Changes in nutritional status and the development of obesity and metabolic syndrome following pediatric heart transplantation.

BACKGROUND: Nutritional status in pediatric patients undergoing heart transplantation (HT) is frequently a focus of clinical management and requires high resource utilization. Pre-operative nutrition status has been shown to affect post-operative mortality but no studies have been performed to assess how nutritional status may change and the risk of developing nutritional comorbidities long-term in the post-transplant period. METHODS: A single-center retrospective chart review of patients ≥2 years of age who underwent heart transplantation between 1/1/2005 and 4/30/2020 was performed. Patient data were collected at listing, time of transplant, 1-year, and 3-year follow-up post-transplant. Nutrition status was classified based on body mass index (BMI) percentile in the primary analysis. Alternative nutritional indices, namely the nutrition risk index (NRI), prognostic nutrition index (PNI), and BMI z-score, were utilized in secondary analyses. RESULTS: Of the 63 patients included, the proportion of patients with overweight/obese status increased from 21% at listing to 41% at 3-year follow-up. No underweight patients at listing became overweight/obese at follow-up. Of patients who were overweight/obese at listing, 88% maintained that status at 3-year follow-up. Overweight/obese status at listing, 1-year, and 3-year post-transplantation were significantly associated with developing metabolic syndrome. In comparison to the alternative nutritional indices, BMI percentile best predicted post-transplant metabolic syndrome. CONCLUSIONS: The results suggest that pediatric patients who undergo heart transplantation are at risk of developing overweight/obesity and related nutritional sequelae (ie, metabolic syndrome). Improved surveillance and interventions targeted toward overweight/obese HT patients should be investigated to reduce the burden of associated comorbidities.

Gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin primes cortical microglia to tissue injury.

Recent studies have shown that the aryl hydrocarbon receptor (AhR) is expressed in the brain's native immune cells, known as microglia. However, while the impact of exposure to AhR ligands is well studied in the peripheral immune system, the impact of such exposure on immune function in the brain is less well defined. Microglia serve dual roles in providing synaptic and immunological support for neighboring neurons and in mediating responses to environmental stimuli, including exposure to environmental chemicals. Because of their dual roles in regulating physiological and pathological processes, cortical microglia are well positioned to translate toxic stimuli into defects in cortical function via aberrant synaptic and immunological functioning, mediated either through direct microglial AhR activation or in response to AhR activation in neighboring cells. Here, we use gene expression studies, histology, and two-photon in vivo imaging to investigate how developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high-affinity and persistent AhR agonist, modulates microglial characteristics and function in the intact brain. Whole cortical RT-qPCR analysis and RNA-sequencing of isolated microglia revealed that gestational and lactational TCDD exposure produced subtle, but durable, changes in microglia transcripts. Histological examination and two-photon in vivo imaging revealed that while microglia density, distribution, morphology, and motility were unaffected by TCDD exposure, exposure resulted in microglia that responded more robustly to focal tissue injury. However, this effect was rectified with depletion and repopulation of microglia. These results suggest that gestational and lactational exposure to AhR ligands can result in long-term priming of microglia to produce heightened responses towards tissue injury which can be restored to normal function through microglial repopulation.

Progressive resistance-loaded voluntary wheel running increases hypertrophy and differentially affects muscle protein synthesis, ribosome biogenesis, and proteolytic markers in rat muscle.

We examined if 6 weeks of progressive resistance-loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational efficiency, ribosome biogenesis, and markers of proteolysis. For 6 weeks, 8 male Sprague-Dawley rats (~9-10 weeks of age, ~300-325 g) rats were assigned to the progressive resistance-loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel-loading paradigm was as follows - days 1-7: free-wheel resistance, days 8-15: wheel resistance set to 20%-25% body mass, days 16-24: 40% body mass, days 25-32: 60% body mass, days 33-42: 40% body mass. Following the intervention, muscles were analysed for markers of translational efficiency, ribosome biogenesis, and muscle proteolysis. Raw gastrocnemius mass (+13%, p < .01), relative (body mass-corrected) gastrocnemius mass (+16%, p < .001), raw plantaris mass (+13%, p < .05), and relative plantaris mass (+15%, p < .01) were greater in EX vs. SED rats. In spite of gastrocnemius hypertrophy, EX animals presented a 54% decrease in basal muscle protein synthesis levels (p < .01), a 125% increase in pan 4EBP1 levels (p < .001) and a 31% decrease in pan eIF4E levels (p < .05). However, in relation to SED animals, EX animals presented a 70% increase in gastrocnemius c-Myc protein levels (p < .05). Most markers of translational efficiency and ribosome biogenesis were not altered in the plantaris or soleus muscles of EX vs. SED animals. Gastrocnemius F-box protein 32 and poly-ubiquinated protein levels were approximately 150% and 200% greater in SED vs. EX rats (p < .001). These data suggest that the employed resistance training model increases hind limb muscle hypertrophy, and this may be mainly facilitated through reductions in skeletal muscle proteolysis, rather than alterations in ribosome biogenesis or translational efficiency.

High-intensity interval training has positive effects on performance in ice hockey players.

In spite of the well-known benefits that have been shown, few studies have looked at the practical applications of high-intensity interval training (HIIT) on athletic performance. This study investigated the effects of a HIIT program compared to traditional continuous endurance exercise training. 24 hockey players were randomly assigned to either a continuous or high-intensity interval group during a 4-week training program. The interval group (IG) was involved in a periodized HIIT program. The continuous group (CG) performed moderate intensity cycling for 45-60 min at an intensity that was 65% of their calculated heart rate reserve. Body composition, muscle thickness, anaerobic power, and on-ice measures were assessed pre- and post-training. Muscle thickness was significantly greater in IG (p=0.01) when compared to CG. The IG had greater values for both ∆ peak power (p<0.003) and ∆ mean power (p<0.02). Additionally, IG demonstrated a faster ∆ sprint (p<0.02) and a trend (p=0.08) for faster ∆ endurance test time to completion for IG. These results indicate that hockey players may utilize short-term HIIT to elicit positive effects in muscle thickness, power and on-ice performance.

ß2 Adrenoceptor signaling-induced muscle hypertrophy from blood flow restriction: is there evidence?

Skeletal muscle hypertrophy and increases in muscular function have been observed following low intensity/load exercise with blood flow restriction (BFR). The mechanisms behind these effects are largely unknown, but have been hypothesized to include a metabolic accumulation induced increase in muscle activation, elevations in growth hormone, and improvements in muscle protein balance. However, many of the aforementioned mechanisms are not present with BFR in the absence of exercise. In these situations, signaling through the ß2 adrenoceptor has been hypothesized to possibly contribute to the positive muscle adaptions, possibly in concert with muscle cell swelling. Signaling through the ß2 adrenoceptor has been shown to stimulate both muscle protein synthesis and an inhibition of protein degradation through increasing cyclic adenosine monophosphate (cAMP) or signaling via the Gßγ subunit, especially in situations where the basal rates of protein synthesis are already reduced. Every study that has investigated the catecholamine response to BFR in the absence of exercise or in combination with exercise has shown a significant increase above resting conditions. However, from the available evidence, it is unlikely that the norepinephrine response from BFR, particularly with exercise, is playing a prominent role with muscle adaptation in skeletal muscle that is not immobilized by a cast or joint injury.

Acute 2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure in adult mice does not alter the morphology or inflammatory response of cortical microglia.

Microglia, the immune cells of the brain, have a canonical role in regulating responses to neurological disease or injury, but have also recently been implicated as regulators of neurophysiological processes such as learning and memory. Given these dual immune and physiological roles, microglia are a likely mechanism by which external toxic stimuli are converted into deficits in neuronal circuitry and subsequently function. However, while it is well established that exposure to environmental toxicants negatively affects the peripheral immune system, it remains unknown whether and how such exposure causes neuroinflammation which, in turn, may negatively impact microglial functions in vivo. Here, we examined how acute 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in adulthood, which negatively impacts immune cells in the periphery, affects microglial characteristics in the cortex of the mouse. We found that microglia density, distribution, morphology, inflammatory signaling, and response to a secondary, pathological activation were unaffected by acute TCDD exposure. These results suggest that acute, peripheral TCDD exposure in adulthood is not sufficient to induce an overt inflammatory phenotype in cortical microglia.

Rates of diagnostic genetic testing in a tertiary ocular genetics clinic.

BACKGROUND: Clinical genetics has evolved significantly to become an efficient and effective means of diagnosing disease. Genetic treatments are now being developed which are showing promising results. However, ophthalmic patients are not utilizing genetic testing as part of their diagnostic workups. This paper explores the patient experience at the Ocular Genetics Clinic (OGC) at the University of Arkansas for Medical Sciences (UAMS) Jones Eye Institute and discusses reasons why patients continue to not pursue genetic testing. MATERIALS AND METHODS: We performed a retrospective chart review to understand the main reasons why patients were referred to the OGC between 2009 and 2018, with a detailed analysis of why patients did not pursue genetic testing. RESULTS: Patients mainly did not undergo testing due to the cost of testing. However, patient availability, patient interest, and diagnostic workup also drove a significant amount of this lack of testing. CONCLUSIONS: Ocular genetic testing is becoming an increasingly beneficial tool for diagnosing ocular disease. However, to date, patients do not utilize this service fully. At the OGC, there are several main drivers for this lack of testing, namely finances, interest/availability, and diagnostic workup. As more ocular genetics clinics are established, it will be imperative to address reasons for forgoing genetic testing and to develop strategies to encourage patients to pursue this testing.

Pediatric ocular injury secondary to a Burmese python bite.

We report the case of a 6-year-old girl with a penetrating ocular injury caused by a Burmese python. She received intravenous cefazolin before presenting and was treated thereafter with daily topical antibiotics and atropine. Six weeks after injury, she underwent cataract extraction and sulcus implantation of an intraocular lens and iris synechiolysis, with postoperative patching. Final visual outcome was excellent despite no globe repair was performed.

Comparison of the Effect of Cycloplegia on Astigmatism Measurements in a Pediatric Amblyopic Population: A Prospective Study.

PURPOSE: To study the effect of cycloplegia on astigmatism measurements in pediatric patients with amblyopia. METHODS: This was a prospective comparative clinical study. Participants 4 to 17 years old were recruited from the patient population at the Arkansas Children's Hospital eye clinic after informed consent was obtained. Autorefractor measurements were used to obtain values of refractive error in amblyopic and non-amblyopic patients before and after cycloplegia. The groups were subdivided into myopia and hyperopia and with and without underlying amblyopia. The refractive error was expressed as sphere, cylinder, axis of astigmatism, and spherical equivalent. The treatment effect was summarized as the mean difference (95% confidence interval) for each outcome. RESULTS: No statistically significant difference was found on the axis and power of astigmatism before and after cycloplegia in the patients with amblyopia (P = .28 and .99, respectively). CONCLUSIONS: Non-cycloplegic autorefraction measurements may be considered safe for refining astigmatism power and axis in pediatric patients with amblyopia. [J Pediatr Ophthalmol Strabismus. 2018;55(5):293-298.].

Cryptic cerebral visual impairment in children.

AIM: To review the medical records of seven children with a delayed diagnosis of cerebral visual impairment. METHODS: The charts of a consecutive series of children examined in a university based ophthalmology clinic with a delayed diagnosis of cerebral visual impairment were reviewed. Their neuroimaging studies were evaluated by a paediatric neuroradiologist. RESULTS: The seven patients ranged in age from 2 years to 10 years at the time of presentation and had acuities ranging from 20/40 to 20/400. Their visual fields ranged from full visual fields to homonymous hemianopias. Neuroimaging findings ranged from subtle occipital lobe abnormalities to obvious cerebral volume loss. CONCLUSIONS: Cerebral visual impairment can be cryptic in children with mild visual impairment. Neuroimaging studies and visual field testing can help to differentiate this condition from other causes of visual impairment.

Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex.

Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, particularly during early development. Here we demonstrate that microglia are critical for ocular dominance plasticity. During the visual critical period, closure of one eye elicits changes in the structure and function of connections underlying binocular responses of neurons in the visual cortex. We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity. These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain.

Deuterated carbohydrate probes as 'label-free' substrates for probing nutrient uptake in mycobacteria by nuclear reaction analysis.

Understanding and probing small molecule uptake in cells is challenging, requiring sterically large chemical labels, or radioactive isotopes. Here, the uptake of deuterated sugars by Mycobacterium smegmatis, a non-pathogenic model of Mycobacterium tuberculosis, has been investigated using ion-beam (nuclear reaction) analysis demonstrating a new technique for label-free nutrient acquisition measurement.

Repair of complex subvalvular aortic aneurysm with a valved conduit.

A subaortic annular aneurysm involving three fourths of the annular circumference was repaired with a valved conduit to which a Teflon felt flange was attached. This unique prosthetic repair assured a strong stable repair and uncompromised coronary flow otherwise unobtainable with previously described repairs.

Primary reconstruction of interrupted aortic arch by total aortic outflow obstruction.

Primary aortic arch reconstruction was undertaken in three neonates with interrupted aortic arch and ventricular septal defect. Total ascending aortic occlusion without cardiopulmonary bypass or profound hypothermia permitted, in each case, a rapid tension-free end-to-side descending-to-ascending aortic anastomosis without resulting neurologic or cardiac sequelae. This technique offers distinct advantages over previously described methods and should be considered whenever interrupted aortic arch is present with a ventricular septal defect.

Prevention of atrial fibrillation after cardiac surgery: the significance of postoperative oral amiodarone.

STUDY OBJECTIVES: Atrial fibrillation (AF) is a common occurrence after cardiac surgery (10 to 53%) that contributes to increased length of stay and hospital cost. Recent evidence suggests that treatment with amiodarone may provide safe and effective prophylaxis against AF in many patients undergoing cardiac operations. This study sought to investigate whether oral amiodarone administered postoperatively would reduce the incidence of postoperative AF. DESIGN: Prospective nonrandomized cohort study. PATIENTS AND PARTICIPANTS: In this prospective study, 1,196 consecutive patients who underwent various open-heart procedures with cardiopulmonary bypass between July 1999 and February 2000 received oral amiodarone, 400 mg bid, from the transfer to the cardiovascular recovery room until the day of hospital discharge, or up to 7 days postoperatively. The incidence of AF in this group of patients was compared with a group of 1,246 patients who underwent cardiac surgery with cardiopulmonary bypass in the preceding 8-month period (November 1998 to June 1999) at the same institution without receiving amiodarone postoperatively. SETTING: Tertiary health-care center. MEASUREMENT AND RESULTS: AF developed in 294 patients (25%) in amiodarone-treated group and in 385 patients (31%) in the control group (p = 0.001). In multivariate logistic regression analysis, oral amiodarone treatment emerged as an independent predictor of lower risk of AF (odds ratio, 0.7; 95%; 95% confidence interval, 0.6 to 0.9; p = 0.002) and shorter hospital length of stay (odds ratio, 0.8; 95% confidence interval, 0.5 to 0.9; p = 0.006). CONCLUSIONS: Postoperative oral amiodarone treatment is a safe and effective regimen associated with a reduced incidence of new-onset AF and decreased length of hospital stay. Prospective randomized trials are needed to evaluate the benefits of amiodarone treatment relative to its side effect profiles.

Successful treatment of multiple simultaneous great vessel disruptions.

Survival following ruptures of the thoracic aorta at sites other than the aortic isthmus is exceedingly rare. Herein we describe a successful outcome in a 62-year-old woman with ascending and isthmic aortic lacerations compounded by disruptions of the subclavian-innominate artery junction and the left vertebral-subclavian junction. Chest wall instability and a myocardial contusion further complicated her case.

Traumatic carotid artery dissection: diagnosis and treatment.

Early diagnosis and successful management of traumatic carotid artery dissections require a high index of clinical suspicion. The diagnostic study of choice is cerebral arteriography. In this paper, 24 cases of traumatic carotid artery dissection are described. Presenting signs and symptoms include Horner's syndrome, dysphasia, hemiparesis, obtundation, and monoparesis. Patients detected early with mild neurological deficits fared well with treatment, while those with profound neurological deficits and delayed diagnoses had poor outcomes. Aggressive nonsurgical treatment is advocated including anticoagulation therapy for prevention of progressive thrombosis and arterial occlusion and/or distal arterial embolization with resultant cerebral ischemia. Direct surgical thromboendarterectomy is considered to carry high morbidity and mortality rates.

Etiologic factors associated with patellofemoral pain in runners.

The purpose of this study was to extend our knowledge of running related injuries by determining whether relationships exist between selected anthropometric, biomechanical, muscular strength and endurance, and training variables and runners afflicted with patellofemoral pain (PFP). Specifically, the objectives of this study were to examine differences in selected measures between a non-injured control group (C) of runners (N = 20) and a group of injured runners (INJ) diagnosed by an orthopedic surgeon as having PFP (N = 16). High speed photography, a force platform, and isokinetic dynamometry were used to determine rearfoot motion, ground reaction forces, and knee muscular strength and endurance. Stepwise discriminant function analyses were performed on the anthropometric, biomechanical, and muscular strength and endurance variables. Q angle was a significant discriminator (P less than 0.01) between the INJ and C groups. The muscular endurance data revealed several significant discriminators with the INJ subjects being weaker in knee extension endurance. Kinetic analysis revealed several significant discriminators whereas rearfoot movement variables were not good discriminators between the groups. The training data revealed that the INJ group ran significantly less (P less than 0.01) miles.wk-1 than the C group. Our results suggest that Q angle is a strong discriminator between runners afflicted with PFP and non-injured runners. In addition, several muscular endurance and kinetic variables may also be important components of the etiology of PFP.

Etiology of iliotibial band friction syndrome in distance runners.

The objectives of our study were: 1) to examine differences between a noninjured cohort of runners (N = 70) and runners afflicted with iliotibial band friction syndrome (ITBFS) (N = 56) according to selected anthropometric, biomechanical, muscular strength, and training measures; 2) to explore multivariate relationships among these measures in both the well and injured groups; and 3) to develop specific hypotheses concerning risk factors for injury that will later be tested in a prospective observational study. High speed videography (200 fps), a force platform (500 Hz), and a Cybex II+ isokinetic dynamometer were used to assess rearfoot motion, ground reaction forces, and knee muscular strength and endurance, respectively. A linear discriminant function analysis of the training data revealed weekly mileage, training pace, number of months using current training protocol, % time spent swimming, and % time spent running on a track to be significant (P < 0.10). Height was a significant anthropometric discriminator, while seven isokinetic strength and endurance measures were found to discriminate significantly between the groups. Calcaneal to vertical touchdown angle, and maximum supination velocity were significant rearfoot movement discriminators. Maximum braking force was the only significant kinetic discriminator. A combined discriminant analysis using those variables found to be significant in the previous analyses revealed weekly mileage, and maximum normalized braking force to be the best discriminators (model P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Etiologic factors associated with Achilles tendinitis in runners.

PURPOSE: The purpose of this study was to determine whether relationships exist between selected training, anthropometric, isokinetic muscular strength, and endurance, ground reaction force, and rearfoot movement variables in runners afflicted with Achilles tendinitis. METHODS: Specifically, we examined differences in selected measures between a noninjured cohort of runners (N = 58) and a cohort of injured runners with Achilles tendinitis (N = 31). Isokinetic, kinetic, and kinematic measures were collected using a Cybex II+ isokinetic dynamometer (Medway, MA), AMTI force plate (500 Hz), and Motion Analysis high-speed videography (200 Hz), respectively. Separate discriminant function analyses were performed on each of the five sets of variables to identify the factors that best discriminate between the injured and control groups. RESULTS: Years running, training pace, stretching habits (injured runners were less likely to incorporate stretching into their training routine), touchdown angle, plantar flexion peak torque at 180 degrees x s(-1) and arch index were found to be significant discriminators. CONCLUSION: A combined discriminant analysis using the above mentioned significant variables revealed that plantar flexion peak torque, touchdown angle, and years running were the strongest discriminators between runners afflicted with Achilles tendinitis and runners who had no history of overuse injury.