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.

Immunogenicity of an Inactivated Senecavirus A Vaccine with a Contemporary Brazilian Strain in Mice.

Senecavirus A (SVA) is a picornavirus that is endemic in swine, causing a vesicular disease clinically indistinguishable from other vesicular diseases, like foot-and-mouth disease. The widespread viral circulation, constant evolution, and economic losses caused to the swine industry emphasize the need for measures to control the agent. In this study, we evaluated the immunogenicity of a whole-virus-inactivated vaccine using a representative contemporary Brazilian SVA strain in Balb/ByJ mice. The animals were vaccinated with two doses by an intramuscular route. The humoral response induced by the vaccination was evaluated by an in-house ELISA assay for IgG detection. The cellular response was assessed by flow cytometry after in vitro SVA stimulation in splenocyte cultures from vaccinated and non-vaccinated groups. Protection against SVA was assessed in the experimental groups following an oral challenge with the homologous virus. The vaccination induced high levels of IgG antibodies and the proliferation of CD45R/B220+sIgM+, CD3e+CD69+, and CD3e+CD4+CD44+CD62L- cells. These results indicate the immunogenicity and safety of the vaccine formulation in a murine model and the induction of humoral and cellular response against SVA.

Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Continuous Flow Synthesis of Hexyl Laurate Using Immobilized Thermomyces Lanuginosus Lipase from Residual Babassu Mesocarp.

Brazil has one of the greatest biodiversities on the planet, where various crops play a strategic role in the country's economy. Among the highly appreciated biomasses is babassu, whose oil extraction generates residual babassu mesocarp (BM), which still needs new strategies for valorization. This work aimed to use BM as a support for the immobilization of Thermomyces lanuginosus lipase (TLL) in an 8.83 mL packed-bed reactor, followed by its application as a biocatalyst for the synthesis of hexyl laurate in an integrated process. Initially, the percolation of a solution containing 5 mg of TLL at 25 °C and flows ranging from 1.767 to 0.074 mL min-1 was investigated, where at the lowest flow rate tested (residence time of 2 h), it was possible to obtain an immobilized derivative with hydrolytic activity of 504.7 U g-1 and 31.7 % of recovered activity. Subsequent studies of treatment with n-hexane, as well as the effect of temperature on the immobilization process, were able to improve the activities of the final biocatalyst BM-TLLF, achieving a final hydrolysis activity of 7023 U g-1 and esterification activity of 430 U ⋅ g-1 against 142 U g-1 and 113.5 U g-1 respectively presented by the commercial TLIM biocatalyst. Desorption studies showed that the TL IM has 18 mg of protein per gram of support, compared to 4.92 mg presented by BM-TLL. Both biocatalysts were applied to synthesize hexyl laurate, achieving 98 % conversion at 40 °C within 2 h. Notably, BM-TLLF displayed exceptional recyclability, maintaining catalytic efficiency over 12 cycles. This reflects a productivity of 180 mg of product ⋅ h-1 U-1 of the enzyme, surpassing 46 mg h-1 U-1 obtained for TLIM. These results demonstrate the efficacy of continuous flow technology in creating a competitive and integrated process offering an exciting alternative for the valorization of residual lignocellulosic biomass.

Correction: Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors.

[This corrects the article DOI: 10.1039/D3CB00126A.].

Dynamics of Redox Metabolism during Complete Metamorphosis of Insects: Insights from the Sunflower Caterpillar Chlosyne lacinia (Lepidoptera).

Complete insect metamorphosis requires substantial metabolic and physiological adjustments. Although oxidative stress has been implicated in metamorphosis, details on redox metabolism during larva-to-pupa and pupa-to-adult remain scarce. This study explores redox metabolism during metamorphosis of a lepidopteran (Chlosyne lacinia), focusing on core metabolism, antioxidant systems and oxidative stress. The larva-to-pupa transition was characterized by increased lactate dehydrogenase and glutathione peroxidase (GPX) activities, coupled with depletion of reduced glutathione (GSH), high disulfide-to-total-glutathione ratio (GSSG/tGSH), and increased lipid peroxidation. As metamorphosis progressed, metabolic enzyme activities, citrate synthase and glucose 6-phosphate dehydrogenase increased, indicating heightened oxidative metabolism associated with adult development. Concurrently, GSH and GPX levels returned to larval levels and GSSG/tGSH reached its most reduced state right before adult emergence. Adult emergence was marked by a further increase in oxidative metabolism, accompanied by redox imbalance and enhanced antioxidant mechanisms. These findings highlight a fluctuation in redox balance throughout metamorphosis, with periods of oxidative eustress followed by compensatory antioxidant responses. This study is the first to identify concurrent changes in metabolism, antioxidants, redox balance and oxidative stress throughout metamorphosis. Our findings extend knowledge on redox metabolism adjustments and highlight redox adaptations and oxidative stress as natural components of complete insect metamorphosis.

LDH-Indomethacin Nanoparticles Antitumoral Action: A Possible Coadjuvant Drug for Cancer Therapy.

Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.

Comparative analysis of uninduced and neuronally-induced human dental pulp stromal cells in a 6-OHDA model of Parkinson's disease.

BACKGROUND: In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA). METHODS: DPSCs were isolated from human teeth, characterized as mesenchymal stromal cells, and induced to neuronal differentiation. Neuronal markers were assessed before and after induction. DPSCs were transplanted into the substantia nigra pars compacta (SNpc) of rats 7 days following the 6-OHDA lesion. In vivo tracking of the cells, evaluation of locomotor behavior, dopaminergic neuron survival, and the expression of essential proteins within the dopaminergic system were conducted 7 days postgrafting. RESULTS: Isolated DPSCs exhibited typical characteristics of mesenchymal stromal cells and maintained a normal karyotype. DPSCs consistently expressed neuronal markers, exhibiting elevated expression of ßIII-tubulin following neuronal induction. Results from the animal model showed that both DPSC types promoted substantial recovery in dopaminergic neurons, correlating with enhanced locomotion. Additionally, neuronally-induced DPSCs prevented GFAP elevation, while altering DARPP-32 phosphorylation states. Conversely, uninduced DPSCs reduced JUN levels. Both DPSC types mitigated the elevation of glycosylated DAT. CONCLUSIONS: Our results suggested that uninduced DPSCs and neuronally-induced DPSCs exhibit potential in reducing dopaminergic neuron loss and improving locomotor behavior, but their underlying mechanisms differ.

REVIEW: Evidence supporting the 'preparation for oxidative stress' (POS) strategy in animals in their natural environment.

Hypometabolism is a common strategy employed by resilient species to withstand environmental stressors that would be life-threatening for other organisms. Under conditions such as hypoxia/anoxia, temperature and salinity stress, or seasonal changes (e.g. hibernation, estivation), stress-tolerant species down-regulate pathways to decrease energy expenditures until the return of less challenging conditions. However, it is with the return of these more favorable conditions and the reactivation of basal metabolic rates that a strong increase of reactive oxygen and nitrogen species (RONS) occurs, leading to oxidative stress. Over the last few decades, cases of species capable of enhancing antioxidant defenses during hypometabolic states have been reported across taxa and in response to a variety of stressors. Interpreted as an adaptive mechanism to counteract RONS formation during tissue hypometabolism and reactivation, this strategy was coined "Preparation for Oxidative Stress" (POS). Laboratory experiments have confirmed that over 100 species, spanning 9 animal phyla, apply this strategy to endure harsh environments. However, the challenge remains to confirm its occurrence in the natural environment and its wide applicability as a key survival element, through controlled experimentation in field and in natural conditions. Under such conditions, numerous confounding factors may complicate data interpretation, but this remains the only approach to provide an integrative look at the evolutionary aspects of ecophysiological adaptations. In this review, we provide an overview of representative cases where the POS strategy has been demonstrated among diverse species in natural environmental conditions, discussing the strengths and weaknesses of these results and conclusions.

Macro and micro-sleep dysfunctions as translational biomarkers for Parkinson's disease.

Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the links between sleep dysfunctions in PD, focusing most closely on those data from animal and mathematical/computational models, as well as in human-based studies that explore the electrophysiological and molecular mechanisms by which PD and sleep may be intertwined, whether as predictors or consequences of the disease. It is possible to clearly state that leucine-rich repeat kinase 2 gene (LRRK2) is significantly related to alterations in sleep architecture, particularly affecting rapid eye movement (REM) sleep and non-REM sleep, thus impacting sleep quality. Also, decreases in gamma power, observed after dopaminergic lesions, correlates negatively with the degree of injury, which brings other levels of understanding the impacts of the disease. Besides, abnormal synchronized oscillations among basal ganglia nuclei can be detrimental for information processing considering both motor and sleep-related processes. Altogether, despite clear advances in the field, it is still difficult to definitely establish a comprehensive understanding of causality among all the sleep dysfunctions with the disease itself. Although, certainly, the search for biomarkers is helping in shortening this road towards a better and faster diagnosis, as well as looking for more efficient treatments.

Nature Forest Reserves in Tanzania and their importance for conservation.

Since 1997 Tanzania has undertaken a process to identify and declare a network of Nature Forest Reserves (NFRs) with high biodiversity values, from within its existing portfolio of national Forest Reserves, with 16 new NFRs declared since 2015. The current network of 22 gazetted NFRs covered 948,871 hectares in 2023. NFRs now cover a range of Tanzanian habitat types, including all main forest types-wet, seasonal, and dry-as well as wetlands and grasslands. NFRs contain at least 178 of Tanzania's 242 endemic vertebrate species, of which at least 50% are threatened with extinction, and 553 Tanzanian endemic plant taxa (species, subspecies, and varieties), of which at least 50% are threatened. NFRs also support 41 single-site endemic vertebrate species and 76 single-site endemic plant taxa. Time series analysis of management effectiveness tracking tool (METT) data shows that NFR management effectiveness is increasing, especially where donor funds have been available. Improved management and investment have resulted in measurable reductions of some critical threats in NFRs. Still, ongoing challenges remain to fully contain issues of illegal logging, charcoal production, firewood, pole-cutting, illegal hunting and snaring of birds and mammals, fire, wildlife trade, and the unpredictable impacts of climate change. Increased tourism, diversified revenue generation and investment schemes, involving communities in management, and stepping up control measures for remaining threats are all required to create a network of economically self-sustaining NFRs able to conserve critical biodiversity values.

Analysis of Factors Related to the Success of Pediatric Kidney Transplantation: A 35 Years Experience.

BACKGROUND: Despite the significant improvement results over the past 20 years, pediatric kidney transplantation remains a challenge. Chronic rejection, thrombosis, and recurrence of the primary disease are frequent causes of graft loss that have been little studied. Therefore, our objective is to analyze factors related to a better prognosis, which can be used to improve future strategies to allow higher pediatric transplant success rates. METHODS: A retrospective cohort study with patients under 15 years old submitted for kidney transplantation at the Hospital das Clínicas da UNICAMP between January 1, 1987, and January 1, 2022. Age, patient weight, time and type of dialysis, use of anticoagulation, complications, ischemia time, and donor weight were analyzed and related to graft loss. The significance level adopted for the statistical tests was 5%. RESULTS: One hundred ninety-two medical records were anaThe mean follow-up time was 11 years, and the mean graft duration was ration 8.5 years. The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Thrombosis presented significantly with the donor's body mass index and second transplantation. There was no correlation between the analyzed variables and chronic dysfunction or acute cellular rejection. DISCUSSION: Thrombosis remains the main cause of early graft loss, followed by acute cellular rejection. Measures such as thrombophilia screening and thromboprophylaxis have been proposed to improve results. However, they are still not standardized. CONCLUSION: The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Only the thrombosis was related to the donor's body mass index and a second transplantation.

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides.

As the world moves towards net-zero carbon emissions, the development of sustainable chemical manufacturing processes is essential. Within manufacturing, purification by distillation is often used, however this process is energy intensive and methods that could obviate or reduce its use are desirable. Developed herein is an alternative, oxidative biocatalytic approach that enables purification of alkyl monoglucosides (essential bio-based surfactant components). Implementing an immobilised engineered alcohol oxidase, a long-chain alcohol by-product derived from alkyl monoglucoside synthesis (normally removed by distillation) is selectively oxidised to an aldehyde, conjugated to an amine resin and then removed by simple filtration. This affords recovery of the purified alkyl monoglucoside. The approach lays a blueprint for further development of sustainable alkylglycoside purification using biocatalysis and, importantly, for refining other important chemical feedstocks that currently rely on distillation.

O mercado das escolinhas de futebol em belo horizonte / The market for football schools in belo horizonte / El mercado de las escuelas de fútbol en belo horizonte

Resumo Este estudo analisa a quantidade e a distribuição territorial das escolinhas de futebol em Belo Horizonte. O objetivo é examinar quantos estabelecimentos desse tipo existem na cidade, onde estão localizados e quais critérios seus proprietários empregam para essa decisão. Para isso, utilizamos dados quantitativos e qualitativos, baseados, respectivamente, em informações sobre a localização desses estabelecimentos e dados censitários, de um lado, e entrevistas semiestruturadas realizadas com proprietários de escolinhas de futebol da cidade, de outro. Nossa interpretação geral é a de que escolinhas de futebol se distribuem aleatoriamente pela cidade em razão de circunstâncias que impõem uma lógica oportunista na tomada de decisão acerca da abertura de um estabelecimento comercial desse tipo.

Abstract The study analyzes the quantity and geographical distribution of "football schools" in Belo Horizonte. The objective is to examine how many of these establishments exist in the city, where they are located and what criteria their owners use to make this decision. For this, we used quantitative and qualitative data, based on information about the location of these establishments and census data, on the one hand, and semi-structured interviews with owners of soccer schools in the city, on the other. Our general interpretation is that football schools are distributed randomly throughout the city due to circumstances impose an opportunistic logic on decision-making.

Resumen Este estudio analiza la cantidad y la distribución territorial de las "escuelas de fútbol" en Belo Horizonte. El objetivo es examinar cuántos establecimientos de este tipo existen en la ciudad, dónde están ubicados y qué criterios utilizan sus propietarios para esta decisión. Para ello, se utilizaron datos cuantitativos y cualitativos, basados en información sobre la ubicación de estos establecimientos y datos censales, por un lado, y entrevistas semiestructuradas a propietarios de escuelas de fútbol de la ciudad, por otro. Nuestra interpretación general es que las escuelas de fútbol se distribuyen aleatoriamente por la ciudad debido a circunstancias que imponen una lógica de opotunismo en la toma de decisiones sobre la apertura de un establecimiento comercial de este tipo.

Zoonotic Parasites in Artiodactyls with Emphasis on the Feral Boar in the Atlantic Forest, State of Rio de Janeiro, Brazil.

BACKGROUND: The purpose of this study was to identify the species of artiodactyl host related to the fecal matter collected in a forest area in Rio de Janeiro state and carry out a parasitological investigation. METHODS: Artiodactyl feces were collected between 2020 and 2021. The fecal samples were examined to identify the host through macroscopic and molecular analysis. The remaining samples were subjected to a fecal parasite analysis using microscopic techniques, and feces containing cysts of the phylum Ciliophora underwent a molecular analysis. RESULTS: Of the 101 samples collected, 71.3% were found in Pavão Valley, the most anthropized area of the park. In the molecular analysis, 79 samples were identified as belonging to Sus scrofa and 2 as Mazama gouazoubira. The most frequently detected forms were cysts of the phylum Ciliophora (39.6%), followed by eggs of Ascaris spp. (11.8%) and Metastrongylus spp. (5.9%). Nucleotide sequences of Balantioides coli were characterized in 26 samples, and in 13 samples variants of type B0 and in 11 type A0 were identified. CONCLUSIONS: It should be noted that this is the first study in the Americas that has identified B. coli in free-living S. scrofa feces, citing this bioinvader as one of the reservoirs of this parasite.

Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors.

Upon undergoing mucoid conversion within the lungs of cystic fibrosis patients, the pathogenic bacterium Pseudomonas aeruginosa synthesises copious quantities of the virulence factor and exopolysaccharide alginate. The enzyme guanosine diphosphate mannose dehydrogenase (GMD) catalyses the rate-limiting step and irreversible formation of the alginate sugar nucleotide building block, guanosine diphosphate mannuronic acid. Since there is no corresponding enzyme in humans, strategies that could prevent its mechanism of action could open a pathway for new and selective inhibitors to disrupt bacterial alginate production. Using virtual screening, a library of 1447 compounds within the Known Drug Space parameters were evaluated against the GMD active site using the Glide, FRED and GOLD algorithms. Compound hit evaluation with recombinant GMD refined the panel of 40 potential hits to 6 compounds which reduced NADH production in a time-dependent manner; of which, an usnic acid derivative demonstrated inhibition six-fold stronger than a previously established sugar nucleotide inhibitor, with an IC50 value of 17 µM. Further analysis by covalent docking and mass spectrometry confirm a single site of GMD alkylation.

Redox Metabolism in Ecophysiology and Evolution.

Aerobic organisms have developed a complex system of endogenous antioxidants to manage the reactivity of oxygen and its byproducts [...].