Selenylated Analogs of Tacrine: Synthesis, in Silico and in Vitro Studies of Toxicology and Antioxidant Properties.

We present our results on the synthesis and preliminary in silico and in vitro studies of the toxicology and antioxidant properties of selenylated analogs of Tacrine. Initially, we synthesized 2-aminobenzonitriles containing an organic selenium moiety, resulting in sixteen compounds with various substituents linked to the portion derived from diorganyl diselenide. These compounds were then used as substrates in reactions with cyclic ketones, in the presence of 1.4 equivalents of trifluoroboroetherate as a Lewis acid, to synthesize selenylated analogs of Tacrine with yields ranging from 20% to 87%. In silico studies explored computational parameters related to antioxidant activity and hepatotoxicity. In vitro studies elucidated the antioxidant effects of Tacrine and its selenium hybrid (TSe) in neutralizing ABTS radicals, scavenging DPPH radicals, and reducing iron ions. Additionally, the acute oral toxicity of one synthesized compound was evaluated.

Functional characterization of a cystatin A from the bat Myotis davidii.

Myotis davidii cystatin A (MdCSTA), a stefin A-like from the Chinese native bat species M. davidii, was expressed as a recombinant protein and functionally characterized as a strong inhibitor of the cysteine proteases papain, human cathepsins L and B and the tick cathepsin L-like BmCL1. Despite the highly conserved amino acid sequences among stefins A from different vertebrates, MdCSTA presents a Methionine-2 residue at the N-terminal region and the second binding loop (pos 73-79) that differs from human stefin A (HsCSTA) and might be related to the lower inhibition constant (Ki) value presented by this inhibitor in comparison to human stefin A inhibition to cathepsin B. Therefore, to investigate the importance of these variable regions in cathepsin B inhibition, recombinant stefins A MdCSTA and HsCSTA containing mutations at the second amino acid residue and second binding loop were expressed and evaluated in kinetic assays. Enzymatic inhibition assays with cathepsin B revealed that switching the amino acid residues at position 2 and second binding loop region between bat and human CSTAs improved the HsCSTA's and reduced MdCSTA's inhibitory activity. Additionally, molecular docking analysis estimated lower energy values for the complex between MdCSTA-cathepsin B, in comparison to human CSTA-cathepsin B, while the mutants presented intermediate values, suggesting that other regions might contribute to the higher inhibitory activity against cathepsin B by MdCSTA. In conclusion, MdCSTA, the first bat's stefin A-like inhibitor to be functionally characterized, presented a higher inhibitory activity against cathepsin B in comparison to the human inhibitor, which is partially related to the glutamine-rich second binding loop and Met-2. Further structural analysis should be performed to elucidate potential inhibitor effects on cysteine proteinases.

The temperature dependence of the Hildebrand solubility parameters of selected hydrocarbon polymers and hydrocarbon solvents: a molecular dynamics investigation.

CONTEXT: To determine the miscibility of liquids at high temperatures using the concept of Hildebrand solubility parameter δ , the current practice is to examine the difference in δ between two liquids at room temperature, assuming that δ is not sensitive to temperature. However, such an assumption may not be valid for certain polymer blends and solutions. Therefore, a knowledge of the δ values of the liquids of interest at high temperatures is desirable. The determination of δ at high temperatures, especially for high-molecular-weight polymers, is impossible, as polymers have vapor pressures of zero. To this end, molecular dynamics (MD) simulations provide a practical means for determining δ over a wide range of temperatures. In this work, we study the temperature dependence of δ of five hydrocarbon polymers: polyethylene (PE), isotactic and atactic polypropylene (i-PP and a-PP), polyisobutylene (PIB), and polyisoprene (PI) in five hydrocarbon solvents: n-pentane, n-hexane, n-dodecane, isobutene, and cyclohexane. The polymers are modeled as monodisperse chains with 100 repeat units. The average δ values of PE, i-PP, a-PP, PIB, and PI at 300 K are determined as 18.6, 14.9, 14.6, 14.3, and 16.4 MPa1/2, respectively, in a good agreement with experimental data. The δ values of these polymers at various temperatures are also determined. The temperature dependence of δ is fitted to two linear equations, one above and the other below the polymer's glass transition temperature Tg. The δ values are more sensitive to temperature at T ≥ Tg. The Tg values of the polymers, determined based upon their specific volumes and δ values agree with the experiment qualitatively. The determination of the temperature dependence of δ has a great potential for industrial applications, such as determining miscibility, developing polymeric organogelators as flocculants and oil spill treating agents, and identifying potential solvents and ideal processing temperatures. METHODS: The MD simulations are performed using the GROMACS 2022.3 package with optimized potential for liquid simulations-all atom (OPLS-AA) force field parameters. All polymers are built as extended chains using CHARMM-GUI Polymer Builder.

High-power Holmium:Yag lithotripsy in bladder urolithiasis: Is it safe and effective? A combined clinical and experimental study.

Objective: To evaluate the efficacy and safety of Holmium: Yttrium-Aluminum-Garnet (Ho:YAG) laser in bladder lithotripsy using high-power settings > 100 W. Materials and Methods: A combined experimental and clinical study was conducted. The Quanta Cyber: Ho 150 with a 550 µm Quanta optical fiber was utilized in all set-ups. Ablation rates for soft and hard artificial stones were tested in vitro using 100 W and 20 W power settings. In the experiment, a porcine bladder was used. The optical fiber was inserted through a rigid cystoscope, whilst a K-type thermocouple was inserted in the bladder dome. The tested high-power settings were 152 W, 120 W and 105 W. In every trial, the lasing time was over 60 s. In the clinical study, 35 patients underwent transurethral high-power bladder lithotripsy. Laser settings were set between 100 W and 150 W. Results: Stone mass (stone weight) was significantly lower after stone ablation independently of the stone type or the laser settings. Significantly higher mass decrease and ablation rate were detected in high-power compared to low-power settings. In the experiment, the highest temperature recorded was 32°C at 152 W. At 120 W and 105 W, the peak temperatures didn't reach 30°C. In the clinical study, a stone-free rate of 100% and a mean operative time of 43 ± 18 min were reported. All patients stayed in the hospital for one day except for one who presented minor hematuria. Additional complications did not occur. Conclusion: Ho:YAG laser lithotripsy > 100 W is an effective, fast and safe modality for the treatment of bladder calculi.

Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic.

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance.

Effects of school-based interventions on blood pressure in obese children: metanalysis / Efeitos de intervenções de base escolar na pressão arterial de crianças com obesidade: metanálise

Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), a systematic review with metanalysis was conducted to identify and summarize the effects of school-based physical activity interventions that sought to control and / or reduce blood pressure (systolic and diastolic) in children and / or adolescents with overweight and / or obesity. In September 2022, potential studies were searched in five electronic databases (Pubmed, Scielo, Scopus, Sportdiscus, and Web of Science) and in reference lists. Randomized controlled trials conducted in schools with interventions involving physical activity and assessment of systolic and diastolic blood pressure in children and adolescents aged 6 to 19 years with overweight and / or obesity were con-sidered for synthesis. The risk of bias was assessed using an adapted version of the Effective Public Health Practice Project tool (EPHPP). Metanalysis was developed from the random model. Four studies were included. For systolic blood pressure, a summary effect of -0.10 (95% CI: -0.39; 0.19; I2 = 0%) was observed. For diastolic pressure, the metanalysis indicated -0.33 (95% CI: -0.62; -0.04; I2 = 11%). Considering the promising effects on diastolic blood pressure, we suggest the develop-ment of more school-based interventions based on physical activity practice for overweight and / or obese populations, which may also add environmental elements, longer duration, multicomponent approaches, and parent / guardian involvement to their strategies.

Com base na declaração Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), foi realizada uma revisão sistemática com metanálise para identificar e sumarizar os efeitos de intervenções escolar baseadas na atividade física que buscaram o controle e / ou redução da pressão arterial (sistólica e diastólica) em crianças e / ou adolescentes com excesso de peso e / ou obesidade. Em setembro de 2022, estudos potenciais foram pesquisados em cinco bases de dados eletrônicas (Pubmed, Scielo, Scopus, Sportdiscus, e Web of Science) e em listas de referências. Foram considerados para a síntese ensaios controlados randomizados realizados em escolas, com intervenções que envolviam a atividade física e avaliação da pressão arterial sistólica e diastólica em crianças e adolescentes dos 6 aos 19 anos com excesso de peso e/ ou obesidade. O risco de viés foi avaliado utilizando uma versão adaptada do instrumento Effective Public Health Practice Project (EPHPP). A metanálise foi elaborada a partir do modelo randômico. Foram incluídos quatro estudos. Para a pressão arterial sistólica, observou-se um efeito sumarizado de -0,10 (IC 95%: -0,39; 0,19; I2 = 0%). Para a pressão diastólica, a metanálise indicou -0,33 (IC 95%: -0,62; -0,04; I2 = 11%). Considerando os efeitos promissores na pressão arterial diastólica, sugerimos o desenvolvimento de mais intervenções escola-res fundamentadas na prática de atividade física às populações com sobrepeso e / ou obesidade, que possam agregar também, em suas estratégias, elementos ambientais, maior duração, abordagens multicomponentes e envolvimento dos pais / responsáveis.

Assessing pain in persons with opioid use disorder: Approaches, techniques and special considerations.

Pain and opioid use disorder (OUD) are inextricably linked, as the former can be a risk factor for the development of the latter, and over a third of persons with OUD suffer concomitant chronic pain. Assessing pain among people with OUD is challenging, because ongoing opioid use brings changes in pain responses and most pain assessment tools have not been validated for this population. In this narrative review, we discuss the fundamentals of pain assessment for populations with OUD. First, we describe the biological, psychological and social aspects of the pain experience among people with OUD, as well as how opioid-related phenomena may contribute to the pain experience in this population. We then review methods to assess pain, including (1) traditional self-reported methods, such visual analogue scales and structured questionnaires; (2) behavioural observations and physiological indicators; (3) and laboratory-based approaches, such as quantitative sensory testing. These methods are considered from a perspective that encompasses both pain and OUD. Finally, we discuss strategies for improving pain assessment in persons with OUD and implications for future research, including educational strategies for multidisciplinary teams. We highlight the substantial gaps that persist in this literature, particularly regarding the applicability of current pain assessment methods to persons with OUD, as well as the generalizability of the existing results from adjacent populations on chronic opioid therapy but without OUD. As research linking pain and OUD evolves, considering the needs of diverse populations with complex psychosocial backgrounds, clinicians will be better equipped to reduce these gaps.

Effects of the combination of chronic unpredictable stress and environmental enrichment on anxiety-like behavior assessed using the elevated plus maze in Swiss male mice: Hypothalamus-Pituitary-Adrenal Axis-mediated mechanisms.

Environmental enrichment (EE) is a paradigm that offers the animal a plethora of stimuli, including physical, cognitive, sensory, and social enrichment. Exposure to EE can modulate both anxiety responses and plasma corticosterone. In this study, our objective was to explore how chronic unpredictable stress (CUS) impacts anxiety-related behaviors in male Swiss mice raised in EE conditions. Additionally, we investigated corticosterone and adrenocorticotropic hormone (ACTH) levels to assess the involvement of the hypothalamic-pituitary-adrenal (HPA) axis in mediating these responses. Mice were housed under either EE or standard housing conditions for 21 days. Afterward, they were exposed to 11 days of CUS while still reared in their distinct housing conditions, with half of the mice receiving daily pretreatment with the vehicle and the other half receiving daily metyrapone (MET) injections, an inhibitor of steroid synthesis, 30 mins before CUS exposure. Blood samples were obtained to assess plasma corticosterone and ACTH levels. The 11-day CUS protocol induced anxiety-like phenotype and elevated ACTH levels in EE mice. Chronic MET pretreatment prevented anxiety-like behavior in the EE-CUS groups, by mechanisms involving increased plasma corticosterone levels and decreased ACTH. These results suggest a role of the HPA axis in the mechanism underlying the anxiogenic phenotype induced by CUS in EE mice and shed light on the complex interplay between environmental factors, stress, and the HPA axis in anxiety regulation.

Effects of supplementation with different zinc-based products on the growth and health of Nile tilapia.

Zinc is one of the essential microelements for the metabolism of animals. Zinc nanoparticles may have higher bioavailability due to their low specific surface area, facilitating absorption by fish. The present study aimed to evaluate the effects of supplementation with different zinc-based products on the growth and health of Nile tilapia Oreochromis niloticus. Zinc, in different sizes (nanoparticles or bulk) and forms (inorganic or organic), were used as a supplement in the tilapia diet at a dose of 15 mg kg feed-1 for 60 days. At the end of the feeding trial, production performance, hemato-immunological parameters, activity of antioxidant system enzymes, exposure to Streptococcus agalactiae and zinc concentration in the muscle were examined. After the bacterial challenge, the mean corpuscular hemoglobin concentration (MCHC) significantly increased in the fish treated with organic zinc, inorganic nano zinc, and organic nano zinc, while in the control group (inorganic zinc), MCHC remained unchanged. Regarding defense cells, dietary inorganic nano zinc increased the number of basophils (1.50 ± 1.10) compared to organic zinc (0.80 ± 0.90). Lymphocyte count increased after the challenge only in the organic zinc treatments (bulk and nanoparticles). Neutrophils decreased in the control (inorganic zinc) (2.20 ± 1.70) and inorganic nano zinc (2.60 ± 2.70) treatments after the challenge. When compared before and after the bacterial challenge, the plasma antimicrobial titer significantly increased after the bacterial challenge in all treatments. No significant differences were observed for total proteins, enzymes (SOD and CAT), cumulative survival and zinc deposition on fillet. In conclusion, organic zinc in nanoparticles or bulk size increased Nile tilapia innate defense during bacterial infection. However, the other parameters evaluated were not affected by zinc particle size or form (organic or inorganic), indicating that further evaluations should be conducted with organic zinc in nanoparticles or bulk size in the tilapia diet.

From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

Finishing of grazing crossbred steers supplemented with detoxified castor bean meal (Ricinus communis L.) in the rainy-dry transition period.

This study evaluated levels of replacement of soybean meal by castor bean meal in the finishing crossbred steers on Brachiaria brizantha cv. Marandu pasture during the rainy-dry transition period. Forty Holstein-Zebu crossbred steers with an average initial weight of 395.93 ± 10 kg were randomly allocated to four treatment groups that were supplemented with concentrate levels of replacing (0, 290, 613, and 903 g/kg DM of the supplement; at 0.4% body weight [BW]). The experimental period was 120 days. A completely randomized experimental design was adopted; with regression analysis using the computational software package (SAS 9.2, USA). Intake and digestibility of dry matter (DM) and nutrients and animal performance were evaluated. The replacement levels did not influence (P > 0.05) the intakes of DM (kg/day), organic matter (OM, kg/day), neutral detergent fiber (NDF, kg/day and %BW), non-fibrous carbohydrates (NFC, kg/day), or total digestible nutrients (kg/day). However, the intake of crude protein (CP) and ether extract (EE, kg/day) decreased as the replacement levels were increased (P < 0.05). The digestibility of DM, OM, NDF, and EE did not change, whereas CP digestibility decreased linearly and NFC digestibility increased linearly (P < 0.05). The replacement levels did not affect (P > 0.05) final body weight, average daily gain, feed conversion, and carcass yield. Castor bean meal can replace up to 903 g/kg DM of soybean meal in the composition of the supplement without compromising the performance of steers on Marandu pasture during the rainy-dry transition period.

Evaluation of the biological function of ribosomal protein S18 from cattle tick Rhipicephalus microplus.

Rhipicephalus (Boophilus) microplus, also known as the cattle tick, causes severe parasitism and transmits different pathogens to vertebrate hosts, leading to massive economic losses. In the present study, we performed a functional characterization of a ribosomal protein from R. microplus to investigate its importance in blood feeding, egg production and viability. Ribosomal protein S18 (RPS18) is part of the 40S subunit, associated with 18S rRNA, and has been previously pointed to have a secondary role in different organisms. Rhipicephalus microplus RPS18 (RmRPS18) gene expression levels were modulated in female salivary glands during blood feeding. Moreover, mRNA levels in this tissue were 10 times higher than those in the midgut of fully engorged female ticks. Additionally, recombinant RmRPS18 was recognized by IgG antibodies from sera of cattle naturally or experimentally infested with ticks. RNAi-mediated knockdown of the RmRPS18 gene was performed in fully engorged females, leading to a significant (29 %) decrease in egg production. Additionally, egg hatching was completely impaired, suggesting that no viable eggs were produced by the RmRPS18-silenced group. Furthermore, antimicrobial assays revealed inhibitory activities against gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria, affecting bacterial growth. Data presented here show the important role of RmRPS18 in tick physiology and suggest that RmRPS18 can be a potential target for the development of novel strategies for tick control.

Efficacy of topiramate in reducing second-generation antipsychotic-associated weight gain among children: A systematic review and meta-analysis.

AIMS: To conduct a systematic review and meta-analysis with the aim of synthesizing existing data on the efficacy and safety of topiramate as an adjunctive treatment for reducing second-generation antipsychotic (SGA)-associated weight gain in children aged 4-18 years. METHODS: We conducted a comprehensive search of PubMed, Embase, PsychNet and Web of Science from time of their inception up to 12 February 2024, including randomized controlled trials that compared SGA treatment with and without topiramate co-administration in children. The primary outcomes were changes in body weight and body mass index (BMI). Heterogeneity was assessed using I2 statistics. RESULTS: This systematic review included five randomized trials, totalling 139 participants (43.9% female; mean [SD] age 11.9 [3.5] years). Four of these trials were included in the meta-analysis, comprising 116 subjects. We found that topiramate was significantly effective both in reducing SGA-associated weight gain, with a mean difference of -2.80 kg (95% confidence interval [CI] -5.28 to -0.31; p = 0.037, I2 = 86.7%) and a standardized mean difference (SMD) of -1.33 (95% CI -2.14 to -0.51; p = 0.014, I2 = 31.7%), and in reducing BMI change compared to placebo (SMD -1.90, 95% CI -3.09 to -0.70; p = 0.02, I2 = 0%). Sedation risk was lower with topiramate than with placebo (odds ratio 0.19, 95% CI 0.11-0.32; p < 0.01, I2 = 0%). No significant differences were found in dropouts, any other side effects, and metabolic parameters, such as triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and glucose. None of the included studies reported assessments on cognitive side effects. CONCLUSION: This meta-analysis suggests that topiramate is an effective and safe option for mitigating SGA-associated weight gain in children.

The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a "super-fuel" because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels-such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

The macroevolutionary singularity of snakes.

Snakes and lizards (Squamata) represent a third of terrestrial vertebrates and exhibit spectacular innovations in locomotion, feeding, and sensory processing. However, the evolutionary drivers of this radiation remain poorly known. We infer potential causes and ultimate consequences of squamate macroevolution by combining individual-based natural history observations (>60,000 animals) with a comprehensive time-calibrated phylogeny that we anchored with genomic data (5400 loci) from 1018 species. Due to shifts in the dynamics of speciation and phenotypic evolution, snakes have transformed the trophic structure of animal communities through the recurrent origin and diversification of specialized predatory strategies. Squamate biodiversity reflects a legacy of singular events that occurred during the early history of snakes and reveals the impact of historical contingency on vertebrate biodiversity.

Use of Inter-Effort Recovery Hypoxia as a New Approach to Improve Anaerobic Capacity and Time to Exhaustion.

Putti, Germano Marcolino, Gabriel Peinado Costa, Matheus Silva Norberto, Carlos Dellavechia de Carvalho, Rômulo Cássio de Moraes Bertuzzi, and Marcelo Papoti. Use of inter-effort recovery hypoxia as a new approach to improve anaerobic capacity and time to exhaustion. High Alt Med Biol. 25:68-76, 2024. Background: Although adding hypoxia to high-intensity training may offer some benefits, a significant problem of this training model is the diminished quality of the training session when performing efforts in hypoxia. The purpose of this study was to investigate the effects of training and tapering combined with inter-effort recovery hypoxia (IEH) on anaerobic capacity, as estimated by alternative maximum accumulated oxygen deficit (MAODALT) and time to exhaustion (TTE). Methods: Twenty-four amateur runners performed, for 5 weeks, 3 sessions per week of training consisted of ten 1-minute bouts at 120% (weeks 1-3) and 130% (weeks 4 and 5) of maximum velocity (VMAX) obtained in graded exercise test, separated by a 2-minute interval in IEH (IEH, n = 11, FIO2 = 0.136) or normoxia (NOR, n = 13, fraction of inspired oxygen = 0.209). Before training, after training, and after 1 week of tapering, a graded exercise test and a maximal effort to exhaustion at 120% of VMAX were performed to determine TTE and MAODALT. The results were analyzed using generalized linear mixed models, and a clinical analysis was also realized by the smallest worthwhile change. Results: MAODALT increased only in IEH after training (0.8 ± 0.5 eq.lO2) and tapering (0.8 ± 0.5 eq.lO2), with time x group interaction. TTE increased for the pooled groups after taper (23 ± 11 seconds) and only for IEH alone (29 ± 16 seconds). Clinical analysis revealed a small size increase for NOR and a moderate size increase for IEH. Conclusions: Although the effects should be investigated in other populations, it can be concluded that IEH is a promising model for improving anaerobic performance and capacity. World Health Organization Universal Trial Number: U1111-1295-9954. University's ethics committee registration number: CAAE: 32220020.0.0000.5659.

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies.

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.

A human cortical adaptive mutual inhibition circuit underlying competition for perceptual decision and repetition suppression reversal.

A model based on inhibitory coupling has been proposed to explain perceptual oscillations. This 'adapting reciprocal inhibition' model postulates that it is the strength of inhibitory coupling that determines the fate of competition between percepts. Here, we used an fMRI-based adaptation technique to reveal the influence of neighboring neuronal populations, such as reciprocal inhibition, in motion-selective hMT+/V5. If reciprocal inhibition exists in this region, the following predictions should hold: 1. stimulus-driven response would not simply decrease, as predicted by simple repetition-suppression of neuronal populations, but instead, increase due to the activity from adjacent populations; 2. perceptual decision involving competing representations, should reflect decreased reciprocal inhibition by adaptation; 3. neural activity for the competing percept should also later on increase upon adaptation. Our results confirm these three predictions, showing that a model of perceptual decision based on adapting reciprocal inhibition holds true. Finally, they also show that the net effect of the well-known repetition suppression phenomenon can be reversed by this mechanism.

Location of ureteral access sheath in the ureter. Does it affect the fluid flow in different calyces?

Introduction: The aim of this study was to evaluate outflow variation in different locations of the pyelocaliceal system with the use of different ureteral access sheath (UAS) sizes and different UAS positioning. Material and methods: The experimental setup included an anaesthetised porcine model, a 7.5-Fr ureteroscope with a 200-µm laser fibre inserted in the working channel, a hand-held pumping irrigating system, and UAS of different sizes, namely: 9.5/11.5 Fr, 12/14 Fr, and 14/16 Fr. Each UAS was placed just below the ureteropelvic junction (UPJ) or in the mid-ureter. The ureteroscope was placed in the renal pelvis, upper and lower calyces, and outflow measurements were obtained with 3-second interval pumping for one minute in every experimental setup. Results: The UAS positioning in the mid-ureter was associated with significantly higher outflow rates in the lower calyx (p = 0.041). While the UAS was below the UPJ, we observed a trend of lower outflow rate in the lower calyx, which was completely inverted when the UAS was in the mid-ureter. Increasing the UAS size from 9.5/11.5 Fr to 12/14 Fr led to a significant increase in outflow in the renal pelvis and upper calyx (p = 0.007), but not in the lower calyx. A further increase to 14/16 Fr did not produce increased flow. Conclusions: Different locations of the pyelocaliceal system have different fluid mechanics during fURS. In the renal pelvis and upper calyx increasing the diameter of the UAS improved the outflow, whereas in the lower calyx the position of the UAS seems to be the most relevant factor. These variables should be considered when performing fURS, especially with high-power laser lithotripsy.

Effects of Different Protocols of Moderate-Intensity Intermittent Hypoxic Training on Mental Health and Quality of Life in Brazilian Adults Recovered from COVID-19: The AEROBICOVID Double-Blind Randomized Controlled Study.

The aim of this study was to investigate the effects of different protocols of moderate-intensity intermittent hypoxic training in patients who had recovered from COVID-19 on quality of life (QoL) and mental health. The sample of this clinical trial-controlled double-blind study consisted of 67 participants aged 30-69 years, who were organized randomly according to Normoxia, Hypoxia, Hypoxia Recovery or Control Group. Eight weeks of cycle ergometer training were performed with a frequency of three training sessions per week in normoxic or hypoxic conditions (with or without hypoxic recovery). Health-related QoL and Mental Health Status were evaluated by 12-Item Short Form Survey and Depression Anxiety and Stress Scale instruments, respectively. All training groups improved the QoL's physical dimensions (Baseline-Post: Normoxia Group 42.1 (11.0)-48.7 (7.0), Hypoxia Group 46.9 (11.8)-53.5 (6.6) and Hypoxia Recovery Group 45.8 (9.2)-51.1 (5.3)) and mental dimensions (Baseline-Post: Normoxia Group 48.8 (7.9)-54.6 (4.6), Hypoxia Group 45.2 (7.7)-53.2 (3.8) and Hypoxia Recovery Group 46.5 (9.7)-52.0 (9.9)). Regarding mental health outcomes, all training groups decreased depressive symptoms (66.7% Normoxia, 31.2% Hypoxia Recovery and 31% Hypoxia groups), anxiety symptoms (46.5% Normoxia, 45.9% Hypoxia Recovery and 39.5% in the Hypoxia groups) and stress symptoms (40.6% Normoxia, 36.3% Hypoxia Recovery and 22.1% Hypoxia groups). Significant statistical difference was not found between groups. Normoxic and hypoxic training showed a similar effect on QoL and the mental health of Brazilian adults who had recovered from COVID-19.