Multiscale Process Intensification of Waste Valorization Reactions.

ConspectusThe central theme of this Account is the development of intensified and sustainable chemical processes for the sequestration of CO2 in synergism with the utilization of wastes of industrial, urban, and agricultural origins. A challenge when working with solid waste-fluid reactions is that mass transfer limitations across solid-liquid, solid-gas, and gas-liquid interfaces and unfavorable thermodynamics lead to slow reaction rates, incomplete reaction conversions, high energy expenditure and processing costs, and inadequate product properties. The traditional macroscale approaches to overcoming slurry reaction limitations can be effective; however, they come at a cost to the environment. In the treatment or valorization of low-grade and waste resources, such conventional approaches are often unfeasible on an industrial scale. Sustainable solutions are thus needed.In the last six years, we have been exploring and developing approaches to overcoming reaction rate limitations of slurry reactions of environmental relevance by concurrently applying process intensification strategies and multiscale engineering approaches. The scientific approach has relied on laboratory-scale experiments to test and refine the devised multiscale process intensification strategies, with thermodynamic and computational modeling work supporting the experimental work and with advanced characterization techniques being used to elucidate reaction and transport mechanisms and aid the development of nanoscale reaction models and micro- and macroscale process models. The research streams, associated with the four key references, discussed next are (a) brine carbonation; (b) mineral carbonation and enhanced weathering; (c) process intensification and integration; and (d) characterization techniques.Within the four research streams, a number of mineral carbonation processes have been investigated and can be classified as (i) ambient weathering and carbonation; (ii) gas-(wet) solid accelerated carbonation; (iii) aqueous accelerated carbonation; (iv) supercritical accelerated carbonation; and (v) CO2 mineralization from brine. In some cases, the research was aimed at producing valuable products with reduced environmental risk or a reduced carbon footprint, such as an organomineral fertilizer and zeolites. In other cases, the aim was to assess the reactivity of minerals to match the right feedstock with the right carbonation process, in view of maximizing net carbon sequestration. There were also cases where the carbonation process was reimagined by the use of innovative reaction conditions, reactors, and reagents. The experience with accelerated weathering and carbonation in engineered processes has been translated into the field of enhanced rock weathering (ERW) in agriculture, where the multidisciplinary approach used has served to advance ERW science and technology in ways that have had a resounding effect on recent commercial deployment.The completed research serves to encourage the adoption of process intensification technologies in place of conventional processes, in industry and among the research community, and to catalyze the development of the types of sustainable processes required by the chemical, metallurgical, and minerals industries (which are critical to the green transition) to reduce their environmental impact and carbon emissions. Moreover, the multiscale process intensification approaches developed may also be extended to other industrial, urban, and agricultural processes where the reduction of energy intensity, carbon intensity, and environmental footprint could be achieved.

Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST). METHODS: Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs. RESULTS: The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo. CONCLUSIONS: Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.

Effects of a Single Dose of Ayahuasca in College Students With Harmful Alcohol Use: A Single-blind, Feasibility, Proof-of-Concept Trial.

BACKGROUND: Ayahuasca is a South American plant hallucinogen rich in the psychedelic N,N-dimethyltryptamine and ß-carbolines (mainly harmine). Preclinical and observational studies suggest that ayahuasca exerts beneficial effects in substance use disorders, but these potentials were never assessed in a clinical trial. METHODS: Single-center, single-blind, feasibility, proof-of-concept study, assessing the effects of one dose of ayahuasca accompanied by psychological support (without psychotherapy) on the drinking patterns (primary variable) of 11 college students with harmful alcohol consumption. Secondary variables included safety and tolerability, craving, personality, anxiety, impulsivity, self-esteem, and social cognition. FINDINGS: Ayahuasca was well tolerated (no serious adverse reactions were observed), while producing significant psychoactive effects. Significant reductions in days per week of alcohol consumption were found between weeks 2 and 3 (2.90 ± 0.28 vs 2.09 ± 0.41; P < 0.05, uncorrected), which were not statistically significant after Bonferroni correction. There were no statistically significant effects for other variables, except for a significant reduction in reaction time in an empathy task. CONCLUSIONS: A significant reduction in days of alcohol consumption was observed 2-3 weeks after ayahuasca intake, but this effect did not survive after Bonferroni correction. The lack of significant effects in alcohol use and other variables may be related to the small sample size and mild/moderate alcohol use at baseline. The present study shows the feasibility of our protocol, paving the way for future larger, controlled studies.

Long-term ayahuasca use is associated with preserved global cognitive function and improved memory: a cross-sectional study with ritual users.

Although several studies have been conducted to elucidate the relationship between psychedelic consumption and cognition, few have focused on understanding the long-term use influence of these substances on these variables, especially in ritualistic contexts.  To verify the influence of ritualistic ayahuasca consumption on the cognition of experienced ayahuasca religious users (> 20 years) and beginners (< 3 years), which participated in rituals of the Centro Luz Divina (CLD), a Santo Daime church in Brazil. Observational, descriptive, and cross-sectional study was carried out in which 48 people participated divided into three groups: (a) experienced ayahuasca users (n = 16), (b) beginner ayahuasca users (n = 16) and (c) control group (n = 16). All groups were matched by sex, age, and education and contained 8 women and 8 men. Cognition was assessed with the WASI (intelligence quotient), Digit Span (verbal working memory), Corsi Block-Tapping Task (visuospatial-related and working memory), Rey-Osterrieth Complex Figure test (visual perception, immediate memory), and Wisconsin Card Sorting and Five Digit Test (executive functions). Groups were homogenous in terms of sociodemographic characteristics, with participants presenting average intellectual performance. There was no evidence of cognitive decline amongst ayahuasca users. The experienced group showed higher scores compared to the less experienced group in the Digit Span and Corsi Block-Tapping tasks, which assess working verbal and visuospatial memories respectively. We confirmed the botanical identities of Psychotria viridis and Banisteriopsis caapi and the presence of the alkaloids both in the plants and in the brew. Short and long-term ayahuasca consumption does not seem to alter human cognition, while long-term use seems to be associated with improvements in aspects of working memory when compared with short-term use.

Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein.

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.

Effect of Preoperative Bilateral Ultrasound-guided Quadratus Lumborum Nerve Block on Quality of Recovery after Minimally Invasive Hysterectomy in an Enhanced Recovery after Surgery (ERAS) Setting.

STUDY OBJECTIVE: To assess the effect of preoperative bilateral ultrasound-guided quadratus lumborum nerve block (QLB) on quality of recovery after minimally invasive hysterectomy, in an enhanced recovery after surgery setting. DESIGN: Randomized, controlled, double-blinded trial (Canadian Task Force level I). SETTING: University-affiliated tertiary medical center. PATIENTS: All women undergoing an elective robotic or laparoscopic hysterectomy. Women with chronic pain, chronic anticoagulation, and body mass index >50 kg/m2 were excluded. INTERVENTION: Patients were randomized with a 1:1 allocation, to one of the following 2 arms, and stratified based on robotic versus laparoscopic approach. 1. QLB: QLB (bupivacaine) + sham local trocar sites infiltration (normal saline) 2. Local infiltration: sham QLB (normal saline) + local infiltration (bupivacaine) MEASUREMENTS AND MAIN RESULTS: The primary outcome was defined as the quality of recovery score based on the validated questionnaire Quality of Recovery, completed 24 hours postoperatively. Secondary outcomes included dynamic pain scores, accumulated opioid consumption up to 24 hours, postoperative nausea and vomiting, surgical complications, length of hospital stay, time to first pain medication administration in the postanesthesia care unit, and adverse events. A total of 76 women were included in the study. Demographic characteristics were similar in both groups. Median age was 44 years (interquartile range 39-50), 47% of the participants were African American, and mean body mass index was 32.8 kg/m2 (standard deviation [SD] 8.1). The mean Quality of Recovery score was 179.1 (SD ± 10.3) in the QLB and 175.6 (SD ± 9.7) for the local anesthesia group (p = .072). All secondary outcomes were comparable between groups. CONCLUSIONS: QLBs do not significantly improve quality of recovery after elective robotic or laparoscopic hysterectomy compared with local anesthetic port site infiltration.

Nonlinear hydrological time series modeling to forecast river level dynamics in the Rio Negro Uruguay basin.

Floods significantly impact the well-being and development of communities. Hence, understanding their causes and establishing methodologies for risk prevention is a critical challenge for effective warning systems. Complex systems such as hydrological basins are modeled through hydrological models that have been utilized to understand water recharge of aquifers, available volume of dams, and floods in diverse regions. Acquiring real-time hydrometeorological data from basins and rivers is vital for establishing data-driven-based models as tools for the prediction of river-level dynamics and for understanding its nonlinear behavior. This paper introduces a hydrological model based on a multilayer perceptron neural network as a useful tool for time series modeling and forecasting river levels in three stations of the Rio Negro basin in Uruguay. Daily time series of river levels and rainfall serve as the input data for the model. The assessment of the models is based on metrics such as the Nash-Sutcliffe coefficient, the root mean square error, percent bias, and volumetric efficiency. The outputs exhibit varying model performance and accuracy during the prediction period across different sub-basin scales, revealing the neural network's ability to learn river dynamics. Lagged time series analysis demonstrates the potential for chaos in river-level time series over extended time periods, mainly when predicting dam-related scenarios, which shows physical connections between the dynamical system and the data-based model such as the evolution of the system over time.

Individual transmembrane domains of SfABCC2 from Spodoptera frugiperda do not serve as functional Cry1F receptors.

The fall armyworm (Spodoptera frugiperda) is a major global pest causing severe damage to various crops, especially corn. Transgenic corn producing the Cry1F pesticidal protein from the bacterium Bacillus thuringiensis (Cry1F corn) showed effectiveness in controlling this pest until S. frugiperda populations at locations in North and South America evolved practical resistance. The mechanism for practical resistance involved disruptive mutations in an ATP binding cassette transporter subfamily C2 gene (SfABCC2), which serves as a functional Cry1F receptor in the midgut cells of susceptible S. frugiperda. The SfABCC2 protein contains two transmembrane domains (TMD1 and TMD2), each with a cytosolic nucleotide (ATP) binding domain (NBD1 and NBD2, respectively). Previous reports have demonstrated that disruptive mutations in TMD2 were linked with resistance to Cry1F, yet whether the complete SfABCC2 structure is needed for receptor functionality or if a single TMD-NBD protein can serve as functional Cry1F receptor remains unknown. In the present study, we separately expressed TMD1 and TMD2 with their corresponding NBDs in cultured insect cells and tested their Cry1F receptor functionality. Our results show that the complete SfABCC2 structure is required for Cry1F receptor functionality. Moreover, binding competition assays revealed that Cry1F specifically bound to SfABCC2, whereas neither SfTMD1-NBD1 nor SfTMD2-NBD2 exhibited any significant binding. These results provide insights into the molecular mechanism of Cry1F recognition by SfABCC2 in S. frugiperda, which could facilitate the development of more effective insecticidal proteins.

Exercise improves respiratory function, body fluid and nitric oxide in hemodialysis patients.

Emerging evidence suggests that resistance training (RT) can mitigate respiratory muscle weakness in hemodialysis (HD) patients. However, the underlying mechanisms responsible for these beneficial effects remain unclear. The purpose of this study was to assess the impact of periodized RT on respiratory muscle strength and its relationship with handgrip strength (HGS), fat-free mass (FFM), nitric oxide (NO), and interdialytic weight gain (IWG) in HD patients. Thirty-three patients were randomly assigned to two groups: control (CTL; n=18) and RT (n=15). RT group did not perform any additional exercise training specific to the respiratory tract. Maximal inspiratory (MIP) and expiratory (MEP) pressures, peak expiratory flow (PEF), HGS, FFM, NO, and IWG were measured before and after the intervention period. Participants in the RT group engaged in a 24-week RT program, three times per week. RT resulted in significant improvements in MIP, MEP, PEF, as well as enhancements in HGS, FFM, NO, and IWG (p<0.05). Notably, inverse correlations were observed between MIP (r= -0.37, p=0.03) and PEF (r= -0.4, p=0.02) with IWG. Thus, the amelioration of HGS and FFM coincided with a reduction in respiratory muscle weakness among HD patients. Decreased IWG and increased circulating NO are plausible mechanisms contributing to these improvements.

Simulating adaptive grazing management on soil organic carbon in the Southeast U.S.A. using MEMS 2.

Grazing lands play a significant role in global carbon (C) dynamics, holding substantial soil organic carbon (SOC) stocks. However, historical mismanagement (e.g., overgrazing and land-use change) has led to substantial SOC losses. Regenerative practices, such as adaptive multi-paddock (AMP) grazing, offer a promising avenue to improve soil health and help combat climate change by increasing SOC accrual, both in its particulate (POC) and mineral-associated (MAOC) organic C components. Because adaptive grazing patterns emerge from the combination of different levers such as frequency, intensity, and timing of grazing, studying AMP grazing management in experimental trials and representing it in models remains challenging. Existing ecosystem models lack the capacity to predict how different adaptive grazing levers affect SOC storage and its distribution between POC and MAOC and along the soil profile accurately. Therefore, they cannot adequately assist decision-makers in effectively optimizing adaptive practices based on SOC outcomes. Here, we address this critical gap by developing version 2.34 of the MEMS 2 model. This version advances the previous by incorporating perennial grass growth and grazing submodules to simulate grass green-up and dormancy, reserve organ dynamics, the influence of standing dead plant mass on new plant growth, grass and supplemental feed consumption by animals, and their feces and urine input to soil. Using data from grazing experiments in the southeastern United States and experimental SOC data from two conventional and three AMP grazing sites in Mississippi, we tested the capacity of MEMS 2.34 to simulate grass forage production, total SOC, POC, and MAOC dynamics to 1-m depth. Further, we manipulated grazing management levers, i.e., timing, intensity, and frequency, to do a sensitivity analysis of their effects on SOC dynamics in the long term. Our findings indicate that the model can represent bahiagrass forage production (BIAS = 9.51 g C m-2, RRMSE = 0.27, RMSE = 65.57 g C m-2, R2 = 0.72) and accurately captured the dynamics of SOC fractions across sites and depths (0-15 cm: RRMSE = 0.05; 15-100 cm: RRMSE = 1.08-2.07), aligning with patterns observed in the measured data. The model best captured SOC and MAOC stocks across AMP sites in the 0-15 cm layer, while POC was best predicted at-depth. Otherwise, the model tended to overestimate SOC and MAOC below 15 cm, and POC in the topsoil. Our simulations indicate that grazing frequency and intensity were key levers for enhancing SOC stocks compared to the current management baseline, with decreasing grazing intensity yielding the highest SOC after 50 years (63.7-65.9 Mg C ha-1). By enhancing our understanding of the effects of adaptive grazing management on SOC pools in the southeastern U.S., MEMS 2.34 offers a valuable tool for researchers, producers, and policymakers to make AMP grazing management decisions based on potential SOC outcomes.

Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon-Like Receptor Like 1 (ARNTL, or Bmal1) and the liver-enriched nuclear factor 4 alpha (HNF4α) are robustly co-expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α- either by isoform switching, or loss of expression- results in an increased risk for HCC, while BMAL1 gain-of-function in HNF4α-positive HCC results in apoptosis and tumor regression. We hypothesize that the transcriptional programs of HNF4α and BMAL1 are antagonistic in liver disease and HCC. Here, we study this antagonism by generating a mouse model with inducible loss of hepatic HNF4α and BMAL1 expression. The results reveal that simultaneous loss of HNF4α and BMAL1 is protective against fatty liver and HCC in carcinogen-induced liver injury and in the "STAM" model of liver disease. Furthermore, our results suggest that targeting Bmal1 expression in the absence of HNF4α inhibits HCC growth and progression. Specifically, pharmacological suppression of Bmal1 in HNF4α-deficient, BMAL1-positive HCC with REV-ERB agonist SR9009 impairs tumor cell proliferation and migration in a REV-ERB-dependent manner, while having no effect on healthy hepatocytes. Collectively, our results suggest that stratification of HCC based on HNF4α and BMAL1 expression may provide a new perspective on HCC properties and potential targeted therapeutics.

Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers: A Pilot, Proof-of-Concept, Feasibility, Randomized-Controlled Trial.

BACKGROUND: Serotonergic hallucinogens and cannabinoids may alter the recognition of emotions in facial expressions (REFE). Cannabidiol (CBD) attenuates the psychoactive effects of the cannabinoid-1 agonist tetrahydrocannabinol. Ayahuasca is a dimethyltryptamine-containing hallucinogenic decoction. It is unknown if CBD may moderate and attenuate the effects of ayahuasca on REFE. PROCEDURES: Seventeen healthy volunteers participated in a 1-week preliminary parallel-arm, randomized controlled trial for 18 months. Volunteers received a placebo or 600 mg of oral CBD followed by oral ayahuasca (1 mL/kg) 90 minutes later. Primary outcomes included REFE and empathy tasks (coprimary outcome). Tasks were performed at baseline and 6.5 hours, 1 and 7 days after the interventions. Secondary outcome measures included subjective effects, tolerability, and biochemical assessments. RESULTS: Significant reductions (all P values <0.05) only in reaction times were observed in the 2 tasks in both groups, without between-group differences. Furthermore, significant reductions in anxiety, sedation, cognitive deterioration, and discomfort were observed in both groups, without between-group differences. Ayahuasca, with or without CBD, was well tolerated, producing mainly nausea and gastrointestinal discomfort. No clinically significant effects were observed on cardiovascular measurements and liver enzymes. CONCLUSIONS: There was no evidence of interactive effects between ayahuasca and CBD. The safety of separate and concomitant drug intake suggests that both drugs could be applied to clinical populations with anxiety disorders and in further trials with larger samples to confirm findings.

The effects of ketamine and classic hallucinogens on neurotrophic and inflammatory markers in unipolar treatment-resistant depression: a systematic review of clinical trials.

Although results are still preliminary, ketamine and classical hallucinogens have shown promise in recent years as novel, fast-acting antidepressants, especially for the treatment of unipolar treatment-resistant depression (TRD). Depression also seems to be related to abnormal levels of peripheral inflammatory and neurotrophic biomarkers, which may one day help to diagnose of this disorder. In this context, this systematic review of clinical trials evaluated the current evidence that relates the antidepressant effects of ketamine and classical hallucinogens on TRD with changes in inflammatory and neurotrophic biomarkers. Twelve studies were found (n = 587), 2 with oral ayahuasca (1 mL/kg) and 10 with ketamine (mostly intravenous 0.5 mg/kg) administration. Results for all biomarkers assessed were contradictory and thus inconclusive. Randomized controlled trials with bigger samples and higher statistical power are warranted to clarify if peripheral biomarkers can confidently be used to indicate and measure ketamine's and classical hallucinogens' antidepressant effect. The PROSPERO ID for this study is CRD42021249089.

Identifying setting factors associated with improved ibogaine safety: a systematic review of clinical studies.

Ibogaine is a psychoactive alkaloid derived from the west-African shrub Tabernanthe iboga. Western cultures are increasing the interest for the substance due to its claimed anti addictive properties, although the evidence supporting this effect is still preliminary. The use of ibogaine often occurs with no medical supervision in uncontrolled settings, and its use has been associated with several reports of severe adverse events. This review aims to evaluate the clinical studies of ibogaine, with a focus on administration settings, to elucidate specific criteria that may promote safer contexts for ibogaine use. A systematic review of the literature was conducted based on PRISMA guidelines. PubMed, Scielo, ClinicalTrials.gov and Core.ac.uk electronic databases were searched, and clinical studies published until November 17, 2022, were retrieved. The final synthesis included 12 sources. Information about general characteristics of the studies, adverse effects, screening of participants and setting characteristics were summarized and discussed. It is concluded that the use of controlled settings, supported by trained professionals and equipment allowing for rigorous medical, psychiatric, and cardiac monitoring, are essential to promote the safety of patients receiving ibogaine.

Four single implant-supported crowns replacing the maxillary incisors: A retrospective report of 10 cases with 2-9 years of follow-up.

OBJECTIVE: This retrospective case series aimed to assess the stability of the papilla around four single crowns supported by narrow-diameter implants replacing all maxillary incisors. Secondary objectives included assessment of marginal bone level stability, incidence of technical and biological complications, and patient satisfaction. MATERIALS AND METHODS: Individuals with four adjacent implants in maxillary incisor sites, placed with a 3 mm inter-implant distance and rehabilitated with single crowns were included. Retrospective data were obtained from photographs and radiographs taken at the delivery of the prosthesis (baseline-T0). Patients were then recalled (≥2 years after T0) for clinical and radiographic examination (follow-up-T1). Photographs were obtained and patient satisfaction was assessed using a visual analogue scale. Papilla height and marginal bone level were compared over time. RESULTS: Data from 10 patients with medium-low smile lines and rehabilitated with 40 implants, in function for 5.4 ± 1.9 years, were analyzed. The papilla height between implants (T0: 2.3 ± 0.9 mm; T1: 2.6 ± 0.7 mm; p = .011) and between tooth and implant (T0: 3.4 ± 0.9 mm; T1: 3.8 ± 0.8 mm; p = .025) increased significantly over the years. The marginal bone level remained stable over time (T0: 0.88 ± 0.57 mm; T1: 0.71 ± 0.67 mm; p = .007). Patients were highly satisfied (97.7 ± 0.3%) with the treatment outcome. CONCLUSION: Within its limitations, this study demonstrated that four single implant-supported crowns placed at maxillary incisor sites may exhibit soft tissue and marginal bone stability over a long period of time. This treatment approach, however, should be restricted to few patients as it requires a proper case selection and skillful execution of all surgical and prosthetic steps.

Kidney Xenotransplantation: Are We Ready for Prime Time?

PURPOSE OF REVIEW: With the exponential increase in interest and great strides toward clinical application, many experts believe we are ready for kidney xenotransplant human trials. In this review, we will examine the obstacles overcome and those yet to be conquered, discussing the human trials performed and the questions they raised. Additionally, we will revisit overlooked aspects that may be crucial for improvements and suggest future approaches for xenotransplant research. RECENT FINDINGS: Improving survival in pig-to-non-human-primate models with the identification of an ideal immunosuppression regimen led to 3 cases of kidney xenotransplant in brain-dead humans with limited follow-up and a single clinical case of pig-to-human heart xenotransplant with 2-month survival. With limited human results and unlimited potential, xenotransplantation shines a beacon of hope for a brighter future. However, we must navigate through the complexities of balancing scientific progress and patient welfare, avoiding being blinded by xenotransplantation's unquestionable potential.

Hallucinations and Hallucinogens: Psychopathology or Wisdom?

Hallucinations are currently associated almost exclusively with psychopathological states. While it is evident that hallucinations can indicate psychopathology or neurological disorders, we should remember that hallucinations also commonly occur in people without any signs of psychopathology. A similar case occurs in the case of hallucinogenic drugs, which have been long associated with psychopathology and insanity. However, during the last decades a huge body of research has shown that certain kinds of hallucinations, exerted by hallucinogenic drugs, may serve to improve mental health. We propose that, in light of historical, epidemiological, and scientific research, hallucinations can be better characterized as a common phenomenon associated sometimes with psychopathology but also with functional and even beneficial outcomes. In the last sections of the manuscript, we extend our argument, suggesting that hallucinations can offer a via regia to knowledge of the mind and the world. This radical shift in the cultural interpretation of hallucinations could have several implications for fields such as drug policy, civil law, and psychiatry, as well as for the stigma associated with mental disorders.

Identification of Mir-182-3p/FLI-1 Axis as a Key Signaling in Immune Response in Cervical Cancer: A Comprehensive Bioinformatic Analysis.

miRNAs modulate gene expression and play critical functions as oncomiRs or tumor suppressors. The miR-182-3p is important in chemoresistance and cancer progression in breast, lung, osteosarcoma, and ovarian cancer. However, the role of miR-182-3p in cervical cancer (CC) has not been elucidated. AIM: To analyze the role of miR-182-3p in CC through a comprehensive bioinformatic analysis. METHODS: Gene Expression Omnibus (GEO) databases were used for the expression analysis. The mRNA targets of miR-182-3p were identified using miRDB, TargetScanHuman, and miRPathDB. The prediction of island CpG was performed using the MethPrimer program. The transcription factor binding sites in the FLI-1 promoter were identified using ConSite+, Alibaba2, and ALGGEN-PROMO. The protein-protein interaction (PPI) analysis was performed in STRING 11.5. RESULTS: miR-182-3p was significantly overexpressed in CC patients and has potential as a diagnostic. We identified 330 targets of miR-182-3p including FLI-1, which downregulates its expression in CC. Additionally, the aberrant methylation of the FLI-1 promoter and Ap2a transcription factor could be involved in downregulating FLI1 expression. Finally, we found that FLI-1 is a possible key gene in the immune response in CC. CONCLUSIONS: The miR-182-3p/FLI-1 axis plays a critical role in immune response in CC.

Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016-2020) systematic review of preclinical and human studies.

Ayahuasca is a hallucinogenic/psychedelic traditionally used for ritual and therapeutic purposes. One such therapeutic use is related to Substance Use Disorders (SUDs). A previous systematic review of preclinical and human studies published until 2016 suggested that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. To conduct an update of this previous review. A systematic review of quantitative studies which analyzed the effects of ayahuasca and its alkaloids on drug use (primary outcome) and other measures (secondary outcomes) related to SUDs was conducted, including articles from 2016 to 2020. Nine studies (four preclinical, five observational) were included in the review. Preclinical studies in rodents reported reductions in amphetamine self-administration and anxiety, and in alcohol- and methylphenidate-induced conditioned place preference. Observational studies among healthy ritual ayahuasca users and patients with SUDs reported reductions in drug use, anxiety, and depression, and increases in quality of life and well-being. We replicated the findings of the previous review suggesting that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. However, translation of preclinical data to humans is limited, observational studies do not allow us to infer causality, and there is a lack of standardization on ayahuasca doses. Although promising, randomized, controlled trials are needed to better elucidate these results. The PROSPERO ID for this study is CRD42020192046.

Effects of ayahuasca on the endocannabinoid system of healthy volunteers and in volunteers with social anxiety disorder: Results from two pilot, proof-of-concept, randomized, placebo-controlled trials.

OBJECTIVE: To assess endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo. METHODS: Post hoc analysis of endocannabinoid plasma levels (baseline, 90 and 240 min after drug intake) from two parallel-group, randomized, placebo-controlled trials. In Study 1, 20 healthy volunteers ingested ayahuasca (average 1.58 mg/ml dimethyltryptamine (DMT)) or placebo, and in Study 2, 17 volunteers with SAD received ayahuasca (average 0.680 mg/ml DMT) or placebo. RESULTS: A significant difference was observed in AEA concentrations in Study 2 after ayahuasca intake (Χ2 (2) = 6.5, p = 0.03, Friedman test), and near significant differences (increases) were observed between baseline and 90 (Z = 0, p = 0.06, Wilcoxon test) and 240 (Z = 10, p = 0.06) minutes after ayahuasca intake. CONCLUSIONS: Although our findings suggest that ayahuasca could modulate AEA levels in SAD patients, the high interindividual variability in both trials and the small samples preclude definitive conclusions. More research with larger samples is needed to better understand the effects of ayahuasca and other hallucinogens in the endocannabinoid system.