Update on Assessment of Ovarian Reserve Testing.

Importance: Women are increasingly postponing pregnancy to achieve specific goals, and as it is known, the ovarian reserve (OR) declines with age, especially after the 30s. Assessing the OR helps in managing the care of women seeking pregnancy. Several OR tests (ORTs) have been advocated for assessing OR. Objectives: This review aims to discuss the different ORTs and the consequences of their use. Evidence Acquisition: For each topic, a PubMed search was conducted using MeSH terms. The following terms were used: ovarian reserve, ovarian reserve tests, anti-Müllerian hormone, antral follicle count, and diminished ovarian reserve. The search for further references was complemented by manual search, review, synthesis, and summarization of retrieved articles. Results: In this review, we clarified the concept of OR and the different ORTs and provided a guide for the ultrasound to assess OR. In addition, the clinical value of ORTs was highlighted to explain the implications of the results of these tests and how they can aid in patient counseling. Conclusion and Relevance: A number of ORTs are available to the clinician. Anti-Müllerian hormone and antral follicle count are the most valuable, but as with all ORTs, they are best used as screening, not diagnostic tests for OR. Screening for OR is most helpful when applied to specific groups.

Youth's energy intake during a laboratory-based loss-of-control eating paradigm: Associations with reported current dieting.

Dieting is theorized as a risk factor for loss-of-control (LOC)-eating (i.e., feeling a sense of lack of control while eating). Support for this association has largely relied on retrospective self-report data, which does not always correlate with objectively assessed eating behavior in youth. We hypothesized that during a laboratory-based LOC-eating paradigm, children and adolescents who reported current (at the time of the visit) dieting would consume meals consistent with LOC-eating (greater caloric intake, and intake of carbohydrates and fats, but less intake of protein). Participants were presented with a buffet-style meal and instructed to "Let yourself go and eat as much as you want." Current dieting (i.e., any deliberate change to the amount or type of food eaten to influence shape or weight, regardless of how effective the changes are) was assessed via interview. General linear models were adjusted for fat mass (%), lean mass (kg), height, sex, protocol, race and ethnicity, pre-meal hunger and minutes since consumption of a breakfast shake. Of 337 participants (Mage 12.8 ± 2.7y; 62.3 % female; 45.7 % non- Hispanic White and 26.1 % non-Hispanic Black; MBMIz 0.78 ± 1.11), only 33 (9.8 %) reported current dieting. Current dieting was not significantly associated with total energy intake (F = 1.63, p = .20, ηp2 = 0.005), or intake from carbohydrates (F = 2.45, p = .12, ηp2 = 0.007), fat (F = 2.65, p = .10, ηp2 = 0.008), or protein (F = 0.39, p = .53, ηp2 = 0.001). Contrary to theories that dieting promotes LOC-eating, current dieting was not associated with youth's eating behavior in a laboratory setting. Experimental approaches for investigating dieting are needed to test theories that implicate dieting in pediatric LOC-eating.

Child Abuse and Neglect Awareness Among Healthcare Students in Saudi Arabia.

Background Healthcare workers are responsible for dealing with pediatric victims of violence. While the awareness and reporting of suspected cases are rising, there is a lack of research that proves the awareness, knowledge, and attitude of healthcare students. Objectives We evaluated the awareness of child abuse and neglect and examined the demographic factors associated with them. Participants and setting The study was conducted at King Abdulaziz University in Jeddah with a sample of 237 undergraduate healthcare students. Methods We utilized the quantitative design and surveyed a convenience sample of 237 healthcare students from March to May 2021. The survey contains questions on child abuse and neglect. Results The respondents' overall mean on the scale was 82.90 (SD = 14.00). The students rated the subscale "Actions considered as child neglect" as the highest (M = 4.18, SD = 1.08), followed by "Actions considered as child abuse" (M = 4.04, SD = 1.21), "Reasons for under-reporting child abuse and neglect cases in Saudi Arabia" (M = 3.34, SD = 0.68), and "Knowledge regarding child abuse and neglect" (M = 3.13, SD = 0.53). The analyses showed that gender (t= -3.88, p< 0.001) and year level (F= 5.98, p= 0.003) were associated with the students' "knowledge regarding child abuse and neglect." Conclusion The findings revealed a good awareness of child maltreatment among healthcare students. However, the students reported a lower awareness of the different reasons for under-reporting child violence cases in Saudi Arabia.

A Comprehensive Review of the Mechanism, Efficacy, Safety, and Tolerability of Ubrogepant in the Treatment of Migraine.

Ubrogepant is an innovative medication designed for the acute treatment of migraine, a debilitating neurological condition that profoundly impairs quality of life, productivity, and social interactions. This comprehensive review assesses the efficacy, safety, tolerability, and mechanism of action of ubrogepant through a rigorous methodology, including an in-depth literature review from reputable databases like PubMed, Web of Science, Embase, Scopus, and Cochrane. Classified as a calcitonin gene-related peptide (CGRP) receptor antagonist, ubrogepant has emerged as a potential revolutionary medication for migraine treatment. CGRP is a peptide integral to migraine pathophysiology, and its blockade has demonstrated great therapeutic potential. Unlike triptans, known for their cardiovascular risks, ubrogepant lacks vasoconstrictive properties, making it a safer alternative for a broader patient population. Ubrogepant offers significant potential for pain relief, symptom reduction, and restoration of normal function during a migraine attack, and it outperforms placebo in terms of efficacy. It also presents favorable safety, with generally mild adverse drug events (ADEs), such as nausea, dizziness, and somnolence, similar to placebo effects. Consistent results from clinical trials confirm its tolerability, with minor ADEs and no safety alerts for the tested doses, indicating that ubrogepant is a safe and well-tolerated option for migraine treatment. As an effective oral medication, ubrogepant could be an alternative to traditional acute migraine treatments. Its benefits include a unique mechanism of action, rapid onset, and favorable safety profile. However, specific contraindications, such as hypersensitivity, severe hepatic impairment, concurrent use of CYP3A4 inhibitors, pregnancy or breastfeeding, and uncontrolled hypertension, require caution or avoidance of ubrogepant. Despite these limitations, ubrogepant signals a promising new direction in migraine therapeutics.

Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types.

Targeting mitochondrial oxidative phosphorylation (OXPHOS) to treat cancer has been hampered due to serious side-effects potentially arising from the inability to discriminate between non-cancerous and cancerous mitochondria. Herein, comprehensive mitochondrial phenotyping was leveraged to define both the composition and function of OXPHOS across various murine cancers and compared to both matched normal tissues and other organs. When compared to both matched normal tissues, as well as high OXPHOS reliant organs like heart, intrinsic expression of the OXPHOS complexes, as well as OXPHOS flux were discovered to be consistently lower across distinct cancer types. Assuming intrinsic OXPHOS expression/function predicts OXPHOS reliance in vivo, these data suggest that pharmacologic blockade of mitochondrial OXPHOS likely compromises bioenergetic homeostasis in healthy oxidative organs prior to impacting tumor mitochondrial flux in a clinically meaningful way. Although these data caution against the use of indiscriminate mitochondrial inhibitors for cancer treatment, considerable heterogeneity was observed across cancer types with respect to both mitochondrial proteome composition and substrate-specific flux, highlighting the possibility for targeting discrete mitochondrial proteins or pathways unique to a given cancer type.

Risk Factors for Fibrous Ingrowth in Eyes Requiring Primary Keratoplasty.

PURPOSE: The aim of this study was to define risks for corneal transplantation associated with fibrous ingrowth among first-time transplant recipients. METHODS: We performed a retrospective case-control study of patients with a histopathologic diagnosis of fibrous ingrowth between 2002 and 2019. Patients with fibrous ingrowth from a first corneal specimen were included. Those with incomplete records were excluded. A 1:2 case-control ratio was used. Controls were matched using surgical indication, surgery year, transplantation method, sex, and age. RESULTS: Seventy-eight eyes (76 patients) were included and matched with 160 control eyes. The incidence of fibrous ingrowth found on a first corneal transplant was 0.6% per year. The most common keratoplasty indications were pseudophakic corneal edema (n = 25, 32%) and aphakic corneal edema (n = 15, 19%). Cases were more likely to have a history of ocular trauma (odds ratio [OR], 2.94; 95% CI, 1.30-6.30; P = 0.007), uveitis (OR, 2.73; 95% CI, 1.12-6.63; P = 0.022), retinal detachment or previous retinal surgery (OR, 2.40; 95% CI, 1.34-4.30; P = 0.003), glaucoma tube-shunt surgery (OR, 2.70; 95% CI, 1.29-5.65; P = 0.007), aphakia (OR, 3.02; 95% CI, 1.61-5.67; P = 0.0004), or iris derangement (OR, 10.52; 95% CI, 5.45-20.30; P <0.0001). A multivariate logistic regression model using iris derangement, history of ocular trauma, history of uveitis, and history of cataract surgery demonstrated 81% sensitivity and 66% specificity in predicting presence of fibrous ingrowth. CONCLUSIONS: A history of ocular trauma, uveitis, retinal detachment or previous retinal surgery, glaucoma tube-shunt surgery, aphakia, and iris derangement are risks for detecting fibrous ingrowth among first-time keratoplasty recipients. Patients with these conditions should be monitored closely for corneal decompensation.

Associated features of pediatric loss-of-control eating severity during a laboratory-based feeding paradigm.

Laboratory-based loss-of-control eating (LOC-eating; i.e., feeling like one cannot stop eating) paradigms have provided inconsistent evidence that the features of pediatric LOC-eating are consistent with those of DSM-5-TR binge-eating episodes. Thus, this study investigated whether recent LOC-eating (in the prior month) and/or greater LOC-eating severity during a meal are positively associated with faster eating rate, energy intake when adjusting for hunger, post-meal stomachache and sickness (a proxy for eating until uncomfortably full), depression, and guilt. Recent LOC-eating was assessed via interview. Participants were presented with a buffet-type meal and instructed to "Let yourself go and eat as much as you want." Immediately following, youth reported on their experience of LOC-eating during the meal (LOC-eating severity). Eating rate (kcal/min) was computed by dividing total energy intake by the duration of the meal. Prior to and following the meal, youth reported hunger, sickness, and stomachache via sliding Visual Analog Scales, depression via the Brunel Mood Scale and guilt via the PANAS-X. Three-hundred-ten youth participated (61.2 % Female; 46.3 % non-Hispanic White, 12.96 ± 2.72 y). Recent LOC-eating was not significantly associated with any DSM-5-TR binge-eating feature during the laboratory meal (ps = 0.07-0.85). However, LOC-eating severity during the meal was positively associated with eating rate, eating adjusted for hunger, post-meal sickness and stomachache, and guilt (ps < 0.045). LOC-eating severity during a laboratory-based feeding paradigm meal, but not recent LOC-eating, was associated with several features of DSM-5-TR binge-eating episodes. Future studies should assess multiple components of LOC-eating to further characterize the phenomenology of pediatric LOC-eating.

Relationships examined: Parent and child readiness to change and sociodemographic characteristics in family based weight loss treatment.

BACKGROUND: Family based treatment is an effective, multipronged approach to address obesity as it plagues families. OBJECTIVE: To investigate the relationships among sociodemographic characteristics (e.g., education and income), body mass index (BMI) and race/ethnicity with readiness to change for parents enrolled in the Primary care pediatrics, Learning, Activity and Nutrition (PLAN) study. METHODS: Multivariate linear regressions tested two hypotheses: (1) White parents will have higher levels of baseline readiness to change, when compared to Black parents; (2) parents with higher income and education will have higher levels of readiness to change at baseline. RESULTS: A positive relationship exists between baseline parent BMI and readiness to change (Pearson correlation, 0.09, p < 0.05); statistically significant relationships exist between parent education level (-0.14, p < 0.05), income (0.04, p < 0.05) and readiness to change. Additionally, a statistically significant relationship exists, with both White (ß, -0.10, p < 0.05), and Other, non-Hispanic (-0.10, p < 0.05) parents exhibiting lower readiness to change than Black, non-Hispanic parents. Child data did not indicate significant relationships between race/ethnicity and readiness to change. CONCLUSIONS: Results demonstrate that investigators should consider sociodemographic characteristic factors and different levels of readiness to change in participants enrolling in obesity interventions.

Associations of food reinforcement and food- related inhibitory control with adiposity and weight gain in children and adolescents.

Some, but not all studies have reported that, among youth with disordered eating and high weight, the relative reinforcing value of food (RRV-F, i.e., how hard a person will work for a high-energy-dense food when another reward is available) is greater, and food-related inhibitory control (i.e., ability to withhold a response to food-related stimuli) is lower, compared to peers without disordered eating or overweight. In most studies, high RRV-F and low food-related inhibitory control have been studied separately, as independent factors, with each suggested to predict excess weight and adiposity (fat mass) gain. We hypothesized that the interaction of these factors would prospectively exacerbate risk for weight and adiposity (fat mass) gain three years later in a sample of healthy youth. At baseline, RRV-F was measured using a Behavior Choice Task with the rewards being standardized servings of chocolate candies, cheese crackers, or fruit snacks. Food-related inhibitory control was determined by performance in response to food and non-food stimuli during a Food Go/No-Go task. At baseline and 3-year visits, total body adiposity was measured by dual-energy X-ray absorptiometry (DXA) and body mass index (BMI) was obtained using measured weight and height. A linear regression was conducted with 3-year adiposity as the dependent variable. RRV-F, food-related inhibitory control, and the RRV-F x food-related inhibitory control interaction as independent variables. Baseline adiposity, age, height, sex, race/ethnicity, and days between visits were included as covariates for model predicting 3-year adiposity. Baseline BMI, age, sex, race/ethnicity, and days between visits were included as covariates for model predicting 3-year BMI. One-hundred and nine youth (mean 12.4±2.7y, mean 0.50±1.02 BMIz, 30.3% with overweight/obesity, 45.9% female, 51.4% non-Hispanic White), 8-17 years at baseline, were studied. Baseline food-related inhibitory control (ßunstandardized = 0.33, p = .037, 95% CI [.02, 0.64]), but not baseline RRV-F (ßunstandardized = -0.003, p = .914), 95% CI [-0.05, 0.05]) was significantly associated with 3-year adiposity such that those with the poorest food-related inhibitory control (great number of commision errors) had the greatest adiposity gain. The interaction between RRV-F and food-related inhibitory control did not predict 3-year adiposity (ßunstandardized = -0.07, p = .648, 95% CI [-0.39, 0.25]). The pattern of findings was the same for models examining non-food related inhibitory control. Neither baseline food-related inhibitory control (ßunstandardized = 2.16, p = .256, 95% CI [-1.59, 5.92]), baseline RRV-F (ßunstandardized = 0.14, p = .660, 95% CI [-0.48, 0.75]), nor their interaction (ßunstandardized = -1.18, p = .547, 95% CI [-5.04, 2.69]) were significantly associated with 3-year BMI. However, non-food related inhibitory control (ßunstandardized = 0.54, p = .038, 95% CI [.22, 7.15]) was significantly associated with 3-year BMI. In summary, food-related inhibitory control but not RRV-F, was associated with changes in adiposity in a sample of children and adolescents. Among generally healthy youth, food-related inhibitory control may be a more relevant risk factor than food reinforcement for adiposity gain. Additional data are needed to determine how inhibitory control and reward systems, as well as other disinhibited eating behaviors/traits, may interact to promote excess weight gain over time in youth.

Negative affect and loss-of-control eating in relation to adiposity among non-Hispanic youth identifying as black or white.

Negative affect and loss-of-control (LOC)-eating are consistently linked and prevalent among youth identifying as non-Hispanic Black (NHB) and non-Hispanic White (NHW), particularly those with high weight. Given health disparities in high weight and associated cardiometabolic health concerns among NHB youth, elucidating how the association of negative affect with adiposity may vary by racial/ethnic group, and whether that relationship is impacted by LOC-eating, is warranted. Social inequities and related stressors are associated with negative affect among NHB youth, which may place this group at increased risk for excess weight gain. Across multiple aggregated protocols, 651 youth (13.0 ± 2.7 y; 65.9 % girls, 40.7 % NHB; 1.0 ± 1.1 BMIz; 37.6 % LOC-eating) self-reported trait anxiety and depressive symptoms as facets of negative affect. LOC-eating was assessed by interview and adiposity was measured objectively. Cross-sectional moderated mediation models predicted adiposity from ethno-racial identification (NHB, NHW) through the pathway of anxiety or depressive symptoms and examined whether LOC-eating influenced the strength of the pathway, adjusting for SES, age, height, and sex. The association between ethno-racial identity and adiposity was partially mediated by both anxiety (95 % CI = [0.01, 0.05]) and depressive symptoms (95 % CI = [0.02, 0.08]), but the mediation was not moderated by LOC-eating for either anxiety (95 % CI = [-0.04, 0.003]) or depressive symptoms (95 % CI = [-0.07, 0.03]). Mechanisms underlying the link between negative affect and adiposity among NHB youth, such as stress from discrimination and stress-related inflammation, should be explored. These data highlight the need to study impacts of social inequities on psychosocial and health outcomes.

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT. METHODS: Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively. RESULTS: Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0 cm (standard deviation [SD] 4.7 cm), 12.2 cm (SD 9.4 cm), and 5.4 cm (SD 5.8 cm), respectively. Two women had a local recurrence, both of whom were black. DISCUSSION: In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.

Who Volunteers? Results From an Internet-Based Cognitive Monitoring Study of Community-Based Older Adults.

Objectives. Volunteering promotes well-being and may provide added purpose to life after retirement. Limited evidence exists regarding the characteristics and study adherence among those who participate in longitudinal studies while also volunteering outside the study. We assessed characteristics and adherence of older adults who volunteered outside of participation in a regular monthly cognitive monitoring study. Method. All 124 participants with complete data were included. Participants were from a regular cognitive monitoring study that required completion of a 15-min monthly online cognitive assessment. Analysis of covariance and logistic regression analysis were performed to examine differences between volunteers and nonvolunteers. Results. Those who volunteered outside the study were significantly less likely to be college-educated (although all participants were highly educated) but the two groups were cognitively similar. Volunteers had significantly lower scores for neuroticism. Those who volunteered also were significantly less likely to drop out but had poorer study adherence. The most frequent type of volunteering was religious activities. Volunteers were motivated mainly by altruism, although most reported multiple reasons. Conclusion. Older adults who enroll in a longitudinal research study and volunteer outside the study have similar personal characteristics as those who opt out of additional volunteering, with somewhat less education and more favorable personality traits. However, they may be more likely to drop out and need more reminders. Therefore, those who volunteer outside a study may need more attention from study administrators and potentially a more individualized schedule that works around their volunteer obligations.

Nephroprotective Effects of Mycophenolate Mofetil and Glibenclamide on Streptozotocin-induced Diabetic Renal Injury in Rats: An Experimental Study.

Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated with hypoglycemic agents to address metabolic perturbations. However, the way to mitigate immunological, inflammation, and oxidative stress have seldom been studied. Hence, in the present study, the nephroprotective role of immunosuppressive and anti-inflammatory drugs, mycophenolate mofetil (MMF) in combination with the oral hypoglycemic agent glibenclamide, on streptozotocin (STZ)- induced diabetic renal damage was studied. Bodyweight, fasting blood glucose, and glycosylated hemoglobin levels were altered in the diabetic rats. Furthermore, renal injury was indicated by abnormal levels of urinary protein and creatinine and serum markers of renal function in diabetic rats. Hyperglycemia-induced oxidative stress and inflammation were also observed in the diabetic rats. The combination of MMF and glibenclamide treatment significantly attenuated the abnormal effects of hyperglycemia, oxidative stress, and inflammation-induced renal injury in diabetic rats. Histopathological studies confirmed the nephroprotective role of MMF and glibenclamide by reversing renal injury in diabetic rats. The present study suggests that MMF and glibenclamide have a protective role in STZ-induced diabetic renal damage.

NHS orthodontic services in Wales: orthodontic workforce distribution and primary care commissioned activity in 2021.

Objectives 1) To ascertain the volume of primary care orthodontic activity commissioned within Wales and compare this to the 12-year-old population; and 2) To ascertain the orthodontic workforce undertaking NHS orthodontic provision within Wales and their distribution.Methods Information was gathered between September and November 2021 from multiple sources within Wales, including: Freedom of Information requests; Welsh Government statistics; orthodontic professional networks; orthodontic provider websites; health boards (HBs); and directors of primary care/contracting/commissioning.Results The HBs had varying levels of orthodontic need and commissioned activity with a significant amount of cross border activity in South Wales. Overall, it indicated that Wales was only commissioning orthodontic activity to meet 76% of the annual orthodontic need. Overall, 97.9% of commissioned primary care orthodontic activity was being used to provide treatment for 9,500 patients per year. Furthermore, 112 GDC-registered clinicians provide NHS orthodontic care within Wales - 52 orthodontic specialists; 32 orthodontic therapists; 24 DwSIs; and 4 orthodontic trainees (StR 1-3). NHS orthodontic care is provided at 47 sites within Wales - 32 sites in the GDS/Specialist Practice, 6 sites within the CDS and 9 secondary care settings.Conclusions NHS commissioned primary care orthodontic activity within Wales is 76% of the potential orthodontic annual need. Primary care orthodontic services are efficient with 97.9% of commissioned activity being used to provide treatment. In total, 112 GDC-registered clinicians provide NHS orthodontic care across 47 sites within Wales, with 29.5% of clinicians working at multiple sites. The distribution of the orthodontic providers is predominately in areas of high population density, resulting in some rural communities being a significant distance from any orthodontic provider.

Heart Rate Variability and Laboratory-Based Loss-of-Control Eating in Children and Adolescents.

Among youth, greater heart rate (HR) and lesser HR variability (HRV) are precursors to loss-of-control (LOC) eating episodes in the natural environment. However, there are limited data examining whether pre-meal HR and HRV are associated with greater LOC-eating in the laboratory setting. We therefore examined temporal relationships between pre-meal HR, frequency- and time-based metrics of pre-meal HRV, perceived LOC-eating, and energy intake during a meal designed to simulate a LOC-eating episode. Among 209 participants (54.5% female, 12.58 ± 2.72 years, 0.52 ± 1.02 BMIz), 19 reported LOC-eating in the prior month. Perceived LOC-eating during the laboratory meal was not significantly linked to pre-meal HR (p = 0.37), but was positively related to pre-meal HRV (ps = 0.02-0.04). This finding was driven by youth with recent LOC-eating, as these associations were not significant when analyses were run only among participants without recent reported LOC-eating (p = 0.15-0.99). Pre-meal HR and HRV were not significantly related to total energy intake (ps = 0.27-0.81). Additional research is required to determine whether early-stage pediatric LOC-eating is preceded by a healthy pre-meal stress response. Longitudinal studies could help clarify whether this pattern becomes less functional over time among youth who develop recurrent LOC-eating episodes.

Bioenergetic Phenotyping of DEN-Induced Hepatocellular Carcinoma Reveals a Link Between Adenylate Kinase Isoform Expression and Reduced Complex I-Supported Respiration.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Increasing evidence suggests that mitochondria play a central role in malignant metabolic reprogramming in HCC, which may promote disease progression. To comprehensively evaluate the mitochondrial phenotype present in HCC, we applied a recently developed diagnostic workflow that combines high-resolution respirometry, fluorometry, and mitochondrial-targeted nLC-MS/MS proteomics to cell culture (AML12 and Hepa 1-6 cells) and diethylnitrosamine (DEN)-induced mouse models of HCC. Across both model systems, CI-linked respiration was significantly decreased in HCC compared to nontumor, though this did not alter ATP production rates. Interestingly, CI-linked respiration was found to be restored in DEN-induced tumor mitochondria through acute in vitro treatment with P1, P5-di(adenosine-5') pentaphosphate (Ap5A), a broad inhibitor of adenylate kinases. Mass spectrometry-based proteomics revealed that DEN-induced tumor mitochondria had increased expression of adenylate kinase isoform 4 (AK4), which may account for this response to Ap5A. Tumor mitochondria also displayed a reduced ability to retain calcium and generate membrane potential across a physiological span of ATP demand states compared to DEN-treated nontumor or saline-treated liver mitochondria. We validated these findings in flash-frozen human primary HCC samples, which similarly displayed a decrease in mitochondrial respiratory capacity that disproportionately affected CI. Our findings support the utility of mitochondrial phenotyping in identifying novel regulatory mechanisms governing cancer bioenergetics.

Loss-of-Control Eating and Cardiometabolic Health in Relation to Overweight and Obesity.

PURPOSE OF REVIEW: Loss-of-control (LOC) eating, the subjective feeling of being unable to control what or how much is being consumed, is common. The purpose of this review was to examine the relationships among LOC eating, cardiometabolic health, and weight management intervention outcomes. RECENT FINDINGS: In youth and adults, LOC eating is associated with and predictive of psychological symptoms, high weight, and worsened cardiometabolic health. While LOC eating pre-intervention does not appear to impact outcomes, LOC eating during or following is associated with worsened outcomes from behavioral and surgical weight management interventions. When individuals are undergoing weight management interventions, it may be important to regularly assess for LOC eating. There is limited research on the examined relationships in diverse populations (e.g., males, individuals of a lower socio-economic status, racial/ethnic minority groups). Future research should examine these relationships across the lifespan in diverse populations, with a focus on how these relationships can be impacted through targeted interventions.

Posterior Embryotoxon Revisited: An Immunohistologic Study.

PURPOSE: This series describes the immunopathologic features of posterior embryotoxon (PE) and demonstrates that it is not an anterior displaced Schwalbe's line as commonly described, but a peripheral corneal stromal nub variable in location with abnormal extracellular matrix. DESIGN: Case series. PARTICIPANTS: Archived specimens from patients with PE. METHODS: Sections from archived formalin-fixed, paraffin-embedded specimens (n = 9; 7 autopsy and 2 trabeculectomy specimens) were examined by light microscopy. Immunohistochemistry was performed on 5 specimens to characterize the extracellular matrix composition of PE. RESULTS: Posterior embryotoxon appeared as nubs of whorled collagen extending from the corneal stroma, lined in some instances, by Descemet membrane. These nubs were located anterior to Schwalbe's line (n = 4), posteriorly (n = 1), partially embedded in the trabecular meshwork (n = 1), or at Schwalbe's line (n = 2). Qualitatively, collagen I labeling of the PE stroma was similar or weaker than the corneal stroma, whereas collagen III staining was focal and slightly more intense compared with the corneal stroma. Lumican and keratan sulfate staining was similar or less intense in PE compared with the corneal stroma. MAIN OUTCOME MEASURES: Identify location of PE and its immunohistochemical features. CONCLUSIONS: In contrast to the widely accepted definition of PE as a prominent, anteriorly displaced Schwalbe line, histologic evidence suggests that it is a direct extension of the corneal stroma with variable locations that may displace the attenuated Descemet membrane when located anterior to or at Schwalbe's line. Immunohistochemical examination revealed that the composition of PE's extracellular matrix was similar to corneal stroma but with some variability in staining intensity.

A direct transcutaneous approach to infraorbital nerve biopsy.

PURPOSE: To describe a novel transcutaneous infraorbital nerve biopsy technique which can be performed to aid in the diagnosis of perineural invasion (PNI) of facial cutaneous squamous cell carcinoma (SCC). METHODS: A single-center retrospective chart review was performed. Patients diagnosed with SCC with PNI via an infraorbital nerve biopsy between February 2019 and February 2020 were included. Data collected consisted of patient demographics, medical history, clinical presentation and exam, histologic and radiographic findings, treatment, and outcomes. RESULTS: Four patients (3 male, 1 female) met inclusion criteria. The mean age at diagnosis was 79.5 years (range 66-85 years). Three of the four patients had a history of facial skin lesions, including actinic keratosis and SCC, involving the nose, cheek, or ear. One patient had no history of cutaneous malignancy. All patients presented with cranial neuropathies, including total V2 hypoesthesia. The most common presenting symptom was facial pain, followed by diplopia, unilateral facial weakness, and hypoesthesia in the V1 and/or V2 distribution. Transcutaneous infraorbital nerve biopsy in all patients revealed squamous cell carcinoma with no biopsy complications. CONCLUSION: Definitive diagnosis of PNI can be challenging but is important to minimize tumor-related morbidity. Infraorbital nerve biopsy can establish this diagnosis, especially in the context of negative or indeterminate imaging findings. This work comprises the first description of a transcutaneous approach to infraorbital nerve biopsy, which is a minimally invasive technique that can be performed in an outpatient procedure suite with limited to no sedation.

Improvement in Surgical Quality Following Pancreaticoduodenectomy With Increasing Case Volume in a Rural Hospital.

BACKGROUND: The literature is replete with studies that define the nexus of quantity and quality in complex surgical operations. These observations have heralded a call for centralization of care to high-volume centers. The purpose of this study was to chronicle improvements in quality associated with pancreaticoduodenectomy (PD) as a rural hospital matures from a low- to very high-volume center. METHODS: A retrospective review of a prospective pancreatic surgery database was undertaken from July 2007 to June 2020. Annual periods were characterized as low (≤12/year), high (13-29/year), and very high volume (≥30/year). Data for the following quality benchmarks were aggregated and compared: length of stay (LOS), 30-day readmissions, 30-day mortality, and 1- and 3-year survival. A subgroup analysis was undertaken in those patients undergoing PD for adenocarcinoma detailing margin status and number of lymph nodes harvested. Outcomes were compared using the Fisher's exact and Student's t-test. RESULTS: 375 PD were completed over the 13-year period; 62.1% were undertaken for ductal adenocarcinoma. There was a significant decrease in LOS and 30-day readmissions as the institution matured toward very high volume. There were no significant differences in 30-day mortality, 1- and 3-year survival, or margin negativity rates associated with volume. Extent of lymph node harvest significantly improved as institutional experience increased. DISCUSSION: Our pancreatic surgery program matured rapidly from low to very high volume with institutional commitment and dedicated resources. As the institution matured, operational efficiencies and surgical quality improved. Not unexpectedly, biology trumped volume as reflected in 1- and 3-year survival rates.