Superficial and Invasive Spread of High-grade Squamous Intraepithelial Lesion and Squamous Cell Carcinoma: A Case Report.

We present a case of extensive spread of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia grade 3 (CIN3) with foci of invasive squamous cell carcinoma (SCC) in a premenopausal woman. Superficial spread of CIN3 and cervical SCC to the endometrium and/or fallopian tubes is rare, especially in countries with cervical cancer screening programs. Our case occurred during the COVID-19 pandemic, which may have been a major contributing factor to delayed detection and, consequently extensive spread.

Reliability of Hip Strength Assessment in Young Active People with Hip Dysplasia: An Examination in Student Circus Artists.

BACKGROUND: Developmental dysplasia of the hip (DDH) is common in performing artists and other young active individuals and involves abnormalities in bony morphology of the acetabulum and proximal femur that can negatively impact walking biomechanics, muscular strength, quality of life, and sleep. Rehabilitation for hip-related conditions should target known modifiable impairments such as hip muscle strength, though a reliable method of assessment in this population remains unclear. OBJECTIVE: To determine the inter- and intra-rater reliability of hip muscle strength assessments using handheld dynamometry (HHD) in young active circus artists with DDH. METHODS: Reliability of hip strength in all planes was assessed using HHD in 21 adult performing circus arts students (mean age 21.3 yrs [3.2]; 13 M, 5 F, 3 NB) with symptomatic radiologically and clinically diagnosed hip dysplasia. The reliability of average peak force and absolute peak force were expressed for each position tested. Reliability was assessed using intraclass correlation coefficients (ICC) with standard error of measurement (SEM) and minimal detectable change (MDC) values calculated to improve clinical interpretability. RESULTS: Good to excellent inter-rater reliability resulted for all hip muscle strength testing positions, ICC=0.88 (95%CI 0.70 to 0.95) to ICC=0.97 (0.92 to 0.99), except average peak hip flexion strength, ICC=0.71 (0.28 to 0.88). Absolute peak hip abduction, ICC=0.77 (0.16 to 0.94), and adduction strength, ICC=0.72 (-0.55 to 0.92), demonstrated the lowest intra-rater reliability. Transverse plane strength measures (rotation) produced the lowest SEM and MDC values followed by the frontal plane (abduction/adduction) and sagittal plane (flexion/extension). CONCLUSION: HHD is an appropriate and reliable method to assess hip muscle strength in circus artists with DDH.

Japanese value set for the EORTC QLU-C10D: A multi-attribute utility instrument based on the EORTC QLQ-C30 cancer-specific quality-of-life questionnaire.

PURPOSE: This study aimed to develop a Japanese value set for the EORTC QLU-C10D, a multi-attribute utility measure derived from the cancer-specific health-related quality-of-life (HRQL) questionnaire, the EORTC QLQ-C30. The QLU-C10D contains ten HRQL dimensions: physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, and bowel problems. METHODS: Quota sampling of a Japanese online panel was used to achieve representativeness of the Japanese general population by sex and age (≥ 18 years). The valuation method was an online discrete choice experiment. Each participant considered 16 choice pairs, randomly assigned from 960 choice pairs. Each pair included two QLU-C10D health states and life expectancy. Data were analyzed using conditional logistic regression, parameterized to fit the quality-adjusted life-year framework. Preference weights were calculated as the ratio of each dimension-level coefficient to the coefficient for life expectancy. RESULTS: A total of 2809 eligible panel members consented, 2662/2809 (95%) completed at least one choice pair, and 2435/2662 (91%) completed all choice pairs. Within dimensions, preference weights were generally monotonic. Physical functioning, role functioning, and pain were associated with the largest utility weights. Intermediate utility weights were associated with social functioning and nausea; the remaining symptoms and emotional functioning were associated with smaller utility decrements. The value of the worst health state was - 0.221, lower than that seen in most other existing QLU-C10D country-specific value sets. CONCLUSIONS: The Japan-specific QLU-C10D value set is suitable for evaluating the cost and utility of oncology treatments for Japanese health technology assessment and decision-making.

Association between hip muscle strength/function and hip cartilage defects in sub-elite football players with hip/groin pain.

OBJECTIVE: To explore associations between hip muscle strength and cartilage defects (presence and severity) on magnetic resonance imaging (MRI) in young adults with hip/groin pain participating in sub-elite football. DESIGN: Sub-elite football players with hip/groin pain (>6 months) completed assessments of isometric hip strength and functional task performance. Hip cartilage defects were assessed using the Scoring Hip Osteoarthritis with MRI tool. This exploratory, cross-sectional study used logistic and negative binomial models to assess the relationships between hip muscle strength or functional task performance and hip cartilage defects, controlling for body mass index, age, testing site and cam morphology, incorporating sex-specific interaction terms. RESULTS: One hundred and eighty-two (37 women) sub-elite (soccer or Australian football) players with hip/groin pain (age 26 ± 7 years) were included. Greater hip extension strength was associated with higher cartilage total score (adjusted incidence rate ratio [aIRR] 1.01, 95%CI: 1.0 to 1.02, p = 0.013) and superolateral cartilage score (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI): 1.01 to 1.06, p < 0.01). In female sub-elite football players, greater hip external rotation strength was associated with lateral cartilage defects (aOR 1.61, 95%CI: 1.05 to 2.48, p = 0.03) and higher cartilage total score (aIRR 1.25, 95%CI: 1.01 to 1.66, p = 0.042). A one-repetition increase in one-leg rise performance was related to lower odds of superomedial cartilage defects (aOR 0.96, 95%CI: 0.94 to 0.99, p < 0.01). CONCLUSIONS: Overall, there were few associations between peak isometric hip muscle strength and overall hip cartilage defects. It is possible that other factors may have relevance in sub-elite football players. Additional studies are needed to support or refute our findings that higher one leg rise performance was associated with reduced superomedial cartilage defect severity and greater hip extension strength was related to higher cartilage defect severity scores.

Assessing the effects of transient weather conditions on airborne transmission risk in naturally ventilated hospitals.

BACKGROUND: Many UK hospitals rely heavily on natural ventilation as their main source of airflow in patient wards. This method of ventilation can have cost and energy benefits, but it may lead to unpredictable flow patterns between indoor spaces, potentially leading to the unexpected transport of infectious material to other connecting zones. However, the effects of weather conditions on airborne transmission are often overlooked. METHODS: A multi-zone CONTAM model of a naturally ventilated hospital respiratory ward, incorporating time-varying weather, was proposed. Coupling this with an airborne infection model, this study assessed the variable risk in interconnected spaces, focusing particularly on occupancy, disease and ventilation scenarios based on a UK respiratory ward. RESULTS: The results suggest that natural ventilation with varying weather conditions can cause irregularities in the ventilation rates and interzonal flow rates of connected zones, leading to infrequent but high peaks in the concentration of airborne pathogens in particular rooms. This transient behaviour increases the risk of airborne infection, particularly through movement of pathogens between rooms, and highlights that large outbreaks may be more likely under certain conditions. This study demonstrated how ventilation rates achieved by natural ventilation are likely to fall below the recommended guidance, and that the implementation of supplemental mechanical ventilation can increase ventilation rates and reduce the variability in infection risks. CONCLUSION: This model emphasises the need for consideration of transient external conditions when assessing the risk of transmission of airborne infection in indoor environments.

Optimal initial position and technique for the front foot contact phase of cricket fast bowling: Commonalities between individual-specific simulations of elite bowlers.

Group-based and individual-based studies in cricket fast bowling have identified common technique characteristics associated with ball release speed. The applicability of these findings to individual bowlers is often questioned, however, due to research approach limitations. This study aims to identify whether the optimal initial body position at front foot contact and subsequent technique to maximise ball release speed exhibit common characteristics for elite male cricket fast bowlers using individual-specific computer optimisations. A planar 16-segment whole-body torque-driven simulation model of the front foot contact phase of fast bowling was customised, evaluated, and the initial body position and subsequent movement pattern optimised, for ten elite male fast bowlers. The optimised techniques significantly increased ball release speed by 4.8 ± 1.3 ms-1 (13.5 ± 4.1%) and ranged between 37.8 and 42.9 ms-1, and in lower peak ground reaction forces and loading rates. Common characteristics were observed within the optimal initial body position with more extended front knees, as well as more flexion of the front and bowling arm shoulders than in current performances. Delays to the onset of trunk flexion, front arm and bowling arm shoulder extension, and wrist flexion were also common in the subsequent movement during the front foot contact phase. Lower front hip extensor and front shoulder flexor torques, as well as greater bowling shoulder extensor torques were also evident. This is useful knowledge for coach development, talent identification, and coaching practice.

Effects of racket moment of inertia on racket head speed, impact location and shuttlecock speed during the badminton smash.

How the racket properties impact performance of the badminton smash is relatively unknown, and further insight could help players/coaches select the most appropriate racket. Three-dimensional position data of the racket and shuttlecock were collected (500 Hz) for 20 experienced badminton players performing a series of forehand smashes with five swingweight ([Formula: see text]) perturbed rackets, ranging from 85-106 kg·cm2. [Formula: see text] was calculated using a balance board and simple pendulum method, and modal analysis was performed using laser vibrometry to capture the fundamental frequency and distal node location for each racket. As [Formula: see text] increased a reduction in racket head speed was found with on average a 0.7 m·s-1 decrease per 5 kg·cm2 increase in [Formula: see text], however this did not lead to slower shuttlecock speeds. The impact location tended to move closer to the tip as the fundamental frequency node moved closer to the tip (as [Formula: see text] increased), providing some evidence that participants may subconsciously strike the shuttlecock at the node location to provide desirable sensory feedback. The increase in racket head speed but not shuttlecock speed was likely due to the distal increase in longitudinal impact location as [Formula: see text] increased, as well as an increase in effective mass for a given impact location. Additionally, removal of the deformation component (additional racket head speed due to the racket noticeably bending and recovering) of racket head speed increased the effect size of the relationship with [Formula: see text], where rackets with greater [Formula: see text] had larger deformation velocities. The research provides further insight into the smash performance characteristics of experienced badminton players, particularly based on racket properties. Further research is required to confirm the coincidence between node location and longitudinal impact location.

The association between hip/groin pain and hip strength in football players: An exploratory analysis of the FORCe cohort.

OBJECTIVES: Explore associations between peak hip strength in football players with hip/groin pain and healthy controls. DESIGN: Cross-sectional study. METHODS: Male and female sub-elite football players (soccer and Australian football) with hip/groin pain >6-month duration and players without hip/groin pain were recruited across Melbourne and Brisbane, Australia. Demographic information and two questionnaires; the Copenhagen Hip and Groin Outcome Score and the International Hip Outcome Tool 33 were collected. Hand-held dynamometry was used to measure isometric hip strength for flexion, extension, abduction, adduction, internal rotation, and external rotation. Linear mixed effects models were used to compare strength measures between groups. RESULTS: 190 football players with hip/groin pain (mean ±â€¯standard deviation age, 27.8 ±â€¯6.3 years) and 64 controls (age, 27.3 ±â€¯5.6 years) were included in this study. Of these, 291 symptomatic limbs and 128 control limbs were used for analyses. Symptomatic players had lower peak hip adduction (adjusted mean difference = -0.18: 95 % confidence interval -0.27 to -0.08, P : 0.001), external rotation (-0.06: 95 % confidence interval -0.09 to -0.02, P : 0.003), and internal rotation strength (-0.06: 95 % confidence interval -0.10 to -0.03, P : 0.001) compared to controls. A sport-specific interaction was observed for hip abduction strength. When separated by football code, abduction strength was lower in symptomatic Australian football players compared to their same sport peers (-0.20: 95 % confidence interval -0.33 to -0.06, P : 0.004), but not in symptomatic soccer players (-0.05: 95 % confidence interval -0.15 to 0.06, P : 0.382). CONCLUSIONS: Hip adduction, internal rotation, and external rotation strength appears lower in football players with hip/groin pain independent of sex and football code. Hip abduction strength was lower in symptomatic Australian football players but not in soccer players.

Cricket fast bowling: The relationship between range of motion and key performance and injury technique characteristics.

Fast bowling technique characteristics associated with performance and injury have been established; however, the effect of joint range of motion (ROM) on technique remains unknown. This study aimed to investigate ROM and its effect on fast bowling technique. Eighteen ROM measures and thirteen technique parameters were determined for 45 elite male fast bowlers. Twenty-three significant correlations were found between the shoulder, hip, and ankle ROM measures and technique parameters (r = 0.300-0.452; p < 0.05). Shoulder ROM was observed to have the highest number of correlations with fast bowling technique. Increased internal rotation, less external rotation, and greater total arc of rotation were associated with technique characteristics previously linked with increased ball release speed and decreased lumbar stress injury risk. Although hip and ankle ROM were also correlated with technique, their association is yet to be understood. Future research should aim to determine the impact of ROM on fast bowling movement patterns. This knowledge is likely to be useful in enhancing the coaching and rehabilitation of fast bowlers from lumbar stress injuries.

Atlantic water intrusion triggers rapid retreat and regime change at previously stable Greenland glacier.

Ice discharge from Greenland's marine-terminating glaciers contributes to half of all mass loss from the ice sheet, with numerous mechanisms proposed to explain their retreat. Here, we examine K.I.V Steenstrups Nordre Bræ ('Steenstrup') in Southeast Greenland, which, between 2018 and 2021, retreated ~7 km, thinned ~20%, doubled in discharge, and accelerated ~300%. This rate of change is unprecedented amongst Greenland's glaciers and now places Steenstrup in the top 10% of glaciers by contribution to ice-sheet-wide discharge. In contrast to expected behaviour from a shallow, grounded tidewater glacier, Steenstrup was insensitive to high surface temperatures that destabilised many regional glaciers in 2016, appearing instead to respond to a >2 °C anomaly in deeper Atlantic water (AW) in 2018. By 2021, a rigid proglacial mélange had developed alongside notable seasonal variability. Steenstrup's behaviour highlights that even long-term stable glaciers with high sills are vulnerable to sudden and rapid retreat from warm AW intrusion.

The association between statistical shape modeling-defined hip morphology and features of early hip osteoarthritis in young adult football players: Data from the femoroacetabular impingement and hip osteoarthritis cohort (FORCe) study.

Objective: To explore the relationship between radiographic hip shape and features of early hip osteoarthritis (OA) on magnetic resonance imaging (MRI) in young male and female football players without radiographic hip OA. Design: We used baseline data from a cohort of symptomatic and asymptomatic football players aged 18-50 years. Hip shape was assessed on anteroposterior radiographs with statistical shape modeling (SSM) for men and women separately. Cartilage defects and labral tears were graded using the Scoring Hip Osteoarthritis with MRI (SHOMRI) system. We used logistic regression with generalized estimating equations to estimate associations between each hip shape variant, called shape modes, and cartilage defects or labral tears. Results: We included 229 participants (446 hips, 77.4% male). For each sex, 15 shape modes were analyzed. In men, three shape modes were associated with cartilage defects: adjusted odds ratios (aOR) 0.75 (95%CI 0.58-0.97) per standard deviation (SD) for mode 1; 1.34 (95%CI 1.05-1.69) per SD for mode 12; and 0.61 (95%CI 0.48-0.78) per SD for mode 15; and one also with labral tears: aOR 1.30 (95%CI 1.01-1.69) per SD for mode 12. These modes generally represented variations in the femoral neck and subtypes of cam morphology, with and without pincer morphology. For women, there was no evidence for associations with the outcomes. Conclusions: Several hip shape variants were associated with cartilage defects on MRI in young male football players. Specifically, one subtype of cam morphology was associated with both cartilage defects and labral tears. Hip shape was not associated with early OA features in women.

Uniparental disomy screen of Irish rare disorder cohort unmasks homozygous variants of clinical significance in the TMCO1 and PRKRA genes.

A uniparental disomy (UPD) screen using whole genome sequencing (WGS) data from 164 trios with rare disorders in the Irish population was performed to identify large runs of homozygosity of uniparental origin that may harbour deleterious recessive variants. Three instances of whole chromosome uniparental isodisomy (UPiD) were identified: one case of maternal isodisomy of chromosome 1 and two cases of paternal isodisomy of chromosome 2. We identified deleterious homozygous variants on isodisomic chromosomes in two probands: a novel p (Glu59ValfsTer20) variant in TMCO1, and a p (Pro222Leu) variant in PRKRA, respectively. The overall prevalence of whole chromosome UPiD in our cohort was 1 in 55 births, compared to 1 in ∼7,500 births in the general population, suggesting a higher frequency of UPiD in rare disease cohorts. As a distinct mechanism underlying homozygosity compared to biallelic inheritance, the identification of UPiD has important implications for family planning and cascade testing. Our study demonstrates that UPD screening may improve diagnostic yields by prioritising UPiD chromosomes during WGS analysis.

The effect of citalopram treatment on amyloid-ß precursor protein processing and oxidative stress in human hNSC-derived neurons.

Selective Serotonin Reuptake Inhibitors (SSRIs) may hold therapeutic benefits for people with Alzheimer's disease (AD). SSRIs may perturb AD progression, or the conversion from MCI to AD, via increased neurogenesis, reduced oxidative stress and/or favourable Amyloid-ß Precursor Protein (AßPP) processing. This study used iPSC derived cortical neuronal cells carrying 3 different PSEN1 mutations, to investigate the effect of treatment with the SSRI, Citalopram on AßPP processing and oxidative stress. Control and PSEN1 mutation (L286V, A246E, M146L) iPSC-derived neurons were treated with Citalopram for 45 days. ADAM10 activity, AßPP processing and Aß generation was measured in addition to cellular redox status. Citalopram treatment reduced the Aß1-42:40 ratio in control but not in fAD PSEN1 cells. ADAM10 activity was increased with Citalopram treatments in fAD PSEN1 cell lines, which was also seen for sAßPPα secretion. Lower superoxide generation in fAD PSEN1 cells following Citalopram treatment was identified, although there was no effect on end markers of oxidative stress. Treatment with Citalopram appears to have little effect on Aß generation in fADPSEN1 cells, but our findings suggest that treatment can significantly increase non-amyloidogenic AßPP processing and reduce oxidative stress. These changes may explain why SSRIs appear most effective in the prodromal period of the disease progression, as opposed to reducing established AD pathology. Further investigation of specific pathways conferring the beneficial effects of SSRIs treatment are warranted.

Influence of spatial-intensity contrast in ultraintense laser-plasma interactions.

Increasing the intensity to which high power laser pulses are focused has opened up new research possibilities, including promising new approaches to particle acceleration and phenomena such as high field quantum electrodynamics. Whilst the intensity achievable with a laser pulse of a given power can be increased via tighter focusing, the focal spot profile also plays an important role in the interaction physics. Here we show that the spatial-intensity distribution, and specifically the ratio of the intensity in the peak of the laser focal spot to the halo surrounding it, is important in the interaction of ultraintense laser pulses with solid targets. By comparing proton acceleration measurements from foil targets irradiated with by a near-diffraction-limited wavelength scale focal spot and larger F-number focusing, we find that this spatial-intensity contrast parameter strongly influences laser energy coupling to fast electrons. We find that for multi-petawatt pulses, spatial-intensity contrast is potentially as important as temporal-intensity contrast.

Farm-level factors associated with lameness prevalence, productivity, and milk quality in farms with automated milking systems.

Impaired locomotion (lameness) may negatively affect the ability and desire of cows to milk voluntarily, which is a key factor in success of automated milking systems (AMS). The objective of this study was to identify factors associated with herd-level lameness prevalence and associations of lameness and other farm-level factors with milking activity, milk yield, and milk quality in herds with AMS. From April to September 2019, 75 herds with AMS in Ontario, Canada, were visited, and data on barn design and farm management practices were collected. Data from AMS were collected, along with milk recording data, for the 6-mo period before farm visits. Farms averaged 98 ± 71 lactating cows, 2.3 ± 1.5 robot units/farm, 43.6 ± 9.4 cows/robot, 36.4 ± 4.9 kg/d of milk, a milking frequency of 3.01 ± 0.33 milkings/d, and a herd average geometric mean SCC of 179.3 ± 74.6 (× 1,000) cells/mL. Thirty percent of cows/farm (minimum of 30 cows/farm) were scored for body condition (1 = underconditioned to 5 = over conditioned) and locomotion (1 = sound to 5 = lame; clinically lame ≥3 out of 5 = 28.3 ± 11.7%, and severely lame ≥4 out of 5 = 3.0 ± 3.2%). Clinical lameness (locomotion score ≥3) was less prevalent on farms with sand bedding, with increased feed bunk space per cow, and on farms with non-Holstein breeds versus Holsteins, and tended to be less prevalent with lesser proportion of underconditioned cows (with body condition score ≤2.5). Severe lameness occurrence (farms with any cows with locomotion score ≥4) was associated with a greater proportion of underconditioned cows and in farms with stalls with greater curb heights. Herd average milk yield/cow per day increased with lesser prevalence of clinical lameness (each 10-percentage-point decrease in clinical lameness prevalence was associated with 2.0 kg/cow per day greater milk yield) and greater milking visit frequency per day, and tended to be greater with increased feed push-up frequency. Lesser herd average somatic cell count was associated with lesser clinical lameness prevalence, herd average days in milk, and proportion of overconditioned cows, and somatic cell count tended to be lesser for farms with sand bedding versus those with organic bedding substrates. The results highlight the importance of minimizing lameness prevalence, using of sand bedding, ensuring adequate feed access and feed bunk space, and maintaining proper cow body condition to optimize herd-level productivity and milk quality in AMS herds.

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

Healthcare-acquired clusters of COVID-19 across multiple wards in a Scottish health board.

BACKGROUND: Healthcare-acquired COVID-19 has been an additional burden on hospitals managing increasing numbers of patients with SARS-CoV-2. One acute hospital (W) among three in a Scottish healthboard experienced an unexpected surge of COVID-19 clusters. AIM: To investigate possible causes of COVID-19 clusters at Hospital W. METHODS: Daily surveillance provided total numbers of patients and staff involved in clusters in three acute hospitals (H, M and W) and care homes across the healthboard. All clusters were investigated and documented, along with patient boarding, community infection rates and outdoor temperatures from October 2020 to March 2021. Selected SARS-CoV-2 strains were genotyped. FINDINGS: There were 19 COVID-19 clusters on 14 wards at Hospital W during the six-month study period, lasting from two to 42 days (average, five days; median, 14 days) and involving an average of nine patients (range 1-24) and seven staff (range 0-17). COVID-19 clusters in Hospitals H and M reflected community infection rates. An outbreak management team implemented a control package including daily surveillance; ward closures; universal masking; screening; restricting staff and patient movement; enhanced cleaning; and improved ventilation. Forty clusters occurred across all three hospitals before a January window-opening policy, after which there were three during the remainder of the study. CONCLUSION: The winter surge of COVID-19 clusters was multi-factorial, but clearly exacerbated by moving trauma patients around the hospital. An extended infection prevention and control package including enhanced natural ventilation helped reduce COVID-19 clusters in acute hospitals.

Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder.

Alcohol use disorder (AUD) is a chronic, relapsing brain disorder, characterized by compulsive alcohol seeking and disrupted brain function. In individuals with AUD, abstinence from alcohol often precipitates withdrawal symptoms than can be life threatening. Here, we review evidence for nutritional ketosis as a potential means to reduce withdrawal and alcohol craving. We also review the underlying mechanisms of action of ketosis. Several findings suggest that during alcohol intoxication there is a shift from glucose to acetate metabolism that is enhanced in individuals with AUD. During withdrawal, there is a decline in acetate levels that can result in an energy deficit and could contribute to neurotoxicity. A ketogenic diet or ingestion of a ketone ester elevates ketone bodies (acetoacetate, ß-hydroxybutyrate and acetone) in plasma and brain, resulting in nutritional ketosis. These effects have been shown to reduce alcohol withdrawal symptoms, alcohol craving, and alcohol consumption in both preclinical and clinical studies. Thus, nutritional ketosis may represent a unique treatment option for AUD: namely, a nutritional intervention that could be used alone or to augment the effects of medications.