Safety and Efficacy of Ethanol for Catheter Salvage and Central Line-Associated Bloodstream Infection Prophylaxis in Polyurethane Catheters in the PICU.

OBJECTIVES: Ethanol lock therapy (ELT) is a potential method of central catheter salvage following central line-associated bloodstream infection (CLABSI) although there is potential risk of catheter damage in polyurethane catheters. Further, there is limited efficacy data across the spectrum of common pediatric catheters, and published ELT protocols describe dwell times that are not feasible for critically ill children. We sought to evaluate the safety and efficacy of ELT in polyurethane catheters using brief (30 min to 2 hr) dwell times in our PICU. DESIGN: Investigational pilot study using historical control data. SETTING: PICU in quaternary care, free-standing children's hospital. INTERVENTIONS: ELT in polyurethane central venous catheters for catheter salvage. RESULTS: ELT with brief dwell times was used in 25 patients, 22 of whom were bacteremic. Ultimately 11 patients, comprising 14 catheters, were diagnosed with a primary CLABSI. The catheter salvage rate in primary CLABSI patients receiving ELT was 92% (13/14) and significantly higher than the salvage rate in patients receiving antibiotics alone (non-ELT) (62%, 39/64; mean difference 0.32, 95% CI [0.14-0.50], p = 0.03). The rate of catheter fracture in all patients receiving ELT was 8% (2/25) while the rate of fracture in the non-ELT group was 13% (8/64; mean difference -0.05, 95% CI [-0.18 to 0.09], p = 0.72). The rate of tissue plasminogen activator (tPA) use in the ELT group was 8% (2/25), whereas the rate of tPA use in the non-ELT group was significantly higher at 42% (26/64; mean difference -0.34, 95% CI [-0.49 to -0.17], p = 0.002). CONCLUSIONS: The use of ELT for catheter salvage and prophylaxis in the PICU is safe in a variety of polyurethane catheters. Dwell times ranging from 30 minutes to 2 hours were effective in sterilizing the catheters while allowing other therapies to continue. This approach may decrease the need for frequent line changes in a medically fragile pediatric population.

Neuroprotective Effect of Sterculia setigera Leaves Hydroethanolic Extract.

Plants are a valuable source of information for pharmacological research and new drug discovery. The present study aimed to evaluate the neuroprotective potential of the leaves of the medicinal plant Sterculia setigera. In vitro, the effect of Sterculia setigera leaves dry hydroethanolic extract (SSE) was tested on cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide (H2O2) or 6-hydroxydopamine (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43, and the quantification of the expression of genes involved in apoptosis, necrosis, or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the expression of some genes in tissue extracts, the thickness of cerebellar cortical layers and motor coordination. In vitro, SSE protected CGN against H2O2 and 6-OHDA-induced cell death at a dose of 10 µg/mL, inhibited the expression of genes Casp3 and Bad, and upregulated the expression of Cat and Gpx7. In vivo, SSE significantly blocked the deleterious effect of ethanol by reducing the activity of caspase-3, inhibiting the expression of Bax and Tp53, preventing the reduction of the thickness of the internal granule cell layer of the cerebellar cortex, and restoring motor functions. Sterculia setigera exerts neuroactive functions as claimed by traditional medicine and should be a good candidate for the development of a neuroprotective treatment against neurodegenerative diseases.

mGlu2 and mGlu3 receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats.

RATIONALE: The subjective effects of alcohol are associated with alcohol use disorder (AUD) vulnerability and treatment outcomes. The interoceptive effects of alcohol are part of these subjective effects and can be measured in animal models using drug discrimination procedures. The newly developed mGlu2 and mGlu3 negative allosteric modulators (NAMs) are potential therapeutics for AUD and may alter interoceptive sensitivity to alcohol. OBJECTIVES: To determine the effects of mGlu2 and mGlu3 NAMs on the interoceptive effects of alcohol in rats. METHODS: Long-Evans rats were trained to discriminate the interoceptive stimulus effects of alcohol (2.0 g/kg, i.g.) from water using both operant (males only) and Pavlovian (male and female) drug discrimination techniques. Following acquisition training, an alcohol dose-response (0, 0.5, 1.0, 2.0 g/kg) experiment was conducted to confirm stimulus control over behavior. Next, to test the involvement of mGlu2 and mGlu3, rats were pretreated with the mGlu2-NAM (VU6001966; 0, 3, 6, 12 mg/kg, i.p.) or the mGlu3-NAM (VU6010572; 0, 3, 6, 12 mg/kg, i.p.) before alcohol administration (2.0 g/kg, i.g.). RESULTS: In Pavlovian discrimination, male rats showed greater interoceptive sensitivity to 1.0 and 2.0 g/kg alcohol compared to female rats. Both mGlu2-NAM and mGlu3-NAM attenuated the interoceptive effects of alcohol in male and female rats using Pavlovian and operant discrimination. There may be a potential sex difference in response to the mGlu2-NAM at the highest dose tested. CONCLUSIONS: Male rats may be more sensitive to the interoceptive effects of the 2.0 g/kg alcohol training dose compared to female rats. Both mGlu2-and mGlu3-NAM attenuate the interoceptive effects of alcohol in male and female rats. These drugs may have potential for treatment of AUD in part by blunting the subjective effects of alcohol.

Clinical characteristics and outcomes of alcohol septal ablation in the era of transcatheter valve interventions.

BACKGROUND: The clinical efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) have been well-established; however, less is known about outcomes in patients undergoing preemptive ASA before transcatheter mitral valve replacement (TMVR). AIMS: The goal of this study is to characterize the procedural characteristics and examine the clinical outcomes of ASA in both HCM and pre-TMVR. METHODS: This retrospective study compared procedural characteristics and outcomes in patient who underwent ASA for HCM and TMVR. RESULTS: In total, 137 patients were included, 86 in the HCM group and 51 in the TMVR group. The intraventricular septal thickness (mean 1.8 vs. 1.2 cm; p < 0.0001) and the pre-ASA LVOT gradient (73.6 vs. 33.8 mmHg; p ≤ 0.001) were higher in the HCM group vs the TMVR group. The mean volume of ethanol injected was higher (mean 2.4 vs. 1.7 cc; p < 0.0001). The average neo-left ventricular outflow tract area increased significantly after ASA in the patients undergoing TMVR (99.2 ± 83.37 mm2 vs. 196.5 ± 114.55 mm2; p = <0.0001). The HCM group had a greater reduction in the LVOT gradient after ASA vs the TMVR group (49.3 vs. 18 mmHg; p = 0.0040). The primary composite endpoint was higher in the TMVR group versus the HCM group (50.9% vs. 25.6%; p = 0.0404) and had a higher incidence of new permanent pacemaker (PPM) (25.5% vs. 18.6%; p = 0.3402). The TMVR group had a higher rate of all-cause mortality (9.8% vs. 1.2%; p = 0.0268). CONCLUSIONS: Preemptive ASA before TMVR was performed in patients with higher degree of clinical comorbidities, and correspondingly is associated with worse short-term clinical outcomes in comparison to ASA for HCM patients. ASA before TMVR enabled percutaneous mitral interventions in a small but significant minority of patients that would have otherwise been excluded. The degree of LVOT and neoLVOT area increase is significant and predictable.

Serotonin transporter knockdown relieves depression-like behavior and ethanol-induced CPP in mice after chronic social defeat stress.

Patients with stress-triggered major depression disorders (MDD) can often seek comfort or temporary relief through alcohol consumption, as they may turn to it as a means of self-medication or coping with overwhelming emotions. The use of alcohol as a coping mechanism for stressful events can escalate, fostering a cycle where the temporary relief it provides from depression can deepen into alcohol dependence, exacerbating both conditions. Although, the specific mechanisms involved in stress-triggered alcohol dependence and MDD comorbidities are not well understood, a large body of literature suggests that the serotonin transporter (SERT) plays a critical role in these abnormalities. To further investigate this hypothesis, we used a lentiviral-mediated knockdown approach to examine the role of hippocampal SERT knockdown in social defeat stress-elicited depression like behavior and ethanol-induced place preference (CPP). The results showed that social defeat stress-pro depressant effects were reversed following SERT knockdown demonstrated by increased sucrose preference, shorter latency to feed in the novelty suppressed feeding test, and decreased immobility time in the tail suspension and forced swim tests. Moreover, and most importantly, social stress-induced ethanol-CPP acquisition and reinstatement were significantly reduced following hippocampal SERT knockdown using short hairpin RNA shRNA-expressing lentiviral vectors. Finally, we confirmed that SERT hippocampal mRNA expression correlated with measures of depression- and ethanol-related behaviors by Pearson's correlation analysis. Taken together, our data suggest that hippocampal serotoninergic system is involved in social stress-triggered mood disorders as well as in the acquisition and retrieval of ethanol contextual memory and that blockade of this transporter can decrease ethanol rewarding properties.

Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model.

AIM: Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model. MATERIALS AND METHODS: In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 104.5 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment. RESULTS: In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns. CONCLUSIONS: Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.

Increased anxiolytic effect in aged female rats and increased motoric behavior in aged male rats to acute alcohol administration: Comparison to younger animals.

The population of most countries in the world is increasing and understanding risk factors that can influence the health of the older population is critical. Older adults consume alcohol often in a risky, binge manner. Previous work has demonstrated that aged rats are more sensitive to many of the effects of acute ethanol. In the current project aged, adult, and adolescent female and male rats were tested on the elevated plus maze and open field following either a 1.0 g/kg alcohol injection or a saline injection. We report sex- and age-dependent effects whereas aged female rats, but not aged male rats, showed an increased anxiolytic effect of alcohol in the elevated plus maze while aged male rats, but not aged female rats, showed increased stimulatory movement in the open field. In addition, significant age effects were found for both female and male rats. It is proposed that the sex- and age-dependent effects reported in the current studies may be due to differential levels of alcohol-induced allopregnanolone for the anxiolytic effects and differential levels of alcohol-induced dopamine for the stimulatory effects. The current work provides insights into factors influencing alcohol consumption in older adults.

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

Surgical incision pain induced an increase in alcohol consumption in mice.

INTRODUCTION: Large population-based studies have suggested a link between increased alcohol use and reduced pain. In addition, these studies suggest that higher levels of pain intensity are associated with an increase in alcohol consumption and rates of hazardous drinking which potentiates the risk of developing alcohol use disorders (AUD). The mechanisms and determinants of the alcohol-pain interaction can be studied in preclinical studies. METHODS: The overall goal of this study is to use animal models to explore the impact of acute postoperative pain on alcohol intake. To achieve this, we characterized the timeline and levels of alcohol intake and preference in mice after laparotomy in the 2-bottle choice paradigm. RESULTS: Our results show that laparotomy surgery increased alcohol intake and preference in male mice but not females in the 2-bottle choice and 3-bottle choice assays. In addition, ketoprofen administration blocked the increase in alcohol consumption in male mice after laparotomy. We also found that changes in alcohol initial sensitivity and acute functional tolerance, using loss of righting reflex (LORR) response, occur after surgery in mice. CONCLUSION: Taken together, these findings suggests that sex, pain and alcohol sensitivity-related factors may modulate the relationship between alcohol consumption and pain.

Limited bedding and nesting increases ethanol drinking in female rats.

Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, and adolescent EtOH drinking in rats. We also sought to determine whether ELAs affect alpha-adrenoceptor density in the brain because the noradrenergic system is involved in problematic alcohol drinking and its treatment. We hypothesized that the combination of POE and postnatal adversity will increase alcohol drinking in rats compared to rats with exposure to either adversity alone or to control. We also predicted that POE and postnatal adversity would increase α1-adrenoceptor density and decrease α2-adrenoceptor density in brain to confer a stress-responsive phenotype. Pregnant rats received morphine (15 mg/kg/day) or saline via subcutaneous minipumps from gestational day 9 until birth. Limited bedding and nesting (LBN) procedures were introduced from postnatal day (PD) 3-11 to mimic early life adversity-scarcity. Offspring rats (PD 31-33) were given opportunities to drink EtOH (20 %, v/v) using intermittent-access, two-bottle choice (with water) procedures. Rats given access to EtOH were assigned into sub-groups that were injected with either yohimbine (1 mg/kg, ip) or vehicle (2 % DMSO, ip) 30 min prior to each EtOH access session to determine the effects of α2-adrenoceptor inhibition on alcohol drinking. We harvested cortices, brainstems, and hypothalami from EtOH-naïve littermates on either PD 30 or PD 70 and conducted radioligand receptor binding assays to quantify α1- and α2-adrenoceptor densities. Contrary to our hypothesis, only LBN alone increased EtOH intake in female adolescent rats compared to female rats with POE. Neither POE nor LBN affected α1- or α2-adrenoceptor densities in the cortex, brainstem, or hypothalamus of early- or late-aged adolescent rats. These results suggest a complex interaction between ELA type and sex on alcohol drinking.

Hesperidin Protects Alcohol-Induced Mitochondrial Abnormalities via the Inhibition of Oxidative Stress and MPT Pore Opening in Newborn Male Rats as a Fetal Alcohol Syndrome Model.

OBJECTIVE: Prenatal alcohol exposure causes fetal developmental abnormalities via mitochondrial dysfunction, reactive oxygen species (ROS) formation, and oxidative stress. Therefore, we aimed to investigate the potential of hesperidin as a mitochondrial protective and antioxidative agent in newborn male rats as a model for fetal alcohol syndrome (FAS). METHOD: Newborn male rats were divided randomly into five groups: a sham group (receiving 27.8 ml/ kg milk solution, orally), an ethanol group (5.25 g/kg in milk solution, orally, 2-10 days after birth), an ethanol + hesperidin group (25 mg/kg/ day orally), an ethanol + hesperidin group (50 mg/kg/day orally), and an ethanol + hesperidin group (100 mg/kg/day orally). Thirty-six days after birth, newborn male rats were sacrificed and brain mitochondria were isolated using differential centrifugation. Mitochondrial toxicity biomarkers of succinate dehydrogenase (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP), and ROS were measured. RESULTS: Offspring neonatally exposed to ethanol showed a significant reduction in SDH activity, mitochondrial swelling, MMP collapse, induction of ROS formation, and lipid peroxidation in isolated mitochondria. Oral administration of hesperidin restored SDH activity, improved MMP collapse and mitochondrial swelling, and reduced ROS formation. CONCLUSIONS: This study demonstrates that hesperidin exerts a potent protective effect against alcohol-induced mitochondrial toxicity in the FAS model. Moreover, these findings indicate that hesperidin might be a useful compound for prevention of alcohol-induced fetal developmental abnormalities during pregnancy.

Traumatic Stress-Induced Increases in Anxiety-like Behavior and Alcohol Self-Administration Are Mediated by Central Amygdala CRF1 Neurons That Project to the Lateral Hypothalamus.

Avoidance stress coping, defined as persistent internal and/or external avoidance of stress-related stimuli, is a key feature of anxiety- and stress-related disorders, and contributes to increases in alcohol misuse after stress exposure. Previous work using a rat model of predator odor stress avoidance identified corticotropin-releasing factor (CRF) signaling via CRF Type 1 receptors (CRF1) in the CeA, as well as CeA projections to the lateral hypothalamus (LH) as key mediators of conditioned avoidance of stress-paired contexts and/or increased alcohol drinking after stress. Here, we report that CRF1-expressing CeA cells that project to the LH are preferentially activated in male and female rats that show persistent avoidance of predator odor stress-paired contexts (termed Avoider rats), and that chemogenetic inhibition of these cells rescues stress-induced increases in anxiety-like behavior and alcohol self-administration in male and female Avoider rats. Using slice electrophysiology, we found that prior predator odor stress exposure blunts inhibitory synaptic transmission and increases synaptic drive in CRF1 CeA-LH cells. In addition, we found that CRF bath application reduces synaptic drive in CRF1 CeA-LH cells in Non-Avoiders only. Collectively, these data show that CRF1 CeA-LH cells contribute to stress-induced increases in anxiety-like behavior and alcohol self-administration in male and female Avoider rats.SIGNIFICANCE STATEMENT Stress may lead to a variety of behavioral and physiological negative consequences, and better understanding of the neurobiological mechanisms that contribute to negative stress effects may lead to improved prevention and treatment strategies. This study, performed in laboratory rats, shows that animals that exhibit avoidance stress coping go on to develop heightened anxiety-like behavior and alcohol self-administration, and that these behaviors can be rescued by inhibiting the activity of a specific population of neurons in the central amygdala. This study also describes stress-induced physiological changes in these neurons that may contribute to their role in promoting increased anxiety and alcohol self-administration.

Double-wire technique to facilitate vein of Marshall cannulation and ethanol infusion in atrial fibrillation: a case series.

BACKGROUND: The vein of Marshall (VOM) ethanol infusion is increasingly performed in combination with catheter ablation in atrial fibrillation (AF). The cannulation of the VOM can sometimes be challenging. This study aimed to evaluate the double-wire technique in cases of difficult cannulation of the VOM. CASE PRESENTATION: Patients with AF scheduled for combined catheter ablation and VOM ethanol infusion were consecutively enrolled. The procedure was performed via the femoral vein. If the regular cannulation technique with one angioplasty wire failed or took more than 20 min, the double-wire technique using a stabilizing wire and a cannulation wire was performed. The unique technique was used mainly in two scenarios, when the Eustachian ridge was too prominent as a barrier for catheter manipulation or when the VOM ostium was close to the coronary sinus ostium. Of 162 patients scheduled for VOM ethanol infusion, the double-wire technique was applied in 6 (3.7%) patients and led to a 100% successful cannulation rate of the VOM. Of the six patients, two had a prominent Eustachian ridge, and four had a VOM ostium close to the coronary sinus ostium. The mean cannulation time was 33.3 ± 7.3 min. The ethanol infusion was successfully performed in 5 patients. One patient had a collateral circulation in the distal VOM, and ethanol infusion was not performed. CONCLUSIONS: The double-wire technique can facilitate VOM cannulation and ethanol infusion in challenging cases. WORD COUNT: 231.

[Ultrasound-guided anhydrous ethanol and microwave ablation for functional parathyroid cyst: a case report].

We report a case of functional parathyroid cyst treated by ultrasound-guided anhydrous ethanol sclerotherapy and microwave ablation. The 63-year-old female patient was diagnosed to have functional parathyroid cyst with hypercalcemia, high PTH and cystic space-occupying lesions in the neck by ultrasound, radionuclide scanning and PTH measurement of the cystic fluid. The patient refused to receive cyst resection, and anhydrous ethanol sclerotherapy with microwave ablation was performed under ultrasound guidance. The procedure was completed smoothly without any complications either during or after the operation. Follow-up examination of the patient at 18 months after the operation showed a significant reduction of the mass and normal blood calcium and iPTH levels, demonstrating a clinical cure of the patient. Ablative treatment of functional parathyroid cyst has not been documented so far. This approach provides a minimally invasive treatment modality for such cases where surgical resection is not an option, but its efficacy and safety need to be evaluated in more cases with longer follow-up time.

Alcohol potentiates multiple GABAergic inputs to dorsal striatum fast-spiking interneurons.

Parvalbumin-expressing dorsal striatal fast-spiking interneurons, comprising ∼1% of the total dorsal striatal neuronal population, are necessary for the expression of compulsive-like ethanol consumption mice. Fast-spiking interneurons are driven to fire by glutamatergic inputs derived primarily from the cortex. However, these neurons also receive substantial GABAergic input from two sources: the globus pallidus and the reticular nucleus of the thalamus. How ethanol modulates inhibitory input onto fast-spiking neurons is unclear and, more broadly, alcohol effects on GABAergic synaptic transmission onto GABAergic interneurons are understudied. Examining this, we found that acute bath application of ethanol (50 mM) potentiated GABAergic transmission from both the globus pallidus and the reticular nucleus of the thalamus onto fast-spiking interneurons in mouse of both sexes. This ethanol-induced potentiation required postsynaptic calcium and was not accompanied by a sustained change in presynaptic GABA release probability. Examining whether this ethanol effect persisted following chronic intermittent ethanol exposure, we found attenuated acute-ethanol potentiation of GABAergic transmission from both the globus pallidus and the reticular nucleus of the thalamus onto striatal fast-spiking interneurons. These data underscore the impact of ethanol on GABAergic signaling in the dorsal striatum and support the notion that ethanol may disinhibit the dorsolateral striatum.

Negative modulation of AMPA receptors bound to transmembrane AMPA receptor regulatory protein γ-8 blunts the positive reinforcing properties of alcohol and sucrose in a brain region-dependent manner in male mice.

RATIONALE: The development and progression of alcohol use disorder (AUD) are widely viewed as maladaptive neuroplasticity. The transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) regulatory protein γ8 (TARP γ-8) is a molecular mechanism of neuroplasticity that has not been evaluated in AUD or other addictions. OBJECTIVE: To address this gap in knowledge, we evaluated the mechanistic role of TARP γ-8 bound AMPAR activity in the basolateral amygdala (BLA) and ventral hippocampus (vHPC) in the positive reinforcing effects of alcohol, which drive repetitive alcohol use throughout the course of AUD, in male C57BL/6 J mice. These brain regions were selected because they exhibit high levels of TARP γ-8 expression and send glutamate projections to the nucleus accumbens (NAc), which is a key nucleus in the brain reward pathway. METHODS AND RESULTS: Site-specific pharmacological inhibition of AMPARs bound to TARP γ-8 in the BLA via bilateral infusion of the selective negative modulator JNJ-55511118 (0-2 µg/µl/side) significantly decreased operant alcohol self-administration with no effect on sucrose self-administration in behavior-matched controls. Temporal analysis showed that reductions in alcohol-reinforced response rate occurred > 25 min after the onset of responding, consistent with a blunting of the positive reinforcing effects of alcohol in the absence of nonspecific behavioral effects. In contrast, inhibition of TARP γ-8 bound AMPARs in the vHPC selectively decreased sucrose self-administration with no effect on alcohol. CONCLUSIONS: This study reveals a novel brain region-specific role of TARP γ-8 bound AMPARs as a molecular mechanism of the positive reinforcing effects of alcohol and non-drug rewards.

Ultrasound-Guided Ethanol Ablation as a Primary Treatment for Thyroglossal Duct Cyst: Feasibility, Characteristics, and Outcomes.

OBJECTIVES: To evaluate the feasibility, characteristics, and outcomes of ultrasound-guided ethanol ablation (US-EA) as a primary treatment for thyroglossal duct cysts (TGDCs). STUDY DESIGN: Prospective case series. SETTING: Single center study. METHODS: The inclusion criteria were as follows: (i) patients with TGDC aged ≥18 years, (ii) benign TGDC in imaging and cytological examinations, and (iii) patients' need for nonsurgical scarless treatment. US-EA was used as the primary treatment strategy. The primary outcome variables were the volume reduction rate (VRR) and cosmetic score at the last follow-up. RESULTS: We enrolled 28 patients with TGDC. The median TGDC volume at baseline was 6.7 mL. The median procedure time of the US-EA was 6.5 minutes. The median volumes of the cyst aspirate and injected ethanol were 4.0 and 2.0 mL, respectively. Overall, 18, 8, and 2 patients underwent 1, 2, and 3 treatment sessions, respectively. There were no complications. The median VRR was 96.2%, and the treatment success rate was 96.4%. The World Health Organization cosmetic score decreased from 4 (baseline) to 1 (after treatment) in all patients. The subjective grade for cosmetic satisfaction was satisfactory or highly satisfactory in all patients. The VRR, treatment success rate, and the number of treatment sessions did not differ as functions of the characteristics of the TGDC, including the initial volume, septation, debris, or viscosity of the cyst fluid. CONCLUSION: US-EA was feasible, safe, and effective in patients with TGDC. Therefore, US-EA can be used as a primary treatment for TGDC, evading general anesthesia and surgical scar.