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A conceptual biorefinery process has been designed for the integration of the protein extraction and the ethanol production from brewers’ spent grain (BSG) and palm kernel meal (PKM). The conceptual process is designed for an industrial scale biorefinery annually processing 20 kton dry weight BSG and 50 kton dry weight PKM with 8000 production hours per year and is used to techno-economically analyse the performance. The techno-economic analysis showed that the biorefinery of BSG has a high economic potential with an internal rate of return of 24 %. However, despite the high raw material costs, the biorefinery of PKM still has a positive internal rate of return of 12 %. The presented virtual biorefinery demonstrated the economic potential of integrating the production of a valuable product, like protein powder for food applications, with the production of biofuel, like ethanol, from the remaining biomass, thereby valorising a larger portion of the biomass with the same raw material costs.

The monoammonium salt of glycyrrhizic acid (AGA) is known to form fibrillar hydrogels and few studies regarding self-assembly of AGA have been published. Yet, the understanding of the fibrillar microstructures and the gelation remains vague. Thus, we attempt to achieve a deeper understanding of the microstructures and the gelation process of binary solutions of AGA in water. Further, we examine the effect of ethanol on the microstructures to pave the way for potential enhancement of drug loading in AGA hydrogels.A partial room temperature phase map of the ternary system AGA/ethanol/water was recorded. Small-angle X-ray and neutron scattering experiments were performed over wide ranges of compositions in both binary AGA/water and ternary AGA/ethanol/water mixtures to get access to the micro-structuring.Binary aqueous solutions of AGA form birefringent gels consisting of a network of long helical fibrils. 'Infinitely' long negatively charged fibrils are in equilibrium with shorter fibrils (≈25 nm), both of which have a diameter of about 3 nm and are made of around 30 stacks of AGA per helical period (≈9nm), with each stack consisting of two AGA molecules. The interaxial distance (order of magnitude ≈20 nm) varies with an almost two-dimensional swelling law. Addition of ethanol reduces electrostatic repulsion and favors the formation of fibrillar end caps, reducing the average length of shorter fibrils, as well as the formation of small, swollen aggregates. While the gel network built by the long fibrils is resilient to a significant amount of ethanol, all fibrils are finally dissolved into small aggregates above a certain threshold concentration of ethanol (≈30 wt%).

Preservation of biological samples is a relevant issue for many scientific disciplines. Although traditional preservers, such as formaldehyde or ethanol, imply major disadvantages related to health risks, DNA degradation and distortion of structures, they are widely used. Hence, the search for viable alternatives preserving morphometry and genetics seems necessary. Here we assess the suitability of DESS solution to preserve adult nematodes and their eggs in faeces. Concretely, faecal samples of terrestrial tortoises with oxyurids were used to: (i) compare the 1-month storage efficacy of eggs from different conservation protocols (faeces without preserver at -20 °C, faeces with DESS solution at room temperature, faeces with DESS solution at -20 °C and faeces with ethanol 70% at room temperature); (ii) address morphological nematode identification after 2 years of storage with DESS. We also corroborated that nematode DNA remained viable after 2 years. Overall, our results showed that DESS solution at room temperature is an advisable alternative to conserve both parasite eggs and adult nematodes for morphological identification and genetic purposes. It also offers the advantages of being low-cost, safe and suitable for fieldwork conditions and shipments without refrigeration for nematode preservation. MG was supported by a contract for postdoctoral researchers from the Generalitat Valenciana with reference APOSTD/2021/181. RCRC was supported by the European Union-Next Generation EU in the Maria Zambrano Program (ZAMBRANO 21-26). This research had the financial support of project PID2019-105682RA-I00, funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033.

Current management of hemorrhagic shock relies on control of surgical bleeding along with resuscitation with packed red blood cells and plasma in a 1-to-1 ratio. Transfusion, however, is not without consequence as red blood cells develop a series of biochemical and physical changes during storage termed "the red blood cell storage lesion." Previous data has suggested that ethanol may stabilize the red blood cell membrane, resulting in improved deformability. We hypothesized that storage of packed red blood cells with ethanol would alter the red blood cell storage lesion.Mice underwent donation and storage of red blood cells with standard storage conditions in AS-3 alone or ethanol at concentrations of 0.07%, 0.14%, and 0.28%. The red blood cell storage lesion parameters of microvesicles, Band-3, free hemoglobin, annexin V, and erythrocyte osmotic fragility were measured and compared. In additional experiments, the mice underwent hemorrhage and resuscitation with stored packed red blood cells to further evaluate the in vivo inflammatory impact.Red blood cells stored with ethanol demonstrated decreased microvesicle accumulation and Band-3 levels. There were no differences in phosphatidylserine or cell-free hemoglobin levels. After hemorrhage and resuscitation with packed red blood cells stored with 0.07% ethanol, mice demonstrated decreased serum levels of interleukin-6, macrophage inflammatory protein-1α, keratinocyte chemokine, and tumor necrosis factor α compared to those mice receiving packed red blood cells stored with additive solution-3.Storage of murine red blood cells with low-dose ethanol results in decreased red blood cell storage lesion severity. Resuscitation with packed red blood cells stored with 0.07% ethanol also resulted in a decreased systemic inflammatory response in a murine model of hemorrhage.

Hand disinfection plays an important role in infection control. Currently, hand sanitizers containing ethanol and chlorhexidine gluconate as active ingredients are widely used. Most of hand sanitizers have a defined expiration date for use. However, there was no rule about the expiration date after opening defined with the evidence. Therefore, we examined the fluctuation of active ingredients and disinfection effect after opening the bottle.Twelve hand sanitizers from 44 to 921 days after opening set in different places in the hospital were examined and unopened hand sanitizer used as a control. Chlorhexidine gluconate and ethanol of each samples were measured by high performance liquid chromatography and gas chromatography, respectively. The correlation between the concentration of each ingredient obtained and the number of days after opening, bottle weight, storage temperature and humidity was analyzed. A time-kill test based on ASTM E2315-03 was performed to confirm the actual disinfection effect.It was observed that active ingredients had not been decreased up to 921 days after opening and were not affected by storage conditions after opening. In addition, a decrease of disinfection effect was not observed in any sample.We found that hand sanitizers do not need to be discard after a number of days have passed because the active ingredients are retained even after opening in it.

Clinical studies indicate that alcohol-dependent patients may develop depressive symptoms during abstinence, which may increase the likelihood of relapse. It is known that both in alcohol exposure and depression, there is an increase in the levels of pro-inflammatory cytokines in the brain. However, the putative contribution of increased levels of pro-inflammatory cytokines in the development of depressive-like behavior during ethanol withdrawal has not been evaluated. In the present study, we aimed to investigate if ethanol withdrawal-induced depressive-like behavior is related to increased levels of pro-inflammatory cytokines in the brain. Male mice were treated with vehicle (saline 0.9%, v.o.) or ethanol (2 g/kg, v.o.) for 14 days. After 5 days of cessation of the ethanol treatment, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT) and then sacrificed. Their brains were analyzed for the levels of pro-inflammatory cytokines. Ethanol withdrawal mice showed increased immobility time in the FST and TST than by the control group, indicating increased depressive-like behavior. No alterations in OFT were observed. Ethanol withdrawal increased the levels of tumor necrosis factor-alpha (TNF-α) in the hippocampus and striatum, interleukin-1 beta (IL-1β) in the hippocampus, and IL-6 in the prefrontal cortex and hippocampus. Treatment of mice with nimesulide (5 or 10 mg/kg/day), a cyclooxygenase-2 inhibitor, during ethanol withdrawal prevented the increase in immobility time in the TST. Similar results were observed in the FST upon nimesulide treatment, although with a higher dose. Nimesulide treatment (10 mg/kg) prevented the ethanol withdrawal-induced alterations in the levels of TNF-α, IL-1β, and IL-6 in the hippocampus, prefrontal cortex, and striatum. Treatment of mice with an atypical antidepressant drug, vilazodone (0.3 or 1 mg/kg) prevented the increase in depressive-like behavior induced by ethanol withdrawal in the TST. In the FST, the increase in immobility time was prevented only by 1 mg/kg vilazodone treatment. Vilazodone prevented the increase in the levels of TNF-α, IL-1β, and IL-6 in the hippocampus, IL-6 in the prefrontal cortex, and TNF-α in the striatum. In conclusion, these data indicate that increased levels of pro-inflammatory cytokines may play a role in the development of depressive-like behavior during ethanol withdrawal in mice.

Ethanol has recently been demonstrated as a suitable carbon source for acetyl-CoA-derived products with high theoretical yield. Herein, the short-chain-length polyhydroxyalkanoates production pathway was constructed in an industrial platform P. putida KT2440, allowing the engineered strain to produce 674.97 ± 22.3 mg/L of Polyhydroxybutyrate (PHB) from ethanol as sole carbon source. Furthermore, the ethanol catabolic pathway was reconstructed to enhance the acetyl-coA pool by expressing the novel Aldehyde dehydrogenases from Klebsiella pneumonia and Dickeya zeae, resulting in a titer of 1385.34 ± 16.5 mg/L and 9300 ± 0.56 mg/L of PHB in shake flask and fermenter, respectively. Furthermore, transcriptome analysis was conducted to provide insights into the central metabolic pathways and different expression patterns in response to changes in substrate. Additionally, the production of co-polymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) was shown using glycerol and ethanol as co-substrates from recombinant P. putida KT2440. This work demonstrates the potential of P. putida KT2440 as a promising industrial platform for short-chain-length PHAs production from structurally unrelated carbon sources.

Ternary mixtures, containing one hydrotrope and two immiscible fluids, both being soluble in the hydrotrope at any proportion, exhibit unexpected solubilization power and unusual mesoscopic properties, which are a subject of long-standing controversies for decades.This work investigates the entire monophasic region of ternary trans-anethol/ethanol/water system, where multiscale nanostructurings with correlation lengths exceeding dimensions of individual molecules are identified by dynamic light scattering. The physical properties of the ternary mixture are characterized, with revealing the compositional dependence of refractive index and dynamic viscosity.In surfactant-free microemulsion (SFME) regime, the single phase consists of two distinct nanoscopic domains in equilibrium, one trans-anethol-rich aggregate at the molecular scale (∼1 nm) and one mesoscopic droplet at the mesoscale (∼100 nm). However, only a tiny fraction of the hydrophobic component trans-anethol (∼0.025%) are initially incorporated in mesoscale structures, and the vast majority are molecularly dissolved or in the form of aggregates. The concentration of mesoscopic droplets increases sharply when shifting toward the miscibility gap, but their size exhibits a weak compositional dependence. The nanoscopic domains exhibit long-term physical stability, and the Ostwald ripening is still the primary mechanism governing such mesoscopic droplet aging, but with a rather low ripening rate.

This study aimed to derive a new score, the Alcohol Septal Ablation-Sudden Cardiac ARREst (ASA-SCARRE) risk score, that can be easily used to evaluate the risk of sudden cardiac arrest events (sudden cardiac death, resuscitation, or appropriate implantable cardioverter-defibrillator discharge) after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy. We analyzed 1,834 patients from the Euro-ASA registry (49% men, mean age 57 ± 14 years) who were followed up for 5.0 ± 4.3 years (9,202 patient-years) after ASA. A total of 65 patients (3.5%) experienced sudden cardiac arrest events, translating to 0.72 events per 100 patient-years. The independent predictors of sudden cardiac arrest events were septum thickness before ASA (hazard ratio 1.09 per 1 mm, 95% confidence interval 1.04 to 1.14, p0.001) and left ventricular outflow tract (LVOT) gradient at the last clinical checkup (hazard ratio 1.01 per 1 mm Hg, 95% confidence interval 1.01 to 1.02, p = 0.002). The following ASA-SCARRE risk scores were derived and independently predicted long-term risk of sudden cardiac arrest events: "0" for both LVOT gradient30 mmHg and baseline septum thickness20 mm; "1" for LVOT gradient ≥30 mm Hg or baseline septum thickness ≥20 mm; and "2" for both LVOT gradient ≥30 mm Hg and baseline septum thickness ≥20 mm. The C statistic of the ASA-SCARRE risk score was 0.684 (SE 0.030). In conclusion, the ASA-SCARRE risk score may be a useful and easily available clinical tool to predict risk of sudden cardiac arrest events after ASA in patients with hypertrophic obstructive cardiomyopathy.

Cannabis legalization and use are outpacing our understanding of its long-term effects on brain and behavior, which is fundamental for effective policy and health practices. Existing studies are limited by small samples, cross-sectional measures, failure to separate long-term from recreational use, and inadequate control for other substance use. Here, we address these limitations by determining the structural brain integrity of long-term cannabis users in the Dunedin Study, a longitudinal investigation of a population-representative birth cohort followed to midlife.We leveraged prospective measures of cannabis, alcohol, tobacco, and other illicit drug use in addition to structural neuroimaging in 875 study members at age 45 to test for differences in both global and regional gray and white matter integrity between long-term cannabis users and lifelong nonusers. We additionally tested for dose-response associations between continuous measures of cannabis use and brain structure, including careful adjustments for use of other substances.Long-term cannabis users had a thinner cortex, smaller subcortical gray matter volumes, and higher machine learning-predicted brain age than nonusers. However, these differences in structural brain integrity were explained by the propensity of long-term cannabis users to engage in polysubstance use, especially with alcohol and tobacco.These findings suggest that diminished midlife structural brain integrity in long-term cannabis users reflects a broader pattern of polysubstance use, underlining the importance of understanding comorbid substance use in efforts to curb the negative effects of cannabis on brain and behavior as well as establish more effective policy and health practices.

Radiofrequency catheter ablation (RFCA) is the first-line therapy for treatment of drug refractory ventricular arrhythmias (VAs), however, creating a safe, transmural lesion can be difficult. Ethanol in the arterial system has been used as an adjunctive therapy to RFCA since 1986, but with limited use due to technical and efficacy limitations. Venous ethanol is emerging as powerful alternative.

Catalytic dehydrogenation of ethanol produces acetaldehyde, an important precursor for several value-added chemicals such as acetic acid and acetate esters. In this paper, we demonstrate that Zn-containing MFI zeolites are highly active and selective catalysts for this process. Furthermore, we show that their activity and selectivity depend on the chemical composition and preparation of the catalysts. The best catalyst comprises 5 wt% Zn on Silicalite-1 zeolite and results in 65.2% conversion and 94.5% selectivity towards acetaldehyde at 400 ℃. We relate the high selectivity to the absence of Brønsted acidic silanol groups, which suppresses the dehydration of ethanol into ethylene. Furthermore, while pure HZSM-5 and NaZSM-5 zeolites result in dehydration products, such as ethylene and diethyl ether, Zn on NaZSM-5 zeolite also results in acetaldehyde, which confirms that Zn is the active site. Finally, we compare different preparation procedures to show that several Zn-species may be active for the catalytic reaction.

The economic production of bioethanol as a sustainable liquid fuel is particularly needed and attractive. Giant reed as a low-cost and renewable biomass can be utilized as a sustainable feedstock for bioethanol development. The current research focuses on optimizing the fermentation parameters to increase ethanol concentration while lowering production costs. In this work, the giant reed was hydrolyzed thermochemically using HCl; cellulose and hemicellulose fractions were maximally converted at optimized hydrolysis conditions (5% HCl, 30 min, and 120 °C), resulting in a high sugar concentration (≈ 55 g/L), which were fermented by Candida tropicalis Y-26 for bioethanol production (≈ 15 g/L). Taguchi design was used to optimize the fermentation parameters (temperatures, pH, incubation period, and nitrogen sources). Under optimum fermentation conditions (25 °C; 24 h.; pH 5.5; and ammonium nitrate as a nitrogen source), the ethanol concentration at flask level accomplished ≈ 21 g/L, while its scale-up to bioreactor level contributed ≈ 25 g/L (equivalent to 250 kg ethanol/ton biomass) with ≈ 67% increase than the fermentation under unoptimized conditions. Overall, these findings proved that optimizing the fermentation parameters by Taguchi design and scaling up at a bioreactor could improve bioethanol production from giant reed biomass.

Although microdialysis is a common in vivo sampling technique, a detailed characterization of the performance of a microdialysis probe used for sampling ethanol molecules has not been conducted. In this work, experimental and computational investigations were carried out to quantitatively study ethanol diffusion characteristics for home-made and commercially available probes. Probe efficiency, i.e. recovery rate (defined as the ethanol concentration in the dialysate to that in the external medium surrounding the probe) was used to characterize the performance. The recovery rate was measured at different perfusion flow rates (0.1, 0.2, 0.5, 1, 1.5, 2 μL/min) and external ethanol concentrations (1, 2.5, 5, 10, 20 mM) with controlled environmental conditions. Effect of temperature was also investigated at 19, 37 and 47 °C. The results show that reducing the flow rate from 2 to 0.1 μL/min at least triples the recovery rate for the home-made probes, and it remains nearly unchanged when varying external ethanol concentration. The performance for two commercial microdialysis probes with different membrane materials and configurations were also determined and have similar recovery rates. Through computational modeling, the diffusion coefficient of ethanol in the semipermeable membrane of the home-made probe was determined by fitting the experimental data, and it was found to be 9 × 10

Nanozymes-functional materials that possess intrinsic enzyme-like characteristics-have gained tremendous attention in recent years owing to their unique advantages; however, further research is required to understand their scope in biological applications. In this study, dextran-coated nanogadolinia (DCNG) was synthesised, and its phosphatase mimetic activity was demonstrated. Specifically, the dephosphorylation of adenosine triphosphate (ATP), an important biomolecule, by DCNG was investigated. The results showed that DCNG could selectively catalyse the hydrolysis of the terminal high-energy phosphate bonds of ATP under physiological conditions. Furthermore, the biocompatible DCNG, with remarkable phosphatase mimicking activity, decreased the intracellular ATP content by dephosphorylation and increased ethanol yield during glucose fermentation by S. cerevisiae. These results indicate potential alternatives for improving ethanol yields and exploring novel biological applications of nanozymes.

Previous studies on alcohol drinking and health largely have ignored the potential impact of the timing of drinking.We aimed to investigate the joint associations of the timing of alcohol intake with respect to meals (i.e., with meals or outside of meals) and the amount of alcohol consumed with the risk of type 2 diabetes (T2D).A total of 312,388 current drinkers from the UK Biobank without T2D at baseline were included. Cox proportional hazards models were used to examine the association between the timing of alcohol intake with respect to meals and the risk of T2D.During a median of 10.9 y of follow-up, 8598 incident cases of T2D were documented. After adjustment for covariates and the amount of alcohol consumed, consuming alcohol with meals was significantly associated with a 12% lower risk of T2D (HR: 0.88; 95% CI: 0.83, 0.93) than was consuming alcohol outside of meals. In addition, we found that the timing of alcohol intake with respect to meals significantly modified the relations between the amount of alcohol consumed and risk of T2D (P-interaction = 0.017); the beneficial association of moderate drinking with T2D risk was only observed in participants who consumed alcohol with meals, but not in others. Further analyses on various types of alcoholic beverages indicated that the beneficial associations between alcohol drinking with meals and T2D were mainly driven by wine consumption. Moreover, we found that when consumed together with meals, drinking more wine, rather than other alcoholic beverages, was related to lower concentrations of C-reactive protein.In current drinkers, moderate drinking of alcohol, especially wine, with meals is associated with a lower risk of T2D.

The replacement of plastic microbeads with biodegradable alternatives is essential due to the environmental persistence of plastics and their accumulation within the human food chain.Cellulose microbeads could be such alternative, but their production is hindered by the high viscosity of cellulose solutions. It is expected that this viscosity can be harnessed to induce filament thinning of jets of cellulose solutions to create droplets with diameters within the micrometre range, which can then be converted to solid cellulose microbeads via phase inversion.A 3D printed rotating multi-nozzle system was used to generate jets of cellulose dissolved in solutions of [EMIm][OAc] and DMSO. The jets were subject to Rayleigh breakup to generate droplets which were captured in an ethanol anti-solvent bath, initiating phase-inversion, and resulting in regeneration of the cellulose into beads.Control of both process (e.g. nozzle dimensions) and operational (e.g. rotational speed and pressure) parameters has allowed suppression of both satellite droplets generation and secondary droplet break-up, and tuning of the filament thinning process. This resulted in the continuous fabrication of cellulose microbeads in the size range 40-500 μm with narrow size distributions. This method can produce beads in size ranges not attainable by existing technologies.

Alcoholic liver disease (ALD) is a leading cause of chronic liver disease worldwide with limited therapeutic options. The role of fibronectin type III domain-containing protein 3B (FNDC3B), an important regulator of metabolism, in ALD, and the underlying mechanism as well as its potential implication in ALD therapeutic strategies remain unknown.Hepatocyte-specific FNDC3B knockdown or control C57BL/6 N mice received a Lieber-DeCarli diet for four weeks, followed by oral gavage (chronic-binge). Primary mouse hepatocytes and cell lines were used for in vitro studies. Liver injury, hepatic steatosis, and lipid peroxidation were assessed.In cultured cells and mouse livers, alcohol exposure increased FNDC3B expression. Hepatocyte-specific FNDC3B deletion aggravated alcohol-induced liver steatosis via AMP-activated protein kinase (AMPK) inhibition. In vitro, FNDC3B expression was negatively regulated by miR-192-5p. Furthermore, FNDC3B deletion significantly exacerbated ethanol-mediated lipid peroxidation. The RNA sequence assay revealed a connection between FNDC3B and ferroptosis, which was verified by the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Additionally, FNDC3B inhibition-mediated AMPK inactivation downregulated transferrin expression, which was associated with marked iron overload and ferroptosis.This study elucidated the critical role of FNDC3B in preventing hepatic steatosis and ferroptosis in response to chronic alcohol consumption. Our findings indicate that FNDC3B is a potential therapeutic target for ALD.

In the present study, we explored the effects of a novel xylanase from camel rumen metagenome (CrXyn) on wheat bran hydrolysis. CrXyn was heterologously expressed in Escherichia coli and showed maximum activity at 40 °C and pH 7.0. Furthermore, CrXyn exhibited preferential hydrolysis of xylan, but no obvious activity toward other substrates, including carboxymethylcellulose and Avicel. Using wheat straw xylan as a substrate, the Km and Vmax values for CrXyn were 5.98 g/L and 179.9 μmol xylose/min/mg protein, respectively. Mn

Caproic acid is the precursor of ethyl caproate, the main representative flavor substance of strong-flavor baijiu (SFB). Caproic acid-producing bacteria are considered to be the most important type of acid-producing microorganisms in the pit mud of the SFB ecosystem. In this study, the Rummeliibacillus suwonensis 3B-1 with a high yield of caproic acid (4.064 g/L) was screened from SFB pit mud. The genome of the R. suwonensis 3B-1 was sequenced, the total size was found to be 4117,671 bp and a calculated GC content of 35.86%. The caproic acid biosynthesis pathway was identified and analyzed, and it showed that 3B-1 could not only use ethanol, but it could also use glucose and other carbon sources as substrates to produce caproic acid. According to the genome analysis and with an optimized medium, the optimal conditions for caproic acid production were yeast powder at 3 g/L, sodium acetate at 15 g/L, and 1% biotin at 8 mL/100 mL. The yield of caproic acid reached 4.627 g/L, an increase of 13.9%, which was higher than that of general caproic acid bacteria. This is the first report of the synthesis of caproic acid by R. suwonensis. This strain could be used to produce caproic acid, an artificial pit mud preparation, and/or an enhanced inoculum in the production of SFB.

Osteosarcoma (OS) is a highly metastatic bone cancer that usually affects children. Rhizoma Paridis saponins (RPS) have been identified to show a broad-spectrum anti-tumor activity. Our previous study has identified vasculogenic mimicry (VM) as an indicator of poor prognosis for OS. Rhizoma Paridis ethanol extract exhibits potent anti-OS property. However, the anti-metastatic effect of RPS on OS and the detailed mechanisms remain unknown. RPS was characterized by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS) analysis. The anti-OS, anti-metastasis and anti-VM activities of RPS were investigated using in vitro biological assays and a xenograft mouse model. Western blot, qRT-PCR, ELISA, Phalloidin staining and immunohistochemistry assays were conducted to investigate the molecular mechanism of RPS. A total of 34 phytochemicals from RPS were identified by LC/Q-TOF/MS. RPS dose-dependently suppressed the OS cell proliferation, metastasis and VM formation in vitro and in vivo. Mechanically, we found that RPS downregulated migration-inducing gene 7 (MIG-7) expression, resulting in inhibition of the PI3K/MMPs/Ln-5γ2 pathway and cell protrusion formation. Additionally, we confirmed that RPS downregulated MIG-7 by upregulating miR-520d-3p expression. Our results suggests that RPS inhibits the VM formation and metastasis of OS by modulating the miR-520d-3p/MIG-7 signaling axis.

Initiating alcohol use in adolescence significantly increases the likelihood of developing adult alcohol use disorder (AUD). However, it has been difficult to replicate adolescent alcohol exposure leading to increased adult alcohol intake across differing preclinical models. In the present study, differentially housed male rats (group vs. single cages) were used to determine the effects of voluntary intermittent exposure of saccharin-sweetened ethanol during adolescence on adult intake of unsweetened 20% ethanol. Adolescent male rats were assigned to group- or isolated-housing conditions and underwent an intermittent 2-bottle choice in adolescence (water only or water vs. 0.2% saccharin/20% ethanol), and again in adulthood (water vs. 20% ethanol). Intermittent 2-bottle choice sessions lasted for 24 h, and occurred three days per week, for five weeks. Rats were moved from group or isolated housing to single-housing cages for 2-bottle choice tests and returned to their original housing condition on off days. During adolescence, rats raised in isolated-housing conditions consumed significantly more sweetened ethanol than rats raised in group-housing conditions, an effect that was enhanced across repeated exposures. In adulthood, rats raised in isolated-housing conditions and exposed to sweetened ethanol during adolescence also consumed significantly higher levels of unsweetened 20% ethanol compared to group-housed rats. The effect was most pronounced over the first five re-exposure sessions. Housing conditions alone had little effect on adult ethanol intake. These preclinical results suggest that social isolation stress, combined with adolescent ethanol exposure, may play a key role in adult AUD risk.

Alcoholism affects about 2 billion people worldwide. Withdrawal causes a neuroinflammatory response that increases anxiety. α-tocopherol is the most important antioxidant that has its in vivo action currently known. Therefore, this study aimed to evaluate the effect of α-tocopherol on the neuroinflammatory process in brain regions involved in anxiety and its anxiolytic potential during alcohol withdrawal. For this, male Wistar rats were divided into four groups and submitted to a procedure of forced and chronic self-administration of liquid diet containing 6% and 8% ethanol for 15 days, followed by abrupt interruption of treatment. Animals in the control group received the liquid diet without ethanol. Twenty-four or 48 h after ethanol discontinuation, and 30 min after the last administration of α-tocopherol or saline, animals were evaluated in the elevated plus maze, light/dark box, and open field tests. At the end of the tests, each experimental group underwent brain tissue collection for analysis of cytokine levels. The results showed that: alcohol induces the neuroinflammatory process and anxiety; the stress generated by withdrawal can induce oxidative stress, which alters the production of inflammatory cytokines in the amygdaloid nuclei (AN) and medial hypothalamic nucleus (mHN); α-tocopherol exhibited anxiolytic and anti-inflammatory activity, attenuating the anxious behavior of abstinent animals and reducing neuroinflammation in AN and mHN; and the intensity of the anxiolytic and anti-inflammatory effect of α-tocopherol is dose-dependent. These results identify α-tocopherol as a potential therapeutic target supporting the fight against relapse during alcohol withdrawal.

Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.

The weight-loss surgery Roux-en Y gastric bypass (RYGB) is a relatively effective, long-term treatment option for patients with morbid obesity. However, accumulating clinical evidence suggests that patients receiving RYGB may be at increased risk of developing alcohol use disorder. This observation has been repeatedly supported by preclinical studies showing rodents increase intake of ethanol (EtOH) after RYGB, and has been further confirmed by human studies. A promising alternative to RYGB is sleeve gastrectomy (SG), which has resulted in decreased EtOH consumption in some rodent studies. The exact mechanism underlying the differential alcohol outcomes after RYGB versus SG has yet to be elucidated. However, the gut hormone ghrelin has emerged as a potential candidate from previous preclinical studies specific to RYGB surgeries and due to its action to stimulate food and alcohol intake and cravings. To directly assess changes in plasma ghrelin levels following weigh loss surgeries in the context of alcohol intake, 24 female rats were separated into three surgical groups receiving RYGB, SG, or Sham surgery followed by caloric restriction to produce adiposity matched controls (Sham-AM). Blood was drawn for fasted and fed plasma ghrelin (acyl and des-acyl) assays at multiple time points: while on a normal diet (ND), after 5-week exposure to a high fat diet (HFD), following surgery, and after a series of two-bottle alcohol choice test with increasing concentrations (2%, 4%, 6%, 8%) of EtOH. Consistent with previous observations, RYGB rats drank more EtOH than SG rats across all concentrations. As expected, fasted ghrelin levels were blunted after HFD feeding, compared to normal diet baseline. After RYGB, fasted ghrelin levels returned to higher levels while remained blunted after SG and Sham-AM. Fed acyl ghrelin levels were significantly increased to above "normal" levels after RYGB, but remain low after SG and Sham-AM. Given that post-RYGB acyl ghrelin levels are raised to a fasted state regardless of actual prandial status, we conclude that RYGB may results in a hormonal state reminiscence of a fasted state with the inability of feeding to inhibit ghrelin production, an effect which could potentially contribute to increased EtOH intake following the surgery. In contrast, following SG, ghrelin levels in rats remain consistent with the fed state regardless of prandial status, potentially explaining lower alcohol intake and lower risk of developing AUD.

We aimed to compare the tolerance and acceptability of alcohol-based surgical hand preparation versus handscrubbing with antimicrobial soap and water by surgeons.Matched quasi-experimental trial in an academic quaternary care hospital in Ribeirão Preto, Brazil, from April 1 to October, 31, 2017. Participants were cardiac and orthopedics surgeons from the study facility. In the first study phase, they performed handscrubbing with either 2% chlorhexidine (CHG) or 10% iodopovidone (PVP-I) and, in the second phase, they performed handrubbing with alcohol-based handrub (ABHR). Surgeons' skin tolerance and acceptability were evaluated using WHO-validated tools. Data were analyzed using the MacNemar's test within STATA.A total of 33 surgeons participated to the "per protocol" population; the majority were male (94%); mean age of 35 years (SD, 8.5). On product tolerance, there was a minimal variation in redness, scaliness, fissures, and visual evaluation of the skin when handrubbing with ABHR was compared to handscrubbing with either PVP-I or CHX. Regarding acceptability, participants rated better handrubbing with ABHR than handscrubbing with PVP-I when assessing product smell (66.6% vs 0%, p=0.002), color (73.3% vs 0%, p=0.001), product texture (60% vs 0%, p=0.004), skin dryness (60% vs 0%, p=0.004), ease of application (66.6% vs 0%, p=0.002) and overall satisfaction (66.6% vs 6.7% p=0.011). Participants rated similarly handrubbing with ABHR and handscrubbing with CHX, except for product texture, where handrubbing rated better (71,4% vs. 0%, p=0.002). Handrubbing with ABHR was preferred by 73.3%.Although handrubbing and handscrubbing were equally well tolerated by surgeons, alcohol-based surgical hand preparation fell into the personal preference for most of them.Brazilian Clinical Trials Registry (ReBEC), RBR-8ym9yj.

In United States military veterans, chronic pain represents a risk factor for opioid and alcohol misuse, yet few studies have examined interactions among chronic pain, opioid prescription, and opioid and alcohol misuse. Previous work found substantial risk of co-morbid alcohol and opioid misuse in a community sample of opioid-prescribed individuals with chronic pain, a finding expanded upon here. Specifically, 211 veterans assessed within a chronic pain treatment service for opioid-prescribed individuals completed self-report measures of opioid misuse, alcohol misuse, pain intensity, depression, pain catastrophizing, and post-traumatic stress symptoms (PTS). Based on the substance misuse measures, 32% (n = 68) were misusing neither opioids nor alcohol, 23% (n = 48) were misusing both opioids and alcohol, 40% (n = 84) were misusing opioids alone, and 5% (n = 11) were misusing alcohol alone. Group comparisons indicated that individuals not misusing either substance were less distressed in comparison to those who were misusing opioids alone or both substances. The latter groups differed in PTS. Overall, misuse frequencies mirrored previous work, with approximately 1 of 3 misusing opioids and approximately 1 of 5 misusing both substances. There is a need for increased focus on both polysubstance misuse and the development of integrated treatment. PERSPECTIVE: Opioid and alcohol misuse was examined in 211 Veterans prescribed opioids for chronic pain. In total, 32% were not misusing either, 23% were misusing both, 40% were misusing opioids, and 5% were misusing alcohol. Veterans not misusing either were generally less disabled and distressed compared to those misusing opioids or both.

Microbial chain elongation is a newly developed carboxylate platform-based bioprocess, which often encounters high salinity stress due to saline feedstock and pH adjustment. In this study, we systematically investigated the effects of salt types (Na

Alcohol use disorder (AUD) is a rapidly growing concern in the United States. Current trending escalations of alcohol use are associated with a concurrent rise in alcohol-related end-organ damage, increasing risk for further diseases. Alcohol-related end-organ damage can be driven by autonomic nervous system dysfunction, however studies on alcohol effects on autonomic control of end-organ function are lacking. Alcohol intake has been shown to reduce insulin secretions from the pancreas. Pancreatic insulin release is controlled in part by preganglionic parasympathetic motor neurons residing in the dorsal motor nucleus of the vagus (DMV) that project to the pancreas. How these neurons are affected by alcohol exposure has not been directly examined. Here we investigated the effects of acute ethanol (EtOH) application on DMV pancreatic-projecting neurons with whole-cell patch-clamp electrophysiology. We found that bath application of EtOH (50 mM) for greater than 30 min significantly enhanced the frequency of spontaneous inhibitory post synaptic current (sIPSC) events of DMV pancreatic-projecting neurons suggesting a presynaptic mechanism of EtOH to increase GABAergic transmission. Thirty-minute EtOH application also decreased action potential firing of these neurons. Pretreatment of DMV slices with 20 μM fluoxetine, a selective serotonin reuptake inhibitor, also increased GABAergic transmission and decreased action potential firing of these DMV neurons while occluding any further effects of EtOH application, suggesting a critical role for serotonin in mediating EtOH effects in the DMV. Ultimately, decreased DMV motor output may lead to alterations in pancreatic secretions. Further studies are needed to fully understand EtOH's influence on DMV neurons as well as the consequences of changes in parasympathetic output to the pancreas.

Mesalazine is a low-permeable and low-soluble drug, which makes it a class IV drug in the Biopharmaceutics Classification System. Hence, its solubilization can be helpful for various stages of formulation development. The purpose of this study was to investigate the solubilization manner and thermodynamics of mesalazine in ternary solvent combinations of {ethanol (1) + propylene glycol (2) + water (3)} using the shake-flask technique at (298.2-313.2) K. In the following, the mathematical representation of the acquired solubility data using some popular models was evaluated. The accuracies of the applied models were described by percentages of mean relative deviation (MRD%). Based on obtained results (MRD%10.0), it can be concluded that the trained models can adequately predict the solubility of mesalazine in the investigated ternary solvent combinations. The findings also revealed that the solution composition and temperatures greatly influence the solubility of mesalazine. In addition, the thermodynamic characteristics of the mesalazine dissolution process indicate that the mesalazine dissolution process is endothermic and entropy-driven. The generating data in the current work also expands the available solubility database for mesalazine in the solvent mixtures.

To evaluate the impact of a multi-component, Aboriginal-led strategy to reduce alcohol-related criminal incidents for Aboriginal people in four rural/remote communities in New South Wales (NSW), Australia.A retrospective multiple baseline design (MBD), using interrupted time series analysis of routinely collected crime data.A statistically significant reduction in alcohol-related criminal incidents was observed in one community for both victims of crime (parameter estimate -0.195; p≤0.01) and persons of interest (parameter estimate -0.282; p≤0.001). None of the analyses show level shifts, meaning there were no measurable changes immediately post the introduction of the Breaking the Cycle (BTC) programs.It is not possible to conclude that the program was effective independently of any other community factors, because the statistically significant result was not observed across multiple communities. The statistically significant result in one community has clear practical benefits in that community: a sustained impact over two years would reduce Aboriginal victims of alcohol-related crime from an estimated 56 incidents per annum to 36, and reduce Aboriginal persons of interest in alcohol-related crime from an estimated 68 alcohol-related person of interest (POI) per annum to 40.The statistically and practically meaningful result in Community 1 highlights the potential of multi-component, Aboriginal-led strategies to reduce alcohol-related criminal incidents. Earlier engagement with researchers, to identify best-evidence strategies to reduce alcohol harms and to facilitate the use of prospective evaluation designs, would help translate the positive outcome in one community across multiple communities.

Atrioventricular block is a frequent major complication after alcohol septal ablation (ASA).The aim of this study was to evaluate the outcomes of patients with implanted permanent pacemaker (PPM) related to a high-grade atrioventricular block after ASA for hypertrophic obstructive cardiomyopathy.We used a multinational registry (the Euro-ASA registry) to evaluate the outcome of patients with PPM after ASA.A total of 1,814 patients were enrolled and followed up for 5.0 ± 4.3 years (median = 4.0 years). A total of 170 (9.4%) patients underwent PPM implantation during the first 30 days after ASA. Using propensity score matching, 139 pairs (n = 278) constituted the matched PPM and non-PPM groups. Between the matched groups, there were no long-term differences in New York Heart Association functional class (1.5 ± 0.7 vs 1.5 ± 0.9, P = 0.99) and survival (log-rank P = 0.47). Patients in the matched PPM group had lower long-term left ventricular (LV) outflow gradient (12 ± 12 mm Hg vs 17 ± 19 mm Hg, P 0.01), more pronounced LV outflow gradient decrease (81% ± 17% vs 72% ± 35%, P 0.01), and lower LV ejection fraction (64% ± 8% vs 66% ± 8%, P = 0.02) and were less likely to undergo reintervention (re-ASA or myectomy) (log-rank P = 0.02).Patients with hypertrophic obstructive cardiomyopathy treated with ASA have a 9% probability of PPM implantation within 30 days after ASA. In long-term follow-up, patients with PPM had similar long-term survival and New York Heart Association functional class but lower LV outflow gradient, a more pronounced LV outflow gradient decrease, a lower LV ejection fraction, and a lower likelihood of reintervention compared with patients without PPM.

Investigation of enhancers to improve recombinant adeno-associated virus 2 (rAAV2) productivity by human embryonic kidney 293 cells (HEK293) suspension culture showed that the addition of ethanol improved the productivity and packaged genome integrity of rAAV2. Further optimization showed that adding ethanol in the range of 0.09%-1.11% (v/v) during rAAV2 production effectively improved rAAV2 productivity and quality. In addition, ethanol addition improved cell viability. Furthermore, proteome and pathway analysis of the cells during rAAV2 production showed that the addition of ethanol resulted in the upregulation of pathways related to intercellular signaling, gene expression, cell morphology, intercellular maintenance, and others. In contrast, pathways related to cell death, immunity, and reactions to infection were downregulated. These changes in pathway regulation were responsible for the improvement in rAAV2 productivity, packaged genome integrity, and cell viability during rAAV2 production. The results of this study can be applied to the production of viral vectors for in vivo gene therapy in an inexpensive and safe manner.

Several food dyes are known to induce amyloid fibrillation when interacting with proteins. Here, we studied the role of sunset yellow (SY) in the amyloid fibrillation of hen egg white lysozyme (HEWL) and characterized the changes using spectroscopy techniques. Turbidity results showed that SY dye induces aggregation in HEWL in concentrations dependent manner. The aggregation induced by SY dye is kinetically very fast, no lag phase was detected, and the kinetics process follows an isodesmic kinetics pathway. The SY-dye induce aggregates have cross-β secondary structure confirmed by far-UV CD measurements. The effect of salts and solvents was also seen on SY-induced aggregates. Turbidity, far-UV CD, and kinetics results suggest that certain concentrations of NaCl and (NH

Chronic pain represents a global health problem with a considerable economic burden. The relation of alcohol intake and chronic pain conditions was assessed in several studies with conflicting results. We used dose-response meta-analysis techniques to answer the question of whether alcohol intake is related to chronic pain occurrence.We searched MEDLINE, Embase, and other databases to identify cohort and case-control studies on alcohol consumption and chronic pain. Sixteen studies were eligible with a total population of 642 587 individuals. Fixed-effects and random-effects pooled estimates were obtained by weighting log odds ratios (ORs) in case-control studies and log incidence rate ratios in cohort studies by the inverse of their variance. A heterogeneity assessment and a dose-response analysis were carried out. Quality scoring was also performed.Our results show that any alcohol consumption was related to lower odds of chronic pain (pooled OR=0.76; 95% confidence interval [CI], 0.61-0.95). The association was non-linear. The ORs by quartile of alcohol doses were as follows: ORAlcohol consumption presents a non-linear inverse association with the occurrence of chronic pain. Although plausible mechanisms could explain this protective effect, other explanations, including reverse causation, are probable.

To assess the association between self-reported alcohol use and prostate cancer (PCa) screening using the U.S.-based Behavioral Risk Factor Surveillance System (BRFSS) survey.A cross-sectional analysis of men aged between 55 and 69 who responded to the PSA screening and alcohol consumption portions of the 2018 BRFSS survey was performed. Alcohol consumption was assessed according with the Centers for Disease Control and Prevention definition of binge and heavy drinking. Rates of PSA screening between binge and non-binge drinkers and among heavy and non-heavy drinkers were compared. A complex weighted multivariable logistic regression model, adjusted for socio-economic covariates and weighted using BRFSS sample weights, was used to test the association between the self-reported alcohol use and the odds of PSA screening.Among 57,774 men eligible for PCa screening, there were 8,276 binge drinkers with an unadjusted PSA screening prevalence of 37% versus 40% in the non-binge drinking group (P = .018). Among 3,836 heavy drinkers, the unadjusted PSA screening prevalence was 34% versus 40% in non-heavy drinkers (P.001). In the multivariable analysis, only heavy drinking status was significantly associated with a lower odds of PSA screening (OR: 0.84, 95% CI: 0.72-0.98, P = .02).Given that alcohol overuse may increase the risk of developing cancer, our finding of lower utilization of PCa screening among heavy drinkers is noteworthy. Efforts to support guideline-concordant cancer screening among heavy drinkers may represent an important strategy to reduce the burden of cancer in these men.

Venous malformations (VMs) and sclerotherapy may disrupt the normal systemic coagulation profile in individuals. This study investigated a correlation between the clinical efficacy of sclerotherapy in the treatment of VMs and the changes in coagulation indexes to provide data that will inform the future application of this therapy.From September 2019 to September 2020, 61 patients were enrolled in this study to receive sclerotherapy with absolute alcohol. The clinical outcomes and the coagulation profile were assessed.Sclerotherapy induced increasing fibrin (original) degradation products (FDP) and D-dimer (D-D) levels. The changes in FDP and D-D level pretreatment and posttreatment were positively correlated with treatment outcomes. Moreover, a repeated treatment with absolute alcohol may restore normal levels of FDP and D-D.Upregulation of FDP and D-D levels after sclerotherapy results in good therapeutic outcomes. Therefore, monitoring changes in FDP and D-D levels in patients with VMs undergoing sclerotherapy may reflect the effects of sclerotherapy.

To compare the postprocedural health care utilization and cost of septal myectomy (SM) and alcohol septal ablation (ASA).Using the OptumLabs Data Warehouse, we analyzed de-identified claims data of adult patients undergoing SM and ASA for obstructive hypertrophic cardiomyopathy from January 1, 2006, through December 31, 2018. We used propensity score weighting to compare the 2-year incidence rates of emergency department visits and rehospitalizations after SM and ASA.We identified 953 patients in total: 660 underwent SM and 293 underwent ASA. There was no difference in the risk (odds ratio, 1.1; 95% CI, 0.6 to 1.8) or frequency (incidence rate ratio, 1.1; 95% CI, 0.8 to 1.5) of emergency department visits, but the annual risk of hospital readmission was 10.8% after SM and 25.9% after ASA during the second postoperative year (P=.004). In those who were ever readmitted, the average length of hospital stay within the first 2 years after ASA was 1.6 times as long as that after SM (incidence rate ratio, 1.6; 95% CI, 1.0 to 2.4). Overall, the 2-year cumulative postprocedural cost was significantly higher after ASA (P.001).Compared with ASA, SM is associated with fewer hospital readmissions and lower 2-year postprocedural health care cost.

A significant amount of binge drinking among adults escapes public health scrutiny because it occurs among individuals who drink at a moderate average level. This observational study examined the role of a binge pattern of drinking in predicting alcohol problems among moderate drinkers in a U.S. national sample of adults.Participants were 1,229 current drinkers aged ≥30 years from 2 waves of the study of Midlife Development in the United States, with a 9-year time lag (2004-2015) (analyzed in 2021‒2022). Negative binomial regression analyses were used to examine the number of alcohol problems, and binary logistic regression analyses were used to examine multiple (≥2) alcohol problems.Independent of the average level of drinking, binge drinking was linked with an almost 3 times increase in the number of concurrent alcohol problems and a 40% increase in the number of alcohol problems prospectively 9 years later. Moderate average level drinkers accounted for most cases of binge drinking and multiple alcohol problems. Among moderate drinkers, binge drinking was linked with a close to 5 times increase in concurrent multiple alcohol problems and a2 times increase in multiple alcohol problems prospectively 9 years later.These results substantially broaden an increasing recognition that binge drinking is a public health concern among adults. Moderate average-level drinkers should be included in efforts to reduce alcohol problems in adults. These findings are applicable to primary and secondary prevention of alcohol problems with the potential to advance population health.

Excessive drinking has detrimental effects on the cardiovascular system. Atrial fibrillation (AF) following alcohol binge drinking, also named "holiday heart syndrome", is well established. However, even chronic lower levels of alcohol intake may also increase AF risk. In this review article, we aim to provide a comprehensive overview of the epidemiology and pathophysiology by which alcohol may be responsible for AF and discuss whether alcohol abstinence is required for optimal rhythm control as well as to maintain sinus rhythm in patients with AF. The pathophysiological mechanisms responsible for the relationship between alcohol consumption and AF may include both direct and chronic effects increasing AF-burden. Acute effects may include arrhythmogenic changes (such as shortening in atrial refractoriness, slowing in conduction velocity and increased atrial ectopy) and an autonomic imbalance. Chronic changes contributing to the development of an arrhythmogenic substrate involve atrial structural and functional remodeling process due to atrial dilatation, elevated pressures and fibrosis formation. Additionally, alcohol consumption contributes to developing concomitant AF risk factors such as obesity, sleep-disordered breathing, and hypertension. Alcohol abstinence is associated with a reduction in AF-recurrence and overall burden and moreover improves AF-risk factor development such as obesity, hypertension, sleep apnea and AF-related consequences such as stroke. In conclusion, alcohol consumption is associated with atrial arrhythmia and a wide range of cardiovascular comorbidities. Although further evidence is needed, current knowledge indicates that there might not be a safe level of alcohol consumption which is not increasing AF-risk.

Cardiovascular disease (CVD), a disease typically associated with aging and the definitive leading cause of death worldwide, now threatens young and middle-aged populations. Recreational abuse of alcohol, marijuana, cocaine, and amphetamine-type stimulants has been an escalating public health problem for decades, but now use of these substances has become a significant contributor to early-onset CVD. While this remains a global phenomenon, the epicentre of substance abuse is rooted in North America, where it has been exacerbated by the response to the COVID-19 pandemic. For the first time in history, the United States crossed 100,000 overdose-related deaths in a calendar year. Sadly, Canada's recreational drug abuse problem closely mirrors that of the US. This is indicative of the larger public health crisis, as we now know that these substances are cardiotoxic and are contributing to the rising levels of premature chronic CVD, including hypertension, arrhythmias, heart failure, stroke, myocardial infarction, arterial dissection, sudden cardiac death, and early mortality.

This research aimed to explore the antidepressant components from Dendrobium officinale flowers (DOF) aqueous extract and their mechanism. Multiple depressive models were successfully used to show that alcohol-soluble polysaccharide-enriched fractions separated from DOF aqueous extract exhibited significant antidepressant effects. Subsequently, a novel alcohol-soluble polysaccharide named ASP was isolated, and its molecular mass was 3.10 × 10

Some individuals with alcohol use disorder (AUD) continue to drink because they have developed a habit where they do not consider the consequences of their actions. Genetically selected lines of alcohol-preferring and non-preferring rats allow for exploration of how specific endophenotypes, such as tendency to form habits, may be risk factors that interact with a genetic predisposition of AUD. While high alcohol drinking (HAD) and alcohol-preferring (P) rats were selectively bred to consume high amounts of freely available ethanol, they exhibit differences in alcohol-seeking behaviors as well as impulsive behaviors, and may represent different behavioral models of AUD. The goal of the current study was to compare the tendency to develop habitual behaviors across female and male HAD1, HAD2, and P rats and their respective alcohol non-preferring counterparts. Alcohol-naïve rats were trained on a variable interval schedule using a non-ethanol reinforcer and were then tested in two extinction sessions, one prior to a reinforcer devaluation (conditioned taste aversion) procedure and one after. There were no differences in total lever presses between P and alcohol non-preferring (NP) rats, but there were differences between HAD and low-alcohol drinking (LAD) rats. All six strains decreased lever pressing after reinforcer devaluation. However, P and NP females did not increase latency to first lever press after devaluation, suggesting some inclination toward habitual behavior that was not apparent in either the HAD or LAD lines. Selective breeding for alcohol preference does not seem to influence the tendency to form habits, whereas background strain and sex may have an influence on this behavior.

Alcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential.HIGHLIGHTSChemogenetic activation of BNST SST neurons reduces binge drinking in female but not male miceChemogenetic activation of these neurons has no effect on anxiety-like behavior in either sexElectrophysiology revealed no clear sex differences in intrinsic excitability BNST SST neurons between males and femalesImaging revealed males had greater overall BNST SST cell numbers than females, but this effect could be explained by normalizing for total BNST volume

Intracranial aneurysms are present in up to 18% of arteriovenous malformations (AVMs) and increase the risk of intracranial hemorrhage. No consensus exists on the optimal treatment strategy for AVM-associated aneurysms. The goal of this study was to systematically review endovascular treatment methods of AVM-associated intracranial aneurysms, radiographic outcomes, and periprocedural complications.A systematic review was performed in accordance with PRISMA guidelines to identify studies that investigated the use of endovascular treatments for management of patients with AVM-associated aneurysms. Collected variables included aneurysm and AVM location, aneurysm size and characteristics, AVM and aneurysm treatment modality, periprocedural complications, and long-term clinical and radiographic outcomes.Eight studies with 237 patients and 314 AVM-associated intracranial aneurysms were included. Two-hundred and twenty-four aneurysms were flow-related (71.3%), 80 were intranidal (25.5%), and 10 were unrelated (3.2%). Complete occlusion was 56.3% (18/32) for aneurysmal coil embolization and 99% (104/105) for parent vessel sacrifice. Of the 13 aneurysms treated with ethanol sclerotherapy, 8 were successfully obliterated (8/13; 61%) using ethanol sclerotherapy alone and the rest required adjunct endovascular embolization for obliteration of the artery and associated aneurysm. The periprocedural complication rate was approximately 12% and consisted of ischemic symptoms, intracranial hemorrhage, and coiling complications.Endovascular management options of AVM-associated intracranial aneurysms are limited and mostly comprised primary aneurysmal coil embolization or parent vessel sacrifice using coils or liquid embolics. Embolization strategy depends on factors such as AVM angioarchitecture, rupture status, and adjunct AVM treatments.

Alcohol has been demonstrated to impair maternal uterine arterial adaptations in Fetal Alcohol Spectrum Disorder (FASD) animal models. However, the exact mechanism remains inconclusive. We hypothesized that phosphatidic acid (PA), a direct target of alcohol metabolism, would alleviate alcohol-induced vascular dysfunction of the maternal uterine artery. Mean fetal weight, and crown-rump length of the alcohol administered rats were ~9 % and 7.6 % lower than the pair-fed control pups, respectively. Acetylcholine (Ach)-induced uterine artery relaxation was significantly impaired in uterine arteries of alcohol-administered rats (P 0.05). Supplementation of 10

The Spontaneously Hypertensive Rats (SHR) strain was developed through selective breeding for high systolic blood pressure. In our laboratory, we established a congenic rat strain named SHR.Lewis-Anxrr16 (SLA16). The SLA16 rat strain is genetically identical to the SHR except for the inserted Anxrr16 region in chromosome 4. Our objective was to evaluate the influence of this genomic region on ethanol consumption and blood pressure. First, we exposed SHR and SLA16 male and female rats to ethanol consumption. Results showed that, regardless of strain, females consumed more ethanol than males during forced (10% v/v) and spontaneous ethanol consumption (SEC; 2.5-20% v/v). Then, females from both strains were used to evaluate sensitivity to ethanol. No strain differences in the loss of righting reflex were observed after ethanol treatment (3 g/kg, 20% w/v, intraperitoneal [i.p.]). But, in the triple test, female SHR rats presented lower sensitivity to the ethanol (1.2 g/kg, 14% w/v, i.p.). Surprisingly, female SHR rats also presented higher blood pressure after SEC (10% v/v). Finally, losartan treatment was effective in decreasing the blood pressure of female rats of both strains, but had specific effects on SHR ethanol consumption. Our data suggest that SLA16 female rats consume less ethanol (10%), are more sensitive to its effects, and present lower blood pressure than SHR female rats. We demonstrated that the Anxrr16 locus in chromosome 4 is a genetic candidate to explain high ethanol consumption and blood pressure, at least in females.

While alcohol use disorder (AUD) is a well-established risk factor for intimate partner aggression (IPA), effective treatments for co-occurring AUD and IPA (AUD/IPA) are lacking. Oxytocin is one promising pharmacological candidate for AUD/IPA given its potential to modulate social behavior and attenuate alcohol use. However, emerging data suggests that oxytocin's prosocial effects are inconsistent, and a small number of studies have also found that oxytocin might have the potential to be aggressogenic. No studies have directly examined the impact of oxytocin on alcohol- or IPA-related outcomes in a dyadic context.The goal of this double-blind, randomized, and placebo-controlled trial was to examine the effects of a single dose of intranasal oxytocin (40 international units) on cue-induced alcohol craving, subjective aggression, laboratory task-based IPA, and cortisol reactivity in a sample of 100 couples (N = 200 individuals) with AUD and physical IPA in their current relationship.There were no statistically significant differences between the oxytocin and placebo conditions for any of the primary outcomes.Findings suggest that a single dose of intranasal oxytocin was not efficacious in mitigating alcohol craving or aggression in this sample. Although hypotheses were not supported, the findings provide important evidence that oxytocin was not aggressogenic in this high-risk sample. Future research investigating dispositional and contextual moderators of oxytocin response in addition to the therapeutic effects of more intensive oxytocin dosing or administration strategies on alcohol craving and aggression is warranted.

Alcohol liver disease (ALD) has become a global threat to human health. It is associated with a wide range of liver diseases including alcohol fatty liver, steatosis, fibrosis and cirrhosis, and finally leads to liver cancer and even death. Centranthera grandiflora is a traditional Chinese medicinal herb commonly used to treat ALD, but no research about its mechanism is available. This study evaluated the hepatoprotective effect and mechanism of C. grandiflora against alcohol-induced liver injury in mice. We found that the ethanol extracts of C. grandiflora (CgW) alleviated the alcohol-induced liver injury, enhanced the levels of antioxidant enzymes, and reduced the amount of lipid peroxides. CgW also affected cell apoptosis by inhibiting the activity of Bax, cleaved-caspase 3 and cleaved-caspase 9, and increasing the activity of Bcl-2. In conclusion, the results showed that CgW can effectively improve ALD through alleviating oxidative stress and inhibiting cell apoptosis for the first time. This study suggested that C. grandiflora is a promising herbal medicine for ALD treatment.