Attitudes towards Nutrition Education among Pediatricians and Guardians

Presented as a poster at 2020 IUSM Education Day.Childhood obesity rates in the United States are at historic highs. In Lake County, Indiana, the obesity rates of WIC children ages 2-5 years old is 12.1%. While the causes of obesity are well known within the scientific community, there appears to be a disconnect when relaying this information to patients. One cause of this disconnect is the inadequate nutrition education that physicians receive during medical school and residency. A survey found that the average medical school devotes less than 20 hours to nutrition education. Additionally, the biochemical nutrition education that students receive in medical school cannot be easily translated to patient intervention. Since 62% of patients believe that their physicians can help them lose weight, having physicians who do not have adequate education on nutrition leaves patients without the help they need. Our surveys were developed to assess the level of nutrition counseling provided by pediatricians and how patients/guardians prefer to be educated. Our hypothesis is that pediatricians will benefit from further nutrition education in medical school, and that guardians will desire in person instructions in pediatric offices as well as easy and accessible online sources. Two surveys were created, one for physicians and another for parents/guardians of children ages 1-12 years old residing in Lake County. The physician survey contained 15 items that evaluated attitudes toward nutrition and obesity education. Topics included level of nutrition counseling education received in medical school and residency, how much time physicians spend educating patients/parents on nutrition, what nutrition education resources they currently provide, opinion on whose responsibility it is to provide nutrition education, and what approach they think would be best to educate patients and parents. The guardian survey contained 21 items that evaluated dietary behaviors. The dietary behaviors included family dynamics (who typically feds the children, if food is prepared in the home, and how much is spent on food each week) and child eating habits (how many snacks per day, how often the child eats fast food, and how often the child consumes sweetened beverages). The surveys will be utilized for future research, and the results will help determine the approach for educating physicians and guardians. A booklet of healthy recipes was also developed to educate on healthy eating and as a participation benefit. The goal of the booklet was to choose easy, child friendly recipes that the family could cook together. To gain background on nutrition education, we observed the different education methods of local pediatricians and reviewed the literature. Intervention at both the clinical and community levels will be important for improving long-term health outcomes in pediatric patients. The knowledge gained from these surveys will aide in the development of programs needed to provide physicians, guardians,and patients with proper nutrition education

Effect of implantation on engineered skeletal muscle constructs

The development of engineered skeletal muscle would provide a viable tissue for replacement and repair of muscle damaged by disease or injury. Our current tissue‐engineering methods result in three‐dimensional (3D) muscle constructs that generate tension but do not advance phenotypically beyond neonatal characteristics. To develop to an adult phenotype, innervation and vascularization of the construct must occur. In this study, 3D muscle constructs were implanted into the hindlimb of a rat, along the sciatic nerve, with the sural nerve isolated, transected and sutured to the construct to encourage innervation. Aortic ring anchors were sutured to the tendons of the biceps femoris muscle so that the construct would move dynamically with the endogenous muscle. After 1 week in vivo , the constructs were explanted, evaluated for force production and stained for muscle, nerve and collagen markers. Implanted muscle constructs showed a developing capillary system, an epimysium‐like outer layer of connective tissue and an increase in myofibre content. The beginning of α ‐bungarotoxin clustering suggests that neuromuscular junctions (NMJs) could form on the implanted muscle, given more time in vivo . Additionally, the constructs increased maximum isometric force from 192 ± 41 μN to 549 ± 103 μN (245% increase) compared to in vitro controls, which increased from 276 ± 23 μN to 329 ± 27μN (25% increase). These findings suggest that engineered muscle tissue survives 1 week of implantation and begins to develop the necessary interfaces needed to advance the phenotype toward adult muscle. However, in terms of force production, the muscle constructs need longer implantation times to fully develop an adult phenotype. Copyright © 2012 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98423/1/term537.pd

P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading

To test the hypothesis that p38α-MAPK plays a critical role in the regulation of E3 ligase expression and skeletal muscle atrophy during unloading, we used VX-745, a selective p38α inhibitor. Three groups of rats were used: non-treated control (C), 3 days of unloading/hindlimb suspension (HS), and 3 days HS with VX-745 inhibitor (HSVX; 10 mg/kg/day). Total weight of soleus muscle in HS group was reduced compared to C (72.3 ± 2.5 vs 83.0 ± 3 mg, respectively), whereas muscle weight in the HSVX group was maintained (84.2 ± 5 mg). The expression of muscle RING-finger protein-1 (MuRF1) mRNA was significantly increased in the HS group (165%), but not in the HSVX group (127%), when compared with the C group. The expression of muscle-specific E3 ubiquitin ligases muscle atrophy F-box (MAFbx) mRNA was increased in both HS and HSVX groups (294% and 271%, respectively) when compared with C group. The expression of ubiquitin mRNA was significantly higher in the HS (423%) than in the C and HSVX (200%) groups. VX-745 treatment blocked unloading-induced upregulation of calpain-1 mRNA expression (HS: 120%; HSVX: 107%). These results indicate that p38α-MAPK signaling regulates MuRF1 but not MAFbx E3 ligase expression and inhibits skeletal muscle atrophy during early stages of unloading

Structure and Functional Evaluation of Tendon–Skeletal Muscle Constructs Engineered in Vitro

During muscle contraction, the integrity of the myotendinous junction (MTJ) is important for the transmission of force from muscle to tendon. We evaluated the contractile and structural characteristics of 3-dimensional (3-D) skeletal muscle constructs co-cultured with engineered self-organized tendon constructs (n = 4), or segments of adult (n = 4) or fetal (n = 5) rat-tail tendon. We hypothesized that the co-culture of tendon and muscle would produce constructs with viable muscle–tendon interfaces that remain intact during generation of force. Construct diameter (lm) and maximum isometric force (µN) were measured, and specific force (kPa) was determined. After measure of force, constructs were loaded at a constant strain rate until failure and surface strains were recorded optically across the tendon, the muscle and the interface and used to determine the tangent modulus (passive stiffness) of the construct. Frozen samples were used for Trichrome Masson staining and immunofluorescent analysis of the MTJ-specific protein paxillin. No differences were observed between the groups with respect to diameter, maximum force, or specific force. The MTJ was robust and withstood tensile loading beyond the physiological strain range. The majority of the constructs failed in the muscle region. At the MTJ, there is an increase in the expression and localization of paxillin. In conclusion, using 3 sources of tendon tissue, we successfully engineered 3-D muscle–tendon constructs with functionally viable MTJ, characterized by structural features and protein expression patterns resembling neonatal MTJs in vivo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63387/1/ten.2006.12.3149.pd

Double p52Shc/p46Shc Rat Knockout Demonstrates Severe Gait Abnormalities Accompanied by Dilated Cardiomyopathy

The ubiquitously expressed adaptor protein Shc exists in three isoforms p46Shc, p52Shc, and p66Shc, which execute distinctly different actions in cells. The role of p46Shc is insufficiently studied, and the purpose of this study was to further investigate its functional significance. We developed unique rat mutants lacking p52Shc and p46Shc isoforms (p52Shc/46Shc-KO) and carried out histological analysis of skeletal and cardiac muscle of parental and genetically modified rats with impaired gait. p52Shc/46Shc-KO rats demonstrate severe functional abnormalities associated with impaired gait. Our analysis of p52Shc/46Shc-KO rat axons and myelin sheets in cross-sections of the sciatic nerve revealed the presence of significant anomalies. Based on the lack of skeletal muscle fiber atrophy and the presence of sciatic nerve abnormalities, we suggest that the impaired gait in p52Shc/46Shc-KO rats might be due to the sensory feedback from active muscle to the brain locomotor centers. The lack of dystrophin in some heart muscle fibers reflects damage due to dilated cardiomyopathy. Since rats with only p52Shc knockout do not display the phenotype of p52Shc/p46Shc-KO, abnormal locomotion is likely to be caused by p46Shc deletion. Our data suggest a previously unknown role of 46Shc actions and signaling in regulation of gait

Three-Dimensional Engineered Bone–Ligament–Bone Constructs for Anterior Cruciate Ligament Replacement

The anterior cruciate ligament (ACL), a major stabilizer of the knee, is commonly injured. Because of its intrinsic poor healing ability, a torn ACL is usually reconstructed by a graft. We developed a multi-phasic, or bone?ligament?bone, tissue-engineered construct for ACL grafts using bone marrow stromal cells and sheep as a model system. After 6 months in vivo, the constructs increased in cross section and exhibited a well-organized microstructure, native bone integration, a functional enthesis, vascularization, innervation, increased collagen content, and structural alignment. The constructs increased in stiffness to 52% of the tangent modulus and 95% of the geometric stiffness of native ACL. The viscoelastic response of the explants was virtually indistinguishable from that of adult ACL. These results suggest that our constructs after implantation can obtain physiologically relevant structural and functional characteristics comparable to those of adult ACL. They present a viable option for ACL replacement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98477/1/ten%2Etea%2E2011%2E0231.pd

Characterization of skeletal muscle effects associated with daptomycin in rats

Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram-positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (≤0.22%) with loss of plasma membrane integrity and/or infiltration by neutrophils and/or macrophages. Multiple doses of daptomycin are required for a quantifiable effect on skeletal muscles of rats. Some fibers were Evans Blue Dye–positive but were not yet infiltrated by neutrophils. This suggests that the sarcolemma may be the primary target for the observed effects. Muscle Nerve, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77978/1/21691_ftp.pd

Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

Unloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq). Male Wistar rats were divided into four groups (eight rats per group): nontreated control (C), three days of unloading/hindlimb suspension (HS) and three days HS with HDACs inhibitor LMK-235 (HSLMK) or Tq (HSTq). Treatment with LMK-235 diminished unloading-induced of MAFbx, myogenin (MYOG), ubiquitin and calpain-1 mRNA expression (p < 0.05). Tq administration had no effect on the expression of E3-ligases. The mRNA expression of MuRF1 and MAFbx was significantly increased in both HS and HSTq groups (1.5 and 4.0 folds, respectively; p < 0.05) when compared with the C group. It is concluded that during three days of muscle unloading: (1) the HDACs 4 and 5 participate in the regulation of MAFbx expression as well as the expression of MYOG, ubiquitin and calpain-1; (2) the inhibition of HDAC 4 has no effect on MAFbx expression. Therefore, HDAC 5 is perhaps more important for the regulation of MAFbx expression than HDAC 4

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice

Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damag