The Effect of Greater Area Deprivation and Medicaid Insurance Status on Timing of Care and Rate of Reinjury After Anterior Cruciate Ligament Reconstruction.

Background: Lower socioeconomic status and public insurance lead to a longer delay to surgery and a higher likelihood of concomitant pathology before undergoing anterior cruciate ligament reconstruction (ACLR). However, few studies have examined the influence of community deprivation on ACLR timing and outcomes. Purpose/Hypothesis: The primary aim of this study was to define the effect of the area deprivation index (ADI) and insurance classification on access to orthopaedic care after an ACL rupture, and the secondary aim was to determine whether these variables were associated with a second ACL injury after primary ACLR. It was hypothesized that patients with a greater national ADI percentile and Medicaid insurance would experience longer delays to care and an increased risk of reinjury after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective study was performed to evaluate patients undergoing primary ACLR between 2016 and 2019. The national ADI percentile was obtained utilizing the Neighborhood Atlas website. The relationship between national ADI percentile and care characteristics (eg, time to specialized care) was investigated using the Spearman rho correlation coefficient (r). The association between patient and care characteristics and second ACL injury after the index procedure (ie, graft rerupture or contralateral ACL rupture) was investigated using binary logistic regression. Results: A total of 197 patients met the inclusion criteria. Longer times from injury to surgery (r = 0.238; P < .001) and from specialized care to surgery (r = 0.217; P = .002) were associated with a greater national ADI percentile. The second injury group reported significantly greater national ADI (P = .026) and included a greater percentage of patients with Medicaid insurance (31.3%) compared with the no second injury group. Patients experienced 5.1% greater odds of a second ACL injury for each additional month between evaluation and surgery. Conclusion: Greater national ADI percentile and Medicaid insurance status were associated with adverse ACLR timing and outcomes. Patients with a greater national ADI percentile took significantly longer to obtain surgery after ACL injury. Those who sustained a second ACL injury after ACLR had an overall higher mean national ADI percentile and included a greater proportion of patients with Medicaid compared with those who did not sustain a second ACL injury. Future studies should critically investigate the underlying factors of these associations to reach equity in orthopaedic care.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).

IMPROVE 2022 International Meeting on Pathway-Related Obesity: Vision of Excellence.

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway-Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early-onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin-4 receptor (MC4R) pathway-related obesity. The meeting co-chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World-leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work-up was used with new genetic testing tools becoming available. This should aid the planning of new evidence-based treatment strategies for the future, as explained by co-chair Martin Wabitsch, Ulm University Medical Center, Germany.

Ovarian non-gestational placental site trophoblastic tumor with lung metastasis: further evidence for a distinct category of trophoblastic neoplasm.

We previously described a series of cases which characterize a distinct group of primary ovarian placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) as a non-gestational set consistent with germ cell type/origin. Here we report a new case of ovarian non-gestational PSTT. The patient was a 13 year-old young female admitted for a spontaneous pneumothorax of the left lung. The pathology of lung wedge excision specimen demonstrated metastatic PSTT and ovarian biopsy showed atypical intermediate trophoblastic proliferation which was found to be PSTT in the subsequent salpingo-oophorectomy specimen. In the ovary, the tumor was composed of singly dispersed or small clusters of predominantly mononuclear cells and rare multinucleated cells extensively infiltrating the ovarian parenchyma, tubal mucosa, and paraovarian/paratubal soft tissue. A minor component of mature cystic teratoma (less than 5% of total tumor volume) was present. Immunohistochemically, the neoplastic cells of main tumor were diffusely immunoreactive for hPL, Gata3 and AE1/AE3, and had only rare hCG-positive or p63-positive cells. The morphology and immunohistochemical results support a PSTT. Molecular genotyping revealed an identical genotype pattern between the normal lung tissue and the metastatic PSTT, indicating its non-gestational nature of germ cell type/origin. This case represents the first case of such tumor with distant (lung) metastasis. This case also provides further evidence to support our recommendation that primary ovarian non-gestational intermediate trophoblastic tumors of germ cell type/origin, including PSTT and ETT, should be formally recognized in classification systems.

Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations : A Clinicopathologic Analysis With Re-evaluation of Diagnostic Criteria.

Human papillomavirus (HPV)-independent primary endometrial squamous cell carcinoma (PESCC) is a rare but aggressive subtype of endometrial carcinoma for which little is known about the genomic characteristics. Traditional criteria have restricted the diagnosis of PESCC to cases without any cervical involvement. However, given that modern ancillary techniques can detect HPV and characteristic genetic alterations that should identify the more common mimics in the differential diagnosis, including endometrial endometrioid carcinoma with extensive squamous differentiation and HPV-associated primary cervical squamous cell carcinoma, those criteria may benefit from revision. To further characterize PESCC, we identified 5 cases of pure squamous cell carcinoma dominantly involving the endometrium that had the potential to be PESCC: 1 case involving only the endometrium and 4 cases with some involvement of the cervix. Clinicopathologic features were assessed and immunohistochemical analysis (p16, estrogen receptor, progesterone receptor, and p53), HPV RNA in situ hybridization (high-risk and low-risk cocktails and targeted probes for 16 and 18), and molecular studies were performed. All tumors showed aberrant/mutation-type p53 expression, were negative for estrogen receptor, progesterone receptor, and p16, and had no detectable HPV. Per whole-exome sequencing, 4 of the 5 tumors demonstrated comutations in TP53 and CDKN2A (p16). Four patients died of disease within 20 months (range, 1 to 20 mo; mean, 9 mo), and 1 patient had no evidence of disease at 38 months. PESCC represents a unique, clinically aggressive subtype of endometrial cancer with TP53 and CDKN2A comutations. This characteristic profile, which is similar to HPV-independent squamous cell carcinoma of the vulva, is distinct from endometrioid carcinoma with extensive squamous differentiation and HPV-associated primary cervical squamous cell carcinoma and can be used to distinguish PESCC from those mimics even when cervical involvement is present. Diagnostic criteria for PESCC should be relaxed to allow for cervical involvement when other pathologic features are consistent with, and ancillary techniques are supportive of classification as such.

Case report of bilateral ovarian fibromas associated with de novo germline variants in PTCH1 and SMARCA4.

BACKGROUND: Ovarian sex cord-stromal tumors (OSCTs) are rare ovarian tumors that can develop from sex cord, stromal cells, or both. OSCTs can be benign or malignant. Bilateral and/or unilateral ovarian fibromas, a type of OSCT of the stromal cells, have been reported in individuals diagnosed with nevoid basal cell carcinoma syndrome (NBCCS). Calcified ovarian fibromas have been reported in 15-25% of individuals diagnosed with NBCCS while 75% of those cases occur bilaterally. The average age at diagnosis of OSCT/ovarian fibromas in patients with NBCSS is in the second to third decade compared with age 50 in the general population. Ovarian tumors are rare in pediatric populations. METHODS: The patient is a 5-year-old female diagnosed with bilateral ovarian fibromas at age 4. Multigene panel for the patient and subsequent targeted molecular evaluation of parents were completed. Histological evaluations on the surgically resected ovaries were performed for microscopic characterization of fibromas. RESULTS: Germline testing identified de novo heterozygous novel likely pathogenic variants in PTCH1 gene, exon 12 deletion, and an SMARCA4 splicing variant c.2002-1G > A. Microscopic examination of bilateral tumors was consistent with an ovarian fibroma. CONCLUSIONS: To our knowledge, this is the first report of bilateral benign ovarian fibroma in a child with a diagnosis of nevoid basal cell carcinoma syndrome (NBCCS) with a potential predisposition to Rhabdoid Tumor Predisposition Syndrome (RTPS).

Increases in physical activity are associated with a faster rate of weight loss during dietary energy restriction in women with overweight and obesity.

This secondary analysis examined the influence of changes in physical activity (PA), sedentary time and energy expenditure (EE) during dietary energy restriction on the rate of weight loss (WL) and 1-year follow-up weight change in women with overweight/obesity.Measurements of body weight and composition (air-displacement plethysmography), resting metabolic rate (indirect calorimetry), total daily (TDEE) and activity EE (AEE), minutes of PA and sedentary time (PA monitor) were taken at baseline, after 2 weeks, after ≥5% WL or 12 weeks of continuous (25% daily energy deficit) or intermittent (75% daily energy deficit alternated with ad libitum day) energy restriction, and at 1-year post-WL. The rate of WL was calculated as total %WL/number of dieting weeks. Data from both groups were combined for analyses.Thirty-seven participants (age=35±10y; BMI=29.1±2.3kg/m2) completed the intervention (WL=-5.9±1.6%) and 18 returned at 1-year post-WL (weight change=+4.5±5.2%). Changes in sedentary time at 2 weeks were associated with the rate of WL during energy restriction (r=-0.38; p=0.03). Changes in total (r=0.54; p<0.01), light (r=0.43; p=0.01) and moderate-to-vigorous PA (r=0.55; p<0.01), sedentary time (r=-0.52; p<0.01), steps per day (r=0.39; p=0.02), TDEE (r=0.46; p<0.01) and AEE (r=0.51; p<0.01) during energy restriction were associated with the rate of WL. Changes in total (r=-0.50; p=0.04) and moderate-to-vigorous PA (r=-0.61; p=0.01) between post-WL and follow-up were associated with 1-year weight change (r=-0.51; p=0.04).These findings highlight that PA and sedentary time could act as modifiable behavioural targets to promote better weight outcomes during dietary energy restriction and/or weight maintenance.

Bizarre Chorionic-type Trophoblast in Second-trimester and Third-trimester Placentas: Clinicopathologic Characterization of a Placental Pseudoneoplastic Lesion.

Bizarre (atypical/symplastic) cells have been described in various gynecologic normal tissues and benign neoplasms. This type of bizarre cytologic change is usually an incidental finding and is regarded as a benign process. We describe 17 cases of bizarre chorionic-type trophoblast in second-trimester and third-trimester placentas that created concern for an underlying/undersampled or incipient intraplacental trophoblastic neoplasm, predominantly found in intervillous trophoblastic islands (11/17), placental septae (6/17), chorionic plate (1/17), and/or the chorion layer of fetal membranes (2/17). The bizarre trophoblastic cells exhibited sheet-like or nested architecture, had a multifocal/patchy distribution, and/or were present as individual cells within hyaline stroma; they were characterized by large nuclei with smudgy chromatin and occasional intranuclear pseudoinclusions. The degree of atypia was classified as mild (0/17), moderate (3/17), or severe (14/17). Mitotic figures and necrosis were not identified. A dual immunohistochemical stain for trophoblast (hydroxyl-delta-5-steroid dehydrogenase) and a proliferation marker (Ki-67), performed in 15 cases, demonstrated 0% to very low proliferative activity within the bizarre trophoblast (0% to 2% [10/15], 3% to 8% [5/15]). Immunohistochemical stains for fumarate hydratase showed intact/retained expression in the bizarre cells in 7 of 7 cases. Clinical follow-up ranged from 1 to 45 months, and all patients were alive and well without subsequent evidence of a gestational trophoblastic or other neoplasms. We conclude that bizarre chorionic-type trophoblast in second-trimester or third-trimester placentas have the potential to mimic an intraplacental trophoblastic neoplasm but are likely a benign degenerative change. This study expands the spectrum of bizarre cells that occur in the gynecologic tract.

Progestin and aromatase inhibitor therapy in recurrent, estrogen/progestin receptor positive uterine carcinosarcoma: A case report.

•A subset of patients with uterine carcinosarcoma will have ER/PR positive disease.•Hormone receptor expression may serve as a therapeutic target in high-grade endometrial tumors.•Hormonal therapy and SBRT may have benefit in the management of recurrent uterine carcinosarcoma.

Spontaneous generation of diversity in Arachis neopolyploids (Arachis ipaënsis × Arachis duranensis)4x replays the early stages of peanut evolution.

Polyploidy is considered a driving force in plant evolution and domestication. Although in the genus Arachis, several diploid species were traditionally cultivated for their seeds, only the allotetraploid peanut Arachis hypogaea became the successful, widely spread legume crop. This suggests that polyploidy has given selective advantage for domestication of peanut. Here, we study induced allotetraploid (neopolyploid) lineages obtained from crosses between the peanut's progenitor species, Arachis ipaënsis and Arachis duranensis, at earlier and later generations. We observed plant morphology, seed dimensions, and genome structure using cytogenetics (FISH and GISH) and SNP genotyping. The neopolyploid lineages show more variable fertility and seed morphology than their progenitors and cultivated peanut. They also showed sexual and somatic genome instability, evidenced by changes of number of detectable 45S rDNA sites, and extensive homoeologous recombination indicated by mosaic patterns of chromosomes and changes in dosage of SNP alleles derived from the diploid species. Genome instability was not randomly distributed across the genome: the more syntenic chromosomes, the higher homoeologous recombination. Instability levels are higher than observed on peanut lines, therefore it is likely that more unstable lines tend to perish. We conclude that early stages of the origin and domestication of the allotetraploid peanut involved two genetic bottlenecks: the first, common to most allotetraploids, is composed of the rare hybridization and polyploidization events, followed by sexual reproductive isolation from its wild diploid relatives. Here, we suggest a second bottleneck: the survival of the only very few lineages that had stronger mechanisms for limiting genomic instability.

Ultrasound-Guided Transthoracic Fine-Needle Aspiration: A Reliable Tool in Diagnosis and Molecular Profiling of Lung Masses.

INTRODUCTION: Pulmonary adenocarcinoma is a major cause of mortality worldwide. The majority of patients present with advanced stage disease, and minimally invasive procedures are desirable for diagnosis and treatment plans. Herein, we report our experience with percutaneous/transthoracic needle aspiration (TT-NA) in the cytologic diagnosis of pulmonary adenocarcinoma. MATERIAL AND METHODS: After institutional review board approval, the cytopathology electronic data system was searched for all consecutive TT-NA of the lung masses from January 2011 to November 2015. Patients' medical records were reviewed and cytologic materials were evaluated. RESULTS: A total of 151 specimens were identified, with a mean age of 62.8 years; 62.9% of the patients had a prior history of malignancy. Carcinoma/adenocarcinoma was the most common (80%) diagnosis. The targeted lesions were predominantly located in the lung (56.3%, 81/151) and pleural based (27.8%, 42/151). The mean size of the lesions was 3.6 cm. Cytology specimens were adequate in 70.9% of the cases, while 72.8% (110/151) of the cases also had concurrent core biopsy. A malignant diagnosis was rendered in the majority of the cases (64.9%). In 71% of the cases, immunohistochemistry/histochemistry studies were successfully performed. Molecular/genetic studies were requested in 80% of the cases and had adequate material. Complications of the procedure were seen in 9.9% of the patients including pneumothorax (7.9%) and hemoptysis (1.9%). CONCLUSION: TT-NA is a relatively safe and reliable technique in the assessment of pulmonary lesions.

A novel RBMX-TFE3 gene fusion in a highly aggressive pediatric renal perivascular epithelioid cell tumor.

We report an Xp11 translocation perivascular epithelioid cell tumor (PEComa) with a novel RBMX-TFE3 gene fusion, resulting from a paracentric X chromosome inversion, inv(X)(p11;q26). The neoplasm occurred in an otherwise healthy 12-year-old boy who presented with a large left renal mass with extension into the inferior vena cava. The patient was found to have multiple pulmonary metastases at diagnosis and died of disease 3 months later. The morphology (epithelioid clear cells with alveolar and nested architecture) and immunophenotype (TFE3 and HMB45 strongly positive; actin, desmin, and PAX8 negative) was typical of an Xp11 translocation PEComa; however, TFE3 rearrangement was initially not detected by routine TFE3 break-apart fluorescence in situ hybridization (FISH). Further RNA sequencing revealed a novel RBMX-TFE3 gene fusion, which was subsequently confirmed by fusion assay FISH, using custom design RBMX and TFE3 come-together probes. This report describes a novel TFE3 gene fusion partner, RBMX, in a pediatric renal PEComa patient associated with a fulminant clinical course. As documented in other intrachromosomal Xp11.2 inversions, such as fusions with NONO, RBM10, or GRIPAP1 genes, the TFE3 break-apart might be below the FISH resolution, resulting in a false negative result.

Consistent high prevalence of undiagnosed blood-borne virus infection in patients attending large urban emergency departments in England.

Understanding local viral hepatitis and HIV epidemiology is essential if WHO elimination targets are to be achieved. We demonstrate a consistently high prevalence of undiagnosed active infection in urban emergency department attendees in England, with variations in local risk groups crucial to informing targeted testing initiatives.

Paraganglioma of the recurrent laryngeal nerve.

Paragangliomas of the head and neck are rare, and most frequently benign, slow growing, and nonsecretory. The most frequent locations these tumors arise in the head and neck include the carotid body, jugular bulb, vagus nerve, tympanic branch of the glossopharyngeal nerve, and sympathetic chain. Here we present, to our knowledge, the second reported case of paraganglioma of the recurrent laryngeal nerve. This case is unique given the patient presentation due to ipsilateral vocal fold paralysis, which has not previously been reported, lack of previous surgery, and demonstration of loss of succinate dehydrogenase iron-sulfur subunit B expression. Laryngoscope, 2019.

Effects of Acute Eccentric Exercise on Appetite-Related Hormones and Food Preferences in Men.

Eccentric exercise has been suggested to improve muscle atrophy, muscle function, and insulin sensitivity. The aim of this study was to examine the effect of acute eccentric exercise on appetite-related hormones, food preferences, and food intake. Fourteen moderately active men were recruited to participate in this study (age 24.2 ± 5.5 years; BMI 23.4 ± 3.3 kg/m2; VO2max 48.9 ± 3.1 ml/kg/min). Three different conditions were implemented; no exercise, flat running "inclination 0" and downhill running "inclination -12%." Appetite-related hormones, subjective appetite sensations, food preference and reward, and ad libitum food intake were measured at pre-, immediately post-, and 24 h post exercise. There were no significant median changes in total ghrelin or pancreatic peptide concentrations between conditions. There were also no median differences in subjective appetite ratings or energy intake between conditions, but the median change in explicit liking of sweet versus savory foods differed significantly between pre-exercise and 24 h post exercise (p = .013). Post-hoc analysis observed a significant difference in the pre-exercise to 24 h post exercise change between front running and downhill running (p = .023), and indicated greater liking of savory foods over sweet foods in downhill running than front running. However, no further differences were seen between conditions for the remaining food preference parameters, suggesting there were no systematic trends in these data. In conclusion, there was no effect of front and downhill running on eating behavior as compared to a nonexercise control condition, but these data need to be replicated in a larger and more heterogeneous sample.

Issues in Measuring and Interpreting Human Appetite (Satiety/Satiation) and Its Contribution to Obesity.

PURPOSE OF REVIEW: The goals of this paper are to report current research practices in investigations of human appetite control and to assess their relationships with emerging theoretical principles. Appetite is often distinguished by the separation of homeostatic and hedonic processes. RECENT FINDINGS: This report assesses the validity of a homeostatic toolkit to measure subjectively perceived hunger and its relationship to the developing processes of satiation (control of meal size) and satiety (control of the post-eating period). The capacity of a procedure to measure the influence of hedonic processes on food intake is also evaluated. A major issue is the relationship between the pattern of eating behaviour (influenced by the underlying drive to eat and the inhibition induced by the act of eating itself) and the parallel underlying profile of hormonal and other metabolic biomarkers. Increasing recognition is being given to individual variability in the expression of appetite, and the fact that the use of the average (mean) response conceals important information about the nature of appetite control. There is a growing interest in the identification of satiety phenotypes that operate in parallel to metabolic phenotypes. Interestingly, energy expenditure (metabolic and behavioural) contributes to an energy balance framework for understanding energy intake (appetite).

Point-of-Care Screening for a Current Hepatitis C Virus Infection: Influence on Uptake of a Concomitant Offer of HIV Screening.

Eliminating hepatitis C as a public health threat requires an improved understanding of how to increase testing uptake. We piloted point-of-care testing (POCT) for a current HCV infection in an inner-city Emergency Department (ED) and assessed the influence on uptake of offering concomitant screening for HIV. Over four months, all adults attending ED with minor injuries were first invited to complete an anonymous questionnaire then invited to test in alternating cycles offering HCV POCT or HCV+HIV POCT. Viral RNA was detected in finger-prick blood by GeneXpert. 814/859 (94.8%) questionnaires were returned and 324/814 (39.8%) tests were accepted, comprising 211 HCV tests and 113 HCV+HIV tests. Offering concomitant HIV screening reduced uptake after adjusting for age and previous HCV testing (odds ratio 0.51; 95% confidence interval [CI] 0.38-0.68; p < 0.001). HCV prevalence was 1/324 (0.31%; 95% CI 0.05-1.73); no participant tested positive for HIV. 167/297 (56.2%) POCT participants lived in the most deprived neighbourhoods in England. HCV RNA testing using finger-prick blood was technically feasible. Uptake was moderate and the offer of concomitant HIV screening showed a detrimental impact on acceptability in this low prevalence population. The findings should be confirmed in a variety of other community settings.

Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: An updated perspective.

The current obesogenic environment promotes physical inactivity and food consumption in excess of energy requirements, two important modifiable risk factors influencing energy balance. Habitual physical activity has been shown to impact not only energy expenditure, but also energy intake through mechanisms of appetite control. This review summarizes recent theory and evidence underpinning the role of physical activity in the homeostatic and non-homeostatic mechanisms controlling appetite. Energy intake along the spectrum of physical activity levels (inactive to highly active) appears to be J-shaped, with low levels of physical activity leading to dysregulated appetite and a mismatch between energy intake and expenditure. At higher levels, habitual physical activity influences homeostatic appetite control in a dual-process action by increasing the drive to eat through greater energy expenditure, but also by enhancing post-meal satiety, allowing energy intake to better match energy expenditure in response to hunger and satiety signals. There is clear presumptive evidence that physical activity energy expenditure can act as a drive (determinant) of energy intake. The influence of physical activity level on non-homeostatic appetite control is less clear, but low levels of physical activity may amplify hedonic states and behavioural traits favouring overconsumption indirectly through increased body fat. More evidence is required to understand the interaction between physical activity, appetite control and diet composition on passive overconsumption and energy balance. Furthermore, potential moderators of appetite control along the spectrum of physical activity, such as body composition, sex, and type, intensity and timing of physical activity, remain to be fully understood.