ResearchPad - muscle Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Relationship between maximal incremental and high-intensity interval exercise performance in elite athletes]]> This descriptive study aimed to explore the physiological factors that determine tolerance to exertion during high-intensity interval effort. Forty-seven young women (15–28 years old) were enrolled: 23 athletes from Taiwan national or national reserve teams and 24 moderately active females. Each participant underwent a maximal incremental INC (modified Bruce protocol) cardiopulmonary exercise test on the first day and high-intensity interval testing (HIIT) on the second day, both performed on a treadmill. The HIIT protocol involved alternation between 1-min effort at 120% of the maximal speed, at the same slope reached at the end of the INC, and 1-min rest until volitional exhaustion. Gas exchange, heart rate (HR), and muscle oxygenation at the right vastus lateralis, measured by near-infrared spectroscopy, were continuously recorded. The number of repetitions completed (Rlim) by each participant was considered the HIIT tolerance index. The results showed a large difference in the Rlim (range, 2.6–12.0 repetitions) among the participants. Stepwise linear regression revealed that the variance in the Rlim within the cohort was related to the recovery rates of oxygen consumption (V˙O2), HR at the second minute after INC, and muscle tissue saturation index at exhaustion (R = 0.644). In addition, age was linearly correlated with Rlim (adjusted R = −0.518, p < 0.0001). In conclusion, the recovery rates for V˙O2 and HR after the incremental test, and muscle saturation index at exhaustion, were the major physiological factors related to HIIT performance. These findings provide insights into the role of the recovery phase after maximal INC exercise testing. Future research investigating a combination of INC and HIIT testing to determine training-induced performance improvement is warranted.

<![CDATA[SAT-567 Hypertriglyceridem...From Mild to Fatal!... Is Time for Awareness]]> Hypertriglyceridemia… From mild to fatal! … Is Time for Awareness.

Hypertriglyceridemia can be primary or acquired. High triglycerides are related to complications such as pancreatitis and there is a positive correlation between hypertriglyceridemia and atherosclerotic burden. In this case series we aim to discuss pancreatitis as a hypertriglyceridemia complication and to acknowledge the importance of prevention and management. Is there something we can do to raise awareness and avoid complications as in the cases?

All cases present with chief complaint of epigastric cramp-like abdominal pain, radiating to the back, nausea/vomiting and with highly lipemic blood samples.

38y/o F admitted after been found with lipase 268 U/L (n<60 U/L), amylase 131 U/L (n<100 U/L) and findings of pancreatitis on CT scan. Patient with one-year history of T2DM refers this is the 4th episode of pancreatitis and reports that last time she was told about having triglycerides in 4,000 mg/dL for which she went to her physician that prescribe her Fenofibrate. Patient triglycerides were 7,931 mg/dL (n<199 mg/dL) and found with poorly controlled diabetes with HgbA1c 8.4%. She was properly managed, and triglycerides decrease to 1,309 mg/dL.

31y/o F with elevated lipase (237 U/L, n<60 U/L) and findings of pancreatitis on CT scan was admitted and found with 7,755 mg/dL triglycerides. She refers to have endometriosis for which she uses OCPs for >5years. She develops intractable abdominal pain along with abdominal distension and progress to Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. She had a prolonged ICU stay and after management triglycerides decrease to 95mg/dL, symptoms resolve, and patient was discharge.

48y/o F with pancreatitis, lipase levels 1,452 U/L, amylase 744 U/L and positive imaging findings. Patient with uncontrolled diabetes (HgbA1c 11.0%) and breast mass s/p lumpectomy for which she used tamoxifen for the last 2 years. Triglycerides 7,444mg/dL on Gemfibrozil started due to previous levels found >4,000 mg/dL on outpatient evaluation. She deteriorates clinically and develops renal failure, abdominal compartment syndrome, respiratory distress and hypotension requiring mechanical ventilation and vasopressors. On repeated abdominal CT pancreas changes were suggestive of fulminant pancreatitis. Patient did not respond to treatment and passed away 48 hours after admission.

Hypertriglyceridemia complications can be mild or fatal as in these cases. They were evaluated by a primary care physician before complications occur and had secondary causes that predispose them to hypertriglyceridemia, but they were not addressed, reason for which these scenarios raise concern of how much we know? How much we are doing to prevent these outcomes?... Awareness of hypertriglyceridemia management and adverse effects is necessary to avoid complications and fatal outcomes. Is time!

<![CDATA[SAT-LB92 Sex Hormones Therapy Differentially Modulates HDL Function in Transgender Individuals]]> Background/aim: The main proposed atheroprotective function of high-density lipoproteins (HDL) lays on their role to promote macrophage cholesterol efflux. An insightful way to learn more about the effects of sex hormones on HDL function is to study changes during hormone therapy. The present study was aimed at evaluating the effects of exogenous sex hormones administration on HDL cholesterol efflux capacity (CEC) within transgender individuals. CEC estimates the ability of HDL to remove cholesterol from cells, i.e. the initial step in reverse cholesterol transport.

Subjects/Methods: Transmen were treated with testosterone gel, a mix of testosterone esters once every three weeks) or testosterone undecanoate once every twelve weeks, whereas transwomen were treated with either oral estradiol valerate or a transdermal application of estradiol (patches). Cyproterone acetate was prescribed as a testosterone-blocking agent to all transwomen. HDL function was evaluated by a radioisotopic technique. Hormone levels, lipids and HDL function were evaluated after one year of follow-up.

Results: In transmen (n= 15), testosterone markedly increased (+ 97%; p < 0.0001), whereas luteinizing hormone (LH) decreased significantly (- 64%; p = 0.049). Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not affected by testosterone treatment, whilst triglycerides (TG) were raised (+ 11.76%; p = 0.0078) and HDL-C reduced (- 19.6%, p=0.0103). Concerning HDL CEC, only the aqueous diffusion process was lowered (- 9.8%; p = 0.0032), an effect directly correlated with HDL-C changes (r = 0.6242, p = 0.0002). Total-, ATP-binding cassette transporter (ABCA1)-, and ABCG1-mediated CEC were not affected by testosterone treatment. In transwomen (n= 15), estradiol levels were raised (+200%, p=0.013) whereas LH and testosterone significantly reduced, i.e. - 97% for both. Relative to lipids, estradiol supplementation reduced total cholesterol (- 10.7%, p=0.0017), HDL-C (- 14.3%, p = 0.0024) and LDL-C (- 10.9%, p = 0.0058). Total HDL CEC decreased (- 11%, p=0.0001) with a specific decrement in CEC mediated by the ATP-binding cassette transporter (ABCA1) (-24%, p = 0.0003) and aqueous diffusion (-4.7%, p = 0.0014). This last was associated to a reduction in HDL-C (r = 0.4084, p = 0.0251). Conversely, the drop in ABCA1 and total CEC did not associate to reductions in HDL-C levels.

Conclusions: In transmen, testosterone supplementation was associated with a reduction in aqueous diffusion-mediated CEC, an effect potentially dependent to HDL-C changes. In transwomen, estrogen significantly decreased HDL function (CEC), independent of HDL-C levels changes.

<![CDATA[SAT-573 Eruptive Xanthomas in a Patient with Hypertriglyceredemia and Type 2 Diabetes Mellitus]]> BACKGROUND: Eruptive xanthomas are rare, asymptomatic, cutaneous lesions and are markers for serious underlying metabolic disorders that demand an early diagnosis to prevent morbidity and mortality.

Clinical Case: A 27 years old obese female presented with generalized, pruritic eruptions. The eruptions had been present for approximately three weeks. Crops of firm yellow-red circumscribed Papules (diameter 1–3 mm) distributed on the extensor surfaces of both the upper and the lower extremities which were few in numbers to begin with but increased in density subsequently spreading to involve her back, abdomen, knees, and posterior thighs. The patient besides being obese had no other significant past medical or family history. Labs: FBS:258 mg/dl (80-100mg/dl), HbA1c:11.7%(<5.6%), Total lipids: 3680 mg/dl (400–1000 mg/dl), Total Cholesterol: 857 mg/dl (120–200 mg/dl), Triglycerides: 5428 mg/dl (70–150 mg/dl), HDL:15mg/dl (45–64 mg/dl), LDL: 371 mg/l(<130 mg/dl),VLDL: 402 mg/dl (<30 md/dl). Results of kidney, liver and thyroid function tests were normal, as well as amylase and lipase. X-ray chest and abdominal ultrasound were unremarkable. Biopsy of the papules was not carried out due to non-affordability on the part of the patient. The patient was managed by an interdisciplinary approach for diabetes mellitus type 2 and hyperlipidaemia. Treatment was started with oral hypoglycaemic along with lipid lowering agents and the required lifestyle modifications including weight control, adopting a low-fat diet, and regular exercise were advised. The papules resolved within six weeks of the treatment and lab reports indicated improvement in her glycemic control and hypertriglyceridemia. It was clinically diagnosed as Eruptive Xanthomas of secondary hypertriglyceridemia due to diabetes mellitus.


Recognizing eruptive xanthomas and being aware of its association with hypertriglyceridemia and diabetes mellitus can help to decrease any lag between a patient being seen by a physician and treatment for a serious medical conditions such as coronary artery disease and pancreatitis.

REFRENCES: Digby M; Belli R; McGraw T; Lee A (2011). “Eruptive xanthomas as a cutaneous manifestation of hypertriglyceridemia: a case report”. J Clin Aesthet Dermatol. 4: 44–6. PMC 3030216Freely accessible. PMID 21278899.

<![CDATA[SAT-577 Severe Asymptomatic Hypertriglyceridemia]]> Background

Case reports of patients with severely elevated serum triglyceride levels (>1000 mg/dL) have been documented where Insulin infusions, heparin and plasmapheresis have demonstrated rapid and successful decrease in serum Triglyceride levels. The benefits of one approach versus the other to prevent major complications such as cardiovascular events or acute pancreatitis has not been well investigated. We present the case of a patient with severely elevated serum triglyceride levels without any manifestations.

Case Description

A 53-year-old male presented from his primary care provider’s office due to elevated Triglycerides levels over 6000 as per outpatient lab work. Inpatient labs were unattainable initially due to hemolysis secondary to the severely high lipid content. Patient was admitted to the medical ICU for closer monitoring and initiated on an insulin drip. Two days after insulin initiation patient’s triglyceride levels returned as 2,887 with a total cholesterol count of 848. His insulin drip was continued until his TAG levels were less than 1000. Upon discharge his levels were less than 600.


Most patients with hypertriglyceridemia are asymptomatic. However, in patients with levels above 1000 mg/dL, the risk of pancreatitis or cardiovascular event is of concern. Hypertriglyceridemia may account for 1 to 14 percent of cases of acute pancreatitis. Treatment is largely based upon symptoms and complications. In the event of pancreatitis or other cardiovascular complication, plasmapheresis is usually recommended. If asymptomatic, Insulin may be used. Insulin promotes synthesis of lipoprotein lipase which functions to hydrolyze triglycerides, and has been shown to be an effective lowering agent in the treatment of such individuals. Case reports of Heparin being used as a lipid lowering agent have also been documented, but was not used in our particular patient.

Normal triglyceride plasma levels are defined as less than 150 mg/dL. Mild hypertriglyceridemia typically ranges between 150-499 mg/dL, moderate between 500-866 mg/dL, and severe is defined as levels greater than 886 mg/dL. Plasma triglyceride levels above 1000 mg/dL occur in fewer than 1 in 5000 individuals. It is said that patients with TAG levels above 2000 mg/dL almost always have both a secondary and a genetic form of Hypertriglyceridemia. For this reason it is very important to identify these patients as early as possible to treat appropriately. Our patient was a known alcohol abuser, yet without the presence of some polygenic familial disorder, the likelihood of our patient having TAG levels >6000 mg/dL, is very unlikely.

<![CDATA[The adipokine vaspin is associated with decreased coronary in-stent restenosis <i>in vivo</i> and inhibits migration of human coronary smooth muscle cells <i>in vitro</i>]]> Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro.MethodsWe studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed.ResultsDuring the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment.ConclusionWe were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment. ]]> <![CDATA[Ion currents, action potentials, and noradrenergic responses in rat pulmonary vein and left atrial cardiomyocytes]]> Effects of noradrenaline on action potential (AP) repolarisation in PV cardiomyocytes. A Representative AP recording from a PV cardiomyocyte in control solution and in the presence of 1 μM noradrenaline (NA). B Representative AP recording from another PV cardiomyocyte in control solution and in the presence of 1 μM NA showing lack of AP prolongation. C Before‐and‐after plot of APD30 in PV cardiomyocytes in control solution and after superfusion with 1 μM NA. D Noradrenaline‐induced fold‐changes in APD30 in LA and PV cardiomyocytes.

<![CDATA[SAT-578 A Rare Case of Laboratory Hypertriglyceridemia: Glycerol Kinase Deficiency]]> Background: Hypertriglyceridemia (HTG) is common; however, pseudo-HTG due to high glycerol in glycerol kinase deficiency (GKD, MIM: 307030) is a rare cause of HTG that need to be delineated for appropriate management. GKD is an X-linked recessive disorder characterized by hyperglycerolemia and glyceroluria. Two of three GKD subtypes are known as “isolate” GKD due to a mutation in GK gene alone: (1) symptomatic juvenile form, and (2) benign adult form, associated with an incidental finding of HTG.

Since most commercial laboratories determine triglyceride (TG) levels by a glycerol measurement, TG-backbone, patients with GKD are mistakenly labelled as having HTG. Glycerol-blanking is required to reveal the actual TG, but it is costly. Since usual TG-lowering medications are ineffective or even harmful, novel methods to screen for individuals with GKD or pseudo-HTG are necessary.

Objective: Through identification of a clinical case of GKD that was diagnosed by glycerol-blanking, we are proposing two potential methods to screen for pseudo-HTG, and presenting their reliability.

Methods: The patient was recruited into an IRB-approved study investigating etiologies of dyslipidemia at the University of Pennsylvania. Patient provided consent for medical record review.

Results: A 49-year-old man was referred for HTG management. His reported TG levels ranged between 490 and 559 mg/dL without any other adverse lipid levels for several years without a history of pancreatitis or diabetes mellitus. Intriguingly, he reported a family history of HTG.

Since TG-lowering medications (fibrates and fish oil) had not reduced his TG levels, specialized lipid analyses were obtained: a non-blanked TG level of 521 mg/dL and a glycerol-blanked TG of 66 mg/dL, consistent with pseudo-HTG or hyperglycerolemia. Repeat glycerol blanked TG levels were 68 and 69 mg/dL, confirming the previous result, and the likely diagnosis of GKD.

With two methods, estimated TG levels were calculated, using some of his laboratory values: (1) modified Friedewald equation to solve for TG with a direct LDL (dLDL) value, and (2) the application of a newly developed formula derived from a collection of 17,545 patient samples, to calculate the absolute TG-gap, using apolipoprotein A and B, estimating TG levels (% deltaTG), and determining whether a TG mesurement might be falsely deviated from the “plausible” TG value.

Although neither methods showed perfect concordance, the calculated TG-valued derived by the two methods were significantly lower than the non-glycerol blanked TG values. The difference was statistically significant (p<0.05).

Conclusion: The patient was clinically diagnosed with GKD, and was taken off of fibrate and the recently added niacin. These two methods can be used quickly to screen for pseudo-HTG or patients with GKD. Currently, it is unknown whether high glycerol levels are associated with high cardiovascular risks.

<![CDATA[The effect of sleep restriction, with or without high‐intensity interval exercise, on myofibrillar protein synthesis in healthy young men]]> Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models.The rate of myofibrillar protein synthesis (MyoPS) is a key variable in regulating skeletal muscle mass and can be increased by performing high‐intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown.In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS; however, rates of MyoPS were maintained at control levels by performing HIIE during this period.Our data suggest that the lower rates of MyoPS in the sleep restriction group may contribute to the detrimental effects of sleep loss on muscle mass and that HIIE may be used as an intervention to counteract these effects.

<![CDATA[SAT-574 Whole Exome Sequencing Identifies Several Variants Associated with Immune Deficiency, Inflammasomopathy and Non-Ischemic Dilated Cardiomyopathy in a Complex Case of Acquired Generalized Lipodystrophy]]> Background: Acquired generalized lipodystrophy (AGL) is characterized by near-total fat loss that develops after birth. Although the molecular pathogenesis of AGL is unclear, there is a link to autoimmunity and inflammation. Notably, the panniculitis associated variety of AGL may present with subcutaneous inflammatory nodules that ultimately progress to generalized fat loss. Here, we report on a complex patient with AGL in whom whole-exome sequencing (WES) identified several pathogenic variants and variants of uncertain significance (VUS) that encourage us to think about AGL more broadly. Clinical Case: This is a 38-year-old male who was first diagnosed with juvenile rheumatoid arthritis at age 2, after being evaluated for delayed ability to ambulate. At that time, he was also diagnosed with Weber-Christian disease following a skin biopsy due to the suspicion of panniculitis. Over time, he progressively lost body fat throughout the body and developed hypertriglyceridemia, hypertension, and nephropathy leading to the diagnosis of AGL. At age 10, he was diagnosed with type 1 diabetes mellitus, and at age 14, with autoimmune hepatitis. Due to the tightening of his hands, calf pain, and increased CPK levels, a muscle biopsy was performed, suggesting polymyositis. He had been treated with azathioprine and steroids, which were discontinued at age 26, after a liver biopsy that showed grade 2 fibrosis. Further, he was diagnosed with non-ischemic dilated cardiomyopathy (DCM), evolving with atrial fibrillation with a rapid ventricular response and complicated with left atrial appendage thrombus. Of interest, his mother and two maternal aunts had been diagnosed with atrial fibrillation. One of his maternal uncles presented non-ischemic cardiomyopathy and an early sudden cardiac arrest. His mother also had mitochondrial myopathy, and his father had type 2 diabetes mellitus and IgG deficiency. WES identified three different variants: a maternally inherited pathogenic variant in TTN (c.88473_88477delAGCTT; p.W29493X) associated with DCM, a paternally inherited pathogenic variant in TNFRSF13B (c.310T>C; p.C104R) associated with CVID/IgA deficiency, and a maternally inherited variant of uncertain clinical significance in NLRP3 (c.1469G>A; p.R490K). Although the frequency of this variant was relatively high, several variants in the NLRP3 gene have been previously associated with inflammasomopathy. Conclusion: This case highlights challenging presentations of AGL and the complexity of the disease. As we are yet beginning to understand the molecular mechanisms behind the so-called “acquired fat loss” and its relation to inflammatory and complex immune system diseases, further efforts are critical to better recognize different AGL phenotypes and phenotype-genotype correlations. Additional efforts should be placed on WES for AGL patients and functional validation of identified VUSs.

<![CDATA[SUN-542 The Effect of Energy Deprivation on Metabolic Hormone Responses to Meals]]> Background: Intermittent caloric restriction (ICR) has recently gained popularity as a weight-loss strategy; however, fasting metabolic hormones and dynamic meal-related responses, are not well-established in this setting. Methods: We measured metabolic hormone responses to 5-days of neutral or decreased energy availability (NEA, 45 kcal/kg LBM*d vs DEA, 20 kcal/kg LBM*d) in the early follicular phase (EFP) in 19 regularly-cycling, sedentary, women (age 23.36± 2.08 yr; mean±SD). Hunger was assessed using a visual analogue scale on the 5th day of each condition. Scheduled breakfast and lunch were administered according to assigned caloric intake, while an afternoon snack based on NEA was provided on both occasions. Blood was sampled for leptin, insulin, glucose, and GH at 10-min intervals and cortisol was measured at 30-min intervals over eight hours starting at 0800 h, while Orexin A and adiponectin were measured in fasting samples. AUC for each hormone for every meal and diet condition were analyzed using linear mixed models. Insulin and insulin/glucose ratio (I/G) were also adjusted for meal calories. Percentage body fat mass was measured every visit using air displacement plethysmography (BodPod®). Results are presented as least square mean ± sem. Results: There were no differences in body mass index or % fat mass after NEA vs DEA although there was a significant increase in hunger with DEA (p=0.002). Fasting levels of glucose and insulin were unchanged while leptin decreased with DEA (1.27±0.07 and 1.04±0.07 ng/mL, NEA and DEA respectively; p<0.0001), and Orexin A increased (0.55±0.04 and 0.60±0.04 ng/mL; p=0.04). The AUC for glucose was lower with DEA across all meals (p<0.0001). Insulin, I/G and I/G normalized for ingested calories (nI/G) decreased in response to DEA (p<0.005, p<0.05 and p<0.0001). The slope of the increase in leptin across the day was not different between NEA and DEA (p=0.20). Adiponectin, GH and cortisol were unaffected by DEA. Conclusion: These studies indicate that although fasting glucose and insulin are unaffected by short-term caloric restriction, the insulin response to glucose is attenuated even when adjusting for meal-related calories. Orexin A increased and leptin decreased with reduced caloric intake, acting, at least in part, to stimulate appetite. Taken together, these hormonal responses, directed at preserving energy homeostasis, have important implications for understanding the potential efficacy of intermittent caloric restriction.

<![CDATA[SUN-543 Real World Evidence of Successful Weight Management for the Obese Population: Complete Reversal of Obesity Related Metabolic Co-Morbidities and Weight Loss in Patients Attending a Multidisciplinary Weight Management Clinic in Australia]]> Over 2.5 billion people worldwide are overweight or obese. Multidisciplinary weight management interventions have evolved to address the complexity of weight loss for those with one or more chronic diseases, and the trend of weight regain. The aim of these interventions is to encourage sustainable lifestyle changes, resulting in weight loss and weight maintenance and improvements in comorbidities. While some prospective clinical trials have demonstrated efficacy, results are often not reported by real life practices.

The aim of this study was to evaluate the effectiveness of a Sydney based multidisciplinary weight management clinic with endocrinology, dietetics, exercise physiology, psychology, and bariatric surgical domains. All patients who attended the clinic for weight loss purposes between March 2017 and April 2019 were included (n=220). A retrospective chart review was conducted. Patient data on weight, BMI, waist circumference, body composition measurements, and selected blood test results and co-morbidities were analysed. All patient therapy included endocrinological input for co-morbidity identification and management, lifestyle intervention (dietetic and exercise physiology input) with optional adjunct pharmacotherapy or psychological counselling. Of the 220 cohort, 20 of the patients had sleeve gastrectomy.

Patient retention in the clinic after the first consultation was 85% (n=186), a high rate within the weight management community. 59% of patients achieved a minimum of 5% total body weight loss, including 18% who achieved greater than 10% total body weight loss. Additionally, 31% of patients lost enough weight to decrease their BMI class by up to 2 or more classes. Of the gastric sleeve cohort average excess body weight loss was 32kg (21-56kg) enhanced by multidisciplinary care in the lead up to surgery. Across the cohort some patients completely reversed co-morbidities; including dyslipidaemia (n=1), hypertension (n=3), NAFLD (n=1), pre-diabetes (n=8) and type 2 diabetes (n=3), OSA (n=1). These results demonstrate that obesity is a chronic condition that can be successfully managed. We have demonstrated significant durable weight loss and improvement in metabolic co-morbidities with holistic coordinated care. Future directions include translating this model of care into standard practice in Australia and other countries where obesity to date not received the same coordinated approach as other chronic conditions.

<![CDATA[SAT-565 Familial Homozygous Lipoprotein Lipase Defect Presenting with Recurrent Chylomicronemia Syndrome: Making a Case for Elective Plasmapheresis as an Adjuvant Treatment Modality]]> Background

The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and fasting chylomicronemia. Type Ia hyperlipoproteinemia is an extremely rare genetic disorder that results from homozygous deficiency in LPL activity. It is characterized by eruptive xanthomas, lipemia retinalis, memory disturbances, hepatosplenomegaly and frequent episodes of pancreatitis. Pharmacologic agents including fibrates, fish oils and statins have been used for treatment. Patients who fail pharmacologic therapy are usually treated with plasmapheresis. This case showed a patient in which joint decision making led to elective plasmapheresis to avoid chylomicronemia syndrome as an adjunct to medical therapy.

Clinical case

A 35-year-old lady without known medical co-morbidity presented with 2 weeks of dull abdominal pain radiating to the back. She developed nausea and vomiting which led to her presentation. There was no history of alcohol use, gall stones, diabetes mellitus or thyroid dysfunction. She was not on any medications. Physical examination was significant for BMI of 18, moderate abdominal tenderness, splenomegaly and an indurated rash in her legs. Laboratory investigation showed elevated lipase and triglyceride level of 3313 (normal 30-50) mg/dL. CT of the abdomen was consistent with acute interstitial pancreatitis. She was managed with insulin drip and fenofibrate and discharged 3 days later on fenofibrate, atorvastatin and long acting insulin. She developed another episode of acute pancreatitis while on medical therapy requiring readmission and initiation of insulin drip 2 months later. However, triglycerides trended upwards when the drip was stopped and symptoms of acute pancreatitis worsened. She subsequently underwent plasmapheresis which led to resolution of symptoms. Despite maximally tolerated pharmacologic therapy, she persistently has triglycerides above 4000s and persistent abdominal discomfort. Genetic testing confirmed homozygous defect in LPL gene. Following an outpatient Endocrinology visit, a decision was made to pursue elective plasmapheresis as an adjunct to therapy. She had on average 2 sessions monthly for 3 months with overall improvement in abdominal discomfort as well as significant improvement in triglyceride levels.


Familial chylomicronemia syndromes often require multimodal therapeutic approaches to prevent morbidity and complications. These include diet and pharmacologic therapy. Although plasmapheresis is often used during hospitalizations for hypertriglyceridemia induced pancreatitis refractory to diet and pharmacologic therapy, it was used in our patient electively and efficaciously to control hypertriglyceridemia and improve symptoms of chylomicronemia syndrome.

<![CDATA[Effect of somatic maturity on the aerobic and anaerobic adaptations to sprint interval training]]> After 4 weeks of sprint interval training, improvements in aerobic and anaerobic exercise performance were observed in youth male athletes. However, prepubertal participants had no changes following training.

<![CDATA[Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes]]>

Transverse and axial tubules (TATS) are an essential ingredient of the excitation-contraction machinery that allow the effective coupling of L-type Calcium Channels (LCC) and ryanodine receptors (RyR2). They form a regular network in ventricular cells, while their presence in atrial myocytes is variable regionally and among animal species We have studied the effect of variations in the TAT network using a bidomain computational model of an atrial myocyte with variable density of tubules. At each z-line the t-tubule length is obtained from an exponential distribution, with a given mean penetration length. This gives rise to a distribution of t-tubules in the cell that is characterized by the fractional area (F.A.) occupied by the t-tubules. To obtain consistent results, we average over different realizations of the same mean penetration length. To this, in some simulations we add the effect of a network of axial tubules. Then we study global properties of calcium signaling, as well as regional heterogeneities and local properties of sparks and RyR2 openings. In agreement with recent experiments in detubulated ventricular and atrial cells, we find that detubulation reduces the calcium transient and synchronization in release. However, it does not affect sarcoplasmic reticulum (SR) load, so the decrease in SR calcium release is due to regional differences in Ca2+ release, that is restricted to the cell periphery in detubulated cells. Despite the decrease in release, the release gain is larger in detubulated cells, due to recruitment of orphaned RyR2s, i.e, those that are not confronting a cluster of LCCs. This probably provides a safeguard mechanism, allowing physiological values to be maintained upon small changes in the t-tubule density. Finally, we do not find any relevant change in spark properties between tubulated and detubulated cells, suggesting that the differences found in experiments could be due to differential properties of the RyR2s in the membrane and in the t-tubules, not incorporated in the present model. This work will help understand the effect of detubulation, that has been shown to occur in disease conditions such as heart failure (HF) in ventricular cells, or atrial fibrillation (AF) in atrial cells.

<![CDATA[Disruption of genes associated with Charcot-Marie-Tooth type 2 lead to common behavioural, cellular and molecular defects in Caenorhabditis elegans]]>

Charcot-Marie-Tooth (CMT) disease is an inherited peripheral motor and sensory neuropathy. The disease is divided into demyelinating (CMT1) and axonal (CMT2) neuropathies, and although we have gained molecular information into the details of CMT1 pathology, much less is known about CMT2. Due to its clinical and genetic heterogeneity, coupled with a lack of animal models, common underlying mechanisms remain elusive. In order to gain an understanding of the normal function of genes associated with CMT2, and to draw direct comparisons between them, we have studied the behavioural, cellular and molecular consequences of mutating nine different genes in the nematode Caenorhabditis elegans (lin-41/TRIM2, dyn-1/DNM2, unc-116/KIF5A, fzo-1/MFN2, osm-9/TRPV4, cua-1/ATP7A, hsp-25/HSPB1, hint-1/HINT1, nep-2/MME). We show that C. elegans defective for these genes display debilitated movement in crawling and swimming assays. Severe morphological defects in cholinergic motors neurons are also evident in two of the mutants (dyn-1 and unc-116). Furthermore, we establish methods for quantifying muscle morphology and use these to demonstrate that loss of muscle structure occurs in the majority of mutants studied. Finally, using electrophysiological recordings of neuromuscular junction (NMJ) activity, we uncover reductions in spontaneous postsynaptic current frequency in lin-41, dyn-1, unc-116 and fzo-1 mutants. By comparing the consequences of mutating numerous CMT2-related genes, this study reveals common deficits in muscle structure and function, as well as NMJ signalling when these genes are disrupted.

<![CDATA[Sex differences in skeletal muscle alterations in a model of colorectal cancer]]>


Cancer cachexia is the loss of lean muscle mass with or without loss of fat mass that is often highlighted by a progressive loss of skeletal muscle mass and function. The mechanisms behind the cachexia‐related loss of skeletal muscle are poorly understood, including cachexia‐related muscle functional impairments. Existing models have revealed some potential mechanisms, but appear limited to how the cancer develops and the type of tumors that form. We studied the C57BL6/J (B6) ApcMin/+ Tg::Fabp1‐Cre TG::PIK3ca* (CANCER) mouse. In this model, mice develop highly aggressive intestinal cancers. We tested whether CANCER mice develop cancer cachexia, if muscle function is altered and if sex differences are present. Both female and male mice, B6 (CONTROL) and CANCER mice, were analyzed to determine body weight, hindlimb muscle mass, protein concentration, specific force, and fatigability. Female CANCER mice had reduced body weight and hindlimb muscle mass compared with female CONTROL mice, but lacked changes in protein concentration and specific force. Male CANCER mice had reduced protein concentration and reduced specific force, but lacked altered body weight and muscle mass. There were no changes in fatigability in either group. Our study demonstrates that CANCER mice present an early stage of cachexia, have reduced specific force in male CANCER mice and develop a sex‐dependent cachexia phenotype. However, CANCER mice lack certain aspects of the syndrome seen in the human scenario and, therefore, using the CANCER mice as a preclinical model does not seem sufficient in order to maximize the translation of preclinical findings to humans.

<![CDATA[A pilot study assessing reliability and age‐related differences in corticomuscular and intramuscular coherence in ankle dorsiflexors during walking]]>


Corticomuscular (CMC) and intramuscular (intraMC) coherence represent measures of corticospinal interaction. Both CMC and intraMC can be assessed during human locomotion tasks, for example, while walking. Corticospinal control of gait can deteriorate during the aging process and CMC and intraMC may represent an important monitoring means. However, it is unclear whether such assessments represent a reliable tool when performed during walking in an ecologically valid scenario and whether age‐related differences may occur. Wireless surface electroencephalography and electromyography were employed in a pilot study with young and old adults during overground walking in two separate sessions. CMC and intraMC analyses were performed in the gathered beta and lower gamma frequencies (i.e., 13–40 Hz). Significant log‐transformed coherence area was tested for intersessions test–retest reliability by determining intraclass correlation coefficient (ICC), yielding to low reliability in CMC in both younger and older adults. intraMC exclusively showed low reliability in the older adults, whereas intraMC in the younger adults revealed similar values as previously reported: test–retest reliability [ICC (95% CI): 0.44 (−0.23, 0.87); SEM: 0.46; MDC: 1.28; MDC%: 103; Hedge's g (95% CI): 0.54 (−0.13, 1.57)]. Significant differences between the age groups were observed in intraMC by either comparing the two groups with the first test [Hedge's g (95% CI): 1.55 (0.85, 2.15); p‐value: .006] or with the retest data [Hedge's g (95% CI): 2.24 (0.73, 3.70); p‐value: .005]. Notwithstanding the small sample size investigated, intraMC seems a moderately reliable assessment in younger adults. The further development and use of this measure in practical settings to infer corticospinal interaction in human locomotion in clinical practice is warranted and should help to refine the analysis. This necessitates involving larger sample sizes as well as including a wider number of lower limb muscles. Moreover, further research seems warranted by the observed differences in modulation mechanisms of corticospinal control of gait as ascertained by intraMC between the age groups.

<![CDATA[PGC‐1α overexpression increases transcription factor EB nuclear localization and lysosome abundance in dystrophin‐deficient skeletal muscle]]>


Duchenne muscular dystrophy (DMD) is caused by the absence of functional dystrophin protein and results in progressive muscle wasting. Dystrophin deficiency leads to a host of dysfunctional cellular processes including impaired autophagy. Autophagic dysfunction appears to be due, at least in part, to decreased lysosomal abundance mediated by decreased nuclear localization of transcription factor EB (TFEB), a transcription factor responsible for lysosomal biogenesis. PGC‐1α overexpression decreased disease severity in dystrophin‐deficient skeletal muscle and increased PGC‐1α has been linked to TFEB activation in healthy muscle. The purpose of this study was to determine the extent to which PGC‐1α overexpression increased nuclear TFEB localization, increased lysosome abundance, and increased autophagosome degradation. We hypothesized that overexpression of PGC‐1α would drive TFEB nuclear translocation, increase lysosome biogenesis, and improve autophagosome degradation. To address this hypothesis, we delivered PGC‐1α via adeno‐associated virus (AAV) vector injected into the right limb of 3‐week‐old mdx mice and the contralateral limbs received a sham injection. At 6 weeks of age, this approach increased PGC‐1α transcript by 60‐fold and increased TFEB nuclear localization in gastrocnemii from PGC‐1α treated limbs by twofold compared to contralateral controls. Furthermore, lamp2, a marker of lysosome abundance, was significantly elevated in muscles from limbs overexpressing PGC‐1α. Lastly, increased LC3II and similar p62 in PGC‐1α overexpressing‐limbs compared to contralateral limbs are supportive of increased degradation of autophagosomes. These data provide mechanistic insight into PGC‐1α‐mediated benefits to dystrophin‐deficient muscle, such that increased TFEB nuclear localization in dystrophin‐deficient muscle leads to increased lysosome biogenesis and autophagy.

<![CDATA[Membrane stabilizer Poloxamer 188 improves yield of primary isolated rat cardiomyocytes without impairing function]]>


Intact cardiomyocytes are used to investigate cardiac contractility and evaluate the efficacy of new therapeutic compounds. Primary enzymatic isolation of adult rodent cardiomyocytes has limitations, including low cardiomyocyte survival, which is likely due to ischemic conditions and/or membrane damage. The addition of Poloxamer 188 (P188) has been used to reduce ischemia‐ and membrane‐related damage in ischemia–reperfusion and muscular dystrophy studies. P188 stabilizes membranes, reducing cell death. Cardiomyocytes were isolated from rats, under three conditions: (1) using standard isolation solutions, (2) with P188 added during cannulation (ischemic event), and (3) with P188 added during cannulation, enzymatic digestion, and trituration. Cell survival was assessed by quantifying the number of rod‐shaped versus contracted cells on the day of isolation and up to 3 days post‐isolation. Adding P188 only during cannulation yielded improved survival on the day of isolation. Little difference in survival was seen among the three conditions in the days post‐isolation. Cardiomyocyte function was assessed by measuring calcium transients and unloaded sarcomere lengths for up to 2 days post‐isolation. P188 did not consistently alter calcium handling or sarcomere shortening in the isolated cardiomyocytes. We conclude that the addition of P188 to the cannulation (e.g., wash) of the isolated heart may improve initial survival of cardiomyocytes upon primary enzymatic isolation.