Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19) infection, with studies demonstrating the prevalence of individuals with obesity admitted with COVID-19 ranging between 30 and 60%. We determined whether early changes in microRNAs (miRNAs) are associated with dysregulation of angiotensin-converting enzyme 2 (ACE2), the specific functional receptor for severe acute respiratory syndrome coronavirus 2. ACE2 is a membrane-bound enzyme that catalyzes the conversion of angiotensin II to angiotensin 1-7 the latter having cardioprotective and vasorelaxation effects. Quantitative real-time PCR analysis of plasma samples for circulating miRNAs showed upregulation of miR-200c and miR-let-7b in otherwise healthy individuals with obesity. This was associated with significant downregulation of ACE2, a direct target for both miRNAs, in individuals with obesity. Correlation analysis confirmed a significant negative correlation between ACE2 and both the miRNAs. Studies showed that despite being the functional receptor, inhibition/downregulation of ACE2 did not reduce the severity of COVID-19 infection. In contrast, increased angiotensin II following inhibition of ACE2 may increase the severity of the disease. Taken together, our novel results identify that upregulation of miR-200c may increase the susceptibility of individuals with obesity to COVID-19. Considering miRNA are the earliest molecular regulators, the level of circulating miR-200c could be a potential biomarker in the early identification of those at the risk of severe COVID-19.

Age- and sex-specific visceral fat reference cutoffs and their association with cardio-metabolic risk.

BACKGROUND: Although excess visceral fat (VAT) is associated with numerous cardio-metabolic risk factors, measurement of this fat depot has historically been difficult. Recent dual X-ray absorptiometry approaches have provided an accessible estimate of VAT that has shown acceptable validity against gold standard methods. The aims of this study were to (i) evaluate DXA measured VAT as a predictor of elevated blood lipids and blood pressure and (ii) calculate thresholds associated with these cardio-metabolic risk factors. SUBJECTS/METHODS: The sample comprised 1482 adults (56.4% women) aged 18-66 years. Total body scans were performed using a GE Lunar Prodigy, and VAT analyses were enabled through Corescan software (v 16.0). Blood pressure and blood lipids were measured by standard procedures. Regression models assessed how VAT mass was associated with each cardio-metabolic risk factor compared to other body composition measures. Measures of sensitivity and specificity were used to determine age- and sex-specific cut points for VAT mass associated with high cardio-metabolic risk. RESULTS: Similar to waist circumference, VAT mass was a strong predictor of cardio-metabolic risk especially in men over age 40. Four cut-offs for VAT mass were proposed, above which the cardio-metabolic risk increased: 700 g in women <40 yrs; 800 g in women 40+ yrs; 1000g in men <40 yrs; and 1200 g in men 40+ yrs. In general, these cut-offs discriminated well between those with high and low cardio-metabolic risk. CONCLUSIONS: In both sexes, DXA measured VAT was associated with traditional cardio-metabolic risk factors, particularly high blood pressure in those 40+ yrs and low HDL < 40 yrs. These reference values provide a simple, accessible method to assess cardio-metabolic risk in adults.

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse model of type 2 diabetes showed that diabetes-induced activation of miR-532 occurs in the later stage of the disease. Importantly, the upregulation of miR-532 preceded the activation of pro-apoptotic caspase-3/7 activity. Finally, inhibition of miR-532 activity in high glucose cultured human cardiomyocytes prevented the downregulation of ARC and attenuated apoptotic cell death. Diabetes induced activation of miR-532 plays a critical role in accelerating cardiomyocytes apoptosis. Therefore, miR-532 may serve as a promising therapeutic agent to overcome the diabetes-induced loss of cardiomyocytes.

Radial access: So much progress but a way to go.

Transradial access is the key bleeding avoidance strategy in percutaneous coronary intervention. This study showed a marked adoption of transradial access over a 10-year period, however, women had a significantly lower rate compared to men and overall bleeding events did not decrease over time. Strategies to overcome barriers to radial access in women and to maintaining competency in femoral access in all patients are needed.

Pharmaceutical interventions for weight-loss maintenance: no effect from cabergoline.

BACKGROUND: Weight regain is a major limitation to successful weight maintenance following weight loss. Observational studies suggest that stimulation of dopamine receptors in the central nervous system is associated with weight loss and inhibition of weight gain. Our objective was to test the hypothesis that dopamine agonist treatment would prevent weight regain following acute weight loss in individuals with obesity. METHODS: We conducted a 2-year double blind randomised controlled trial comparing the effect of a dopamine agonist, cabergoline, with placebo on weight regain in obese individuals who had lost at least 5% of their body weight using an 800 kcal/day commercial meal replacement programme. The primary outcome measure was the difference in mean weight between the treatment and control groups over the 2-year period following randomisation. RESULTS: At 24 months, there was no difference in body weight between cabergoline and placebo treatment after adjustment for age, gender and baseline values (0.6 kg (95% CI: -1.5, 2.6), p = 0.58). The mean (±SD) baseline body weight of the randomised participants was 101.8 kg, the mean (±SD) weight loss with the 800 kcal/day diet was 7.1 ± 1.8 kg and the mean (±SD) weight regain at 24 months was 5.1 ± 7.5 kg. There were no significant differences in BMI, percent weight loss, waist circumference, resting energy expenditure, blood pressure or metabolic parameters at 24 months between the two groups. CONCLUSIONS: Treatment with the dopamine agonist cabergoline does not prevent weight regain in obese individuals following weight loss.

The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion.

PURPOSE: Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults. METHODS: Adults aged 18-40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as µg/L (UIC), µg/g of creatinine (I:Cre), and µg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4). RESULTS: The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16-350) µg/L, 90 (range 33-371) µg/g, 129 (range 41-646) µg/day, and 16.4 (range 0.8-178.9) µg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 µg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20-48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52. CONCLUSIONS: The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status.

High definition transcranial pink noise stimulation of anterior cingulate cortex on food craving: An explorative study.

Dysfunctional neural activity in the cortical reward system network has been implicated in food addiction. This is the first study exploring the potential therapeutic effects of high definition transcranial pink noise stimulation (HD-tPNS) targeted at the anterior cingulate cortex (ACC) on craving and brain activity in women with obesity who showed features of food addiction (Yale Food Addiction Scale score of ≥3). Sixteen eligible females participated in a randomized, double-blind, parallel group study. Participants received six 20-minute sessions of either 1 mA (n = 8) or sham (n = 8) stimulation with HD-tPNS over two weeks. Anode was placed above the ACC (Fz) with 4 cathodes (F7, T3, F8, and T4). Food craving was assessed using the Food Cravings Questionnaire State (FCQ-S) and brain activity was measured using electroencephalogram (EEG). Assessments were at baseline, and two days, four weeks, and six weeks after stimulation. A 22% decrease (mean decrease of -1.11, 95% CI -2.09, -0.14) was observed on the 5-point 'intense desire to eat' subscale two days after stimulation in the HD-tPNS group compared to sham. Furthermore, whole brain analysis showed a significant decrease in beta 1 activity in the ACC in the stimulation group compared to sham (threshold 0.38, p = 0.04). These preliminary findings suggest HD-tPNS of the ACC transiently inhibits the desire to eat and, thus, warrants further examination as a potential tool in combating food craving.

Down-regulation of miR-15a/b accelerates fibrotic remodelling in the Type 2 diabetic human and mouse heart.

Aim: Myocardial fibrosis is a well-established cause of increased myocardial stiffness and subsequent diastolic dysfunction in the diabetic heart. The molecular regulators that drive the process of fibrotic events in the diabetic heart are still unknown. We determined the role of the microRNA (miR)-15 family in fibrotic remodelling of the diabetic heart.Methods and results: Right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic (ND) patients undergoing coronary artery bypass graft surgery showed significant down-regulation of miR-15a and -15b. This was associated with marked up-regulation of pro-fibrotic transforming growth factor-ß receptor-1 (TGFßR1) and connective tissue growth factor (CTGF), direct targets for miR-15a/b and pro-senescence p53 protein. Interestingly, down-regulation of miR-15a/b preceded the development of diastolic dysfunction and fibrosis in Type 2 diabetic mouse heart. Therapeutic restoration of miR-15a and -15b in HL-1 cardiomyocytes reduced the activation of pro-fibrotic TGFßR1 and CTGF, and the pro-senescence p53 protein expression, confirming a causal regulation of these fibrotic and senescence mediators by miR-15a/b. Moreover, conditioned medium (CM) collected from cardiomyocytes treated with miR-15a/b markedly diminished the differentiation of diabetic human cardiac fibroblasts.Conclusion: Our results provide first evidence that early down-regulation of miR-15a/b activates fibrotic signalling in diabetic heart, and hence could be a potential target for the treatment/prevention of diabetes-induced fibrotic remodelling of the heart.

Psychosurgery Reduces Uncertainty and Increases Free Will? A Review.

OBJECTIVE: A definition of free will is the ability to select for or against a course of action to fulfill a desire, without extrinsic or intrinsic constraints that compel the choice. Free will has been linked to the evolutionary development of flexible decision making. In order to develop flexibility in thoughts and behavioral responses, learning mechanisms have evolved as a modification of reflexive behavioral strategies. The ultimate goal of the brain is to reduce uncertainty inherently present in a changing environment. A way to reduce the uncertainty, which is encoded by the rostral anterior cingulate, is to make multiple predictions about the environment which are updated in parallel by sensory inputs. The prediction/behavioral strategy that fits the sensory input best is then selected, becomes the next percept/behavioral strategy, and is stored as a basis for future predictions. Acceptance of predictions (positive feedback) is mediated via the accumbens, and switching to other predictions by the dorsal anterior cingulate cortex (ACC) (negative feedback). Maintenance of a prediction is encoded by the pregenual ACC. Different cingulate territories are involved in rejection, acceptance and maintenance of predictions. Free will is known to be decreased in multiple psychopathologies, including obsessive compulsive disorder and addictions. METHODOLOGY: In modern psychosurgery three target structures exist for obsessive compulsive disorder and addiction: the dorsal ACC, the nucleus accumbens, and/or the anterior limb of the internal capsula. Research in all three areas reports favorable results with acceptable side effects. Psychosurgical interventions seem to exert their effect by a common final common pathway mediated via the pregenual ACC. CONCLUSION: Successful neuromodulation increases the capacity to choose from different options for the affected individual, as well as inhibiting unwanted options, therefore increasing free will and free won't.

Optimizing Deep Brain Stimulation of the Nucleus Accumbens in a Reward Preference Rat Model.

OBJECTIVE/HYPOTHESIS: Deep brain stimulation (DBS) has become the preferred therapy for a growing number of treatment-resistant neuropsychiatric conditions, offering the benefit of being amenable to fine-tuning to enhance its efficacy. However, while some DBS parameters are routinely adjusted, the stimulation is almost always delivered in a continuous "tonic" pattern, which may be suboptimal at times. Our overall aim is to investigate the application of differing levels of rewarding DBS to the reconditioning of behavioral "trigger" and "non-trigger" stimuli in impulse-control disorders (including addiction). As a first step, we used a rat model of nucleus accumbens (NAc) DBS to rigorously compare the relative reward values of different stimulation paradigms. We hypothesized that delivering pulses in a more physiological pattern would prove more rewarding than delivering tonic stimulation. MATERIALS AND METHODS: We implanted microelectrodes in the left NAc shell and trained rats to initiate and terminate DBS to demonstrate their "preference" between different brain stimulation reward (BSR) paradigms. We tested a range of BSR paradigms, including tonic, intermittent tonic, and burst paradigms. Two paradigms were compared at a time, and paired t-tests were used to determine whether the rats significantly "preferred" one paradigm over another. RESULTS: The rats significantly preferred intermittent tonic BSR paradigms to continuous and burst paradigms, and generally preferred paradigms that delivered more pulses over the stimulation period. CONCLUSIONS: These findings highlight that the standard approach of delivering tonic DBS is not optimal under all circumstances. Further research should investigate which DBS paradigms are best for different brain disorders.

'Exercise snacks' before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether small doses of intense exercise before each main meal ('exercise snacks') would result in better blood glucose control than a single bout of prolonged, continuous, moderate-intensity exercise in individuals with insulin resistance. METHODS: Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate [HRmax]) incline walking before dinner; (2) exercise snacking (ES), consisting of 6 × 1 min intense (90% HRmax) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6 × 1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions. RESULTS: ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4 ± 1.5 mmol/l, p = 0.02) but not lunch (0.4 ± 1.0 mmol/l, p = 0.22), and was more effective than CONT following dinner (0.7 ± 1.5 mmol/l below CONT; p = 0.04). ES also reduced 24 h mean glucose concentration by 0.7 ± 0.6 mmol/l (p = 0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6 ± 0.4 mmol/l vs CONT, relative to their baselines; p = 0.01). CES was just as effective as ES (p > 0.05 for all glycaemic variables) at improving glycaemic control. CONCLUSIONS/INTERPRETATION: Dosing exercise as brief, intense 'exercise snacks' before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.

Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease.

Diabetic heart disease (DHD) is the leading cause of morbidity and mortality among the people with diabetes, with approximately 80% of the deaths in diabetics are due to cardiovascular complications. Importantly, heart disease in the diabetics develop at a much earlier stage, although remaining asymptomatic till the later stage of the disease, thereby restricting its early detection and active therapeutic management. Thus, a better understanding of the modulators involved in the pathophysiology of DHD is necessary for the early diagnosis and development of novel therapeutic implications for diabetes-associated cardiovascular complications. microRNAs (miRs) have recently been evolved as key players in the various cardiovascular events through the regulation of cardiac gene expression. Besides their credible involvement in controlling the cellular processes, they are also released in to the circulation in disease states where they serve as potential diagnostic biomarkers for cardiovascular disease. However, their potential role in DHD as modulators as well as diagnostic biomarkers is largely unexplored. In this review, we describe the putative mechanisms of the selected cardiovascular miRs in relation to cardiovascular diseases and discuss their possible involvement in the pathophysiology and early diagnosis of DHD.

Assessment of markers of glycaemic control in diabetic patients with chronic kidney disease using continuous glucose monitoring.

AIM: Due to altered red blood cell survival and erythropoietin therapy glycated haemoglobin (HbA1c) may not accurately reflect long-term glycaemic control in patients with diabetes and chronic kidney disease (CKD). Glycated albumin (GA) and fructosamine are alternative markers of glycaemia. The aim of this study was to investigate the accuracy of HbA1c, GA and fructosamine as indicators of glycaemic control using continuous glucose monitoring. METHODS: HbA1c, GA and fructosamine concentrations were measured in 25 subjects with diabetic nephropathy (CKD stages 4 and 5 (estimated glomerular filtration rate <30 mL/min per 1.73 m(2) )) matched with 25 subjects with diabetes and no evidence of nephropathy. Simultaneous real-time glucose concentrations were monitored by continuous glucose monitoring over 48 h. RESULTS: GA correlated significantly to mean glucose concentrations in patients with and without CKD (r = 0.54 vs 0.49, P < 0.05). A similar relationship was observed with fructosamine relative to glucose. A poor correlation between HbA1c and glucose was observed with CKD (r = 0.38, P = ns) but was significant in the non-CKD group (r = 0.66, P < 0.001). The GA/HbA1c ratio was significantly higher in diabetic patients with CKD compared with controls (2.5 ± 0.4 vs 2.2 ± 0.4, P < 0.05). HbA1c values were significantly lower in CKD patients, relative to non-CKD patients at comparable mean glucose concentrations. CONCLUSION: HbA1c significantly underestimates glycaemic control in patients with diabetes and CKD stages 4 and 5. In severe CKD, GA more accurately reflects glycaemic control compared with fructosamine and HbA1c and should be the preferred marker of glycaemic control.

Durable biochemical response and safety with oral octreotide capsules in acromegaly.

Objective: The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long-term durability of therapeutic response. Design: The study design is an OLE of a double-blind placebo-controlled (DPC) trial. Methods: Patients completing the 36-week DPC period on the study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/day OOC dose, with the option to titrate to 40 or 80 mg/day. The OLE is ongoing; week 48 results are reported. Results: Forty patients were enrolled in the OLE, 20 each having received OOC or placebo, with 14 and 5 patients completing the DPC period as responders, respectively. Ninety percent of patients completing the DPC period on OOC and 70% of those completing on placebo completed 48 weeks of the OLE. Maintenance of response in the OLE (i.e. insulin-like growth factor I (IGF1) ≤ 1.0 × upper limit of normal (ULN)) was achieved by 92.6% of patients who responded to OOC during the DPC period. Mean IGF1 levels were maintained between the end of the DPC period (0.91 × ULN; 95% CI: 0.784, 1.045) and week 48 of the OLE (0.90 × ULN; 95% CI: 0.750, 1.044) for those completing the DPC period on OOC. OOC safety was consistent with previous findings, with no increased adverse events (AEs) associated with the higher dose and improved gastrointestinal tolerability observed over time. Conclusions: Patients with acromegaly maintained long-term biochemical response while receiving OOC, with no new AEs observed with prolonged OOC exposure.

Impact of metabolic syndrome and its components on cardiovascular disease event rates in 4900 patients with type 2 diabetes assigned to placebo in the FIELD randomised trial.

BACKGROUND: Patients with the metabolic syndrome are more likely to develop type 2 diabetes and may have an increased risk of cardiovascular disease (CVD) events.We aimed to establish whether CVD event rates were influenced by the metabolic syndrome as defined by the World Health Organisation (WHO), the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) and to determine which component(s) of the metabolic syndrome (MS) conferred the highest cardiovascular risk in in 4900 patients with type 2 diabetes allocated to placebo in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. RESEARCH DESIGN AND METHODS: We determined the influence of MS variables, as defined by NCEP ATPIII, IDF and WHO, on CVD risk over 5 years, after adjustment for CVD, sex, HbA1c, creatinine, and age, and interactions between the MS variables in a Cox proportional-hazards model. RESULTS: About 80% had hypertension, and about half had other features of the metabolic syndrome (IDF, ATPIII). There was no difference in the prevalence of metabolic syndrome variables between those with and without CVD at study entry. The WHO definition identified those at higher CVD risk across both sexes, all ages, and in those without prior CVD, while the ATPIII definition predicted risk only in those aged over 65 years and in men but not in women. Patients meeting the IDF definition did not have higher risk than those without IDF MS.CVD risk was strongly influenced by prior CVD, sex, age (particularly in women), baseline HbA1c, renal dysfunction, hypertension, and dyslipidemia (low HDL-c, triglycerides > 1.7 mmol/L). The combination of low HDL-c and marked hypertriglyceridemia (> 2.3 mmol/L) increased CVD risk by 41%. Baseline systolic blood pressure increased risk by 16% per 10 mmHg in those with no prior CVD, but had no effect in those with CVD. In those without prior CVD, increasing numbers of metabolic syndrome variables (excluding waist) escalated risk. CONCLUSION: Absence of the metabolic syndrome (by the WHO definition) identifies diabetes patients without prior CVD, who have a lower risk of future CVD events. Hypertension and dyslipidemia increase risk.

Anti-inflammatory effect of an insulin infusion in patients on maintenance haemodialysis: a randomized controlled pilot study.

AIM: A pilot study to investigate the anti-inflammatory effect of insulin in patients on maintenance haemodialysis. BACKGROUND: Elevated concentrations of pro-inflammatory and oxidative mediators are thought to contribute to the increased cardiovascular risk in haemodialysis. Insulin has been demonstrated to have anti-inflammatory properties and a continuous low-dose insulin infusion in critically ill patients is associated with improved outcomes. The anti-inflammatory effects of insulin in haemodialysis have not been investigated. METHODS: In a single-blind cross-over study, 11 stable, non-diabetic, haemodialysis patients received a continuous insulin infusion (Actrapid 2 IU/h) during a dialysis of 4 h or a conventional dialysis in random order. Normoglycaemia was maintained by a modified glucose dialysate and glucose infusion. Blood samples were collected at baseline, 1, 4, 6 and 24 h. C-reactive protein (CRP), tumour necrosis factor-α, interleukin-6, neopterin, vascular cell adhesion molecule 1, protein thiols, dityrosine and peroxides were measured. RESULTS: Insulin produced a significant reduction in median CRP over the immediate dialysis phase (confidence interval) by 6% (2-9% (95% CI), P=0.006) and an even greater decline at 24 h (19% (8-28%, 95% CI), P=0.001) compared with values of the conventional dialysis. No significant changes were observed in the other markers. Median glucose levels were comparable during both dialysis sessions. CONCLUSIONS: During haemodialysis, insulin may have a modest anti-inflammatory effect as evident by a reduction in CRP that appears to have a persistent effect over the next 24 h post dialysis. More studies are required to examine longer-term benefits as well as the potential role in more high-risk individuals.

Severe Tricuspid Valve Endocarditis: A Tale of 2 Circuits.

A 25-year-old woman with severe tricuspid valve endocarditis and septic pulmonary emboli required VA-ECMO for recurrent hypoxemia-induced cardiac arrest. We present the clinical challenges requiring ECMO circuit reconfiguration and a percutaneous approach for vegetation debulking. (Level of Difficulty: Intermediate.).

Anterior Cingulate Cortex Implants for Alcohol Addiction: A Feasibility Study.

Abnormal neural activity, particularly in the rostrodorsal anterior cingulate cortex (rdACC), appears to be responsible for intense alcohol craving. Neuromodulation of the rdACC using cortical implants may be an option for individuals with treatment-resistant alcohol dependence. This study assessed the effectiveness and feasibility of suppressing alcohol craving using cortical implants of the rdACC using a controlled one-group pre- and post-test study design. Eight intractable alcohol-dependent participants (four males and four females) were implanted with two Lamitrode 44 electrodes over the rdACC bilaterally connected to an internal pulse generator (IPG). The primary endpoint, self-reported alcohol craving reduced by 60.7% (p = 0.004) post- compared to pre-stimulation. Adverse events occurred in four out of the eight participants. Electrophysiology findings showed that among responders, there was a post-stimulation decrease (p = 0.026) in current density at the rdACC for beta 1 band (13-18 Hz). Results suggest that rdACC stimulation using implanted electrodes may potentially be a feasible method for supressing alcohol craving in individuals with severe alcohol use disorder. However, to further establish safety and efficacy, larger controlled clinical trials are needed.