Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twinning whereby a donor twin perfuses an acardiac twin via aberrant vascular anastomoses. The resulting paradoxical retrograde blood flow supplying the acardiac twin is oxygen-poor, leading to some of the most severe malformations encountered in humans. Though the first descriptions of acardiac twins date back to at least the 16th century, the pathophysiologic processes which underpin the development of TRAP sequence are still being elucidated. Theories on the pathogenesis of TRAP sequence include deficiencies intrinsic to the embryo and primary abnormalities of the placental vasculature. Autopsy studies continue to provide clues to the underlying pathogenesis of TRAP sequence, and the characterization of the spectrum of manifestations that can be observed in acardiac twins. Herein, we present the clinical, autopsy, and molecular findings in a unique case of TRAP sequence. Novel findings include a primitive cloaca-like structure and chromosomal aberrations involving 6q11.1 and 15q25.1.

Lifestyle changes are a powerful way to combat many chronic illnesses. However, education on appropriate instruction of physical activity appears to be insufficient among medical students. This manuscript highlights development, incorporation, and feedback of the Exercise is Medicine elective at the West Virginia School of Osteopathic Medicine. Twenty-four medical students attended ten weekly sessions, each of which lasted 2 h and covered a different topic. Participants were selected based on previous experience with exercise-based medicine and their personal beliefs on incorporating it into clinical encounters. Outcomes were gathered using surveys consisting of the Likert Scale, rating, yes/no/maybe, and free text questions. Confidence in prescribing lifestyle changes increased (p < 0.0001) from pre- to post-elective. Feelings of incorporating course material into practice increased (p < 0.05) after the elective. Feelings that physicians could impact their patients’ physical activity did not change. Implementation of the Exercise is Medicine elective was well received among students and increased student knowledge and confidence in prescribing lifestyle changes to a variety of patient populations.

Objectives: Maintaining lean soft tissue and bone mineral density during early to middle adulthood is important for delaying the effects of sarcopenia and osteopenia later in life. Physical activity high in intensity and volume is associated with optimal bone health. CrossFit® (CF) training combines high-intensity aerobic, resistance, and floor exercises to stimulate physical fitness and health responses. We tested differences in total and regional body composition between adult CF participants and nonactive (NA) adults. Methods: 24 CF trained (at least 3 times/wk for the past 3 months, n=11 women) and 24 NA (exercise no more than 1 time/wk for the past 3 months, n=12 women) adults were measured for body composition by iDXA (Lunar Corporation, Madison, WI). Subjects were further categorized into early (≤29y, mean=24y) and middle (30-49y, mean=37y) adulthood. Results: Linear models testing the main and interactive effects of training group and age group demonstrated no difference (p=0.82) in body weight of CF (77.5kg) and NA (76.6 kg) groups. CF had lower trunk (p< 0.002), android (p=0.001), gynoid (p=0.01), arm (p< 0.003), leg (p< 0.05), and total body (p=0.01) fat mass, lower total body %fat (p=0.002) and greater trunk (p=0.01), arm (p< 0.03), leg (p< 0.02), and total body (p=0.002) lean soft tissue (LST) mass. Younger adults had lower android (p< 0.04) and arm (p< 0.02) fat. CF had greater pelvis (p=0.004), arms (p< 0.01), legs (p< 0.04), spine (p< 0.02), trunk (p< .0009), and total body (p< 0.03) bone mineral density. Conclusions: CF training, typically high in intensity and volume, is associated with beneficial body composition and bone health with few differences between early- and middle-aged adults. CF training maintained through at least middle adulthood may delay the onset of difficulty performing daily activities, falls, and morbidities associated with the effects of sarcopenia and osteopenia. Funding Sources: USDA-Agriculture Research Service.

The First2 Network is an alliance of higher education institutions across the State of West Virginia striving to improve science, technology, engineering or math (STEM) education by supporting rural, first-generation, and underrepresented college students pursuing STEM majors. Over the summers of 2019 and 2020, the First2 Network delivered two-week summer research immersion experiences at various institutions throughout West Virginia. The 2019 program was delivered on-campus at four universities while the 2020 program was delivered virtually, due to the COVID-19 pandemic, across nine sites. Before and after the immersion experience, students who participated in the program completed a variety of survey questionnaires for the assessment of their interests, expectations, identity and belonging in STEM. We found that the in-person experience in 2019 had better outcomes compared to the virtual experience, suggesting students conducting research directly under their faculty supervisors in-person and on-site will have a more positive impact on their STEM education and career. However, participation in the virtual format still resulted in an improvement in belonging and STEM identity, indicating that connecting with students remotely is still worthwhile when it is the most viable option. The student population in Appalachia faces a number of academic barriers, so there is much to gain by finding new ways to reach as many students as possible with early career development programs.

Compared to continuous-moderate or low-intensity training, high-intensity interval training (HIIT) is a more time-efficient alternative method that results in similar physiologic benefits. This paper presents a HIIT protocol that can be used to assess various health markers in a Sprague-Dawley rat model of diet-induced obesity. Female Sprague Dawley rats aged 21 days old were randomly assigned to the following groups: control (CON, n = 10), exercise-trained (TRN, n = 10), high-fat diet (HFD, n = 10), and high-fat diet/exercise training (HFD/TRN, n = 10). The control diets consisted of commercial laboratory chow with 10% kilocalories (kcal) from fat (3.82 kcal/g), and the high-fat diets (HFD) consisted of 45% kcal from fat (4.7 kcal/g). The animals had ad libitum access to their assigned diet throughout the study. After an 8 week diet induction period, the exercise cohorts completed four HIIT sessions per week for 8 weeks. Each HIIT session consisted of 10 intervals of 1 min sprints/2 min rest using a rodent treadmill with a motor-driven belt. After the 8 weeks of training, the animals were sacrificed for tissue collection. The results revealed no differences in the distance run between the TRN and HFD/TRN groups, and the training speed steadily increased over the duration of the study, with a final running speed of 115 cm/s and 111 cm/s for the TRN and HFD/TRN groups, respectively. The weekly caloric intake was decreased (p < 0.05) in the TRN group relative to the CON group but increased (p < 0.05) in the HFD/TRN group relative to the HFD group. Lastly, the animals on the HFD had greater (p < 0.05) adiposity, and the trained animals had reduced (p < 0.05) adiposity relative to controls. This protocol demonstrates an efficient method to evaluate the effects of HIIT on various physiologic outcomes in a diet-induced obesity model.

Introduction:Elastic stable intramedullary nailing (ESIN) is currently the technique of choice for pediatric femoral fractures. Submuscular plating (SMP) allows reliable healing associated with an early range of motion. The following systematic review and meta-analysis was carried out to reveal the functional and surgical outcomes of SMP and ESIN for fixation of pediatric femoral fractures and to aid in the decision-making processes for those who perform these procedures. Methods:An extensive systematic literature review was implemented from inception to 23 February 2022. All clinical studies included had patients that were younger than 18 years old with femoral shaft fractures that compared outcomes between SMP and ESIN. Studies including patients with pathological fractures, closed femoral physis, multiple fractures, or refractures were excluded. Results:This meta-analysis included six articles encompassing 568 patients. Of them, 206 patients were treated with SMP, while 362 were subjected to ESIN procedure. There was significantly more blood loss among patients treated with SMP (MD -45.45; 95% -61.62, -29.27; p < 0.001). The risk of postoperative adverse surgical events was significantly higher among patients subjected to the ESIN (RR 2.97 19.5; 95% 1.27, 6.98; p = 0.01). The mean hospital stay was significantly shorter among patients subjected to ESIN (SMD -1.47; 95% -2.43, -0.51; p = 0.003). Patients subjected to SMP showed significantly more EFOs when comparing Flynn Scores (OR 0.24; 95% 0.09, 0.64; p = 0.004). There was no significant difference between SMP and ESIN regarding the mean operation time, limb length discrepancy, and mean time to union. Conclusions:Children with femoral shaft fractures can be managed effectively and safely with SMP. There was a similar surgical outcome between SMP and ESIN, but SMP had more EFOs. While SMP was associated with a low risk of postoperative adverse surgical events, it was associated with a more significant blood loss and prolonged hospital stays.

Obesity continues to be a significant global health issue and contributes to a variety of comorbidities and disease states. Importantly, obesity contributes to adverse cardiovascular health outcomes, which is the leading cause of death worldwide. Further, maternal obesity during gestation has been shown to predispose offspring to adverse phenotypic outcomes, specifically cardiovascular outcomes. Therefore, we hypothesized that diet-induced obesity during gestation would result in adverse cardiovascular phenotypes in first-generation offspring that would have functional consequences in juvenile and advanced ages. Multiparous Rambouillet/Columbia cross ewes (F0) were fed a highly palatable, pelleted diet at either 100% (CON), or 150% (OB) of National Research Council recommendations from 60 days prior to conception, until necropsy at d 135 (90%) of gestation (CON: n = 5, OB: n = 6), or through term for lambs (F1: 2.5 mo. old; CON: n = 9, OB: n = 6) and ewes (F1:9 years old; CON: n = 5, OB: n = 8). Paraffin-embedded fetal aorta section staining revealed increased collagen:elastin ratio and greater aortic wall thickness in OBF1 fetuses. Invasive auricular blood pressure recordings revealed elevated systolic blood pressure in OBF1 lambs, but no differences in diastolic pressure. In aged F1 ewes, systolic and diastolic blood pressures were reduced in OBF1 relative to CONF1. Echocardiography revealed no treatment differences in F1 lambs, but F1 ewes show tendencies for increased end systolic volume and decreased stroke volume, and markedly reduced ejection fraction. Therefore, we conclude that maternal obesity programs altered cardiovascular development that results in a hypertensive state in OBF1 lambs. Increased cardiac workload resulting from early life hypertension precedes the failure of the heart to maintain function later in life.

Purpose Models of appetite control have been largely based on negative feedback from gut and adipose signaling to central appetite centers. However, contemporary models posit that fat-free mass (FFM) or the energy demand of FFM [i.e., resting metabolic rate (RMR)] may play a primary role in the motivational drive for food intake (i.e., food reinforcement). The relative reinforcing value of food (RRV food ) is associated with energy intake (EI) and increases with an acute energy deficit. Chronic exercise-induced energy deficits lead to alterations in fat mass (FM), FFM, and RMR and provide an opportunity to test whether change in (∆) FM, ∆FFM, ∆usual EI, or ∆RMR are associated with ∆RRV food . Methods Participants ( n = 29, BMI = 25–35 kg/m 2 ) engaged in aerobic exercise expending 300 or 600 kcal, 5 days/weeks for 12 weeks. The reinforcing value of food (PMax food ) was measured via a computer-based operant responding task and RRV food was calculated as the reinforcing value of food relative to non-eating sedentary behaviors. RMR was determined by indirect calorimetry and body composition by DXA. Results Post-training FFM correlated with usual post-training EI ( r s = 0.41, p < 0.05), PMax food ( r s = 0.52, p < 0.01), and RMR ( r s = 0.85, p < 0.0001). ∆RMR negatively correlated with ∆PMax food ( r s = − 0.38, p < 0.05) and with ∆RRV food ( r s = − 0.37, p < 0.05). ∆PMax food and ∆RRV food were not associated with ∆FFM ( p = 0.71, p = 0.57, respectively). Conclusions Reductions in RMR with weight loss may increase food reinforcement as means of restoring FFM and RMR to pre-weight loss amounts. Limiting reductions in RMR during weight loss may benefit weight maintenance by restricting increases in food reinforcement after weight loss.

Accumulating evidence suggests that indications of metabolic syndrome can be inherited through the germline as a result of maternal obesity. We hypothesized that diet-induced maternal obesity during gestation would program metabolic consequences for multiple generations of offspring, e ven when first, second, and third generation offspring (F1, F2, F3, respectively) were fed only to requirements. Control (CON) and obese (OB) ewes (generation 0; F0) were bred to a single ram to produce the first generation of offspring (F1). From 60 d prior to conception through term, CONF0 ate 100% National Research Council recommendations (NRC), while OBF0 ewes ate 150% NRC. All F1, F2, and F3 ate 100% NRC after weaning. All mature F1 ewes were bred to a single ram to generate CONF2 (n = 6) and OBF2 (n = 10). All mature F2 ewes were bred to a single ram to produce CONF3 (n = 6) and OBF3 (n = 10). OBF2 ewes exhibited greater ( P < 0.0 0 01) plasma cortisol than CONF2 throughout gestation. A glucose tolerance test at 90% gestation revealed OBF2 ewes had higher ( P < 0.05) insulin response with similar glucose, resulting in greater ( P < 0.05) insulin resistance. OBF3 neonates had similar weight, lean mass, and body fat mass to CONF3 neonates. These data suggest that multigenerational programming of adverse metabolic phenotypes occur in association with F0 maternal obesity, yet adiposity may return to CON levels in F3 neonates. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Evidence links parent-offspring weight status, but few studies have evaluated whether markers of socioeconomic status moderate this relation. The 2014 Family Life, Activity, Sun, Health, and Eating study was used to assess intergenerational weight status in a national sample of parent-teen dyads. Multivariable logistic regression models assessed the relation between parent-teen weight status, controlling for teen and parent dietary factors, physical activity, demographic factors, and socioeconomic factors. Models with interaction assessed moderation by household food security status and participation in federal assistance programs. In fully adjusted models, sons were 2.66 (95% CI: 1.56, 4.55) times more likely to have overweight/obesity if their mother had overweight/obesity, and daughters were 3.35 (95% CI: 1.91, 5.86) times more likely. This relation was stronger in mother-son pairs in households with lower food security. These findings provide important new information that can be used to inform nutritional counseling efforts and educational programs that support families with socioeconomic disadvantage.

AbstractExposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol. Control ewes ate 100% National Research Council recommendations (CON) and OB ewes ate 150% CON diet from 60 days before conception until necropsy at day 135 gestation. At necropsy, maternal jugular and umbilical venous blood, fetal liver, perirenal fat, and cotyledonary tissues were harvested. Maternal plasma cortisol and fetal cortisol and cortisone were measured. Fetal liver, perirenal fat, cotyledonary 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PD), and 11β-HSD2 protein abundance were determined by Western blot. Maternal plasma cortisol, fetal plasma cortisol, and cortisone were higher in OB vs. CON (p < 0.01). 11β-HSD2 protein was greater (p < 0.05) in OB cotyledonary tissue than CON. 11β-HSD1 abundance increased (p < 0.05) in OB vs. CON fetal liver and perirenal fat. Fetal H6PD, an 11β-HSD1 cofactor, also increased (p < 0.05) in OB vs. CON perirenal fat and tended to be elevated in OB liver (p < 0.10). Our data provide evidence for increased 11β-HSD system components responsible for peripheral tissue cortisol production in fetal liver and adipose tissue, thereby providing a mechanism for an ACTH-independent increase in circulating fetal cortisol in OB fetuses.

Objective: The objective of this research was to determine the effects of increasing Zn concentrations during late gestation on serum metabolites, serum mineral element transfer efficiency ratios (TE), and ewe and lamb performance in a semi-extensive management system. Materials and Methods: Commercial white-face (WF; n = 23) and black-face (BF; n = 24) ewes (age approximate to 18 mo; BW 87.48 +/- 8.37 kg) were sorted into breed-type groups and within groups ranked by BW and randomly divided into 3 dietary supplement treatment groups along the rank: CON (n = 13, 40 mg/kg Zn, approximate to 1 x NASEM recommendations), Zn500 (n = 19, 500 mg/kg Zn, approximate to 4 x NASEM recommendations), and Zn1000 (n = 15, 1,000 mg/kg Zn, approximate to 7 x NASEM recommendations). Treatments were administered in pelleted alfalfa (0.45 kg/ewe per day) fortified with Zn sulfate to increase Zn concentratons fed from 87.5 +/- 8.9 d of gestation until parturition. Results and Discussion: Maternal treatment did not affect ewe BW change throughout the experiment, nor serum metabolites, mineral element TE, or progeny performance through weaning (P >= 0.06). However, ewe greasy fleece weight the following year was greater for Zn500 than Zn1000 ewes (4.13 +/- 0.18 kg vs. 3.48 +/- 0.19 kg; P = 0.03) but did not differ between CON and the other treatments (3.68 +/- 0.22 kg; P >= 0.22). The most marked effects were observed between breeds where Zn TE of WF ewes and lambs (264.3 +/- 23.2) was approximately twice that of BF ewes and their lambs (165.4 +/- 19.7; P < 0.01). Serum Fe was greater in WF ewes and lambs (2.24 +/- 0.10 and 1.34 +/- 0.09 mu g/mL, respectively) than in BF ewes and their lambs (1.82 +/- 0.09 and 1.05 +/- 0.09 mu g/mL, respectively; P < 0.01). At birth, WF lambs had greater serum BHB and cortisol (4.44 mg/dL and 31.9 +/- 3.89 ng/mL, respectively) concentrations compared with BF lambs (3.97 mg/dL and 22.0 +/- 3.62 ng/mL, respectively; P < 0.03) and also exhibited 6.8% greater vigor (P = 0.02). Implications and Applications: The results suggest feeding Zn supplemented from Zn sulfate beyond current NASEM recommendations from d 87 of gestation until parturition had minimal beneficial effects on fine-wool or meat-type ewes and lambs. Breed differences observed in serum mineral element concentrations (Fe and Zn) and related TE of the neonatal lamb may provide insights into adaptive trace mineral supplementation strategies based on breed type and related levels of production.

Similarities in offspring phenotype due to maternal under- or over-nutrition during gestation have been observed in studies conducted at University of Wyoming. In these studies, ewes were either nutrient-restricted (NR) from early to mid-gestation, or fed an obesogenic diet (MO) from preconception through term. Offspring necropsies occurred at mid-gestation, late-gestation, and after parturition. At mid gestation, body weights of NR fetuses were ~30% lighter than controls, whereas MO fetuses were ~30% heavier than those of controls. At birth, lambs born to NR, MO, and control ewes exhibited similar weights. This was a consequence of accelerated fetal growth rates in NR ewes, and reduced fetal growth rates in MO ewes in late gestation, when compared to their respective controls. These fetal growth patterns resulted in remarkably similar effects of increased susceptibility to obesity, cardiovascular disease, and glucose intolerance in offspring programmed mostly during fetal stages of development. These data provide evidence that maternal under- and over-nutrition similarly induce the development of the same cadre of physical and metabolic problems in postnatal life.

Background: : Exercise is a reinforcing behavior and finding exercise highly reinforcing is characteristic of habitual exercisers. Genotypes related to dopamine metabolism moderate the reinforcing value of behaviors, but genetic moderators of exercise reinforcement have not been established. Purpose: : Determine whether singular nucleotide polymorphisms (SNPs) that moderate central reward pathways and pain neurotransmission are associated with exercise reinforcement, tolerance for exercise intensity, and usual physical activity. Methods: : Adults (n = 178) were measured for the reinforcing value of exercise relative to sedentary activities (RRVexercise), minutes of moderate-to-vigorous physical activity (MVPA) and completed the Preference for and Tolerance of the Intensity of Exercise Questionnaire. Genotyping of 23 SNPs known to influence central dopamine tone, pain, or physical activity was performed. ANOVA tested differences in RRVexercise, tolerance, and MVPA among genotype groups. Linear regression controlling for BMI, sex, and liking of exercise was used to further predict the association of genotype on RRVexercise, tolerance, and MVPA. Results: : Having at least one copy of the G allele for the DRD2/ANKK1 polymorphism (rs1800497) conferred greater RRVexercise. Greater tolerance for exercise intensity was observed among those homozygous for the T allele for the CNR1 polymorphism (rs6454672), had at least one copy of the G allele for the GABRG3 polymorphism (rs8036270), or had at least one copy of the T allele for the LPR polymorphism (rs12405556). Homozygous individuals for the T allele at rs6454672 exhibited greater MVPA. Conclusion: : Similar to other reinforcing behaviors, there is a genetic contribution to exercise reinforcement, tolerance for exercise intensity, and MVPA.

USDA, Agricultural Research Service, Project 3062-51000-051-00D.