session using the Computerized Alcohol Infusion System. Serial subjective response measures included the Drug Effects Questionnaire and Alcohol Urge Questionnaire. To characterize the motivational aspects of alcohol consumption prior to potential acute adaptation, the number of self-infusions in the first 30 minutes of the free-access session was used to classify participants as low- and high-responders. Results: High-responders showed greater subjective responses during i.v. alcohol self-administration compared with low responders, reflecting robust exposure-driven hedonic responses to alcohol. High-responders also reported heavier drinking patterns and lower scores for negative alcohol expectancies on the Alcohol Effects Questionnaire. High-responders also showed higher measures of impulsivity on a delayed discounting task, supporting previous work associating impulsivity with greater alcohol use and problems. Conclusions: These findings indicate that early-phase measures of free-access i.v. alcohol self-administration are particularly sensitive to the rewarding and motivational properties of alcohol and may provide a unique phenotypic marker of alcohol-seeking behavior.

Neuropsychiatric Symptoms in Alzheimer Disease, Vascular Dementia, and Mixed Dementia.

BACKGROUND/AIMS: Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD) and vascular dementia (VaD), and are distressful to patients and caregivers. NPS are likely related to the underlying pathology. Previous studies suggest that frontal lobe lesions and vascular changes such as white matter hyperintensities (WMH) have a significant association with specific NPS. The current study aimed to compare NPS in patients with AD, VaD, and mixed AD/VaD, and to evaluate the differences in the prevalence of NPS in relation to frontal WMH volume. METHODS: In total, 180 patients with NPS and MRI data (92 probable AD, 51%; 34 probable VaD, 19%; and 54 probable mixed AD/VaD, 30%) were included in the study. Regression analyses were performed to determine the relationships between NPS prevalence and diagnosis, and between NPS and frontal WMH. RESULTS: VaD patients had significantly more agitation (p < 0.05; 40 vs. 14%) and sleep disturbances (p < 0.05; 57 vs. 32%) than AD patients, and significantly more depression (p < 0.05; 48 vs. 20%) and aberrant motor behaviors (p < 0.05; 31 vs. 13%) than mixed AD/VaD patients. AD patients with delusions had significantly greater right frontal WMH volumes than those without (p < 0.05; delusions 1/0 = 314.8/112.6 mm3). CONCLUSION: Differences in NPS prevalence are likely related to the underlying pathology and warrant further study as they have implications for treatment.