A highly resolved nuclear phylogeny uncovers strong phylogenetic conservatism and correlated evolution of fruit color and size in Solanum L.

Mutualisms between plants and fruit-eating animals were key to the radiation of angiosperms. Still, phylogenetic uncertainties limit our understanding of fleshy-fruit evolution, as in the case of Solanum, a genus with remarkable fleshy-fruit diversity, but with unresolved phylogenetic relationships. We used 1786 nuclear genes from 247 species, including 122 newly generated transcriptomes/genomes, to reconstruct the Solanum phylogeny and examine the tempo and mode of the evolution of fruit color and size. Our analysis resolved the backbone phylogeny of Solanum, providing high support for its clades. Our results pushed back the origin of Solanum to 53.1 million years ago (Ma), with most major clades diverging between 35 and 27 Ma. Evolution of Solanum fruit color and size revealed high levels of trait conservatism, where medium-sized berries that remain green when ripe are the likely ancestral form. Our analyses revealed that fruit size and color are evolutionary correlated, where dull-colored fruits are two times larger than black/purple and red fruits. We conclude that the strong phylogenetic conservatism shown in the color and size of Solanum fruits could limit the influences of fruit-eating animals on fleshy-fruit evolution. Our findings highlight the importance of phylogenetic constraints on the diversification of fleshy-fruit functional traits.

Proteomics of serum-derived extracellular vesicles are associated with the severity and different clinical profiles of patients with COVID-19: An exploratory secondary analysis.

BACKGROUND AIMS: Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical manifestations with the potential to progress to multiple organ dysfunction in severe cases. Extracellular vesicles (EVs) carry a range of biological cargoes, which may be used as biomarkers of disease state. METHODS: An exploratory secondary analysis of the SARITA-2 and SARITA-1 datasets (randomized clinical trials on patients with mild and moderate/severe COVID-19) was performed. Serum-derived EVs were used for proteomic analysis to identify enriched biological processes and key proteins, thus providing insights into differences in disease severity. Serum-derived EVs were separated from patients with COVID-19 by size exclusion chromatography and nanoparticle tracking analysis was used to determine particle concentration and diameter. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to identify and quantify protein signatures. Bioinformatics and multivariate statistical analysis were applied to distinguish candidate proteins associated with disease severity (mild versus moderate/severe COVID-19). RESULTS: No differences were observed in terms of the concentration and diameter of enriched EVs between mild (n = 14) and moderate/severe (n = 30) COVID-19. A total of 414 proteins were found to be present in EVs, of which 360 were shared while 48 were uniquely present in severe/moderate compared to mild COVID-19. The main biological signatures in moderate/severe COVID-19 were associated with platelet degranulation, exocytosis, complement activation, immune effector activation, and humoral immune response. Von Willebrand factor, serum amyloid A-2 protein, histone H4 and H2A type 2-C, and fibrinogen ß-chain were the most differentially expressed proteins between severity groups. CONCLUSION: Exploratory proteomic analysis of serum-derived EVs from patients with COVID-19 detected key proteins related to immune response and activation of coagulation and complement pathways, which are associated with disease severity. Our data suggest that EV proteins may be relevant biomarkers of disease state and prognosis.

Trends in Nonfatal Overdose Rates Due to Alcohol and Prescription and Illegal Substances in Colombia, 2010‒2021.

Objectives. To examine drug overdoses in Colombia by type of substance, sex, age, and intent using data from a health surveillance system from 2010 to 2021. Methods. We characterized data by year, type of substance, and sociodemographic variables. We calculated age-adjusted overdose rates by substance type, sex, age groups, and intent. We used Poisson regression models to examine trend differences across sex and age groups. Results. Age-adjusted rates of drug overdoses increased from 8.51 to 40.52 per 100 000 during 2010 to 2021. Men, compared with women, had higher overdose rates for every substance, except for opioids and psychotropics. Drug overdose rates involving cannabis and stimulants increased steadily until 2017 but decreased afterward. Overdose rates involving psychotropic medication increased greatly during 2018 to 2021, mainly because of intentional overdoses in young women. Conclusions. Overdoses involving illegal drugs decreased in recent years in Colombia; however, the continuous increase in intentional psychotropic overdose rates highlights the need for prevention efforts to curb this trend. Health surveillance systems are an important tool that can guide overdose prevention efforts in countries with limited data resources. (Am J Public Health. 2024;114(11):1252-1260. https://doi.org/10.2105/AJPH.2024.307786).

Contingency Management for Cannabis Use Disorder Treatment.

INTRODUCTION: Although recreational cannabis use and abuse are expressive worldwide, the comparison of worldwide used psychotherapies, such as cognitive behavior therapy, with contingency management in the treatment of cannabis use disorder remains inconclusive. METHODS: We screened all articles published on MEDLINE (via PubMed) published until October 2023 and conducted a systematic review with meta-analysis. RESULTS: Sixteen studies were included, and contingency management intervention likely promotes abstinence outcomes and more negative urinalyses for adults or adolescents with cannabis use disorder. DISCUSSION: This review provides moderate- to high-quality evidence that contingency management can be used to treat cannabis use disorder. However, further trials need to be developed to analyze the quantity of substance use, personal achievements, and operational improvements after treatment.

The risk of vector transmission of Trypanosoma cruzi remains high in the State of Paraná.

BACKGROUND: Monitoring and analysing the infection rates of the vector of Trypanosoma cruzi, that causes Chagas disease, helps assess the risk of transmission. OBJECTIVES: A study was carried out on triatomine in the State of Paraná, Brazil, between 2012 and 2021 and a comparison was made with a previous study. This was done to assess the risk of disease transmission. METHODS: Ecological niche models based on climate and landscape variables were developed to predict habitat suitability for the vectors as a proxy for risk of occurrence. FINDINGS: A total of 1,750 specimens of triatomines were recorded, of which six species were identified. The overall infection rate was 22.7%. The areas with the highest risk transmission of T. cruzi are consistent with previous predictions in municipalities. New data shows that climate models are more accurate than landscape models. This is likely because climate suitability was higher in the previous period. MAIN CONCLUSION: Regardless of uneven sampling and potential biases, risk remains high due to the wide presence of infected vectors and high environmental suitability for vector species throughout the state and, therefore, improvements in public policies aimed at wide dissemination of knowledge about the disease are recommended to ensure the State remains free of Chagas disease.

First assessment of atmospheric pollution by trace elements and particulate matter after a severe collapse of a tailings dam, Minas Gerais, Brazil: An insight into biomonitoring with Tillandsia usneoides and a public health dataset.

In this study, samples of bromeliad Tillandsia usneoides (n = 70) were transplanted and exposed for 15 and 45 days in 35 outdoor residential areas in Brumadinho (Minas Gerais state, Brazil) after one of the most severe mining dam collapses in the world. Trace elements aluminum (Al), arsenic (As), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni) and zinc (Zn) were quantified by atomic absorption spectrometry. Scanning electron microscope generated surface images of T. usneoides fragments and particulate matter (PM2.5, PM10 and PM > 10). Aluminum, Fe and Mn stood out from the other elements reflecting the regional geological background. Median concentrations in mg kg-1 increased (p < 0.05) between 15 and 45 days for Cr (0.75), Cu (1.23), Fe (474) and Mn (38.1), while Hg (0.18) was higher at 15 days. The exposed-to-control ratio revealed that As and Hg increased 18.1 and 9.4-fold, respectively, not showing a pattern associated only with the most impacted sites. The PM analysis points to a possible influence of the prevailing west wind on the increase of total particles, PM2.5 and PM10 in transplant sites located to the east. Brazilian public health dataset revealed increase in cases of some cardiovascular and respiratory diseases/symptoms in Brumadinho in the year of the dam collapse (1.38 cases per 1000 inhabitants), while Belo Horizonte capital and its metropolitan region recorded 0.97 and 0.37 cases, respectively. Although many studies have been carried out to assess the consequences of the tailings dam failure, until now atmospheric pollution had not yet been evaluated. Furthermore, based on our exploratory analysis of human health dataset, epidemiological studies are required to verify possible risk factors associated with the increase in hospital admissions in the study area.

Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.

Cocaine use is a public health concern in many countries worldwide, particularly in the Americas and Oceania. Overdose deaths involving stimulants, such as cocaine, have been increasing markedly in North America, especially with concurrent opioid involvement. To date, no pharmacological treatment is available to treat stimulant (including cocaine) use disorders. Prescription psychostimulants (PPs) could be useful to treat cocaine use disorder (CUD) as they share the pharmacological effects with cocaine, as evidenced by a recent meta-analysis that assessed 38 randomized clinical trials (RCTs). PPs were found to promote sustained abstinence and reduce drug use in patients with CUD. The aim of this paper is to provide a narrative review of the clinical pharmacology of PPs and comment on the current stage of evidence supporting PPs to treat CUD. We also propose a model of care that integrates PPs with evidence-based psychosocial interventions (such as cognitive-behavioural therapy [CBT] and contingency management [CM]), a harm reduction approach and case management with social support.

Marked Increase in Amphetamine-Related Emergency Department Visits and Inpatient Admissions in Toronto, Canada, 2014-2021.

BACKGROUND: We report emergency department and inpatient amphetamine-related trends focusing on co-occurring substance use and psychiatric diagnoses at the Centre for Addiction and Mental Health, the largest mental health teaching hospital in Canada. METHODS: We describe yearly trends in amphetamine-related Centre for Addiction and Mental Health emergency department visits and inpatient admissions out of all emergency department visits and inpatient admissions between 2014 and 2021, along with proportions of concurrent substance-related admissions and mental/psychotic disorders emergency department visits and inpatient admissions among amphetamine-related contacts; joinpoint regression analyses assessed changes in amphetamine-related emergency department visits and inpatient admissions. RESULTS: Amphetamine-related emergency department visits rose from 1.5% in 2014 to 8.3% in 2021, with a peak of 9.9% in 2020. Amphetamine-related inpatient admissions rose from 2.0% to 8.8% in 2021, with a peak of 8.9% in 2020. Significant increasing trends in the percentage of amphetamine-related emergency department visits happened especially between the second and the fourth quarter of 2014 (quarterly percent change = + 71.4, P <0.01). Similarly, the percentage of amphetamine-related inpatient admissions increased mostly between the second quarter of 2014 and the third quarter of 2015 (quarterly percent change = + 32.6, P <0.01). The proportion of concurrent opioid-related contacts among amphetamine-related emergency department visits and inpatient admission increased markedly between 2014 and 2021; psychotic disorders in amphetamine-related inpatient admissions more than doubled from 2015 to 2021. DISCUSSION: Prevalence of amphetamine use, mostly from methamphetamine, has been increasing in Toronto as have co-occurring psychiatric disorders and opioid use. Our findings highlight the need for increases in accessible efficacious treatments for complex populations with polysubstance use and co-occurring disorders.

Outcomes of Orthotopic Heart Transplantation in the Setting of Acute Kidney Injury and Renal Replacement Therapy.

OBJECTIVE: Heart transplantation in the setting of renal insufficiency is controversial. The objective of this study was to perform a descriptive analysis of patients who underwent orthotopic heart transplantation and renal replacement therapy (RRT) due to acute kidney injury (AKI). DESIGN: An observational cohort study with retrospective data collection. SETTING: A tertiary care hospital. PARTICIPANTS: Fifty-one patients underwent orthotopic heart transplantation with cardiogenic shock under inotrope dependence, with nine patients having preoperative RRT and 42 patients not having preoperative RRT. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: Hospital mortality occurred in eight (15.6%) patients. Although there were no significant differences between the study groups (preoperative RRT 33.3% v controls 11.9%, p = 0.1), this study was underpowered to detect differences in mortality. Dialysis also was required in 52.4% of patients who were not on preoperative RRT. All survivors had full recovery of kidney function with similar timing after transplant (18.5 days v 15 days, p = 0.75). Actuarial survival was 82.4%, 76.5%, and 66.5% at six months, one year, and five years, respectively. A cold ischemic time greater than 180 minutes (hazard ratio [HR] 4.37 95% confidence interval [CI] 1.51-12.6; p = 0.006) and pretransplant RRT (HR = 7.19 95% CI 1.13-45.7; p = 0.04) were independent predictors of long-term mortality. CONCLUSIONS: In a health system with limited funding and availability of mechanical circulatory support, heart transplantation in the setting of AKI, RRT, and low Interagency Registry for Mechanically Assisted Circulatory Support profile was associated with important hospital mortality. Among hospital survivors, however, all patients had full renal recovery and by 25 months there was no difference in mortality between those who required preoperative RRT and those who did not.

Empirical and semi-empirical chlorophyll-a modeling for water quality assessment through river-lake transition in extreme Southern Brazil.

Mirim lagoon is the second largest lacustrine water body in Southern Brazil, providing water for local communities. However, algae growth and water quality in the lagoon and in tributaries rivers is influenced by nutrient's increase. In this context, this study performs the empirical and semi-empirical chlorophyll-a (Chl-a) modeling using remote sensing and in situ data for water quality assessment. Water quality data were collected at 15 sample locations in the lagoon on the date of Sentinel-2 satellite overpass. Surface reflectance data were derived from the Sen2Cor atmospheric correction method and correlated with Chl-a concentration. The best model presented a Pearson's correlation coefficient = 0.81 and Mean Absolute Error = 0.13µg.L-1. Low Chl-a concentration is observed at the Northern lagoon, possibly due to suspended solids presence. The same occurs in the left margin, being associated with the influence of land use for agriculture. High Chl-a concentrations are associated with shallower and lentic areas. The mean Chl-a concentration predicted by the model was 17.34µg.L-1, similar to the observed value in situ (16.32µg.L-1). Overall, the empirical model developed can be applied as a tool to reduce costs and efforts in fieldwork measures and to understand eutrophication in this river-lake transition ecosystem.

Oxidative Precipitation Synthesis of Calcium-Doped Manganese Ferrite Nanoparticles for Magnetic Hyperthermia.

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (CaxMn1-xFe2O4) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.

Identification of Glycycometus malaysiensis (for the first time in Brazil), Blomia tropicalis and Dermatophagoides pteronyssinus through multiplex PCR.

Blomia tropicalis and Dermatophagoides pteronyssinus play an important role in triggering allergy. Glycycometus malaysiensis causes IgE reaction in sensitive people, but is rarely reported in domestic dust, because it is morphologically similar to B. tropicalis making the identification of these species difficult. The identification of mites is mostly based on morphology, a time-consuming and ambiguous approach. Herein, we describe a multiplex polymerase chain reaction (mPCR) assay based on ribosomal DNA capable to identify mixed cultures of B. tropicalis, D. pteronyssinus and G. malaysiensis, and/or to identify these species from environmental dust. For this, the internal transcribed spacer 2 (ITS2) regions, flanked by partial sequences of the 5.8S and 28S genes, were PCR-amplified, cloned and sequenced. The sequences obtained were aligned with co-specific sequences available in the GenBank database for primer design and phylogenetic studies. Three pairs of primers were chosen to compose the mPCR assay, which was used to verify the frequency of different mites in house dust samples (n = 20) from homes of Salvador, Brazil. Blomia tropicalis was the most frequent, found in 95% of the samples, followed by G. malaysiensis (70%) and D. pteronyssinus (60%). Besides reporting for the first time the occurrence of G. malaysiensis in Brazil, our results confirm the good resolution of the ITS2 region for mite identification. Furthermore, the mPCR assay proved to be a fast and reliable tool for identifying these mites in mixed cultures and could be applied in future epidemiological studies, and for quality control of mite extract production for general use.

Experiences and mediating factors in nurses' responses to electronic device alarms: A phenomenological study.

AIM: This study aims to explore the experiences and mediating factors of nurses' responses to electronic device alarms in critical care units (CCUs). BACKGROUND: Alarm fatigue occasionally has adverse consequences for patient safety. METHODS: This qualitative study was designed and analysed following Giorgi's descriptive phenomenological approach. Seventeen nurses were theoretically sampled, reaching information saturation. Semistructured interviews were used to collect the data. RESULTS: Three central themes explained nurses' experiences: general perceptions about alarms (basic equipment of the CCU), strategies to reduce false alarms (training in the configuration of monitors, customization of the alarms to fit he patient's condition. teamwork and taking advantage of the development of technology) and key elements of the response to alarms (information about patient's condition, nurses' clinical experience, type of CCU, 'cry-wolf' phenomenon and nurse/patient ratio). CONCLUSIONS: To reduce false alarms, nurses need further postgraduate training, training on monitors and customizing alarms to fit the patient's health status. The complex process of deciding to respond to an alarm includes environmental, professional variables and patient status. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should ensure that nurses have sufficient experience and training in the CCU, improve the nurse/patient ratio, promote teamwork and ensure that the devices are the latest generation.

SicknessMiner: a deep-learning-driven text-mining tool to abridge disease-disease associations.

BACKGROUND: Blood cancers (BCs) are responsible for over 720 K yearly deaths worldwide. Their prevalence and mortality-rate uphold the relevance of research related to BCs. Despite the availability of different resources establishing Disease-Disease Associations (DDAs), the knowledge is scattered and not accessible in a straightforward way to the scientific community. Here, we propose SicknessMiner, a biomedical Text-Mining (TM) approach towards the centralization of DDAs. Our methodology encompasses Named Entity Recognition (NER) and Named Entity Normalization (NEN) steps, and the DDAs retrieved were compared to the DisGeNET resource for qualitative and quantitative comparison. RESULTS: We obtained the DDAs via co-mention using our SicknessMiner or gene- or variant-disease similarity on DisGeNET. SicknessMiner was able to retrieve around 92% of the DisGeNET results and nearly 15% of the SicknessMiner results were specific to our pipeline. CONCLUSIONS: SicknessMiner is a valuable tool to extract disease-disease relationship from RAW input corpus.

Free Molecule Studies by Perturbed γ-γ Angular Correlation: A New Path to Accurate Nuclear Quadrupole Moments.

Accurate nuclear quadrupole moment values are essential as benchmarks for nuclear structure models and for the interpretation of experimentally determined nuclear quadrupole interactions in terms of electronic and molecular structure. Here, we present a novel route to such data by combining perturbed γ-γ angular correlation measurements on free small linear molecules, realized for the first time within this work, with state-of-the-art ab initio electronic structure calculations of the electric field gradient at the probe site. This approach, also feasible for a series of other cases, is applied to Hg and Cd halides, resulting in Q(^{199}Hg,5/2^{-})=+0.674(17) b and Q(^{111}Cd,5/2^{+})=+0.664(7) b.

Responses of matrix metalloproteinases to hyperbaric oxygen treatment: changing for good or ill?

Background: Hyperbaric oxygen (HBO2) is currently emerging as a promising therapeutic option for diseases involving impaired tissue repair and remodeling. In this regard, HBO2 has been shown to modulate signaling pathways responsible for matrix metalloproteinases (MMPs) regulation, which makes the MMPs interesting targets for investigation. However, the understanding regarding how HBO2 treatment affects the expression and activity of the MMP family members in different tissues and diseases needs to be clarified. The precise roles of MMPs in the physiopathology of various tissue repair disorders also remain unclear. Because of potential off-target systemic effects of the HBO2 on MMPs, researchers and physicians should carefully consider whether their patients could be affected adversely by HBO2 exposure. Aims: This narrative review provides an overview of MMP biology (structure, function, and regulation) and summarizes available data showing how MMPs respond to HBO2 in different tissues and pathologies, also highlighting possible mechanisms.

Frugivory and seed dispersal in a hyperdiverse plant clade and its role as a keystone resource for the Neotropical fauna.

BACKGROUND AND AIMS: Much of our understanding of the ecology and evolution of seed dispersal in the Neotropics is founded on studies involving the animal-dispersed, hyperdiverse plant clade Miconia (Melastomataceae). Nonetheless, no formal attempt has been made to establish its relevance as a model system or indeed provide evidence of the role of frugivores as Miconia seed dispersers. METHODS: We built three Miconia databases (fruit phenology/diaspore traits, fruit-frugivore interactions and effects on seed germination after gut passage) to determine how Miconia fruiting phenology and fruit traits for >350 species interact with and shape patterns of frugivore selection. In addition, we conducted a meta-analysis evaluating the effects of animal gut passage/seed handling on Miconia germination. KEY RESULTS: Miconia produce numerous small berries that enclose numerous tiny seeds within water- and sugar-rich pulps. In addition, coexisting species provide sequential, year long availability of fruits within communities, with many species producing fruits in periods of resource scarcity. From 2396 pairwise interactions, we identified 646 animal frugivore species in five classes, 22 orders and 60 families, including birds, mammals, reptiles, fish and ants that consume Miconia fruits. Endozoochory is the main dispersal mechanism, but gut passage effects on germination were specific to animal clades; birds, monkeys and ants reduced seed germination percentages, while opossums increased it. CONCLUSIONS: The sequential fruiting phenologies and wide taxonomic and functional diversity of animal vectors associated with Miconia fruits underscore the likely keystone role that this plant clade plays in the Neotropics. By producing fruits morphologically and chemically accessible to a variety of animals, Miconia species ensure short- and long-distance seed dispersal and constitute reliable resources that sustain entire frugivore assemblages.

Enhanced strain-induced magnetoelectric coupling in polarization-free Fe/BaTiO3 heterostructures.

The search for magnetoelectric materials typically revolves around the struggle to make magnetic and ferroelectric orders simultaneously coexist in the same material, using either an intrinsic or an extrinsic/composite approach. Via ab initio calculations of a prototypical Fe/BaTiO3 interface, we predict that it is possible to tune the magnitude of the individual magnetic moments even for non-polar BaTiO3. By comparing polar and non-polar Fe/BaTiO3 heterostructures, we show that the Fe, Ti and equatorial O atomic magnetic moments are induced and enhanced as a result of their local crystal field. The crystal field may be controlled solely by manipulation of the inter-atomic distances of their neighbouring atoms (which will affect their electrostatic fields and orbital hybridizations), or by the BaTiO3 electric dipole moments, working as a local polarization. When this polarization is present, it dominates the crystal field contributions, thus constraining the effects of other perturbations such as strain. We also find that, contrary to conventional expectations, the non-polar heterostructure shows higher strain induced magnetization sensitivity than its polar counterpart.

Induction and detection of pressure waves by pulsed thermal lens technique in water-ethanol mixtures.

The mode-mismatched dual-beam thermal lens technique is widely applied in the characterization of optical and thermo-physical properties of solids and liquids. The technique has also been used to investigate transient acoustic waves induced by pulsed laser excitation at the nanosecond time scale. In this paper, we developed a semi-analytical model to describe the transient acoustic wave that allows a fitting procedure to get the physical properties of fluid samples. The method was used to investigate samples with different mixtures of ethanol and water, and quantitative information of piezo-optic coefficient and sound speed are evaluated for the fluid mixtures.

Cannabis and Inflammatory Mediators.

INTRODUCTION: Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive. METHODS: We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019. RESULTS: Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers' levels. DISCUSSION: Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators' levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.