Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis

Abstract Background Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome. Case presentation A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation. Conclusions This is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.https://deepblue.lib.umich.edu/bitstream/2027.42/142870/1/40842_2018_Article_58.pd

Use of Pie Charts in Cognitive Therapies

One of the major goals of cognitive therapy is to generate cognitive restructuring for clients. While generating cognitive restructuring plenty of cognitive interventions can be useful. One of those interventions is building a Pie Chart (PC) prepared collaboratively with clients. In literature large amount of example related to target areas of PC has been stated. Investigating reasons of an event or a situation, appraising ones responsibility, testing catastrophic evaluations regarding a life event, challenging labeling thoughts and setting goals are some of the major target areas of PC. When using PC it is aimed at expanding perspectives of clients and helping them achieve an objective point of view towards life events and situations. The goal of the current paper is to explain the target areas for PC as a tool for cognitive restructuring. Key Words: Cognitive Therapy, Cognitive Restructuring, Pie Chart Technique [JCBPR 2016; 5(1.000): 38-43

Tissue Sodium in Patients With Early Stage Hypertension: A Randomized Controlled Trial

Background Sodium (Na+) stored in skin and muscle tissue is associated with essential hypertension. Sodium magnetic resonance imaging is a validated method of quantifying tissue stores of Na+. In this study, we evaluated tissue Na+&nbsp;in patients with elevated blood pressure or stage I hypertension in response to diuretic therapy or low Na+&nbsp;diet. Methods and Results In a double-blinded, placebo-controlled trial, patients with systolic blood pressure 120 to 139 mm Hg were randomized to low sodium diet (&lt;2 g of sodium), chlorthalidone, spironolactone, or placebo for 8 weeks. Muscle and skin Na+&nbsp;using sodium magnetic resonance imaging and pulse wave velocity were assessed at the beginning and end of the study. Ninety-eight patients were enrolled to undergo baseline measurements and 54 completed randomization. Median baseline muscle and skin Na+&nbsp;in 98 patients were 16.4 mmol/L (14.9, 18.9) and 13.1 mmol/L (11.1, 16.1), respectively. After 8 weeks, muscle Na+&nbsp;increased in the diet and chlorthalidone arms compared with placebo. Skin sodium was decreased only in the diet arm compared with placebo. These associations remained significant after adjustment for age, sex, body mass index, systolic blood pressure, and urinary sodium. No changes were observed in pulse wave velocity among the different groups when compared with placebo. Conclusions Diuretic therapy for 8 weeks did not decrease muscle or skin sodium or improve pulse wave velocity in patients with elevated blood pressure or stage I hypertension. Registration URL: https://www.clinicaltrials.gov; Unique identifier:&nbsp;NCT02236520.</span

High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals.

BACKGROUND AND AIMS: High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. METHODS AND RESULTS: In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using (23)Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r=-0.45, p=0.01) and skin sodium (r=-0.46, p=0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction= 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction= 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction=0.01). CONCLUSIONS: Higher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies. Clinicaltrials.gov registration: NCT02236520

Additional file 1: of Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis

Appendix 1. Antibodies used for immunohistochemistry. Histopathological examination using fresh frozen muscle biopsy specimen from the patient was performed using the immunostains for: MHC1, Lamin A/C, C5b9, CD163/CD4, CD3/CD20. The antibodies used and respective protocols are shown. Appendix 2 Sanger sequencing chromatogram completed by a CLIA certified laboratory. Data from Sanger sequencing was used to confirm the patient’s whole exome sequencing (WES) results. Similar to the WES data, Sanger sequencing chromatogram revealed a heterozygous c.29 C > T mutation in exon 1. In the figure, both the wild type and the patient’s data with this mutation are shown. (PDF 618 kb