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Robo advising is an emerging business model that aims to popularize investment advisory services by automating all the activities involved. The robo-advisor (RA) stream of research is relatively new, yet it has started to attract the attention of numerous scholars. This manuscript aims to analyze the academic literature on RA based on its impact on the different phases that make up the investment advice process. Our aim is to investigate which phases of the investment advice service prove of most interest to scholars. Since selecting relevant and precise keywords increases the visibility, accessibility, and indexing of a research paper, we explore the RA research landscape using keyword relational analysis. We analyze metadata from 195 identified papers combining the Scopus and Web of Science databases until May 2022. The analysis unfolds in two parts. First, we examine the relationships and associations of keywords in titles, abstracts, and author keywords to extract knowledge patterns from said associations. As a novelty, a specific dictionary of RA-synonyms formed by 19 disjoint families of concepts is obtained. The second part presents the RA's conceptual and relational structure. For this, five clusters are determined to identify and organize those studies dealing with similar topics. The results of our study suggest that research is more interested in aspects related to the human factor, namely, those with phases requiring more direct contact with the client or investor. The most relevant research interests include the automation of client profiling functions and client response to the latter automation.

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BACKGROUND: The implementation of population screening for prostate cancer has increased the number of patients with biochemical suspicion. Prediction models may reduce the number of unnecessary biopsies by identifying patients who benefit the most from them. Our aim is to develop a prediction model that is easily applicable in patients with suspicion of prostate cancer in the urology clinic setting to avoid unnecessary biopsies. METHODS: We developed prediction models based on risk scores for the detection of prostate cancer and clinically significant prostate cancer using the TRIPOD guidelines. For this, we conducted an observational and retrospective review of computerised medical records of 204 patients undergoing prostate fusion biopsy between 2018 and 2021. We also reviewed other prediction models for prostate cancer including radiological parameters and targeted sampling of suspicious lesions. RESULTS: A total of 204 patients underwent a biopsy, 138 were diagnosed of prostate cancer, and from them, 60 of clinically significant prostate cancer. Multivariate regression and random forest analysis were performed. Age, PSA density, diameter of the index lesions and PIRADS score on MRI were identified as predictors with an Area Under the Curve ranging between 0.71 and 0.80 and acceptable calibration results. Risk scores may avoid between 21.7% and 48.1% of biopsies. CONCLUSION: Our prediction models are characterised by ease of use and may reduce unnecessary biopsies with satisfactory discrimination and calibration results while bringing benefits to the healthcare system and patients.

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Uncertainty in ecosystem restoration can be mitigated by information on drivers of variability in restoration outcomes, especially through experimental study. In southeastern USA pine savannas, efforts to restore the perennial bunchgrass wiregrass (Aristida beyrichiana) often achieve variable outcomes in the first year. Although ecotypic differentiation and competition with other native vegetation are known to influence wiregrass seedling establishment and growth, to our knowledge, no studies have examined interactions between these drivers. We experimentally quantified individual and interactive effects of competition, seed source, and soil type on wiregrass density, size, and flowering culm production in the field. We sowed seeds from dry and wet sites reciprocally into dry and wet soils and weeded half of the plots. We found that competition removal resulted in significantly larger plants and a greater proportion of flowering plants with more culms on average, regardless of seed source or soil type. Seeds sourced from a wet site resulted in more plants per plot than seeds from a dry site, which might have been influenced by the greater number of filled seeds from the wet site. After seedlings become established, competition contributes to variation in growth and reproduction. Although competition removal could help start wiregrass populations, the necessity of mitigation depends on fire management needs.

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There is high comorbidity of opioid use disorder (OUD) and chronic pain (CP), which is often addressed by prescribing buprenorphine (BUP). While BUP is effective in preventing overdose, it does not address the psychological aspects of OUD and CP comorbidity and treatment retention rates are as low as 50%. The Virtual Opioid use disorder Integrated Chronic Pain Treatment (VOICE) study (NCT05039554) is a novel effectiveness-implementation trial to test a 12-week virtual group Acceptance and Commitment Therapy (ACT) protocol and a care management smartphone application (app; Valera Health) on pain and opioid use in patients with OUD and CP receiving BUP. Using a 2 × 2 factorial design, participants (expected N = 280) are randomized into: ACT, Valera app, ACT + Valera, or Treatment as Usual arm. This study is taking place in the Bronx, NY, a racially/ethnically diverse community that faces numerous socioeconomic stressors and is one of the nation's epicenters of the opioid epidemic. We created a culturally responsive ACT group protocol, and Valera psychoeducational material. Outcome measures include NIH HEAL Common Data Elements and ACT and Valera-specific measures. We are conducting a novel 2 × 2 trial investigating augmenting BUP treatment with ACT and Valera, with the goal that improved mental health and access to care will result in decreased and opioid use and pain interference.

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INTRODUCTION: We used clinical assessment records to provide pan-Canadian estimates of the prevalence and risks associated with recent (within the last 3 days) critical wandering among home care clients, with and without dementia. METHODS: The data source is interRAI Home Care (interRAI HC) assessments. The population was all long-stay home care clients assessed between 2004 and 2021 in seven Canadian provinces and territories (N = 1,598,191). We tested associations between wandering and cognition and dementia diagnoses using chi-square tests and logistic regression. RESULTS: Approximately 84% of the sample was over the age of 65. The overall rate of recent wandering was 3.0%. Dementia diagnosis was strongly associated with two to four times higher rates in the prevalence of recent critical wandering. DISCUSSION: InterRAI HC offers insights into the wandering risk of home care clients. This information should be used to manage risks in the community and could be shared with first responders. HIGHLIGHTS: In all the study regions combined, the rate of recent wandering is 3.0%. Dementia was associated with 18 times greater prevalence of recent critical wandering. Home care clients at risk of wandering have complex clinical profiles that pose important risks for their health and well-being. Collaboration and information sharing between search and rescue and health professions is essential for managing risks related to critical wandering.

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INTRODUCTION: Despite its crucial role in Epidermal Growth Factor Receptor (EGFR) activation, and the resulting impact on the health-disease process, epidermal growth factor (EGF) is an underexplored molecule in relation to how its serum concentrations relate to other analytes and clinical variables in pathological contexts. OBJECTIVE: To clarify the possible correlation between EGF and clinical and analytical variables in the context of COVID-19. METHODS: Cross-sectional observational and analytical study, in patients with virological and clinical diagnosis of COVID-19, selected by simple random sampling, admitted between August and September 2021. UMELISA-EGF commercial kits were used. RESULTS: Differences in overall EGF values were observed between groups (566.04 vs. 910.53 pg/ml, p = .0430). In COVID-19 patients, no notable correlations were observed for neutrophil, platelet, triglyceride or liver enzyme values (p > .05). Significant correlations were observed with the neutrophil-lymphocyte indicator (r = 0.4711, p = .0128) as well as with the platelet-lymphocyte index (r = 0.4553, p = .0155). Statistical results of multivariate regression analysis suggest NLR (ß = .2232, p = .0353) and PLR (ß = .2117, p = .0411) are predictors of inflammation in patients with COVID-19. CONCLUSIONS: Serum EGF concentrations in COVID-19 correlate positively with prognostic inflammatory markers of severity and could presumably act as an independent risk factor for the development of inflammation in response to new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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BACKGROUND: There is a lack of integrated treatment for chronic pain and opioid use disorder (OUD). Yoga and physical therapy (PT) may improve pain and physical function of people living with (PLW) chronic low back pain (CLBP) and may also reduce opioid craving and use, but PLW with OUD face barriers to accessing these interventions. We hypothesize that compared to treatment as usual (TAU), providing yoga and PT onsite at opioid treatment programs (OTPs) will be effective at improving pain, opioid use, and quality of life among people with CLBP and OUD, and will be cost-effective. METHODS: In this hybrid type-1 effectiveness-implementation study, we will randomly assign 345 PLW CLBP and OUD from OTPs in the Bronx, NY, to 12 weeks of onsite yoga, onsite PT, or TAU. Primary outcomes are pain intensity, opioid use, and cost-effectiveness. Secondary outcomes include physical function and overall well-being. DISCUSSION: This trial tests an innovative, patient-centered approach to combined management for pain and OUD in real-world settings. We rigorously examine the efficacy of yoga and PT onsite at OTPs as nonpharmacologic, cost-effective treatments among people with CLBP and OUD who face barriers to integrated care.

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This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNPs), varying in size, against clinical isolates of Mycobacterium tuberculosis (MTB), E. coli, S. aureus, E. faecalis, and C. albicans, as well as the antimicrobial effects of aqueous extracts and lyophilized powders of Allium (garlic) species. CNPs were synthesized through ionotropic gelation and characterized by Z potential, hydrodynamic diameter (dynamic light scattering, DLS), and SEM. Aqueous garlic extracts were prepared via decoction. We assessed antimicrobial activity using disk diffusion and broth microdilution methods; in addition, a modified agar proportion method in blood agar was used for antimicrobial activity against MTB. CNPs inhibited MTB growth at 300 µg for 116.6 nm particles and 400 µg for 364.4 nm particles. The highest antimicrobial activity was observed against E. faecalis with nanoparticles between 200 and 280 nm. Allium sativum extract produced inhibition for C. albicans at 100 µg. The results indicate that CNPs possess significant antimicrobial properties against a range of pathogens, including MTB, at high concentrations. On the other hand, aqueous Allium sativum extracts exhibited antimicrobial activity. Nonetheless, due to their instability in solution, the use of lyophilized Allium sativum powder is preferable.

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Workplace violence (WPV) is a commonly reported occupational hazard in healthcare and its prevalence is increasing. WPV occurs in all types of practice settings, but little is known about WPV in primary care settings in the United States (US). Because primary care practice settings differ from the inpatient settings, further examination of WPV in primary care is warranted. Our objective was to summarize the available literature highlight important gaps. We conducted a search using Pubmed and OVID for US studies of WPV in US-based adult primary care practices. Studies including only pediatric populations were excluded. Due to the lack of available literature conducted in US primary care settings, we expanded our search to include international studies. We identified 70 studies of which 5 were US based. Due to the lack of significant numbers of US-based studies, we opted to conduct a narrative review of all available studies. The evidence shows that WPV is a common occurrence in primary care settings in many countries and that the majority of primary care clinicians have experienced at least some form of non-physical violence in their careers. Most of the studies conducted were cross-sectional in design and reported on both non-physical and physical forms of WPV. There was not a consistent trend between genders in experiencing the major forms of WPV, but women were consistently more likely to be subjected to sexual harassment. Potential root causes for WPV could generally be categorized as patient-level, clinician-level, clinical encounter specific, and operational root causes. While most WPV was found to be non-physical, it still had significant emotional and job-related impacts on clinicians. These troubling results highlight the need for further studies to be conducted in the US.

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The ongoing transition within the Chinese economy assumes a pivotal role in shaping the landscape of the cultural and creative industries (CCI). Renowned for its environmentally sustainable attributes, coupled with high productivity, CCI has garnered considerable attention across diverse societal strata. This study endeavors to delineate the determinants influencing the developmental trajectory of CCI, with a focal point on City A as the primary subject of investigation, juxtaposed against Cities G, D, B, H, and X for comparative analysis, leveraging developmental data from the year 2021. Initially, the study elucidates the conceptual framework underpinning CCI and its intrinsic significance in facilitating urban metamorphosis. Subsequently, the positive impact of CCI through deep learning and information management technology is emphasized, and a cultural and creative recommendation model based on LSTM algorithm is constructed. Through performance evaluation, the recommendation accuracy for cultural and creative projects reaches 94.74 %. A robust developmental assessment model for CCI is then constructed via meticulous factor analysis of pertinent influencers. Employing factor analysis techniques, the study identifies two primary determinants exerting sway over CCI development: sustainable profitability factors and cultural influence factors. Noteworthy among the factors influencing CCI development within City A are fixed asset investment, cultural industry financing, the proliferation of university-based research institutions, and per capita cultural expenditure by residents. Of these, fixed asset investment, cultural industry financing, and the density of university research institutions prominently impinge upon sustainable profitability, with a discernible impact weight of 0.738 in the evaluative framework of CCI development, thus significantly shaping its trajectory. Moreover, consumer psychological factors, particularly market consumption patterns, are observed to exert a discernible influence on CCI evolution. This study augurs fresh insights into the realm of CCI development, infusing it with renewed vigor and vitality. Moreover, it underscores the inherent interdependence and positive correlation among the various research factors, offering novel perspectives and methodologies germane to the advancement of urban CCI.

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Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan-Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1-1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions.

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BACKGROUND: With the population aging, the number of people living with dementia is expected to rise, which, in turn, is expected to lead to an increase in the prevalence of missing incidents due to critical wandering. However, the estimated prevalence of missing incidents due to dementia is inconclusive in some jurisdictions and overlooked in others. OBJECTIVE: The aims of the study were to examine (1) the demographic, psychopathological, and environmental antecedents to missing incidents due to critical wandering among older adult MedicAlert Foundation Canada (hereinafter MedicAlert) subscribers; and (2) the characteristics and outcomes of the missing incidents. METHODS: This study used a retrospective descriptive design. The sample included 434 older adult MedicAlert subscribers involved in 560 missing incidents between January 2015 and July 2021. RESULTS: The sample was overrepresented by White older adults (329/425, 77.4%). MedicAlert subscribers reported missing were mostly female older adults (230/431, 53.4%), living in urban areas with at least 1 family member (277/433, 63.8%). Most of the MedicAlert subscribers (345/434, 79.5%) self-reported living with dementia. MedicAlert subscribers went missing most frequently from their private homes in the community (96/143, 67.1%), traveling on foot (248/270, 91.9%) and public transport (12/270, 4.4%), during the afternoon (262/560, 46.8%) and evening (174/560, 31.1%). Most were located by first responders (232/486, 47.7%) or Good Samaritans (224/486, 46.1%). Of the 560 missing incidents, 126 (22.5%) were repeated missing incidents. The mean time between missing incidents was 11 (SD 10.8) months. Finally, the majority of MedicAlert subscribers were returned home safely (453/500, 90.6%); and reports of harm, injuries (46/500, 9.2%), and death (1/500, 0.2%) were very low. CONCLUSIONS: This study provides the prevalence of missing incidents from 1 database source. The low frequency of missing incidents may not represent populations that are not White. Despite the low number of missing incidents, the 0.2% (1/500) of cases resulting in injuries or death are devastating experiences that may be mitigated through prevention strategies.

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OBJECTIVE: To evaluate patients' satisfaction with opioid versus opioid-sparing postoperative analgesia in patients undergoing outpatient head and neck surgery. STUDY DESIGN: Prospective randomized trial. SETTING: Tertiary care academic hospital. METHODS: Adult patients undergoing outpatient head and neck surgery were randomly assigned to 1 of 3 analgesic regimens. First- and second-line medications were the following by group (1) Hydrocodone-acetaminophen with ibuprofen, (2) ibuprofen with hydrocodone-acetaminophen, and (3) ibuprofen with acetaminophen. Preoperative counseling was provided to patients regarding expected pain and proper medication use. Postoperative questionnaires were administered to assess satisfaction. RESULTS: One hundred three patients were enrolled in the study (mean age, 56.5 years; women, 75 [73%]). The mean satisfaction score with the pain regimen assigned was similar between the 3 groups (scale 0-10, [7.7, 8.3, 8.5, P = .46]). A similar percentage of patients in each group reported that surgery was more painful than anticipated (25%, 32%, 26%, P = .978), and a similar percentage of patients reported willingness to utilize the same analgesic regimen following future surgeries (75%, 83%, 76%, P = .682). Additional questions evaluating the side effect profile, maximum and minimum pain scores, and difficulty of recovery were not statistically different between the 3 groups. CONCLUSION: In the postoperative population for outpatient head and neck surgeries, there was no significant difference in patient satisfaction and pain control between the opioid and nonopioid arms. Providers should discuss opioid-sparing regimens preoperatively with patients and describe them as effective in providing adequate pain control without a significant impact on patient's perception of care.

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BACKGROUND: Critical wandering occurs when an individual living with dementia leaves a location and is unaware of place or time. Critical wandering incidents are expected to increase with the growing prevalence of persons living with dementia worldwide. We investigated the association between demographic, psychopathological, and environmental factors and a history of critical wandering among Medic-Alert subscribers, both with and without dementia. METHODS: Our retrospective study included data of 25,785 Canadian Medic-Alert subscribers who were aged 40 years or older. We used multivariable logistic regression analysis to examine the associations between a history of critical wandering and dementia status as psychopathological independent variable, controlled by demographic (age, ethnic background, sex at birth, Canadian languages spoken) and environmental (living arrangement, population density) factors. RESULTS: The overall study sample comprised of mainly older adults (77.4%). Medic-Alert subscribers who were older, male sex at birth, living with dementia, of a minority ethnic group and who did not have proficiency in an official Canadian language had a higher likelihood of a history of critical wandering. Residing in an urban environment, in an institution or with a family member, were environmental factors associated with a higher likelihood of a history of critical wandering. CONCLUSIONS: People living with dementia experience a higher likelihood of a history of critical wandering compared to those without dementia. Medic-Alert and similar organizations can develop algorithms based on the associated factors that can be used to flag risks of critical wandering. This can inform preventative strategies at the individual and community levels.

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BACKGROUND: Adults living with HIV have disproportionately high chronic pain, prescription opioid use, history of substance use, and incarceration. While incarceration can have long-lasting health impacts, prior studies have not examined whether distant (>1 year prior) incarceration is associated with opioid use for chronic pain, or with opioid misuse or opioid use disorder among people living with HIV and chronic pain. METHODS: We conducted a secondary analysis of a prospective cohort study of adults living with HIV and chronic pain. The independent variables were any distant incarceration and drug-related distant incarceration (both dichotomous). Dependent variables were current long-term opioid therapy, current opioid misuse, and current opioid use disorder. A series of multivariate logistic regression models were conducted, adjusting for covariates. RESULTS: In a cohort of 148 participants, neither distant incarceration nor drug-related incarceration history were associated with current long-term opioid therapy. Distant incarceration was associated with current opioid misuse (AOR 3.28; 95% CI: 1.41-7.61) and current opioid use disorder (AOR 4.40; 95% CI: 1.54-12.56). Drug-related incarceration history was also associated with current opioid misuse (AOR 4.31; 95% CI: 1.53-12.17) and current opioid use disorder (AOR 7.28; 95% CI: 2.06-25.71). CONCLUSIONS: The positive associations of distant incarceration with current opioid misuse and current opioid use disorder could indicate a persistent relationship between incarceration and substance use in people living with HIV and chronic pain. Additional research on opioid use among formerly incarcerated individuals in chronic pain treatment is needed.

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Mexican President Andrés Manuel López Obrador's historic election victory in 2018 marked a sharp break from past decades of neoliberal socioeconomic policies. López Obrador campaigned on the promise of deep reform, with health care high on his agenda. The public health care sector had been decimated by decades of budget cuts, eroding workers' morale and patients' confidence, and crippling all aspects of the system. This article looks back to the creation of the nation's public health care system in the early twentieth century during the administration of President Lázaro Cárdenas (1934-1940). This "universal" system was designed to implement a central social justice goal of the Mexican Revolution of health care for all. The program rested on two pillars: providing care to the nation's vast, impoverished rural population and actively engaging communities in their own health care. Our objective is to critically assess the two presidents' health care initiatives within the distinct historical contexts of their administrations.

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Worldwide, over 55-million people have dementia, and the number will triple by 2050. Persons living with dementia are exposed to risks secondary to cognitive challenges including getting lost. The adverse outcomes of going missing include injuries, death, and premature institutionalization. In this scoping review, we investigate risk factors associated with going missing among persons living with dementia. We searched and screened studies from four electronic databases (Medline, CINAHL, Embase, and Scopus), and extracted relevant data. We identified 3,376 articles, of which 73 met the inclusion criteria. Most studies used quantitative research methods. We identified 27 variables grouped into three risk factor domains: (a) demographics and personal characteristics, (b) health conditions and symptoms, and (c) environmental and contextual antecedents. Identification of risk factors associated with getting lost helps to anticipate missing incidents. Risk factors can be paired with proactive strategies to prevent incidents and inform policies to create safer communities.

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OBJECTIVE: To estimate the incidence rate of tuberculosis (TB) in the Highlands (Tsotsil-Tseltal) region of Chiapas and to analyze sociodemographic factors that might influence the success of anti-TB treatment from the period of January 2019 to June 2022. METHODS: Retrospective study in which the TB databases of the National Epidemiological Surveillance System (SINAVE) were analyzed. TB incidence rates were calculated based on the number of registered TB cases and estimated annual populations. The success-failure of anti-TB treatment was analyzed according to sociodemographic indicators, degree of concentration of indigenous population of the municipality of residence and admission to SINAVE. RESULTS: Two hundred thirty-three cases were analyzed. The variables associated to a lower success rate of treatment against TB were: living in a municipality with high-very high concentration of indigenous population, being indigenous, having a primary school education or lower, and agricultural occupation. The number of TB diagnosed from 2020-2022 and the incidence rates from 2020-2021 decreased significantly compared to 2019. CONCLUSIONS: It is necessary to strengthen the follow-up of TB cases in the region, mainly in areas with high-very high indigenous concentration, in people with low levels of education and engaged in agricultural work.

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OBJECTIVES: In a longitudinal cohort of patients with HIV and chronic pain, we sought to (1) identify trajectories of opioid misuse and opioid use disorder (OUD) symptoms, and to (2) determine whether prescription opioid dose was associated with symptom trajectories. METHODS: We leveraged an existing 12-month longitudinal observational study, Project PIMENTO, of persons living with HIV and chronic pain who received care at a hospital system in the Bronx, New York. A quota sampling strategy was used to ensure variability of prescribed opioid use in the recruited sample. Research interviews occurred quarterly and assessed opioid behaviors and criteria for OUD. To describe symptom trajectories, we conducted 2 separate longitudinal latent class analyses to group participants into (1) opioid misuse and (2) OUD trajectories. Finally, we used multinomial logistic regression models to examine the relationship between baseline prescription opioid dose and symptom trajectories. RESULTS: Of 148 total participants, at baseline 63 (42.6%) had an active opioid prescription, 69 (46.6%) met the criteria for current opioid misuse, and 44 (29.7%) met the criteria for current OUD. We found 3 opioid misuse and 3 OUD symptom trajectories, none of which showed worsened symptoms over time. In addition, we found that higher prescription opioid dose at baseline was associated with a greater OUD symptom trajectory. CONCLUSIONS: Opioid misuse and OUD were common but stable or decreasing over time. Although these results are reassuring, our findings also support prior studies that high-dose opioid therapy is associated with greater OUD symptoms.

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According to the opponent-process theory of drug addiction, the intake of an addictive substance initiates two processes: a rapid primary process that results in the drug's rewarding effects, and a slower opponent process that leads to the aversive motivational state of drug aftereffects. This aversive state is integral in the desire, pursuit, and maintenance of drug use, potentially leading to dependence and addiction. However, current observational and experimental evidence suggests that the administration of a 5-hydroxytryptamine receptors-type 2A (5-HT2A) agonist, while capable of inducing a positive mental state in humans, may not generate the behavioral patterns typically associated with drugs of abuse. In this study, we found that administering the 5-HT2A agonist 4-Acetoxy-N,N-dimethyltryptamine fumarate (4-AcO-DMT) did not result in place preference in male rats compared to control saline administration 24 h later, after the drug has been cleared from the organism. However, in a modified place preference test where only the acute motivational effects of the drug were evaluated (excluding withdrawal), 4-AcO-DMT was found to be rewarding. Furthermore, in another modified place preference test where only the motivational effects of drug withdrawal were evaluated (excluding the acute effects of drug administration), the 24-hour aftereffect of 5-HT2A agonist administration also resulted in a robust place preference. Therefore, while 4-AcO-DMT administration was able to induce place preference, its 24-hour aftereffect also produced a strong reward. In the counterbalanced test, this reward from the aftereffect effectively overshadowed its acute rewarding properties, which could potentially create a false impression that 4-AcO-DMT lacks motivational properties. This suggests that 5-HT2A agonist administration follows a different dynamic than that proposed by the opponent-process theory of motivation and implies that the administration of 5-HT2A agonists may lead to behavioral patterns less typical of drugs associated with addiction.

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