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.

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.

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.].

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.

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.

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.

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.

Unilateral strabismus surgery in patients with exotropia results in postoperative lateral incomitance.

PURPOSE: To determine whether unilateral strabismus surgery creates lateral incomitance in patients with exotropia. METHODS: Patients >7 years of age with intermittent or constant exotropia who underwent unilateral horizontal rectus muscle surgery between December 2009 and January 2012 were prospectively evaluated. Prism and alternate cover testing was performed with distance fixation in primary position, right gaze, and left gaze after 1 hour of monocular occlusion. Measurements were obtained within 1 month prior to surgery, within 1 week after surgery, and >3 months after surgery. The surgical procedure varied according to the surgeon's discretion. The change in deviation induced by strabismus surgery in lateral gaze was expressed as a percentage of the change in deviation induced in primary position. RESULTS: A total of 12 patients met inclusion criteria. Of the 11 patients with postoperative examinations within 1 week after surgery, 10 (91%) had greater surgical effect with gaze toward the operated eye (P = 0.007). All 9 patients with >3 months' follow-up had greater surgical effect with gaze toward the operated eye (P = 0.003). On average, the surgical effect in gaze toward the operated eye was 120% of that achieved in primary position; in gaze away from the operated eye, 75% (P < 0.001). Three patients had diplopia in lateral gaze toward the operated eye that remained >6 months after surgery. CONCLUSIONS: Unilateral strabismus surgery induces lateral incomitance that may cause diplopia >6 months after surgery in patients with exotropia. This should be considered when planning strabismus surgery and counseling patients.

Congenital ocular motor apraxia, the NPHP1 gene, and surveillance for nephronophthisis.

We present an 11-month-old girl with congenital ocular motor apraxia (COMA) and Joubert syndrome found to have a compound heterozygous mutation in the NPHP1 gene that is responsible for juvenile nephronophthisis type 1. The association of congenital ocular motor apraxia and juvenile nephronophthisis is reviewed. The patient does not currently manifest signs of renal failure, although her mutation indicates that she is at risk for the development of juvenile nephronophthisis type 1.

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.

An unusual case of aicardi syndrome.

PURPOSE: Report of an unusual case of Aicardi syndrome. METHODS: Case report of an infant with severe chorioretinal lacunae and Aicardi syndrome. RESULTS: Despite severe chorioretinal lacunae, a 25-month-old white girl with infantile spasms/seizures had better visual acuity than expected. CONCLUSION: The extent of chorioretinal lesions is not necessarily a prognostic factor for visual function.

Long-term visual acuity and initial postoperative refractive error in pediatric pseudophakia.

OBJECTIVE: To examine the long-term best-corrected visual acuity (BCVA) in children who, during the amblyogenic period, underwent cataract extraction with intraocular lens (IOL) implantation and to see if initial postoperative refractive error following cataract extraction correlates with long-term BCVA. DESIGN: Retrospective chart review. PARTICIPANTS: Thirty-six eyes of 26 patients were included in the study. At least 2 years of follow-up, an age , 8.5 years at time of IOL implantation, an ability to participate in subjective visual acuity measurement, and an absence of congenital glaucoma and significant trauma were required for inclusion in the study. METHODS: Retrospective review of pseudophakic patients' charts at a tertiary care centre, with attention to initial and long-term pseudophakic refractive error, long-term BCVA, total myopic shift, length of follow-up, age at IOL implantation, and unilateral or bilateral cataract extraction with IOL implantation. RESULTS: Initial pseudophakic spherical equivalent (SE) showed a significant nonlinear relationship with most recentBCVAin unilateral cases and no relationship in bilateral cases (interaction p 0.001). Unilateral cases with initial pseudophakic SE between +1.75 D and +5.00 D showed better long-term BCVA than those with values below +1.75 D or above +5.00 D; this was irrespective of the refractive error of their fellow eye. CONCLUSIONS: In patients receiving lens implants in the first 8 years of life, we recommend aiming for low early postoperative hyperopia, taking into consideration each patient's situation and age.

Emmetropization in accommodative esotropia: an update and review.

Many children with accommodative esotropia are able to successfully discontinue spectacle wear, while others require spectacle correction into adulthood. Parents often ask about the likelihood of glasses being required on a long-term basis and whether use of spectacles will cause dependency. Most infants are hyperopic and gradually become emmetropic. The extent to which accommodation and spectacle use affect this process is still debated. However, certain characteristics, such as degree of hyperopia, can help predict long-term spectacle requirement.

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.

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.

Analysis of opioid binding to UDP-glucuronosyltransferase 2B7 fusion proteins using nuclear magnetic resonance spectroscopy.

The UDP-glucuronosyltransferase UGT2B7 is an important human UGT isoform that catalyzes the conjugation of many endogenous and exogenous compounds, among them opioids, resulting in the formation of D-glucuronides. The binding site of the aglycone is located in the N-terminal half of the protein. In this study, we demonstrate that the opioid binding site in UGT2B7 is within the first 119 amino-terminal amino acids. Two maltose binding protein fusion proteins, 2B7F1 and 2B7F2, incorporating the first 157 or 119 amino acids, respectively, of UGT2B7 were expressed in Escherichia coli and purified by affinity chromatography. NMR spectroscopy using one-dimensional spectra, the inversion recovery method, and the transferred nuclear Overhauser effect spectroscopy was used to study the binding properties of opioids to the fusion proteins. Morphine was found to bind at a single site within the first 119 amino acids and to undergo a conformational change upon binding, as demonstrated by transferred nuclear Overhauser effect spectroscopy. Dissociation constants were obtained for morphine, naloxone, buprenorphine, and zidovudine, and the results were confirmed by equilibrium dialysis determinations. Two possible opioid binding sites, based on the nearest neighbors from opioid binding to the micro-receptor and to cytochrome 2D6, are proposed.

Complete myocardial revascularization on the beating heart with epicardial stabilization: anesthetic considerations.

OBJECTIVE: To describe an anesthetic management protocol for patients undergoing cardiac surgery with multiple coronary artery bypass grafts without cardiopulmonary bypass (off-pump CABG surgery) by median sternotomy with mechanical stabilization. DESIGN: Retrospective nonrandomized analysis. SETTING: Tertiary care hospital. PARTICIPANTS: Sixty-six consecutive patients on whom off-pump CABG surgery by median sternotomy was attempted. INTERVENTIONS: Anesthesia was induced with a combination of etomidate and fentanyl; pancuronium bromide was given for muscle relaxation; and anesthesia was maintained with isoflurane, desflurane, or sevoflurane in 100% oxygen. Maintenance of normothermia was attempted by keeping the room temperature at 70 degrees F, warming all fluids to 41 degrees C, and using 2.5 L/min of fresh gas flows and a heat and humidity exchanger. When available, a convective forced-air blanket was used to cover patients' head and shoulders. Patients who were not slated for revascularization of the circumflex vessels and who had good ventricular function received central venous pressure monitoring (26%); all other patients received a pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Of the 66 patients, 36% required an epinephrine infusion at a mean rate of 1.45+/-2.05 microg/min intraoperatively to maintain hemodynamic stability; 25% required inotropic support for < 12 hours in the intensive care unit. CONCLUSION: Institution of systematic hemodynamic management was associated with the successful completion of the surgical procedure in 61 patients (92%). Only 5 patients required conversion to regular CABG surgery with cardiopulmonary bypass.